dfi cm33 tl
Transcription
dfi cm33 tl
LIFIIVERSIDAD METRDWLITANñ MITONOMA TRABAJO I DE MEDICINA - IZTAPALAPA IV PRQFECOR: ALFONSO MARTINEZ. - , INTEGRANTES: P f I L JIMENEZ MORALE5 JESUS. JIMENEZ MORALES MA. SILVA CEDILLQ MIA. TERESA. DE LOURDEC. . . r. ! I 1 *-= -_ F- APENDI CE. L c .................... 1 .........- 2 d e l hipotalamo. Lk d e l a t e a p r e o p t i c a ...................... 3 MARCO T E O R I C O . . . . . . . . . . . . . . . . . . . . . . . D e f i n i c i o n e s d e temperatura. . . REGLJLACION DE LA TENPERATUHA CORPORAL......... Funcioh DETECCION TERMOCTATICA DE EXCESIVA-papel ‘TENPERATUHA CORPORAL, D e t e c c : i o h t e r m o s t a t i c a d e l f r i b - p a p e l de los r e c e p t , o r e s d e l a p i e l y m e d u l a osea. I n t e g r a c i o h f i n a l d e ambas s e n a l e s t e r m o s t a t i c a s d e c a l o r y f r i d en e l h i p o t a l a m o . MECANISMOS DE AUMENTO DE LA PERDIDA DE CALOR CUANDO EL. CCIERPD SUFRE SORRECALENTAMIENTD......................4 M e c a n i s m o s p a r a l a c o n s e r v a c i o h y a u m e n t o d e la p r o d i i c c i o h de c a l o r c u a n d o el c u e r p o se e n f r i a . REFL-EJOS C I T A N E O C . . . . . . . . . . . . . . . . . . . . 5 EXPOSICION DEL CUERPO A FRIOC I W T E N C O C . . . . . . . . . . . . . . . . . . 6 MRRCO MEDICO FISDIOLKOGICO... MARCO F I S I O L O G I C O . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . E H I P E R T E R M I ~ ~ . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . l ü ............................ Marcc; m e d i c o y b i o l a g i c o : T r a t a m i en to. 7 y RehabilitacioA y ........................... HIPERTERMIG FEBRIL. O NO FEERIL Un a r g u m e n t o e s p e c i a l e n h i p e r t e r m i a y t e r a p i a d e cancer-. HIPERTERMIA PARA LA INGENIERIA: UN CORTO CDMPRENDID BIOLOGICO. PRINCIF‘IOS DE MEDICINA FISICA...........................19 EFECTOS FICIDLOGICOC DEL CALOR Y EFECTOS CLINICDS DE EL CALOR....... FICHA DE M1:STORIA CLINICFI.. ................................... ............................. ............................ 14 15 2ü .22 R e h a b i l i t a c i o h d e p a c i e n t e s con enfermedades vascular p e r i f e r i c a T E R M O T E R A P I A . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 ~ ANALISIS DE TUMORES INTRACRF+NEALES......................25 MRRCO INREFIIERIL... REFERENCIC R REFERENCIR I? REFERENCIA C “........................................59 REFERENCiG r? REFERENCIA El REFERENCIA E2 REFERENCIA F REFERENCIA G REFERENCIA H “........................................82 REFERENCIR I REFERENCIA J “ . . . . . . . . . . . . . . . . . . . . E 7 REFERENCIA 1: REFERENCIA 1REFERENCIA 1’1 REFERENCIA N RIPL~TORRAFñA. ....................................... .. .......................................... .......................................... ... .......................................... ........................................ .. .......................................... ........................................ .. .......................................... .. .......................................... .. ......................................... .......................................... .. .......................................... ......................................... ........................................... 2i3 52 58 64 -67 -69 72 Tí3 E~ ,90 74 98 .IO0 1ü3 MCIRCO TEORICO. TEMPERfiTURE;Es el g r a d o d e i n t e n s i d a d d e Lin c u e r p o , e s p e c i a l m e n t e c u a n d o se m i d e p o r l a e s c a l a d e un termometro,la temperatura normal es d e 98.6F (3712) con v a r i a c i o n e s o c a c i o n a l e s d u r a n t e el d i a , l l e g a n d o a n o mas d e un g r a d o . La t e m p e r a t u r a es un p o c o mas a l t a h a c i a l a n o c h e , c u a n d o l l e g a a ser d e 99.1F (37.3C),y e n l a mafiana p u e d e c a e r h a s t a 97.3F ( 3 6 . 3 C ) El c u e r p o m a n t i e n e un e q u i l i b r i o entre l a p r o d u c c i d n y la p e r d i d a d e calor, que el c u e r p o e x p e l e o p r o d u c e c a l o r s e g ü n el caso. E l c a l o r es p e r d i d o m a y o r m e n t e a t r a v e z d e l a p e r s p i r a c i 6 n y a t r a v e z d e l a i r e y v a p o r i e x p e l i d o d e los p u l m o n e s . E l c a l o r es producido por a c c i b n q u i m l c a d e 105 m u s c u l o s y l a s glandulas e s p e c i a l m e n t e e n el h i g a d o , el t e m b l o r es una a c c i o n i n v o l u n t a r i a que p r o d u c e c a l o r . La s e n s a c i d n d e c a l o r y f i - i o n o es d e b i d o a un cambio en la temperatura corporal sino un c a m b i o e n l a t e m p e r a t u r a d e la piel. Cuando l a p i e l se s i e n t e f r i a o c a l i e n t e , un m e n s a j e es enviado al c e r e b r o que a l b e r g a el m e c a n i s m o que controla l a t e m p e r a t u r a es p u e s t o e n f u n c i o n a m i e n t o c o n una c o r r e s p o n d i e n t e caida o e l e v a c i b n d e temperatura. L a t e m p e r a t u r a d e una p e r s o n a e n f e r m a , con f i e b r e puede llegar h a s t a i 0 4 f F ( 4 0 $ C ) , e n c a s o s severos t a l e s como el momento como l a muerte iCV-109LF í42-43fC) , l a muerte por insolacibn son t e m p e r a t u r a s m a y o r e s a 11OF í43.3LC). Una t e m p e r a t u r a menor d e 96$F 'í35.5$C) , p r o d u c e un c o l a p s o . En algi.inas e n f e r m e d a d e s y p r o c e d i m i e n t o s o p e r a t o r i o s l a t e m p e r a t u r a corporal puede e s t a r considerablemente p o r d e b a j o d e esta c i f r a , p o r p l e r i o d o s mas o menos l a r g o s . E l e n f r i a m i e n t . 0 d e l c u e r p o es g e n e r a l m e n t e d a h i n o p a r a l a s a l u d y es mas s e r i a p a r a una p e r s o n a c o n una i n f e c c i b n c r o n i c a d e l a n a r i z y d e l a g a r g a n t a q u e p a r a una p e r s o n a s a n a . La t e m p e r a , t r r r a e n el i n t e r i o r - d e l " nuc1eo"-- d e l . organismo es notab1ement.e c o n s t a n t e , c a m b i a n d o e n menos d e 0 . 5 t C d i a tras d i a , s a l v o e n caso d e e n f e r m e d a d f e b r i l . De h e c h o , un individuo d e s n u d o p u e d e qi.iedar e x p u e s t o a t e m p e r a t u r a s b a j a s , d e l orden de iZ$C,o r e l a t i v a m e n t e a l t a s p o r e j e m p l o 60YC, c o n s e r v a n d o sin e m b a r g o , una t e m p e r a t u r a c a s i c o n s t a n t e . . Temperatura" d e l n u c l e o " y temperatura d e l a s u p e r f i c i e . C u a n d o se h a b l a de t e m p e r a t u r a c o r p o r t a l , suele entenderse t e m p e r a t u r a d e l i n t e r i o r , denominada l a t e m p e r a t u r a d e l n u c l e o , y n o l a t e m p e r a t u r a d e l a p i e l o de t e j i d o s s i t u a d o s i n m e d i a t a m e n t e d e b a j o d e l a misma, l a t e m p e r a t u r a i n t e r n a se h a l l a r e g u l a d a e n f o r m a muy p r e c i s a ; n o r m a l m e n t e su v a l o r m e d i o n o v a r i a mas d e O.S$C. Por o t r a p a r t e l a t e m p e r a t u r a s u p e r f i c i a l s u b e y b a j a segun l a d e l medio. Al hablar d e r e g u l a c i b n t e r m i c a d e l c u e r p o casi s i e m p r e nos referimos a l a t e m p e r a t u r a d e l n c i c l e o a l t r a t a r d e l a c a p a c i d a d d e l a p i e l p a r a p e r d e r c a l o r h a c i a el m e d i o solemos e n t e n d e r la temperatura d e l a s u p e r f i c i e , cuando deseamos c a l c u l a r la cantidad d e c a l o r a l m a c e n a d a e n el cuerpo utilizamos la t e m p e r a t u r a c o r p o r a l media. La t.emperatura c o r p o r a l media p u e d e 1 v a l o r a r s e aproximadamente 1a s i q u i e n t e formula: Temperatura media = Temperatura interna + s u p e r f i c i a l . í Ver r e f e r e n c i a F.) 0.3 Temperatura Temperatura c o r p o r a l normal. hay una t e m p e r a t u r a determinada que pueda c o n s i d e r a r s e norma1,las mediciones en d i v e r s a s personas normales han mostrado una amp1 itud. No rL r L c t c f i c L r i i Relaciones e n t r e l a temperatura corporal y el calor del cuerpo;calor e s p e c i f i c o de 105 t e j i d o s . cada En promedio l a temperatura c o r p o r a l aumenta un grado por 0.83 c a l o r i a s p o r Kg,de peso c o r p o r a l . En o t r a s p a l a b r a s e l Calor e s p e c i f i c o de l o s t e j i d o s es de O.B3Cal/Kg/gradosC. C o n t r o l de l a conduccion de c a l o r h a c i a l a p i e l . La conduccibn de c a l o r p o r l a sangre h a c i a l a p i e l depende de e l grado de v a s o c o n s t r i c c i d n de l a s a r t e r i o l a s y de l a s anastombsis a r t e r i o v e n o s a s que mandan sangre a l p l e x o venoso de l a p i e l ; e s t a es c o n t r o l a d a c a s i t o t a l m e n t e p o r e l sistema vasoconstriccion n e r v i o s o simpatico. De o r d i n a r i o , e l s i m p a t i c o mantiene una actividad tonica, provocando un c i e r t o grado de c o n s t r i c c i o n s o s t e n i d o de l a s a r t e r i o l a s de l a p i e l . Cuando son e s t i m u l a d o s 105 c e n t r o s s i m p a t i c o s d e l h i p o t a l a m o p o s t e r i o r , se produce una c o n s t r i c c i d n de l o s vasos sanguineos mayor t o d a v i a y e l paso se l a sangre h a c i a l a p i e l cesa c a s i totalmente; cuando e s t o s c e n t r o s p o s t e r i o r e s d e l h i p o t a l a m o son i n h i b i d o s , disminuye un numero de i m p u l s o s s i m p a t i c o s t r a n s m i t i d o s a l a p e r i f e r i a y los vasos sanguineos se d i l a t a n . ( v e r r e f e r e n c i a DI. REOU~CION DE La TENFERATURCI CORPDRAL~FUNCION DEL HIWTCILCIMO. La t e m p e r a t u r a d e l organismo e5 r e g u l a d a c a s i enteramente por mecanismos de r - e t r o a l i m e n t a c i d n n e r v i o s o s en los cuales i n t e r v i e n e c a s i siempre un c e n t r o de r e g u l a c i b n de l a temperatura situado en e l hipotalamo. S i n embargo p a r a que e s t o s mecanismos debe e x i s t i r de r e t r o a l imentaci dn f u n c i o n e n s a t is f a c t o r i amente, tambien un sistema de i d e n t i f i c a c i d n de l a temperatura p a r a establecer s i l a t e m p e r a t u r a c o r p o r a l es demasiado a l t a o b a j a . Algunos de e s t o s r e c e p t o r e s son l o s s i g u i e n t e s : Receptores de temperatura. Probablemente l o s r e c e p t o r e s de temperatura m a s i m p o r t a n t e s p a r a l a r e g u l a c i b n de l a t e m p e r a t u r a c o r p o r a l sean muchas neuronas s e n c i b l e s a l c a l o r s i t u a d a s en l a r e g i d n p r e d p t i c a d e l h i p o t a l a m o anterior. E s t a s neuronas aumentan su f r e c u e n c i a de descarga cuando l a t e m p e r a t u r a sube, y l a reducen criando l a temperatura baja. La f r e c u e n c i a de descarga puede aumentar 10 veces por una elevation de t e m p e r a t u r a de 10 C. Ademas de e s t a s neuronas s e n c i b l e s al calor en l a r e g i o n predptica, e x i s t e n o t r o s r e c e p t o r e s de temperatura: 1 ) Algunas neuronas s e n s i b l e s a l f r i o en d i s t i n t a s p a r t e s d e l hipotalamo, 5eptLw-1 y s u s t a n c i a r e t i c u l a r del mesencefalo; aumentan su f r e c u e n c i a de descarga p o r e x p o s i c i b n a l f r i o (hay pocas neuronas de e s t e t i p o ; no se sabe s i i n t e r v i e n e n en l a r e g u l a c i b n de l a temperatura c o r p o r a l en c o n d i c i o n e s normales); 2) Receptores ccitsneos de temperatura i n c l u y e n d o r e c e p t o r e s al frio y receptores a l calor; mandan impulsos n e r v i o s o s a l a medula espinal, y luego a l a r e g i b n hipotalamica d e l cerebro, para c o n t r i b u i r a l a r e q u l a c i b n de l a temperatura c o r p o r a l , 3 ) E x i s t e n r e c e p t o r e s de temperatura en l a médula e s p i n a l , abdomen y posiblemente en algunos brganos i n t e r n o s , que mandarian Senales a l s i s t e m a n e r v i o s o c e n t r a l con e l mismo o b j e t o . DETECCIDN mm-maTuRcI TERMOBTATICA EN EXCESO) DE LA TEMPERATURA -PAPEL DFEL AREA CORPORAL PREOPTICA EXCESIVA DEL HIPM6LARO. En l o s rSltimos ahos, 5e han l l e v a d o a cavo experimentos que c o n s i s t i e r o n en c a l e n t a r o e n f r i a r - zonas pequehas d e l encbfalo, empleando l o que se ha Hamado un térmodo. Se t r a t a de un d i s p o s i t i v o que puede c a l e n t a r s e p o r medios e l é c t r i c o s , o haciendo pasar a su t r a v e s ayua c a l i e n t e . La p r i n c i p a l r e g i o n d e l e n c e f a l o en donde e l c a l o r di31 termodo m o d i f i c a l a r e g u l a c i b n de l a t e m p e r a t u r a es l a r e g i b n p r e á p t i c a d e l h i p o t a l a m o y en menor A e s t e n i v e l hay grado en zonas v e c i n a s d e l h i p o t a l a m o a n t e r i o r . v a r i a s neuronas s e n s i b l e s ,al c a l o r cuya i n t e n s i d a d de descarga aumenta considerablemente cu,nndo se c a l i e n t a n ; se c r e e que e s t a s papel d e c i s i v o en e l control de l a neuronas desempehan u n temperatura, c o r p o r a l . DETECCIDN ERMOSTATICA DEL FRIO -PAPEL DE RECEPTDRES DE PIEL MEDULA ESPINAL. Una de l a 5 formas en l a s c u a l e s e l cuerpo descubre e l f r i o es a l disminuir 105 r i t m o s de descarga de l a s neuronas s e n c i b l e s al calor que hay en e l area p r e o t i c a . Pero cuando l a t e m p e r a t u r a c o r p o r a l i n t e r n a ha b a j a d o ~ m a 5 , p o c a sdecimas de grado p o r d e b a j o de l a normal, e s t a s nei.ironas generalmente se vuelven inactivas, de manera que y a no puede d e s c u b r i r s e mas que produzcan sehales. Cuando la t e m p e r a t u r a cae mas t o d a v i a o t r o s r e c e p t o r e s , a p a r t e de l o s que hay en e l h i p o t a l a m o parecen ser 105 que proporcionan. sehales p r i n c i p a l e s de f r i o . E s t o s r-eceptores e s t a n l o c a l i z a d o s sobre t o d o en medula e s p i n a l y p i e l , y sus senales c o n t i t u y e n un impulso init.ensa p a r a que e l cuerpo conserve c a l o r y p a r a que aumente mucho l a p r o d u c c i d n d e l mismo por el proceso de " e s c a l o f r i o". INTEQRACION FINAL DE AMBAS SENALEC TERMOSTATICAS DE CALOR Y FRIO EN EL H I P M A L M -EL "TERm)STAlO HIPOTALAMICO". Aunque l a mayor p a r t e de s e k a l e s p a r a f r i o nacen en r e c e p t o r e s periféricos, son t r a n s m i t i d a s a l h i p o t a l a m o p o s t e r i o r , donde se integra con l a s s e h a l e s d e l receptor del Brea preotica, integrando l a s sekalers eferentes f i n a l e s para c o n t r o l a r l a p e r d i d a y l a p r o d u c c i b n de c a l o r . Por l o t a n t o , solemos h a b l a r del c e n t r o de c o n t r o l de r e g u l a c i d n de l a t e m p e r a t u r a como el t e r m o s t a t o h i p o t a l ami co. L a c u r v a c o n t i n u a muestra que c a s i presisamente en 37$C,empieza l a sudacion, que aumenta rapidamente cuando l a temperatura se e l e v a mas. Por o t r a p a r t e , cesa a c u a l q u i e r temperatura p o r debajo de e s t e mismo v a l o r c r i t i c o ( v e r figuras 1,Z en l a r e f e r e n c i a R). 3 Y c i . c. I ..__ rb r i c r , i r I c L Í L r L [: i P i r i r i L c t L- F - r i f -. .a I ...,. .. ..., ....- J,, 366 . W6 310 572 lEh!PERAl!li:A DE LA L A H I M ' a i i d o l C) L. c ... rmwrsme DE ALJNEMTO SUFRE BOBRECALENTMIENTO. DE LA PERDIDA DE CALOR CUANDO EL CUERPO El s o b r e c a l e n t a m i e n t o d e l a r e a t e r m o s t a t i c a p r e o p t i c a aumenta l a p e r d i d a de c a l o r de dos maneras; 1 ) estimulando l a s glandulas sudoriparas para perder icalor por evaporacibn, y 2) por i n h i b i c i o n de c e n t r o s s i m p a t i c o s d e l h i p o t a l a m o p o s t e r i o r que suprime e l v a s o c o n s t r i c t o r de l o s vasos cutaneos y de e s t a forma tambien permite una v a s o d i l a t a c i o n mas. i n t e n s a t o d a v i a y i n h i b i e n d o e l mecanismo d e l e s c a l o f r i o p a r a e v i t a r una p r o d u c i b n e x c e s i v a de c a l o r . NECcIFIISMüS PARA CONSEWñCION Y AUMENTO DE PRODUCCION EL CUERPO SE ENFRIA. DE CALOR CUANM) i - i - r L Cuando l a zona p r e o p t i c a d e l h i p o t a l a m o se e n f r i a p o r debajo de e n t r a n en juego mecanismos e s p e c i a l e s p a r a aproximadamente 37XC, conservar e l c a l o r e x i s t e n t e en l a economia y o t r o s p a r a aumentar l a p r o d u c c i b n d e l mismo en l a s i g u i e n t e forma. Conservacinn de c a l o r . V a s o c o n ~ t r i c c i b nen l a p i e l . Uno de l o s p r i m e r o s e f e c t o s e s l a i n t e n s a v a s o c o n s t r i c c i b n de 105 vasos cutaneos en t o d a l a economia. E l l o depende de l a l i b e r a c i b n de l a s zonas s i m p a t i c a s h i p o t a l a m i c a s p o s t e r i o r e s , que se l i b e r a n i n h i b i c i b n p o r l a s sehales t e r m o s t a t i c a s p r e o p t i c a s y de la probablemente mas t o d a v i a d e l impulso p r o v e n i e n t e de 106 r e c e p t o r e s d e l f r i o en p i e l y medZila e s p i n a l . En consecuencia, l a s areas s i m p a t i c a s aumentan 5u a c t i v i d a d , y en t o d o el cuerpo 5e p r aduce int enso vasoconstr ic c i bn adrener g i ca. Esta v a s o c o n s t r i c c i b n i m p i d e que l a conduccibn de c a l o r de l a s p a r t e s i n t e r n a s d e l cuerpo a l a p i e l . ( v e r r e f . D).Cupresion d e l sudor. El sudor queda completamente s u p r i m i d o cuando se e n f r i a e l termostato prebptico por debajo de ~ i n o s 37YC. Est0 manifiestamente interrumpe e l enfriamiento del cuerpo por lo que se r e f i e r e a l a evaporacibn evaporacibn, excepto insensible. Flumento d e p r o d u c c i d n de c a l o r . L.a p r n d u c c i b n de c a l o r aumenta en t r e s formas d i f e r e n t e s cuando l a t e m p e r a t u r a d e l t e r m o s t a t o h i p o t a l a m i c o cae por debajo de 37C: i E s t i mu1 a c i an h i p o t a l amica d e l escal O F r i o . L o c a l i z a d a en l a p a r t e dorsomedial del hipotalamo p o s t e r i o r , c e r c a de l a pared d e l t e r c e r v e n t r i c f i l o , e s t a una zona denominada c e n t r o motor p r i m a r i o p a r a e s c a l o f r i o . E s t a area normalmente e s i n h i b i d a p o r s e h a l e s procedentes d e l a r e a t e r m o s t a t i c a pr-ebpotica pero estimulada por s e k a l e s p r o v e n i e n t e s de p i e l y medola espinal. Por l o t a n t o en r e s p u e s t a al f r i o e s t e c e n t r o es activado y t r a n s m i t e impulsos s i g u i e n d o haces b i l a t e r a l e s que b a j a n p o r e l t a l l o c e r e b r a l pasan a l o s cordones l a t e r a l e s de l a medhla, y f i n a l m e n t e van a l a s motoneuronas a n t e r i o r e s . El metAbolismo muscular aumenta l , a p r o d u c c i d n de c a l o r muchas veces elevando l a p r n d u c c i b n t o t a l h a s t a 50% i n c l u s o a n t e s de i n i c i a r s e 10s e s c a l o f r i o s . E s t o probablemente r e s u l t e de una r 4 .... " r . o s c i l a c i h n c o n r e t r o a l i m e n t a c i & n d e l mecanismo d e r e f l e j o d e e s t i r a m i e n t o de 105 husos musculares. D u r a n t e e1 escaiofrio maximo l a p r o d c i c c i & n c o r p o r a l d e c a l o r p u e d e a u m e n t a r h a s t a c i n c o veces 1a n o r m a l . - I - L c L c c i c L c r L c E x c i t a c i b n s i m p a t i c a "quimica" d e l a produccidn d e c a l o r . L.a e x c i t a c i d n s i m p a t i c a , o l a adrenalina y noradrenalina circulantes, podian dar Irigar a un a u m e n t o i n m e d i a t o d e l m e t a b o l i s m o c e l u l a r ; este e f e c t o se l l a m a termogLnesis q u i m i c a , y p a r a c e d e b e r s e en p a r t e c u a n d o menos, a l a capacidad de l a noradrenalina y adrenalina d e desacoplar la fosforilacibn oxidativa, con l o c u a l se h a c e n e c e s a r i o una mayor o x i d a c i b n d e los e l e m e n t o s p a r a o b t e n e r io5 c o m p u e s t o s d e f o s f a t o d e a l t a e n b r g i a r e q u e r i d o s p o r l a f u n c i d n normal d e l o r g a n i s m o El g r a d o d e t e r m o g h e s i s q u i m i c a q u e t i e n e l u g a r e n un animal es casi directamente proporcional a l a cantidad d e grasa parda que e x i s t e e n su5 t e j i d o s . E s t e e5 Lln t i p o d e g r a s a q u e c o n t i e n e gran numero d e m i t o c o n d r i a s e n s u s c e l u l a s p r o v i s t a s d e una r i c a inervacion simpaticd. Por e s t i m u i a c i b n s i m p a t i c a , el metabolismo o x i d a t i v o d e l a s m i t o c o n d r i a , s se e s t i m u l a c o n s i d e r a b l e m e n t e , p e r o esto p r o b a b l e m e n t e t i e n e l u g a r s i n a c o p l a m i e n t o , d e manera q u e 5 0 1 ~ 1se f o r m a n p e q u e h a s c a n t i d a d e s d e ñTP. REFLEJOS CUTCIMOS LOCALES. Cuando una p e r s o n a p o n e su p i e d e b a j o d e una l a m p a r a c a l i e n t e y l o d e j a ahi por b r e v e tiempo, p e r c i b e un c a l e n t a m i e n t o l o c a l y l i g e r o s u d o r l o c a l . I n v e r s a m ~ n t e , c u a n d o se c o l o c a un p i e e n a g u a f r i a h a y v a s o c o n s t r i c c i d n y cesa l a p r o d u c c i b n d e s u d o r . Estas r e a c c i o n e s d e p e n d e n d e r e f l e j o s m e d u l a r e s l o c a l e s q u e se p r o d u c e n a p a r t i r d e 105 r e c e p t o r e s c u t a n e o s h a s t a l a m e d h l a y d e regreso hacia l a misma z o n a c i i t a n e a . S i n embargo, su i n t e n s i d a d es r e g u l a d a p o r el t e r m o s t a t o h i p o t a l a m i c o , d e m a n e r a q u e el e f e c t o global es a p o r x i m a d a m e n t e p r o p o r c i o n a l a l a s e h a i termoatatica m u l t i p l i c a d a p o r l a sePial l o c a l . E f e c t o s p e r j u d i c i a l e s d e l a temperatura elevada. C u a n d o l a t . e m p e r a t u r a c o r p o r a l se e l e v a p o r e n c i m a d e 41.5tC suele empezar a p r o d u c i r l e s i o n p a r e n q u i m a t o s a d e muchas celulas. El e s t u d i o h i s t b l o g i c o e n una p e r s o n a m u e r t a d e hiperpirexia descubre hemorragi a s l o c a l e s y degeneracion parenquimatosa de c e l u l a s en toda l a econornia. El cerebro tiene particular t e n d e n c i a a s u f r i r p o r q u e una v e z d e s t r u i d a s l a s n e u r o n a s n o son substituidas. Cuando l a t e m p e r a t u r a c o r p o r a l se e l e v a h a s t a 4345.!WC, el p a c i e n t e suele t e n e r u n a s p o c a s h o r a s d e v i d a a m e n o s q u e l a t e m p e r a t u r a se h a g a d e s c e n d e r r a p i d a m e n t e h a s t a v a l o r e s n o r m a l e s m o j a n d o el c u e r p o con a l c o h o l q u e se e v a p o r a y lo e n f r i a , o sumergiendo10 en agua h e l a d a ( v e r ref. E 1,2). Efectos de medicamentos y p r o d u c t o s quimicos sobre la t e m p e r a t Lira. Un numero e x t r a o r d i n a r i a m e n t e d e s u b s t a n c i a s e x t r a h a s i n y e c t a d a s los l i q u i d o s c o r p o r a l e s p u e d e h a c e r q u e l a t e m p e r a t u r a en corporal se el eve O 5ea que resulten pir&genos,bacterias,polenes,pOiVOs y v a c u n a s s o n t o d o s p i r b g e n o s por su contenido proteinico. 5 EXPOSICION DEL C U E R W A FRIOS INTENSOS. Una persona expuesta a l agua h e l a d a d u r a n t e unos 20 o 30 m i n . suele morir p o r f i b r i l a c i b n o p a r o d e l corazbn a menos que se t r a t e de inmediato. Por entonces l a temperatura i n t e r n a del cuerpo habra c a i d o h a s t a a l r e d e d o r de 25C. S i n embargo, si se c a l i e n t a rapidamente p o r a p l i c a c i b n de c a l o r externo, l a vida muchas veces puede s a l v a r s e . El t r a t a m i e n t o de un p a c i e n t e cuya t e m p e r a t u r a c o r p o r a l a c a i d o alrededor de 22 a 26C s u e l e c o n s i s t i r en a p l i c a r c a l o r humedo en forma de bako, o compriesas empapadas en agua caliente, S i l a temperatura del aproximadamente a temperaturas de 43tC. agua e s menorl e l cuerpo reclupera c a l o r demasiado lentamente p a r a si l a t e m p e r a t u r a es mayor l a piel lograr b e n e f i c i o mhimo; puede l e s i o n a r s e gravemente p o r c a l e n t a m i e n t o e x c e s i v o m i e n t r a s no dispone de r i e s g o sangui neo adecuado. MCIRCO MEDICO FISIOLOC~CO. Temperatura; Hay dos t i p o s de organos s e n s i b l e s a l a temperautra.Los que responden a l mawimo a temperaturas l i g e r a m e n t e s u p e r i o r e s a l a del cuerpo y 105 de r e s p u e s t a mawima a temperaturas escasamente i n f e r i o r e s a l a corporal. L o s p r i m e r o s son 105 organos s e n s i b l e s llama p a r a 10s que se l l a m a c a l o r y 105 segundos p a r a l o que se frio. S i n embargo,los e s t i m u l o s adecuados son en r e a l i d a d do5 grados d i f e r e n t e s de c a l o r , p u e s t o que e l f r i o no r e p r e s e n t a forma de e n e r g i a alguna y l a sensacibn de c a l i e n . t e es una combinacibn de c a l o r y d o l o r l i g e r o . Aunque l a presente controversia acerca de l a especifidad h i s t b l o g i c a de l a 5 t e r m i n a c i o n e s cutaneas h a p u e s t o en duda l a e s t r u c t u r a d e t a l l a d a de 105 organos s e n s i b l e s a l c a l o r y al f r i o . l..as pequeñas f i b r a s m i e l i n i z a d a s que t r a n s m i t e n l a s e n s i b i l i d a d t e r m i c a son de 2 a 5 micras,de d i a m e t r o y pertenecen a l grupo Ad de E a r l a n g e r y Gasser ( v e l o c i d a d de conduccibn 12-3üm/sog, d u r a c i b n de l a e s p i g a 0.4-0.5m/seg, p e r i o d o r e f r a c t a r i o 0.4lmseg). L.os i m p u l s o s que v i a j a n p o r e l l a s llegan a l a circonvolucibn posrol&ndica a traves del f a s c i c u l o espinot a l a m i c o l a t e r a l y de la r a d i a c i b n t a l a m i c a . Debido CI que los organos . s e n s i t i v o s estan situados subepitelialmente, e5 l a temperat.ura de l o s t e j i d o s subcutaneos l a que determina l a 5 respuestas. Los o b j e t o s m e t a l i c o s f r i b s se sienten ma5 f r i b s que l o s o b j e t o s de madera a l a misma temperatura, p o r que l o s m e t a l e s conducen e l c a l o r de l a p i e l mas rapidamente, e n f r i a n d o a los t e j i d o s subcutaneos en mayor grado. Regulacibn de l a temperatura; En e l organismo e l c a l o r e s p r o d u c i d o p o r e l e j e r c i c i o muscular, por l a e s t i m u l a c i b n de l o s a l i m e n t o s y p o r t o d o s l o s procesos v i t a l e s que c o n t r i b u y e n a l a t a z a m e t a b o l i c a b a s a l . E l calor es p e r d i d o del cuerpo p o r r a d i a c i o n e s , conduccibn y v a p o r i z a c i b n d e l agua es l a s v i a s r e s p i r a t o r i a s y en l a p i e l . Pequekas cantidades de c a l o r tambien se p i e r d e n en o r i n a y 6 en l a s h e c e s el b a l a n c e o entre l a produccibn y p e r d i d a d e c a l o r d e t e r m i n a l a temperatura c o r p o r a l . D e b i d o a que l a v e l o c i d a d d e l a s r e a c i o n e s q u i m i c a s v a r i a r i con l a t e m p e r a t u r a y a causa d e que IDS sistemas e n z i m a t i c o s d e l o r g a n i s m o s t i e n e n un margen e s t r e c h o e n el cual su f u n c i o n es optima, l a s f u n c i o n e s normales d e l c u e r p o dependen d e una t e m p e r a t u r a r e l a t i v a m e n t e c o n s t a n t e . -Porkilotermos ( a n i m a l e s d e s a n g r e f r i a ) . Los mecanismos d e a j u s t e s o n r u d i m e n t a r i o s y son los r e p t i l e s , e n l o s a n f i b i o s y e n l o s peces. -Homeotermos (animales d e sangre c a l i e n t e ), o p e r a un grupo d e r e s p u e s t a s r e f l e j a s que se i n t e g r a n e n el h i p o t a l a m o para mantener l a t e m p e r a t u r a c o r p o r a l d e n t r o d e un estrecho margen a p e s a r d e l a s a m p l i a s f l ~ ~ c t u a c i o n edse l a t e m p e r a t u r a ambiente. En los p a j a r o s y e n 105 mamiferos. 1-05 a n i m a l e s i n v e r n a n t e s son una e,:cepcibn p a r c i a l , p u e s m i e n t r a s e s t a n d e s p i e r t o s son hemeot&rmicos, p e r o d u r a n t e l a i n v e r n a c i b n uu t e m p e r a t u r a c o r p a r a l baJa. Temperatura normal d e l cuerpo. el hombre, l a c i f r a t r a d i c i o n a l normal p a r a l a t e p W & W a oral e5 d e 37SC. con una v a r i a c i b h e s t a n d a r d e 0.21C. V a r i a s p a r t e s d e l c u e r p o 5e encuentran a d i f e r e n t e s t e m p e r a t u r a s y l a magnitud d e l a d i f e r e n c i a d@ trmpmratura entre l a s d i v e r s a s p a r t e s v a r i a con l a t e m p e r a t u r a ambiente. Las extremidades estan g e n e r a l m e n t e mas f r i a s que e l resto d e l cuerpo, l a temperatura r e c t a l es r e p r e s e n t a t i v a d e l e j e d e l c u e r p o y v a r i a menos coi;, los cambios e n l a t e m p e r a t u r a ambiente ( v e r ref.C y H). La t e m p e r a t u r a d e l q a boca es normalmente 0.32 mas b a j a q u e l a rectal, p e r o es a f e c t a d a por muchos f a c t o r e s , i n c l u y e n d o la ingestion d e alimentos frios y c a l i e n t e s , l a masticacion de c h i c l e , fumar y l a r e s p i r a c i o n bucal. 1.a t.emperatura d e l a p a r t e c e n t r a l d e l c u e r p o humano normal e x p e r i m e n t a una f l u c t u a c i b n d i u r n a r e g u l a r d e O.CJ-O.7WZ. En i n d i v i d u o s que duermen d u r a n t e l a noche y e s t a n d e s p i e r t o s e n el dia, l a t e m p e r a t u r a es mas b a j a d u r a n t e el suePlo, ligeramente mayor e n e s t a d o d e v i g i l i a t r a n q u i l a y sube con l a a c t i v i d a d . En l a mujer tamhien existe un c i c l o menstrfial d e l a v a r i a c i b n d e t e m p e r a t u r a c a r a c t e r i z a d o por un cambio d e temperatura b a s a l en el tiempo d e l a o v ~ l a c i & n , l a regulac.ibn d e l a temperatura es menos p r e c i s a e n los riihos pequekos y normalmente ellos pueden tener una t e m p e r a t u r a que es aproximadamente C).5$C mayor que l a normal e s t a b l e c i d a p a r a 105 a d u l t o s . Durante el e j e r c i c i o el c a l o r p r o d u c i d o p o r l a concentracibn muscular se acumula e n el cuerpo y l a temperatura r e c t a l normalmente sube h a s t a 4 0 X . E s t a e l e v a c i b n es d e b i d a e n p a r t e a la i n c a p a c i d a d d e 105 mecanismos d i s i p a d o r e s d e c a l o r p a r a e n f r e n t a r E\ l a c a n t i d a d grandemente incrementada d e c a l o r que es p r o d u c i d a , p e r o hay e v i d e n c i a d e que, ademas ocurre una e l e v a c i b n d e l a t e m p e r a t u r a c o r p o r a l a l a cual 105 mecanismos d i s i p a d o r e s d e c a l o r son a c t i v a d o s d u r a n t e el e j e r c i c i o . La t e m p e r a t u r a d e l c u e r p o tamhien sube l i g e r a m e n t e d u r a n t e l a e x c i t a c i b n emocional, probablemente d e b i d o a l a t e n s i o n i n c o n s i e n t e d e 105 musculos. Cronicament:e e s t a e l e v a d a h a s t a 0.5K cuando l a t a z a m e t a b o l i c a es En a l t a por e j e m p l o e n e l h i p e r t i r o i d i s m o , 7 y disminuida por e j e m p l o en e l mixidema. FIlgunos a d u l t o s aparentemente normales t i e n e n una t e m p e r a t u r a cronicamente a r r i b a d e l l i m i t e normal í h i p e r t e r m i a c o n s t i t u c i o n a l ). P e r d i d a de c a l o r ; -La radiacian: Es l a t r a n s S e r e n c i a de c a l o r de un o b j e t o a o t r o con e l c u a l no e s t a en c o n t a c t o . -La conduccibn: Es e l i n t e r c a m b i o de c a l o r de un o b j e t o a d i f e r e n t e s t e m p e r a t u r a s que se encuentran en c o n t a c t o e n t r e s i . -La conveccibn: O sea e l movimiento de l a s moleculas de un gas o de un l i q u i d o o de una temperatura a o t r o s i t i o de diferente temperatura ayuda a l a conduccibn, cuando un i n d i v i d u o se haya en un ambiente f r i o p i e r d e c a l o r por conduccibn a l a i r e que lo rodea y p o r r a d i a c i o n a l o s iobjetos v e c i n o s f r i o s (ver r e f . D ) . MARCO FISIOLOOICO. ' Temperatura del cuerpo 'y su control: Los mecani smos especialmente mantienen un n i v e l , en muchos mamiferos, aves e t c , un e s t a d o c l a r o e n t r e l a p r o d u c c i b n de c a l o r y su p e r d i d a h a c i a el medio, a5i que e l i m i n a d e l cuerpo y e s t a c e r c a be un n i v e l normal, s i n l i m i t e restringido. Todos 105 organismos producen calor m e t a b o l i c o y reaccionlas e x o t & r m i c a s cuando e l cuerpo e s t a en descanso, e l corazon, cerebro, v i s c e r a s ( y notablemente el h i g a d o ) ? y l l e g a a 5er de un 50% d e e l t o t a l d e l calor. En e l ejercicio grandes c a n t i d a d e s de c a l o r son p r o d u c i d a s mas p e r i f e r i c a m e n t e por 105 mu5culos. La c i r c u l a c i b n d e l cuerpo tiende a i g u a l a r s e l a temperatura s i n un corazbn c e n t r a l , dado 105 a c a r r e o s de c a l o r de l a s u p e r f i c i e d e l cuerpo h a c i a por afuera. El tamaho de e l cuerpo d e l corazbi; en d i c h a temperatur-a e s m a s o menos uniforme, depende de e l estado p a r t i c u l a r de e l s i s t e m a y su amhient,e,Fig.Al, muestra dos p o s i b l e s d i s t r i b u c i o n e s de t e m p e r a t u r a en e l cuerpo. Comparada con e l cuerpo en un ambiente caliente, e5 r e l a t i v a m e n t e pequeho en e l corazbn y es cercano a l a temperat.ura normal en e x p o s i c i b n f r i a . La t e m p e r a t u r a de l a p i e l e s mas frecuentemente e n t r e l a del cuerpo d e l corazdn y l a temperatura ambiente, excepto cuando e l calor evaporado y son grandes p e r d i d a s . Siempre un mecanismo de f u e n t e de vapor, son a v i a b l e s p a r a mantener l a temperatura d e l cuerpo d e l corazbn, e s t o e s p r o t e c c i b n de organos i n t e r n o s , o t r a v e s en l a r g o s cambios de temperatura. Nosotros d e f i n i m o s e s t r u c t u r a s en l a i n f o r m a c i b n procesada p o r e l h i p o t a l a m o en l a temperatura l o c a l d e l cerebro, de l a t e r m i n a c i b n n e r v i o s e n s i t i v a de temperatura en l a p i e l y q u i z a s de l a temperatura de 105 sensores d e l cuerpo l a c u a l es d e s i n t e g r a d a hacia e l e x t e r i o r d e l cerebro,. y p o r c o n s i g u i e n t e . e l c o n t r o l externo y todos l o s mecanismos de c a l o r en l a s perdidas. production y preservacibn, actividad vasomotora, rangos "control metabolicos, actividad sudomotora. Esto es el central",tiene una f i n a s e n s i b i l i d a d para desviaciones de temperatura, pone puntos. Nosotros podemos d i b u j a r un diagrama general de bloques 8 Fig,A2, i n d i c a n d o l a s p r i n c i p a l e s componentes d e el c o n t r o l , l a p a r t e d e l control d e #el s i s t e m a t e r m o r e g u l a t o r i o , y s u 5 muchas 'conexiones. La c o n s t r u c c i d n d e un modelo d e l s i s t e m a d e r e t r o a l i m e n t a c i b n es un termost,ato, que f u e p r o v i s t o p a r a ser usado, especialmente para d e t a l l a r l a a c c i b n d e el c o n t r o l y m o d i f i c a c i b n d e poner puntos, es una f i e b r e . Ademar; d e v e r l a r e l a c i b n entre el sistema c o n t r o l y l a r e g u l a c i b n d e l a t e m p e r a t u r a y los l a t i d o s c a r d i a c o s (ver R e f . 1 ) . El sistema d e c o n t r o l ; E l c a l o r es p r o d u c i d o a t r a v e s d e l c u e r p o por un p r o c e s o m e t a b o l i c o , esto induce estremecimiento por un camino d e el sistema neuromuscular p r o d u c i e n d o calor usualmente de p r o t e c c i b n , c o n t r a el frio, a t r a v e s d e el incremento e n l a c i r c u l a c i b n , da e s c a l o f r i o e n 105 m u s c u i o s p a r a traer mas s a n g r e e n la periferia, particularmente para c o n t r a r e s t a r el i n c r e m e n t o d e calor p r o d u c i d o a t r a v e s d e g r a n d e s cantidades de calor perdido. L a s c o n t r a c c i o n e s r i t m i c a s d e el corazon a s i como el recur!so d e c a l o r , e n e r g i a disipada en la circulacidn, d e b i d o a l a v i ! i c o c i a d d e l a s a n g r e a p a r e c e como una pequeha cantidad d e calor. En e j e r c i c i o s v i g o r o s o s el c a l o r producido por el c u e r p o p u e d e ser d e 10-2Omin. el basic0 r e s t r i n g i m i e n t o d e el n i v e l . A s i que el c u e r p o r e q u i e r e un muy E l i n c r e m e n t o d e a c t i v i d a d e s e n el sistema e f i c i e n t e termostato. nervioso adrenergico autonomo puede ser bajo control el r a n g o m e t , a b o l i t o a t r a v e s d e l cuerpo. Estos centra1,dirige c o n s t i t u y e n u n r e c ~ t r s oa d i c i o n a l d e c a l o r p o s i b l e l l a m a d o p a r a v e r s e en medios f r i o s . Los e f e c t o s a l a r g o p l a z o pueden tambien i n c l u i r un incremento e n l a s e c r e s i d n de t i r o x i n a por glandula t i r o i d e a , que e n turno e s t i m u l a el r a n g o m e t a b o l i c o í d e s p u e s d e un retraso d e s e v e r o s d i a s ) . Este mecanismo, es i m p o r t a n t e en l a a d a p t a c i d n a irn c l i m a f r i o ya q u e hay un i n t e r c a m b i o entre l a 5 vena5 y a r t e r i a s d e el s i s t e m a c i r c u l a t o r i o , se c i e r r a uno o otro y esto puede ser b e n e f i c i o s o e n e x p o s i c i o n e s a l f r i o , siendo l a s a r t e r i a s s a n g u i n e a s r e f r e s c a d a s por un c o n t o r n o o retorno v e n o s o enfriador (ver Ref. J). S e n s o r e s d e temperatura:Control c e n t r a l homeotermico y modos d e control de temperatura; En l a s e c c i b n a n t e r i o r nosotros ennumeramos los e f e c t o s que a t r a v e s d e un c i r c u i t o r e f l e j o a u t o m a t i c 0 d e el sistema d e l t e r m o s t a t o pueda a c t u a r p a r a m a n t e n e r un r a n g o d e t e m p e r a t u r a e n el c u e r p o s i n un r a n g o optimo f i si o1 o g i camen te. L.a c o n s t r i cc i bn a r ter i a l cutanea o d i 1a t a c i bn, el metabolismo es c o n t r o l a d o p a r a aumentar o d i s m i n u i r , y los muscul OS pueden setexcitados ritmicamente para dar e s c a l o f r i o ( q u e es tambien un control v o l u n t a r i o p a r t i c u l a r m e n t e ) . Ademas g l andul as e s p e c i a l es pueden ser esti mu1 adas p a r a s e c r e t a r sudor, asi que l a s g r a n d e s c a n t i d a d e s d e c a l o r e v a p o r a d o son dadas por el c u e r p o cuando hay p e r d i d a d e c a l o r por c o n v i c c i b n y r a d i a c i b n son l i m i t a d a s . E l c o n t r o l d e esos e f e c t o s depende d e l a integracidn de mas D m e n o s a r e a s b i e n definidas en el h i p o t a l amo ( q u e tiene f uncciones a d i c i o n a l e s importantes e n l a r e g u l a c i o n d e el b a l a n c e e l e c t r o l i t i c o , v o l d m e n sanguineo,presibn sanguinea,et.c.) Hay e v i d e n c i a p a r t i c u l a r m e n t e c o n t r a d i c t o r i a y ademas c o n t e s t a l o a n t e r i o r que el h i p o t a l a m o es el centro de p r o t e c c i b n c o n t r a el c a l o r t o t a l , hipotalamo p o s t e r i o r e l i g e l a defensa c o n t r a el e n f r i a m i e n t o y 105 e s t a d o s d e e s t a s d o s a r e a s . 9 T I a t i e n e i n f l u e n c i a i n h i h i t o r i a s en cada una. El modelo p a r t i c u l a r de t e r m o - c o n t r o l e l e g i d o p a r a a c t i v i d a d e s sin dependencia d e l h i p o t a l a m o dependen en forma local, temperatura h i p o t a l a m i c a y de i n f o r m a c i ó n a f e r e n t e n e u r a l de e l l a c o n j u n t o de n e r v i o s s e n s i t i v i ~ sp e r i f e r i c o s de l a temperatura, temperatura local de el c e n t r o t e r m o - - c o n t r o l es determinado por l a s a r t e r i a s sanguineac por el f l u i d o sanguine0 c e r e b r a l , p o r el rango m e t a b o l i c 0 l o c a l , y p o r su b a j a c o n d u c t i v i d a d c a l o r i f i c a p a r a SLI e n t r a d a en o t r a s p a r t e s d e l cer-ebroíver r e f ,medicas). HIPERTERNIA: r , i c r i r L r i c L c Es c u a l q u i e r aumento de l a temperatura i n t e r n a del, cuerpo provocado p o r e l desequi 1i b i - i o de los procesos termoreguladores organicos, t a n t o p o r l a p r o d u c c i d n exagerada de c a l o r como p o r l a eliminacibn insuficiente del mismo;generalmente estos dos factores se suman. Las causas de la hipertermia son d i v e r s a s ; enf ermedades infecciosas (se habla entonces de f i e b r e ) ,causas f i s i c a s i g o l p e de s o i , g o l p e de calor-,etc),causas t o d a s u b s t a n c i a que to:: ic a s ( e s t r ic n i na, t ebai na, e t c en g e n e r a l e x c i t e e l s i s t e m a n e r v i o s o produce h i p e r t e r m i a ) . , HI POTERMIA : Es e l descenso de l a t e m p e r a t u r a c o r p o r a l p o r debajo de 1 0 5 36C de l a e s c a l a termometrica. Se p r e e s n t a en l o s r e c i e n nacidos, en l o s p e r i o d o s de h i p o n u t r i c i b n p r o l o n g a d a ( i n a n i c i b n ) , despues de hemorragias p r o f u s a s , de 'traumas sobre e l c e r e b r o y sobre el abdomen,de i n t e r v e n c i o n e s q u i r ? ~ r g i c a s , en algunas enfermedades algunos inf e c c i osas ( c o l era, d i s e n t e r i a ) en en venami en t os (por quinina, morfina,etc.). P e r u l a forma mas grave de h i p o t e r m i a 5e p r e e s n t a en e l " A l t e r i s m o " , d e b i d o a l a e x p o s i c i o n prolongada de frio. E x i s t a tambien l a h i p o t e r m i a provocada denominada i n v e r n a c i b n a r t i f i c i a 1 , q u e c o n s i s t e en el e n f r i a m i e n t o g e n e r a l d e l organismo de enfermos que deben someterse o c i e r t a s intervenciones g e n e r a l i z a d o que q u i r u g i c a s graves: e s t e enf v i amiento c o r p o r a l l l e v a c o n s i g o l a d i s m i n u c i b n n o t a b l e d e l metabolismo b a s a l de l o s t . e j i d o s y p o r l o t a n t o provoca una a c t i v i d a d v i t a l r e d u c i d a que permite a l p a c i e n t e sopor,tar l a i n t e r v e n c i b n s i n r e c u r r i r al empleo de s u s t a n c i a s a n e s t e s i c a s , H M C O MEDICO Y BIOLWICO: Y REHAEILITACION Y TRATMIENTüSl c Tumbr; L i t e r a l m e n t e un nud'o o hinchazon,aunque el t e r m i n o usado p a r a d e s c r i b i r l a hinchazon de t e j i d o s normales como o c u r r e n en una i n f l a c i b n o edema d e l agrandamiento de organos t a l e s como el hazo,higado o rinones. Un tumar es una masa de c e l u l a s que recuerdan al tejido ordinario y que se desarro11a independientemente como c r e c i m i e n t o nuevo, s i r v i e n d o a ninguna funcibn u t i 1 (ver ref.D). Cuando un t e j i d o se forma en i o 5 vasos sanguineos e5 llamado angibma. Cuando t a l t e j i d o se forma en l o s t e j i d o s g r a s o s es llamado 1 ipoma. Cuando t a l t e j i d o se forma en 105 c a r t i l a g o s es llamado condrdma. Algunas veces aparecen tumoi-es compuestos de t e j i d o s q u e no son p a r e c i d o s a l d e los o r g a n o s que los a l b e r g a n , a l g u n o s e j e m p l o s son tumores c a r t i l a g i n o s o s o g r a s o 5 que se d e s a r r o l l a n e n una g l a n d u l a por e j e m p l o 1a g l a n d u l a c a r o t i d e a . Un tumor m a l i g n o o sarcoma d e tina masa c a r n o s a d e r i v a d a d e l t e j i d o conectivo. Un tumbi- benigno,no tiene e f e c t o s dahinos, e x c e p t o e n q u e producen pi-esion d e b i d o a su crecimiento. El tumor m a l i g n o no e j e r c e p r e s i t i n e n el t e j i d o a d y a c e n t e , s i n o Que l o i n v a d e y l o d e s t r u y e o d e s i n t e g r a , y produce nuevos tumores e n o t r a s p a r t e s d e l c u e r p o es una c o n d i c i t i n llamada metastasis. El sarcama d e l a s f i b r a s n e r v i o s a s e5 l l a m a d o f i b r o n e u r o s a r c o m a , y tambien encontrado e n t e j i d m l i n f d i d e y g r a s o y para d e t e c t a r l o se usa l a b i n p s i d i e s el d i a g n o s t i c o p o r examen m i c r o s c o p i c o d e un t r o z o d e t e j i d o d e l tumbr).Viw r e f . 1 e F. E l cancer, es un anormal y a menudo i m p r e v i s i b n l e c r e c i m i e n t o d e celulas. L a s neoformacionea c a n c e r o s a s poseen l a p r o p i e d a d de invadir l o s t e j i d o s n o r m a l e r que pueden d e s t r u i r o r e m p l a r a r con ~ L I anarquico d e s a r r o l l o, y e n s u c a r r e r a d e s e n f r e n a d a d pueden a f e c t a r a los nervios,producir dolor, a los v a s o s s a n g u i n e o s que rompe, p r o d u c i e n d o h e m o r r a g i a s a io5 t e j i d o s pulmo n a r e s , a r t e r i a s , r i n o n e s y v e j i g a que o b s t r u y e n a l i n f i l t r a r s e y lo mas s u c e p t i b l e a iie invasitin cancerosa, ron el estomago,intestinos,pulmones y o r g a n o s s e x u a l e s i v e r ref .D). DONDE ATACA E L CANCER Hombres Mujeres (%) (%) 2.5 5.3 11.9 piel 1.5 boca 1.2 aparato respi ra t o ri o 3.2 mamas 18.2 51.5 aparato d i g e s t i v o 40 12.6 aparato g e n i t a l 24.9 6. 3 aparato u r i n a r i o 3.3 9.9 o t r a s partes 7.7 Se s a b e que hay r e l a c i t i n entre l a s hormonas s e x u a l e s y el d e s a r r o l l o d e l c a n c e r , e s p e c i a l m e n t e e n el d e l a 5 mamas y o r g a n o s genitales. Rara v e z l a 5 esposas del circunciso a p a r e c e el cancer,de c e r v i x por que en el o r g a n o d e l i n c i r c u n c i s o r e t e n g a alguna s e c r e c i o n c a n c e r l g e n a e n el p r e p u c i o . (Ver ref .E21 Diagnostico; U n o d e 105 matodos mas r e c i e n t e s en el campo d e l d i a g n o s t i c o es l a prueba d e F a p a n i c o l a o u s , q u e p r e v e e l a toma d e r a s p a d u r a s s u p e r f i c i a l e s d e l c u e l l o uterino d e l a s p a r e d e s d e l a v a g i n a y son t r a t a d a s con s u s t a n c i a s q u i m i c a s y c o l o c a d a s e n la platina y ver si hay o n o p r e e s n c i a d e p r e c o s e s cambios c a n c e r o s o s , l a prueba puede ,ampliarse a e s p u t o 5 o j u g o s g a s t r i c o s cuando se sospecha d e un tumor e n el estomago o pulmbn. ( v e r ref .R). Rronscoscopia; Se i n t r o d u c e un t u b o l a r g o e n l a s e s t r u c t u r a s pulmonares p a r a tomar t e j i d o s por g a s t r o s c b p i a , hecha con un t u b o e n el esto mago,^ l a r e c t o s c a p i a e n el que se hace p e n e t r a r e n e1 r e c t o un instrumento p a r e c i d o a un a n t e o j o , y estos a p a r a t o s van p r e v i s t o s d e l u z que p e r m i t s " v e r " a l o b s e r v a d o r el i n t e r i o r de l o s organos. L.os r a y o s X, l a introduccion de bario, e n el 11 estomago o r e c t o f a c i l i t a r a cual qui er p o s i b l e tumbr . el reconocimiento al siluetear Tratamiento; La o p e r a c i a n q u i r u r q i c a puede proporcionar al p a c i e n t , e l a c u r a t o t a l e n un tumor l o c a l i z a d o , e n muchos t i p o s d e c a n c e r d e p e l v i s se emplea l a R a d i o t e r a p i a , a b a s e d e r a y o s X. La t e r a p e u t i c a q u i m i c a , e s l a administr-acibn d e hormonas en el c a n c e r d e mamas y prostata, y d e drogas e n l a leucemia o cancer d e sangre,y a v e c e s se combinan l a c i r u g i a , l o s rayosX y l a s d r o g a s , 105 i s n t o p o s r a d i a c t i v o s s u s t a n c i a s que poseen r a d i a c t i v i d a d combinada con el elementos iquimicos,ei p r e p a r a d o q u i m i c o d e g a s mostaza,creado con f i n e s b e l i c o s , h a ayudado a destruir c e l u l a s cancerosas en l a sangre, el yodo r e d i a c t i v o í p a r a c a n c e r d e t i r o i d e s ) , f o s f o r o r a d i a c t i v o ( p a r a v e r r u g a s y l u n a r e s externos). I...a r a d i o t e r a p i a se usa p r e f e r e n t e m e n t e e n c a n c e r d e p i e 1 , l a b i o s y cervix. Terapeut.ica hormonal; es is1 t r a t a m i e n t o que c o n s i s t e e n l a e x t i r p a c i b n d e g l a n d u l a e s e x u a l e s y a v e c e s d e l a s adrenales para e l i m i n a r l a f u e n t e d e l a s hormonas que e s t i m u l e n el d e s a r r o l l o d e t a l e s canceres. E l c a n c e r #de p r o s t a t a , s e a d m i n i s t r a n hormonas se:.:uales f e m e n i n a s p a r a n e u t r a l i z a r l a a c c i b n d e l a s hormonas masculinas. En el cancBr d e mamas a l c o n t r a r i o q u e en e l d e p r o s t a t a e n mujeres p r e m e n o p ñ u s i c a s y eri 1a5 postmenopausi cas se u t i l i z a n hormonas femenina's. En l a q u i m i o t e r a p i a , algunas el metotrexato s u s t a n c i a s son e l g a s mostaza, l a mercaptopurinab, y dos p r o d u c t o s d e l a r g a denNDminacion que son TEN y .TEPA. LA FIERRE; Elevacibn anormal d e l a temperatura e n e l cuerpo humanoihipertermia) , que se p r e e s n t a a c o n s e c u e n c i a d e l estimulo d i r e c t o d e l o s centros t e r m o r r e g u i a d o r e s c e r e b r a l e s s i t u a d o s e n el tuber cinereum y en 105 nucleos anteriores del hipota1amo;estos centros mantienen l a temperatura d e nuestro organismo,en c u a n t o asegirran el. e q u i l i b r i o e n t r e l a produccibn d e calor ( t e r m o g e n e s i s ) y l a d i s p e r s i o n der1 mismo h a c i a el ambiente e x t ern0 ( t ermod i spersi bn ) En e.fecto, de estos centros termorreguladores c e r e b r a l es parten los impulsos de dos ordenes,los ciales,a t r a v e s d e l s i s t e m a n e r v i o s o v e g e t a t i v o ysubsidiariamente-a traves del sistema enaocrino (hormona t i r o i d e a , s o b r e t o d o ) , i n + luyeri poderosamente s o b r e : -los procec.os t e r m o g e n e t i c o s í p r o d u c t o r e s d e c a l o r ) consti t u i d o s por todas aquellas reaciones d e l metabolismo o r g a n i c o , q u e se denominan e x o t e r m i c a s por que se l l e v a n a efecto con e l i m i n a c i b n d e c a 1 o r ; s o n r e a c c i o n e s d e n a t u r a l e z a prefer-entemente e x u d a t i v a s que t i e n e n l u g a r sobre todo e n el h i g a d o y eri los musculos; -y s o b r e l o s p r o c e s o s t e r m o d i f u s o r e s , q u e son tres p r i n c i p a l m e n t e : l a v e n t i l a c i b n pulmonar (con a i r e e s p i r a d o se e l i m i n a vapor acuoso c a l i e n t e y , p o r i o t a n t o , c a l o r ) , l a s e c r e c i b n s u d o r a l icon sudor- se e l i m i n a tambien o t r a f r a c c i o n d e c a l o r i n t e r n o ) y s o b r e t o d o l a d i l a t a c i a n d e 105 v a s o s s a n g u i n e a s . s u p e r f i c i a l e s c u t a n e o s i q u e producen el c o n s i g u i e n t e aumento d e l a f l u j o . sanquineo c a l i e n t e d e l o s organcis internos a l a p i e 1 , e n l a que t i e n e l u g a r la d i s p e r s i o n e n el ambiente e x t e r n o d e l c a l o r t r a n s p o r t a d o por la sangre. Segun Meyer, el p r i n c i p a l c e n t r o ter-morregulador d e l hipotalamo esta constituido: . 12 -por un c e n t r o d e l c a l o r que t i e n d e a e l e v a r l a temperatura c o r p o r a l ,estimulando por una p a r t e l o s procesos de l a termog&nesis y,por o t r a parte, deprimiendo los procesos termodifusores~mediante el siguiente mecanismo triple: d i s m i n u c i b n de l a f r e c u e n c i a y de l a a m p l i t u d r e s p i r a t o r i a , o sea, de l a v e n t i l a c i b n pulmonar; i n h i b i c i d n de l a s e c r e s i b r i sudoral; c o n s t r i c c i d n d e l c a l i b r e de l o s vasos sanguineos cUtaneOS,con l a consiguiente disminucidn d e l a f l u j o sanguineo c a l i e n t e a l a s u p e r f i c i e c o r p o r a 1 , l o que provoca una e l i m i n a c i b n menor de c a l o r a t r a v e s de l a p i e l ) ; -.por un c e n t r o de f r i o que t i e n d e s e n cambio a a l t e r a r - l a t e m p e r a t u r a c o r p o r a l ,disminuyendo p o r un l a d o l o s procesos de la termoghesis y por el o t r o e s t i m u l a n d o l o s procesos de la termodifusidn (aumento de l a v e n t i l a c i b n pulmonar,aumento de l a s e c r e c i d n s u d o r a l , d i l a t a c i h n d e l c a l i b r e de l o s vasos sanguineos cutaneos,con e l c o n s i g u i e n t e aumento de a - F l u j o sanguineo c a l i e n t e a l a s u p e r f i c i e c o r p o r a 1 , l o que provoca una mayor e l i m i n a c i b n de c a l o r a t r a v e s de l a p i e l ) . Moderna concepcidn p a t o g e n i c a de l a f i e b r e . Hasta hace ~ i n o sahos l a f i e b r e se consideraba como un fenomeno de origen periferico,en el s e n t i d o de que el aumento de l a t.emperatura c o r p o r a l no t e n i a su o r i g e n en el sistema n e r v i o s o c e n t r a l , s i n o en l a s p e r i f & i a , m e d i a n t e e l aumento d i r e c t o de io5 procesos de t e r m o g h e s i s en e l seno de algunos organos y tejidos(higado,muscrilos) y mediante l a d i s m i n u c i b n de 105 procesos t e r m o d i f u s o r e s a n i v e l de io5 p u l m o n e s i v e n t i l a c i b n y de l a p i e l ( s e c r e c i b n s u d o r i p a r a , i r r a d i a c i ¿ m de c a l o r pulmanar) a t r a v e s de l a s u p e r f i c i e c u t a n e a ) . En cambio,hoy en d i a , l a c a s i t o t a l i d a d de 1 0 5 i n v e s t i g a d o r e s concuerdan en a f i r m a r que la f i e b r e e s un fenomeno de o r i g e n n e r v i o s o c e n t r a 1 , c o n s e c u t i v o a un e s t i m u l o d e l o s c e n t r o s t e r m o r r e g u l a d o r e s por- p a r t e de 105 agentes e s p a c i a l e s p r o d u c t o r e s de l a . f i e b r e ( d e lo que hablaremos 1uego);este e s t i m u l o se r e s u e l v e en un aumento d e l a temperatura CL f i . e b r e cuando l o s c e n t r o s r e g u l a d o r e s c e r e b r a l e s corporal elevan e l p u n t o t e r - m i c o i g r a d o de temperatura) ,a cuyo n i v e l se e s t a b l e c e normalmente(e5 d e c i r , e n un organismo no f & b r i l ) l a termorregulacibn,o sea, el e q u i l i b r i o e n t r e 105 procesos de termog8nesis y 105 d e t e r m o d i f t i s i o n p e r i f e r i c a . Es d e c i r , segdn l a concepcian a c t u a 1 , l a f i e b r e se d e b e r i a a un proceso de r e a j u s t e d e l p u n t o de t e r m e r r e g u l a c i b n o r g a n i c a a un nivel ma5 elevado que en c o n d i c i o n e s norma1es;esta e l e v a c i b n 5e e f e c t u a r i a en 105 c e n t r o s t e r m o r r e g u l a d o r e s d e l hipotalamicos sometidos a l e s t i m u l o d i r e c t o de c i e r t o s f a c t o r e s p i r e t o g e n o s , l o s cuales, al excitar dichos centros cerebrales,provocarian la a p a r i c i o n de l a f i e b r e . E s t o s e s t i m u l o s p i r e t o g e n o s pueden ser: -mecanices, como e5 l a comprension e j e r c i d a sobre d i c h o s c e n t r o s termorreguladores p a r l a masa de un tumor b a s i l a r d e l c e r e b r o o l a sangre extravasada d e una hemorragia c e r e b r a l (especialmente d e l t e r c e r v e n t r i c u 1 o ) ; p o r eso l a f i e b r e que se observa en muchos Cd505 de tumores y de hemorragias c e r e b r a l e s debe c o n s i d e r a r s e como de o r i g e n m k a n i c o ; -qui m i C 0 5 (mucho ma5 numerosos) y que c o n s i sten: i ) e n prodctctos de d i s t i n t a i n d o l e y e s t r u c t u r a d e r i v a d o s de l a L _ r . e5c is i on proteica(a1buminosas peptonas,polipeptido~,aminobases,etc.);productos que forman,por ejemplo,en l a d e s i n t e g r a c i o n de l a s p r o t e i n a s de se io5 t e j i d o s quemadosífiebre de l ~ quemaduras s de una c i e r t a e x t e n s i o n y p r o f u n d i d a d ) y por l a l i o s i s de 105 cuerpos m i c r o b i a n o s i f i e b r e de naturaleza s e p t i c a que se p r e s e n t a en las diversas enfermedades i n f e c c i o s a s g i i n e r a l e s o en los procesos s e p t i c o s 1oca1 e s ) ; 2) en s u s t a n c i a s de i n d o l e d i v e r s a i n t r o d u c i d a s desde el exterinr:es p o r ejemplb c l a s i c a l a a c c i o n . f e b r i l d e l c l o r h i d r a t o de t e t r a - - h i d r o n a f t i l - a m i n a , d i s l que b a s t a i n y e c t a r un c e n t r i m e t r o c u b i c n de una s o l u c i o n acuosa a l "J% en un c o n e j o p a r a que rapidamente se e l e v e su t e m p e r a t u r a h a s t a 44$C. Entre l a s s u s t a n c i a s c o r r i e n t e s capaces de provocar f i e b r e e s t a e l c l o r u r o de sodio ( f i e b r e por l a s a l ) . HIPERTERMIA FEBRIL O ND FEBRIL.Pero no t o d a s l a s h i p s r t e r n i a % ( e %d f c i t - , nri todos los aumentos de la t e m p e r a t u r a c o r p o r a l i n t e r i : por encima de l o norma1,que en e l orgaiRffimo humanos se c o n s i d e r a de 37SC) se r e a l i z a n p o r el nervioso central de l a fiebre;cabe,por lo m u a n i0 0 tanto, d i f erenci ar : - l a h i p e r t e r m i a de o r i g e n n e r v i o s o c e n t r a l o h i p e r t e r m i a f e b r i l o fiebre: es a q u e l l a en l a que e l aumento de l a . t e m p e r a t u r a corporal debe c o n s i d e r a r s e como un r e a j u s t e d e l p u n t o de l a t e r m o r r e g u l a c i o n a un n i v e l termico-o sea, a un grado de temperatura-mas elevado que e l normal; es l a consecuencia de un e s t im u 1 o d i r e c t o de 1 0 5 c e n t r o s t e r m o r r e g u l adores c e r e b r a l es h i p o t a l a m i c o s p o r c i e r t o s fasctores macanicos o quimicos; -la h i p e r t e r m i a de o r i g e n p e r i f e r i c o , h i p e r t e r m i a no, f e b r i l o hipertermia. simp1 e: es a q u e l l a en l a que e l ' mecanismo p a t o g e n e t i c o debe buscarse nso en el s i s t e m a n e r v i o s o c e n t r a l s i n o en l a p e r i f e r i a j e n e s t e caso el aumento de l a temperatura los corporal e s t a provocada p o r f a c t o r e s que o b s t a c u l i z a n procesos de t e r m o d i s p e r s i a n a t r a v e s de l a s u p e r f i c i e cutanea,con e l c o n s i g u i e n t e acumulo en e l i n t e r i o r de n u e s t r o organismo de un c a l o r que d e b e r i a e l i m i n a r s e en c o n d i c i o n e s normales. El ejemplo c l a s i c o d e h i p e r t e r m i a no f e b r i l es el Golpe de c a l o r , e n e l c u a l e l aumento d e l a temperatura c o r p o r a l se produce l a grave d i f i c u l t a d de l a d i s p e r s i b n t r a n s c u t a n e a d e l calor por n r g a n i c n i n t e r n o a l ser e l ambiehte e x t e r n o muy c a l u r o s o ( s o b r e t o d o cuando e x i s t e tambien 'humedad;en e f e c t o l a humedad e x c e s i v a del ambiente o b s t a c u l i z a e l fenomeno de l a sudoracibn y por lo t a n t o l a e l i m i n a c i o n p o r d i c h a v i a d e l c a l o r i n t e r n o ) . V e r t-fsf.de t i p o s de f i e b r e y causas. UN A R B ü " T 0 ESPECIAL EN HIPERTERMIA Y TERAPIA DE CCINCER.t o d o s sabemos el cancer e s l a segunda causa de muerte desesos del corazbn,de hecho unicamente excedida por aproximadamente de cada c u a t r o personas una puede c o n t r a e r cancer en a l g u n p u n t o d u r a n t e su v i d a . Y debido a l tremendo e s f u e r z o c e r c a de l a m i t a d d e l total de los dedicado a e s t a cura, p a c i e n t e s s o b r e v i v e de l a s v a r i a s enfermedades c a t e g o r i z a d a s es cancer. Llna forma de h i p e r t e r m i a de cancer es que t i e n e Como 14 I c F i r i recibimiento y r e s u r g i m i e n t o d e un r e c i e n t e e s t u d i o en los u l t i m o s ahos es el u s o d e l c a l o r p a r a o r i g i n a r temperaturas e l e v a d a s en el t u m o r e n el. r a n g o d e 4 2 - 4 5 X y q u e es l l a m a d o h i p e r t e r m i a ( v e r ref . A ) . En c i e r t o s e n t i d o , e s t o es un p r o b l e m a i n q i e n e r i l e n el d e s a r r o l l o de metodns d e calentamiento,monitoreos termai,tratamientos planeados y d e t e r m i n i a c i o n termal no son t r i v i a l e s p e r o n u n c a tratables. T o d o s l o s a s p e c t o s r e q u i e r e n d e la mas m o d e r n a t e c n o l o g i a d i s p o n i b l e d e un r a n g o a m p l i o d e d i s c i p l i n a s f i s i c a s e i n g i e n e ~ i l e s , e s ' t a m b i e n d e acceso i n t i m o p a r a p e r s p e c t i v a s biologicas y m e d i c a s p a r a g u i a r l o a en s u d e s a r r o l l o . Hay alrededor de un n u m e r o d e sistemas c o m e r c i a l m e n t e d i s p o n i b l e s b a s a d o s e n muy d i f e r e n t e s p r i n c i p i o s e l e c t r o m A g n e t i c o s , y muchos d e estos sistemas s o n o r i g i n a l e s y son i n v e s t i g a d o s y p r o b a d o s e n u n i v e r s i d a d e s y c e n t r o s mediilos. D e b i d o a l o s t r e m e n d o s e s f u e r z o s es l a o p i n i o n u n a n i m e d e este editor que en l a m a y o r i a de 105 casos c l i n i c 0 5 h a y Sistemd5 i n m o v i 1es y d i s p o n i b l e s q u e p u e d e n p r o d u c i r , o d a r distribuidores d e t e m p e r a t u r a ( o c o n t r o l a d o r ) , e n un r a n g o d e 42--45LCe n el t u m o r s i n c a l e n t a r s e el t e j i d o n o r m a l . Hay una anecdota promisoria interesante d e l o s r e s ~ l t ~ a d o sd a t o s s o l i d o s q u e i n d i c a n un beneficioso positivo terapeutico de l a hipertermia,y son u n i c a m e n t e o b t e n i d o s p o r p r i ~ e b a s . La e f i c a c i a d e l a h i p e r t e r m i a es una moda.1idad c l i n i c a , b a s t a q u e e l c a l o r d e l sistema l l e g u e a un g r a d o d e s o f i s t i c a c i d n qiue e s t a d a d a e n el d e s a r r o l l o c l i n i c 0 e n el c u a l p u e d e p r o d u c i r - una d i s t r i b u c i b n d e l a t e m p e r a t u r a e n t u m o r e s e l c u a l es d e 42$C D mas. En g r a n p a r t e , l o s sucesos o un f r a c a s o dE: l a h i p e r t e r m i a p i i e d e . s e r una m o d a l i d a d d e cancer en r e p o s o en l a s manos d e un i n g e n i e r o o f i s i c o , y s u h a b i l i d a d a resolver ic15 p r o b l e m a s e x t r e m a d a m e n t e d i f i c i l e s d e l a e f e c t i v i d a d d e 105 t u m o r e s p o r c a l e n t a m i e n t o e n un t i e m p o d e t e r m i n a d o e n el t e j i d o normal. Uno d e l o s p r o b l e m a s c r i t i c o 5 e n el campo d e la h i p e r t e r m i a es el diseno,desarrollo y p r ~ i e b a sd e m e j o r a r el e q u i p o y los sistemas de hipertermia. Los p r i m e r o s d o c u m e n t o r ( 3 ) , s o n intentos para p r o v e e r mas d e un c o n j u n t o b i o l o g i c 0 y d a r i m p o r t a n c i a a l fluido s a n g i t i n e o b a j o el problema de transferencia de calor,y las propiedades electricas d e l t e j i d o . Hay v a r i o s sistemas y que s o n ; a m p l i f i c a d o r e s e l e c t r o m a g n e t i c o s s e g u i d o s p o r d o s sistemas d e t i l t r a s o n i da, dosimetri a termal, los p r i m e r o s d o s conti e n e n modelos d e computadora y 105 d o s u l t i m o s e n sistemas d e m e d i c i o n de temper a t ura. HIPERTERMIA PAR6 LA INBIMRIA: UN CORTO COMPRENDIO BIOLOCIC0.- E l c o n c e p t o coman de el c e n t r a d e t r a t a m i ' e n t o d e cancer a l r e d e d o r d e l a n e c e s i d a d p r e f e r e n t e m e n t e d e i r e l i m i n a n d o l a s celulas malignas. L.a h i p e r t e r m i a p u e d e o f r e c e r un m e d i o d e h e c h o s i , n o por que el m e d i o i i s i c o e n el c u a l muchas c e l u l a s d e los t u m o r e s pueden e n c o n t r a r s e e l l o s mismos y son solidos. La p r i v a c i b n nutricional ,bajo ph, y una h i p o x i a c r o n i c a c a r a c t e r i z a a l interior de muchos t u m o r e s y e s t a s c o n d i c i o n e s q u e e n t r e g a tambien l a s e n s i b i l i d a d d e l c a l o r en las celulas. El calor t a m b i e n e n g r a n d e c e l a e f e c t i v i d a d d e i r r a d i a c i o n X, y agrandando t- g r a d o s ma5 a r r i b a , l a s c a l e n t u r a s t a m b i e n p u e d e n i n h i b i r y mas d e s p a c i o y p o r o t r a p a r t e en l a m u l t i p l i c a c i o n d e a l g u n o s v i r u s . Pero n o s 0 t . r - o s s i m p l e m e n t e n o es s e g u r o y a sea, p o r q u e n o sea c u a l q u i e r a d e e s a s e n c o n t r a r e m o s y que s o n r e a l m e n t e p a r a el 16 b e s t e metodo l a emplean en el t r a b a j o de i p e r t e r m i a y t r a b a j a n par atener un minimo de algunos n i v e l e s de e n t e n d i m i e n t o de b i o l o g i a termal. I .i c I - C c i c L r i ir c b P L a i m p o r t a n c i a d e l e s t u d i o de l a s c e l u l a s ; el tratamiento del cancer comun se c o n c e n t r a en l a e l i m i n a c i b n de c e l u l a s malignas y es p o s i b l e que un pequena p a r t e v i t a l d e l t e j i d o sea dahada. La c i r t q i a remueve l a s c e l u l a ' s cancerosas p o r afeccibn cortante h a c i a afuera de l o s volumenes de t e j i d o ; l a l i m i t a c i o n de l a c i r á g i a es que p a r t e s no v i t a l e s de l a anatomia pueden s e r removidas. Los t e r a p e u t a s de r a d i a c i b n matan c e l u l a s m a l i g n a s p o r Aqui el e x p o s i c i o n p a r a l a s d o s i s de l e t a l e s de r a y o s X. t r a t a m i e n t o , e5 l i m i t a d o p o r l a r e s p u e s t a de el t e j i d o normal son e l volumen d e l t r a t a m i e n t o , l a s drogas a n t i c a n c e r o s a s tambien en el a c t o e l i m i n a n l a s c e l u l a , ~malignas i n d i v i d u a l e s . Por que l a naturaleza sistemica del t r a t a m i e n t o de l a droga e l tejido l i m i t a n t e e5 e l sistema c e l u l a r mas s e n s i t i v o p a r a una droga p a r t i c u l a r usada, l a i p e r t e r m i a tambien mata c e l u l a s y p a r a l a calefaccibn lwcalizamos i en c o n t r a s t e p a r a el calentamiento e5 l a r e s p u e s t a d e l t e j i d o normal s i n el i n t e g r o d e l cuerpo), volumen de c a l e n t a m i e n t o que d e c i d e l a d o s i s de c a l o r que puede s e r aplicadw. En mas s i t u a c i o n e s e s t a es r e l a t i v o p a r a matar l a s c e l u l a s malignas y e s p e c i f i c a s normal q u e suceda determina o f a l l a de e l p r o t o c o l o d e l t r a t a m i e n t o . Dosis de c a l o r ; Fundamental par-a una c u a n t i f i c a c i b n de un fenomeno b i o l o g i c 0 es l a d o s i s en l a c u r v a de respuesta. For ejemplo en e l caso i r r a d i a c i b n X, l a s r e s p u e s t a s r e l a t i v a s en l a curva l a c a n t i d a d de e n e r g i d a b s o t i v a p o r las celulas supervivientes. Para l a h i p e r t e r m i a e s t o es fundamental que l a s dos c a n t i d a d e s s e a n . d e impor-tancia i g u a l en l a d e t e r m i n a c i b n de l a p r o b a b i l i d a d de s u p e r v i v e n c i a de algunas c e l u l a s , e s t a s son t e m p e r a t u r a y t i e m p o ( @nl a t e m p e r a t u r a ) . E s t a r e l a c i b n e n t r e s u p e r v i v e n c i a de c e l u l a s y esos parametros no l i n e a l e s ( REF d e l mismo f i g . l ) , y p o r eso no hay una s i m p l e v a r i a b l e f i s i c a de combinacibn l i n e a l de v a r i a b l e s que pueda ser i d e n t i f i c a d a que pueda d e f i n i r una d o s i s de c a l o r , rango, un r e g i s t r o d e tiempo y t e m p e r a t u r a que n e c e s i t a ser provisto. La necesidad de una d e f i n i c i b n de d o s i s de c a l o r es una de 106 u r g e n t e s r e q u e r i m i e n t o s en l a h i p e r t e r m i a c l i n i c a , l a d o s i s de r e s p u e s t a en l a f i g , e a mas complicada p o r el h a l l a r mas c e l u l a s diferent.emente conducida a temperaturas a b a j o de 451C que es l a t e m p e r a t u r a b a j a en l a f i g . L O 5 parametros ; en l a s c e l u l a s t i e n e n c o n d i c i o n e s estandares, y son a b a s t e c i d a s con n u t r i m e n t o s de oxigeno, t e m p e r a t u r a de 37SC y un PH d p t i m o excepto cuando aumenta l a temperatura esas c o n d i c i o n e s no p r e v a l e t e n en e l i n t e r i o r de muchos tumores. Hay n u t r i e n t e s y oxigeno e x i s t e n t e s unicamente l i m i t a d o s y PH menor que en e l t e j i d o normal. L.os experimentos muestran una b a j a de n u t r i e n t e s , h i p o x i a c r o n i c a y b a j o PH, y t o d a s t i e n d e n a hacer que l a s c e i u l a s Sean s e n s i t i v a s a l calor. Muchos e s t u d i o s muestran que l a s c e l u l a s mas s e n s i t i v a s son l a s c e l u l a s normales o similar-iis, es verdad que p o r medios l a r g o s de tiempo l a s c e i u l a s pueden ser e l i m i n a d a s y puede el p a c i e n t e ser curado. 17 O 1s 45 75 w de c a l o r multiple, una p a r a d o j a ; En l a s c l i n i c a l a hipertermia l o c a l i z a d a n o d a una dos15, p e r o el tratamiento es fraccionado por t e r a p i s t a s (en c u r s o s d e r a d i a c i b n X. Siempre el t r a t a m i e n t o i n i c i a l empieza t e m p e r a t u r a s mas b a j a s d e 4StC, l a s c e l c i l a s muchas v e c e s son ma!% rtesistentes a l calentamiento, si l a s c e l u l a s son t y r a t a d a s a 43C o mas se r e g r e s a a l incubador de 37#C. Esto es por l a re!;puesta d e l a s c e l u l a s a m u l t i p l e s tratamientos de c a l o r , aqui hay un c u r i o s o t r a t a m i e n t o , si la6 c e l u l a s son t r a t a d a s a una temperatura d e 43tC o mas p o r un corto tiempo de tratamiento, si l a s c e l u l a s s u p e r v i v i e n t e s p a r a unos POCOS (menos d e 4 ) , son inas s e n s i t i v a s p a r a el t r a t a m i e n t o subsecuente a b a j a temperatwra ( s t & p - d o w n ) . E l c a l e n t a m i e n t o e x c e s i v o e n el comienzo d e el t r a t a m i e n t o cuando por p o c o s minutos p u e d e 5er t r a t a m i e n t o d e b a j a temperatura, y por eso para una i n e s p a r a d a t o x i c i d a d a s o c i a d a por f a s e s e n l a de l a s celulas. Mas, importantemerite el sendo mueryte Calentamiento, d u r a n t e q u e l e p a c i e n t e se a p r e s u r e . Esto es i m p o r t a n t e ya que el c a l e n t a m i e n t o e s r-apido, y cuando n o es p o s i b l e en que l a t e m p e r a t u r a d e d i s t r i b u c i b n e n tumores y t e j i d o limite bien definido, la normal para c o n t r o l a r con un t e r m o t o l e r a n c i a puede ser c o n s i d e r a d a cuando l o s p r o t o c o l o s f i s i camente d e s i g n a d o s p a r a el t r a t a m i e n t o f r a c c i o n a d o . La h i p e r t e r m i a y l o s e f e c t o s d e r a y o s X y d e c i e r t a s drogas; Un r a t o d e t r a t a m i e n t o con c a l o r p o r que e l l o s mismos son d e U50 p a r a o t r o s tumores a c a s o l a yran a t r a c c i o n p a r a l a h i p e r t r m i a es ofrecer uno que es mas e f e c t i v o y engrandece a muchos otros a g e n t e s drat i c a n c e r o s o s . Los ejemplos s e v e r o s e s t a n mostrados e n la fig. 2, ( d e l mismo a r t i c u l o ) . Tal v e z el mas g r a n d e p o t e n c i a l y c i e r t a m e n t e d e uso mas c o r r i e n t e , e5 el s i g e r g i s t a entre el calor y l o s r a y o s X. La t e r a p i a d e r a d i a c i b n es el segundo mas angular usada como arma a n t i c a n c e r y un metodo p a r a h a c e r esto ma5 e f e c t i v o puede ser t r a t a d o e n un r a n g o i n p r o v i s a d o p a r a curacibn. Eso se muestra e n l a f i g . 2 , el c y t o t b x i c o d e r a y o s X apreciablemente incrementando sus c e l u l a s son expuestos p a r a elevar l a temperatura a n t e s d e o t r a s i r r a d i a c i o n e s . Despues d e mil rads, d e rayos X en cien, sin c a l e n t a m i e n t o s o b r e v i v e n c e l u l a s pero unicamente 1 e n 10,C)CiCi d e l a s c e l u l a s s o b r e v i v e a l calentamiento. Otro camino es observando 105 d a t o s e s t a n o t i c i a hace que aproximadamente 30% menos d e l a d o s i s p a r a morir sea s i m i l a r a 105 n i v e l e s d e s u p e r v i v e n c i a (0.001) cuando el c a l o r es ahadidn p a r a l a r a d i a c i o n l a usual t e r m i n o l o g i a es p a r a d e c i r que e f e c t o t i e n e una d o s i s d e f a c t o r m o d i f i c a d o d e 1.3, l a celulas qLie puede resistir altamente l a h i p o x i c a s s o n una muestra r a d i a c i o n X. Probabl emente mas tumores humanos c o n t i e n e n e n mas o menos c e l u l a s h i . p o x i c a s y esto e5 a t r - a v e s y p u e d e 5er r e s p o n s a b l e d e muchas f a l l a s e n r a d i t . e r a p i a , matar c e l u l a s h i p o x i c a s con el calor es el mas pequeilo y mas e f i c i e n t e y es el mejor o x i g e n a d o d e l a 5 c e l ~ i l a s . De 1150 l o s t e r a p e u t a s pueden unicamente tomar v e n t a j a d e eso5 b e n e f i c i o s incrementando a 5 i el dano a 105 t e j i d o s normales y no acentuando i g u a l d a d . E l camino mas f a c i l para acoplar conceptualmente e5 l a v i a de calentamiento preferencial d e el volumen d e l tumor-, a s i nosotros r e g r e s a m o s a la p r e g u n t a d e que e q u i p o d i s e n a r . El c a l o r puede ser incrementado p a r a ayudar a l a m u e r t e d e l a s c e l u l a s y muchas Dosis 18 ,... BCNU Iicliiwe dosel (b) I 05101520 30 40 50 60 I d r o g a s í f i g . 2b,c y d ) . La q u i m i o t e r a p i a es usada primeramente p a r a a l g u n o s canceres esto es cuando se e%pande a t r a v e s d e l cuerpo, los b e n e f i c i o s d e tratamientos l o c a l e s no es o b v i o , el uso d e h i p e r t e r m i a f u e un potencial considerable. En un t r a t a m i e n t o frecuentemente encontraremos s i t u a c i o n e s en que una o mas l a r g a s etapas d o l o r o s a s e n l a misma v i d a di21 t r a t a m i e n t o p a r a e l i m i n a r l e s i o n e s y no responde a l a quimioterapia. Esto es l a combinacion d e un t r a t a m i e n t o d e c a l o r y a l g u n o s tumores y una t e r a p i a s i s t e m a t i c a d e d r o g a s p u e d e ser i n d u c i d a e n r e g r e s i o n e s d e e s a s lesiones, la aparencia e n l a combinacion puede ser b e n e f i c o s o tambien e n l a quimiaterapia d e los tejido's. Y a s e a o n o t o d o el c u e r p o puede a c o p l a r s e por h i p e r t e r m i a y q u i m i o t e r a p i a y algunos b e n e f i c i o s pueden ser v i s t o s . PRINCIPIOS DE MEDICINA F1CICA.- Este e s c r i t o describe l a terapeutica y aplicación de energid f i s i c a e n medicina d e r e h a b i l i t a c i b n . Esto i n c l u y e t e r m o t e r a p i a ( c a l o r y f r i o ) , r a y o s u1 t r a v i o l e t a , electroterapia, masaje, mani pul a c i cm d e a l argami e n t a y t r a c c i on. CALOR; Lor; p r o c e s o s b i o l o g i c o s p a r a g e n e r a l y son a f e c t a d a s por e n e r g i a s f i s i c a s , una d e l a s c u a l e s es c a l o r . Esto es comunmente mas usado e n l a modalidad d e medicina d e r e h a b i l i t a c i b n y usualmente e5 a p l i c a d a , antes de e j e r c i c i o s d e alargamient,~, O electroterapia. Esto es empleado p a r a ambas 105 puntas y desordenes c r o n i c o s y los e f e c t o s f i s i o i b g i c o s y mismos c u a l q u i e r a d e 105 r e c ~ i r s o s , v a r i a n d o unicamente la profundidad d e penetracion. FICICA; E l c a l o r es p a r t e d e el e s p e c t r o e l e c t r o m a g n e t i c o y es un e s t a d o d e e c c i t a c i b n d e l a p a r t i c u l a ( e n t r b p i a ) . Todos 105 atom05 o m o l e c u l a s a b a j o d e c e r o g r a d o s K e l v i n tiene e x c i t a c i b n y es capar d e t r a n s m i t i r erihrgia p a r a o t r o t i p o d e p a r t i c u l a s por La e n e r g i d d e t r a n s f e r e n c i a por d i r e c t a c o l i s i o n o radiacion. colision E m s a l i d a s es conduccibn y e n l i q u i d o s o gases conveccion. Esto ocurre unicamente cuando l a p a r t i c u l a e s t a a b s o r v i e n d o y t i e n e b a j a e n t r b p i a ( t e m p e r a t u r a ) . P o r eso el c a l o r puede unicamente ser t r a n s m i t i d o d e a l t a s t e m p e r a t u r a s a b a j a s es l a emision d e f o t b r i e s (cuantos temperaturas. La r a d i a c i b n paquetes d e e n e r g i d ) , con l u g a r e s t r a n s v e r s a l e s y puede ser absorvido (1) aumenta l a s p a r t i c u l a s en e s t a d o e x c i t a d o , (2) varia esto en l a quimica, y ( 3 ) e s t a r e e m i t i d a es c a l o r o luz íf1uorecent:e y f o s f o r e c e n t e s ) . La p i e l es un buen r e f l e c t o r e q u i t a t i v o r a d i a d o r y p o b r e conductor d e c a l o r . El c a l o r es a b s o r v i d o inmediatamente se encuentra l a a l t a concentracibn d e m o l e c u l a s d e agua e n l a subcutanea c a p i l a r y un l e c h o g r a s o s o , los c u a i e s s o n sujetos en f i s i c a y reacciones f i s i o l o g i c a s . El calor especifico, l a ganancia d e c a l o r i a s o l a s p e r d i d a s n e c e s a r i a s p a r a 1 0 5 cambios d e l a t e m p e r a t u r a d e un gramo d e una substancia, es por l o t a n t a , aproimadamente grande, p a r a agua que esto e=. p a r a o t r a s m o l e c u l a s d e l t e j i d o . El agua subcutanea a s i v i e n e e n e c e l e n t e s r e e s r v a s almecenadas d e c a l o r o a i s l a d o y contribuye significativamente h a c i a el mantenimiento d e la r e l a t i v a t e m p e r a t u r a del cuerpo. E l c a l a r puede ser a b s o r v i d o e n 19 t e j i d o s potl a coriveccion d e ondas e l e c t r o m a g n e t i c a s de a l t a f r e c u e n c i a d e n t r o ( 1 ) d e una pequeha c o r r i e n t e ( o n d a s cortas -0 microondas, ( 2 ) esqui l e o , v i b r a c i o n a l f r i c c i o n a l o ondas mecanicas d e comprension (U. C. ) Estan d e s c r i t a s e n D I A T E R M I A o "calor- profundo" en su modalidad y puede penetrar al musci.ilo. Conductividad,convencional o penetracibn d e c a l o r r a d i a n t e d e 1 a '3 mm. y es l l a m a d o calor superficial. En resumen, e:l c a l o r es e r i e r g i a e l e c t r o m a g n e t i c a , l a s cual es a b s o r v i d a a vo'luntad ( 1 ) e l e v a r l a t e m p e r a t u r a , ( 2 ) producir r e a c c i o n e s qriimicas, ( 3 ) t r a n s m i t i r e s a ei-iergia a o t r a p a r t i c u l a a, ( 4 ) reemitir e n ,si mismaesa l u z y c a l o r . . , EFECTOS FISIOLOGICOS DEL CALOR.L a s funciones f i s i o l o g i c a s son gobernadas por l a s m a n i p u l a c i o n e s d e e n e r g i a d e m o l e c u l a s e s p e c i a l i z a d a s u s u a l m e n t e p r o t e i n a s en las c e l u l a s , e s t a membrana y c o m p a r t i m i e n t o s e x t r a c e l u l a r e s . Esa6 m o l e c u l a s tiene mecanica i n l h e r e n t e , e l e c t r i c a y e n e r g i a quimica que e s t a g e n e r a d o O t r a n s f i r i e n d o . La suma d e e n e r g i a t e r m a l en los s i s t e m a s a v o l u n t a d pliiede acumularse en esos p r o c e s o s d e t,ransduccion. La e n e r g i d t e r m a l e n l a s m o l e c u l a s d e agua d e el s o l e n t e acuoso actrra como una .fi.ier-za d e conduccion d e esas r e a c i o n e s y puede aumentar- e l moimiento d e o s c i l a m i e n t o cambios o s e p a r ac i on de dipalos o producir cambios electricos. Adicionalmente 105 e n l a c e s d e h i d r o g e n o pueden ser hechos o r o m p e r l o s y r e s u l t a e n cambios q u i m i c o s d e l a s a l t e r a c i o n e s e n las c o n f i g u r a c i n e s molecular y atomica. Esos e f e c t o s son metabolicos D cataliticos y f u n c i o n e s en l a v i d a s o n los r e q u e r i m i e n t o s d e s u b s t r a t o e n l a s ~ m l e c ~ i l a s . Nosotros con estos postu1adDs dar l a s i g ~ i i e n t e secuencia d e resultados de la aplicacion de calor a l a s celulas: 1 ) aumenta 105 r e q u e r i m i e n t o s c e l u l a r e s metabolicos y c a t a l i s i s , 2 ) produccidn d e e n e r g i d d e 3) v a s o d i l a t a c i b n mnleculas(~xigeno, proteinas y carbohidratos) y aumento e n l a presion c a p i l a r con 4 ) tr-ansudoracidn y d e a l t e r a c i o n e s d e l a c o n f i y u r - a c i o n d e l a membrana o dinamica 5) d e bombeo i d n i c o d e e l e c t . r o l i t o s y f l u i d o s . Continuando con l a s aplicacionEs o r e d u c c i o n e s d e temperatura puede r e s u l t a r , en (1) d e g r a d a c i o n d e p r o t e i n a s c r e a t i n i n a , t i i s t i m i n a y s u b s t a n c i a s , (2) 1e u c o c i t o s y ( 3 ) concumi t a n t e i n f 1amator-i a o a n t i - i n f l a m a t o r i a r e a c i o n f v r e ref pag.76 d e este mismo a r t i c u l o . ) , EFECTOS CLINICOS DE EL CALOR.La r e a c i b r i d e l a p i e l l o c a l m e n t e i n c l u y e sensores d e c a l o r , vasndilatacibn (eritema), reducidn en l a sudoracion d e l a r e s i s t e n c i a d e l a p i e l y aumento e n el metabolismo l o c a l d e l tejido. S i el c a l e n t a m i e n t o es c o n t i n u o mas a l l a d e 40 a 60 min, l a temperat.ura d e l corazdn p u e d e ser e l e v a d a y l a respuesta h o m e o s t a t i c a ,de v a s o d i l a t a c i b n . d i s t a l ocurre. U s u a l m e n t e la temperatura, p u l s o y p r e s i o n sanguinea n o son a f e c t a d a s y s o n los sistemas r e n a l y g a s t r o i n t e s t i n a l . La v e l b c i d a d d e conduccibn d e l nervio y p o t e n c i a l e s d e a c c i o n pueden aumentarse. E l tono muscular o t e n s i o n p u e d e a b l a n d a r s e P l a e l a s t i c i d a d aumenta. Los ligamentos y f i b r a s caps.1.11ares pueden similarmente Qanar elasticidad, y movimiento d e aumento d e u n i o n e s . El dolor ocasionalmente a voluntad puede ser m i t i g a d o por- c a l o r , la @ > : p l i c a c i o n es p o s i b l e m e n t e r e l a c i o n a d a e n un e j e aferente d e s a l i d a gama pero aun esto n o es una e x p l i c a c i o n es p o s i b l e m e n t e relacionada satisfactoria. La a c c i b n a n t i - i n f l a m a t o r i a d e c a l o r incluye leucocitos, incremento e n l a prerion c a p i l a r y en loo e f e c t o s d e l a 5 enzima5 humorales,toda a c c i o n h a c i a l a s u p r e s i b n d e l a r e a c c i b n d e los t e j i d o s . La c a n t i d a d , r a n g o y d i r e c c i o n d e l a g a n a n c i a d e c a l o r e n t e j i . d o s D p e r d i d a es d e p e n d i e n t e d e i d s siguientes (1) o r i g e n d e e s t a temperatura y d u r a c i o n e n la aplicacion, (2) l a s propiedades o p t i c a s d e l a p i e l , (3) el g r a d i e n t e d e t e m p e r a t u r a e n r a z o n - p i e l , e l c u a l ; v a r i a d e 5$-10tC dependiendo e n el s i t i o d e pri.teba, l o s promedios d e t e m p e r a t u r a d e l corazon es. d e 37ta 408C!, y e r i l a p i e l d e 298 a 35tC, (4) l a cantidad d e agua y g r u e s o e n l a c a p i l a r i d a d subcutanea y capa gruésa, ( 5 ) i n s c o n t r o l e s neuraies h i p o t a l a m i c o s y piel, los c u a l e s mantienen constante!% l a s mecani5mos d e temperatura, el cual es un r e f l e j o vasomotore e n l a s r e a c c i o n e s d i s t a l en a r e a s t r a t a d a s , ( 6 ) IDS macariismo!% r e s p i r a t o r i o y excretorio, (7) temperatura ambiente y humedad y ( 8 ) edad( e n io5 ancianos e i n f a n t e s t o l e r a n el c a l o r b a s t a n t a mal, 5 e x o, n u t r i c i bin, e j e r c i c i o , h i d r a t a c i b n , s e n s i b i l i d a d y enfermedad). Indicaciones: El c a l o r e5 i n d i c a d o r d e esos e f e c t o s a n a l g e s i c o s p r i meramente. La aplicacibn usual son de desordenes munculoesqueleticos, neuro,muscular tales como neuralgias, torceduras, dislocacion d i s p a r a d o r d e puntos y el a n f i t r i o n d e p e r i o d o s que d e s c r i b e el prob1,ema vagamente d e el d o l o r muscular. Simmons,; e n un e s t u d i o e;:hau5tivo r e v i s o el d o l o r muscular y los sindromes E? i n t e n t a n d o d e f i n i r l o s los muchos terminos usados p a r a el problema y r e p o r t a r l a s c o n d i c i o n e s p a t o l o g i c a s describir dadas por una i n v e s t i g a c i b n d e b i l . Contradicciones; e l c a l o r todo 1 0 que este r e c u r s o , no puede ser usado e n i n f l a m a c i o n e s agudas O traumas u t i 1 e n l a r e a c c i b n inicial tiene s u b s i d i o , no e n o b s t r u c c i o n venosa insuficiencia arterial o isquemia, h e m o r r a g i a s tesis, O defectos de ccagulacion, e n l a a u s e n c i a d e c a s o s e s p e c i a l e s d e sensacion, En la presencia de fallas pueden setexaminados. cardiovasculares, respirator-ios o r e n a l e s , el c a l o r puede ser u s a d o con rnoderacion, el uso d e c a l o r e n t o d a s l a s a r e a s d e m a l i g n i d a d s o l i d a es c o n t r a d i c t o r i a , a t r a v e s de l a p o s i b i l i d a d d e o t r a s u p e r f i c i a l o c a l e n t a m i e n t o p r o f u n d o que a f e c t a n a los tumores y puede ser c u e s t i o n a d o por temperatura. RECURSOS.- La c o n d u c t i v i d a d por c a l e n t a m i e n t o es l l e v a d a a cabo por el c o n t a c t o d i r e c t o con l a piel, e n l i q r n i d o s p a r a el c o n t r o l d e l a t e m p e r a t u r a e n h i d r o t e r a p i a que puede ser r e d u c i d o a temperaturas d e s e a b l e s D e l e v a r l a s . CALOR RADIANTE.- E l c a l o r r a d i a n t e es r a d i a c c i b n infraroja, la cual t i e n t i una l o n g u i t u d d e 770 a 12,OüOnm, y se acerca a l e s p e c t r o v j , s i b l e (390 a 770rirn). E s t a p r o f u n d i d a d o p e n e t r a c i b n es aproximadamente d e 10 a 1 mm, d e cei-ca(770 P 150ünm1, y d o 1 a 0.05mm d e l e j o s (i,SOO a lZ,000nm), los fotones a 1 0 l a r g o a, 1a l o n g u i t u d d e onda pueden t a n e r e n e r b i a menor anL.-., ,de p e n e t r a r lentamente ( t a b l a 3.1 del a r t i r u l o b .. ref.) el efecto fisiologico ric 1 3 r a d i a z i ? m - 50,'; i d e n t i c a s a los de la cntdctctivida.3 d e c a l o r ( v r e ref ,G, I y d i a g n o s t i c r a d i o l o g y ) . ULTRCISEIJX30:l o s e f e c t o s f i s i o l o g i c o s d e c o n d u c t i v i d a d y calor- , 21 > i radiante , ondas cortasímic:roondas), u l t r a s o n i d o y d i d t a r m i d , esas i n d i c a c i o n e s y c o n t r a d i c c i o n e s son esncialmonte o1 mismo, l a 5 c o n s e c u e n c i a s es que l a d i a t P r m i a y u l t r a s o n i d o producen e f c t o s c l i n i c o s unicamente por produccibn d e c a l o r sin t e j i d o s , a t r i b u y e n d o l e s u n o o otrorj efectos,en e s a modalidad es comun p r e s e n t e n o r e p o r a t a d o por e v i d e n c i a l a 5 m o d i f i c a c i o n e s d e lo6 descubrimientos de esas energids por pulso o optras h i b r i d a c i o n e s , no e5 o t r a qui? esos a g e n t e s t e r m a l e s unicamente. FRI0.-- l a r e d u c c i d n d e temperatura d e l c u e r p o o p i e l e5 usado en medicina d e r e h a b i l i t a c i b n p a r a ( 1 ) a n a l g e s i a l o c a l , ( 2 ) efectos a n t i - i n f l a m a t o r i o s , 13) h i p o t e r m i a d e c o n t r o l o p i r e x i a o p o s i b l e control de plasticidad (ver ref f isicas, fisiologicas, efectos anti-inflamatorios, analgesia, e f e c t o a n t i p i r e t i c o y refE2). , HISTDRIA CLINICA a NOMBRE DEL PACIENTE EDAD DIA DIAGNOSTICO CLINICO; DIAGNOSTICO DESEADO; FORMATO DE TRATAMIENTO; FRECUENCIA DEL TRATAMIENTO Y DURACION; ELECTRODO (TIFO U APARATO); TIPO DE APL.ICACI0N; INSTRUCCIONES ESPACIALEC; MD PRECAUCIONES; . REHABILITACION DE PhCIENTE5 CON ENFEREDAD VhsCUuIR PERIFERIAI referida e n e s t a d i s c u c i b n a b a r c a l a s enfermedades d e l a s arterias, venas y v a s o s l i n f a t i c o s e n l a s e x t r e m i d a d e s ( v e r r e f . 1). Los p r o c e s o s d e e s a s enfermedades i n c l u y e n o unicamente condiciones patologicas s i n l i m i t a r s e a esos v a s o s pero a s i muchas c o n d i c i o n e s i n i c i a l e s e n d i s t u r b i o s d e r e f l e j o e n esos vasos secundarios e n simpatico, parasimpatico y i n f l u e n c i a s en l a medttla espinal. El e s t u d i o d e e a s a enfermedades p e r i f e r i a vascular r e q u i e r e e s e n c i a l m e n t e l a s mismas t e c n i c a s que uno genera1ment.e e m p l e a e n l a medicina i n t e r n a : h i s t o r i a , examinacibn fisica, y t e c n i c a s d e e-valuacibn e s p e c i a l . Hay ciertos a s p e c t o s b a s i c o s en este grupo d e enfermedades que r e q u i e r e un e n f h s i s especial e n l a examinacibn y que puede ser o b t e n i d o , uno por sondeo h i s t o r i c o . Esto e s p o r l o t a n t o mas i m p e r a t i v o que a traves de un c o n o c i m i e n t o d e l a c i a s i f i c a c i b n de esas enfermedades es mostrada. Examinacidn; La examinacidn f i s i c a e n l a s enfermedadss v a s c u l a r p e r i f e r i c a p u e d e ser a t r a v e s de, un a r e a a f e c t a d a . La i m p o r t a n c i a d e o b t e n e r un h i s t o r i a a t r a v e s d e un m i n u c i o s o y de p r i o r i d a d general e n un a r e a d e c o n c e n t r a c i o n como traumas, Es 1 22 diabetes ‘y p r e v i a s t r o m b o c i t o s i s v e n o s a s o enfermadades cardiacas, es l a misma e v i d e n c i a . C i e r t a m e n t e el c o n o c i m i e n t o e n una m a l i g n i d a d m e t a s t a s i s existe e n un p a c i e n t e con r e c u r r e n t e s t r o m b o s i s v e n o s a s que n o responde a a n t i c o a g u l a n t e s es un f a c t o r p o t ente gobernante de otro esfuerzo terapeutico. El d e s c u b r i m i e n t o f i s i c o d e una l e s i o n v a s c u l a r m i t r a l a s o c i a d a con una f i b r i l a c i a n a u r i c u l a r e n un p a c i e n t e con e v i d e n c i a d e una oclur;ion a r t e r i a l aguda puede ser d e una i m p o r t a n c i a soberana e n el e s t a b l e c i m i e n t o d e b a s e s e t i o l o g i c a s d e el p r e e s n t e sintoma. For c o n s i g u i e n t e e l uso d e pruebas d e May’s p a r a l a c l a u d i c a c i o n intermitente, l e c t u r a s o s c i l o m e t r i c a s , lecturas d e t e m p e r a t u r a y d e v a r i a s pruebas d e est.ab:i l i d a d vasomotora puede ser empleada ciiando indican. Angi ogrikf i a y venograf i a son usadas frecuentemente; f o t a g r a f i a i n f r a r o j a , p l ei smograf i a y m e d i c i o n e s d e . f l u j o d e u l t r a s o n i d o dopp:ler tambieri pueden ser usados. E l ambit0 d e t r a t a m i e n t o s d e enfermedades v a s c u l a r Trat.amiento; perifericas s i n l a d i s c i p l i n a d e l a medicina d e r e h a b i l i t a c i o n p u e d e ser e l p e r f i l d e l a s s i g u i e n t e s ; 1) termot er a p i a; a ) h i per.terini a ( c a l e n t ami ento directo e i n d i r e c t o ) , b)hipotermia y c ) a l t e r a c i o r l d e temperatur~as(contra5te d e banos). 2 ) el e c t r o t er a p i a; a ) est i mu1 ac i on d e l muscul o, b ) i ontof oresi 5. 3 ) mecanoterapia; a l o c l u s i o n intermitente venosa, b ) p r e s i o n d e s u c c i o n d e un tubo, c ) a l o j a m i e n t o d e o s c i l a c i o n e s , d ) compresion vaso neumatica, e ) masaje s i n c a r d i a l y f ) masaje. 4) e j e r c i c i o s terapeuticos; a ) e j e r c i c i o s B u e r g e r , b ) caminado6 t e r a p e u t i c05. 5 ) mediciones p r o f i l a c t i c a s ; a ) general y b ) calzado. 6 ) m e d i c i o n comprensiva d e r e h a b i l i t a c i o n ( v e r r e f . E2). TERMITERAPI A. - Hipertermia; El i n d u c i m i e n t o d e e p i s o d i o s r e p e t i d o s d e maxima v a s o dilatacictin d e a l i v i o d e angiosespasmo y d e promocion d e las p a r a l e l i s m o es un o b j e t i v o e s t a b l e c i d o e n el t r a t a m i e n t o e n enfermedades a r t e r i a l e s c r o n i c a s , y a s i d e a l g u n o s g r a d o s mas a b a j o e n trombosis venosa. La e f e c t i v i d a d d e 105 p r o c e s o s siempre, depende d e el g r a d o d e descompensaci¿~nd e el empleados, f l u i d o sanguineo a r t e r i a l . En t o d a l a e m b o l i z a c i a n a r t e r i a l y un avance d e b i l e n l a s enfermedades t r o m b o t i c a s , siempre, esos p r o c e s o s pueden n o ser a v i a b l e s ( v e r r e f . C ) . Calor directo; E l c a l e n t a m i e n t o d i r e c t o d e miembros es el medio l a temperatura mas mas e f i c i e n t e d e v a s o d i l a t a c i o n e f e c t i v a , alta(opico) de los r e s u l t a d o s d e t e m p e r a t u r a l o c a l , e n un i n c r e m e n t o d e a c t i v i d a d c e l u l a r con un aumento i n c i d e n t e en l a concentracion d e a c i d o s metabolicos e histamina y otras substancias. Esos a g e n t e s q u i m i c o s son potentes v a s o d i l a t a d o r e s , e n a d i c c i a n ( o suma) d e l p i c o d e l a s t e m p e r a t u r a s d e un centro medril armente esti mu1 ado por sangre, para ejercer una vasodilatacion refleja; aumentando l a temperatura y f l u i d o s a n g u i n e o e n un extremo por c a l e n t a m i e n t o d e alguna p a r t e remota d e l c u e r p o y es basado e n e l p r i n c i p i o d e l a r e s p u e s t a r e f l e j a . E l c a l o r d i r e c t o p u e d e ser a p l i c a d o por uso d e lamparae d e c a l o r radiante, c a l e n t a m i e n t o por conduccibn d e e l e c t r o d o s electrices, b o t e l l a s d e a g u a c a l i e n t e y fomeritos, c o n t r o l a d o r e s d e calor termostaticamente y l a c o n v e r s i o n d e calor por Diatermia y Microondas. E l e m p l e o s i e m p r e d e c a l o r l o c a l e n v u e l v e y asume 01 calcular el p i c o , el c a l e n t a m i e n t o e f e c t i v o d e l a e x p o s i c i b n d e t e j i d o s es e n t o d o el t i e m p o mas g r a n d e q u e el e f e c t o m e t a b o l i c o asi que, sin m o d e r a r n u n c a el c a l e n t a m i e n t o , esto es un gran p e l i g r o d e quemadura, manteniendose l a temperatura d e 1 i s u p e r f i c i e b i e n con a p l i c a c i o n l o c a l d e c a l o r d e p e n d e d e l a capacidad absotiva d e calor e n el f l u i d o sanguine0 Sin impedancia, l a s enfermedades d e arterias o c l u i d a s e x c l u y e esta funcibn d e el sistema vascular, y l a cantidad d e c a l o r es p e r m i t i d a p a r a a c u m u l a r s e en un p u n t o c r i t i c o e n l a d e s t r - u c c i b n d e l o s t e j i d o s . En l a suma di2 una i n a d e c u a d a d i s p e r s i b n d e Calor, el concomi t a n t e d e un proceso metabolico local puede ser deteriorado por c o m p o s i c i o n d e los r e q u e r i m i e n t o s d e o x i g e n o alrededor d e los t e j i d o s anoxicos, si b i e n es p o r acumuldCibn local d e productos y metabolitos .finales. Calor Indirecto; Esto es r e c i e n t e m e n t e l a h i p o t e r m i a g e n e r a l d e el cuerpo o “invernacion” a r t i f i c i a l , p u e d e g a n a r o b i e n merece el reconocimiento en este uso e n c i r a g i a c a r d i o v a s c u l a r y neurologica. E s t e es l a mejor c o n d i c i o n d r a m a t i c a m e d i c a q u e n o p u e d e ser e x p l o t a d a , e n una ,aguda o c l u s i o n a r t e r i a l l a a p l i c a c i b n d e m e d i c i o n e s h i p o t e r m i c a s p u e d e ser l e i d a y a p o y a d a en las ecuaciones basicas d e 1 0 5 r e q u e r i m i e n t o s m e t a b o l i c o s d e io5 tejidos, con l a disminucib,n d e s a n g r e a d i c i o n a l Practicamente siempre, e s t a c e r c a n i a t e : r a p e u t i c a n o p u e d e ser c l a r a m e n t e d e f i n i d a y es d i g n o d e e s t u d i o mas . f u e r t e . E s t o es u n i v e r s a l m e n t e mejor a c e p t a d a q u e l a a p l i c a c i d n de c a l o r e5 a n t i f i s i o l o g i c o y p u e d e ser a d v e r t i v o . 1.a r e f r i g e r a c i d n a c t u a l d e u n m i e m b r o p u e d e p r o v e e r y p u e d e ser extremadamente usada e n control d e s e g u r i d a d e n una s i t u a c i o n d o n d e es i r r e v e r s i b l e y c a m b i o s i s q u m i c o s e x t e n s i v o s , p e r o donde otras c o n s i d e r a c i o n e s m e d i c a 5 m i t i g a n otros procedimientos i n m e d i a t a m e n t e , el p a n o c a l i e n t e d e un m i e m b r o d i s t a l e n un p u n t o d e a m p u t a c i b n c o n t e m p l a d a es u s u a l m e n t e s e g u i d a p o r i m p r o v i s a c i t m r a p i d a d e el p a c i e n t e , s u b s e c u e n t e d e s i n t o m a s toxicos, d e una c a i d a d e t e m p e r a t u r a y a b a t i m i e n t o d e el d o l o r , el e n s a n c h a m i e n t o distal no e s t a a s o c i a d o c o n d i s t r i i r b i o s d e u n a h e r i d a b o r d e a d a d e l a c a b e z a y p u e d e ser una i n f e r c i o n s e c u n d a r i a . k..OS e s t u d i o s d e h i p o t e r m i a e n el t r a t a m i e n t o d e t u m o r e s l o c a l e s p u e d e e s t a b l e c e r q u e el f r i o . p u e d e ser e f e c t i v o e n l a d i s m i n u c i b n d e un edema y e f u s s i o n y r e l i e v e con un pafio. Estas r e s p u e s t a s aparecen y p u e d e n ser u s a d a s e n el uso d e b o l s a 5 d e h i e l o a p l i c a d o en l a p a n t o r r i l l a y m u s l o p o r a l g u n o s f i s i c o s e n el t r a t a m i e n t o d e p a c i e n t e s con t r o m b o f l e b i t i s y t r o m b o s i s venosa. Inflamacidn, indoracidn (endurecimiento) edema y a p a r e c e p a n o que p u e d e ser c o n t r o l a d o r a p i d a m e n t e , a s i e l f r i o p a r e c e ser mucho mas efecti.vo q u e los fomentos c a l i e n t e s , un tratamiento ocasional e n p a c i e n t e s d en e s t a m a n e r a p u e d e 5er el f r i o intolerable asi q u e su a p l i c a c i b n p u e d e ser t e r m i n a d a . &si un i n d i v i d u o s i e m p r e , e5 el u n i c o que m a n i f i e s t a 5u g r a d o i n u s u a l d e v a s o e s p a s m o s e c u n d a r i o s q u e r e s p o n d e n mejor‘ a los b l o q u e s d e l C. N S i mpat ic o Temperaturas a l ternantes; E l L L ~ Od e b a h o s d e a g u a c o n t r a s t a n t e s , e n el c u a l el p a c i e n t e es s u m e r g i d o a l t e r n a d a m e n t e si sus p i e s e n , . . 24 el baho y agua f r i a , e s ahora empleado e n a v a n c e s pequeños d e en el t r a t a m i e n t o d e enfermedades v a s c u l a r e s í v e r ref . A ) . Con io5 problemas a r t e r i a l e s , por e-iemplo l a c o n s t r i c c i b n d e l a imersion en f r i o pesa mas que el supuesto e f e c t o b e n e f i c i o s o d e a l t e r a r 1 0 5 c a l i b r e s d e los vasos, en los p a c i e n t e s a l e r q i c o s a l f r i o , siempre esto es a l g u n a s v e c e s b e n e f i c i o s o p a r a efectos g r a d u a l e s d e s e n s i b i l i i a c i b n por t r a t a m i e n t o s d i a r i o s con imersion d e los efectos e x t r emadamente d e n t r o d e l agua, que es progresivamente enfriado(Ver c a p i t u l o 29 y r e f , d e diagnostico radiologico). CINALISIS i DE TUMORES INTRACRANEALE6.- Sumario.Un analisis de 145 tumores ,intracraneaieí o b s e r v a d o s e n el departamento d e p a t o l o g i a , Maulana MPdical College y a s o c i a d o con I r w i n g ti. R, H o s p i t a l . P a n t s fueron sacados, . l a f r e c u e n c i a r e l a t i v a d e 1 0 5 d i f e r e n t e s tumores, son sitios, l a edad y sexo d e 1135 p a c i e n t e s es r e p o r t a d a y comparada con reportes p r e v i o s d e l a l i t e r a t u r a . 1 n t r o d u c c i o n . - Reportes ien el a n a l i s i s d e lesiones que ocupan el e s p a c i o i n t r a c r a n i a l pueden ser d e s c r i t o s por d i f e r e n t e s autores d e d,iferentes p a r t e r d e l a India. En 1967 l a r e l a t i v a i n c i d e n c i a d e l a s . l e s i o n e s que ocupan e l . e s p a c i o 11itraCranidl fueron r e p o r t a d a s por R a t h c e t , a l l), y Chandra (et,al 2) r e p o r t a n una r e l . a c i b n entre l a e d a d y sexo d e otros p a c i e n t e s y la i n c i d e n c i a d e gliomas intracraneales. En 1966 D a s t u r e I y e r ( 3 ) r e v i s a r o n 450 'lesiones qu'e ocupan, el espacio lntracraniai. Nosotr'oe consideramos :un p r o f u n d o e s t u d i o d e e n f er-medades c l i n i c o p a t ~ d o g i c a sy lesiones n e o p l a s t i c a s . d e l c e r e b r o y r e p o r t a n SLI p r e s e n c i a d e l a 5 d i f e r e n t e s p a r t e s d e l p a i s . Material y Metodo.- E l m a t e r i a l comprendido d e especimenes q u i r u r g i c o s r e c i b i d o s en el departamento d e p a t o l o g i a d e Maulana, el estudio i n c l u y e 145 tumores i n t r a c r a n e a l e s c o l l e c i o n a d o s por un p e r i o d o d e 5 ' a h o s d e 1970 a 1974, los tumores fueron c l a s i f i c a d o s d e a c o r d e a l a c l a s i f i c a c i o n d e Kernohan y Cagre. R e s u l t a d o s . - E l numero t o t a l d e v a r i o s tumores i n t r a c r a n e a a l ~ s y el r e l a t i v o p o r c e n t a j e e s dado en l a t a b l a 1 , l a edad y sexo d e 105 p a c i e n t e s y e l s i t i o d e esos ,tumores e s mostrado e n l a t a b l a 2, i o 5 s u b t i p o s d e g l i o m a s , son una e v i d e n c i a r e l a t i v a y el X d e edad d e l o s p a c i e n t e s es mostrado e n l a tab1.a 3. Gliomas y maningiomas c o n s t i t u y e n l a mayoria d e los tumores i n t r a c r a n e a l e s ( c e r c a d e l 77%). A s t r o c i toma: Constituye 78% d e el total de gliomas intracraneales, el p a c i e n t e mas j o v e n e n e s t a serie f u e d e cinco ahos y m e d i o (hombre) y el mas v i e j o f u e d e 62 años (hombre), la mas a l t a i n c i d e n c i a o c u r r e e n p a c i e n t e s con edad e n t r e 30 y 40 ahos, los hombres e n pr-oporcibn d e l a s mujeres f u e d e 1 . 6 : 1 , de i o 5 62 tumores, 36 son d e g r a d o 1 y 2 y 26 son d e g r a d o 3 y 4. Eperidi omas: Constituye el 12% d e t o d o s 105 gliomas i n t r a c r a n e a l . e s , e l p a c i e n t e mas j o v e n f u e d e 3 ahos (hombre) y el mas v i e j o Cue d e 35 años ( m u j e r ) . E l 8% d e los p a c i e n t e s son d e una edad entre 1 y 20 ahos, l a r e l a c i b n hombr-e-mujeres es d e 3 : 2 , ocho d e i o 5 d i e z tumores son i n f r a t e n t o r i a l e s y unicamente 2 son supratentoriales, microscopicamente 3 son e p i t e l i a l e s , uno u f e p a p i l a r m e n t e y los r e s t a n t e s 6 son d e t i p o c e l u l a r . Medulablastoma: Estos son d o s c a s o s d e meduloblastoma en 25 . . . . ,mujeres; u n o f u e d e 5 y o t r o d e 13 ahos, ambos tumores fueron l o c a l i z a d o s e n l a - . p a r t y e i z q u i e r d a d e l l b b u l o . d e el cerebelo, y m i c r o s c o p i c a m e n t e son d e t i p o c l a s i c o . Estos son d o s casos d e o l i g o n d e n d r o g l i a s Oligodendrogliomas:. (.3X d e l o s g l i o m a s i n t r a c r a n e a l e s ) , . ainbos p a c i e n t e s son hombres d e , 22 y 36 ahos.Un tumor f u e l o c a l i z a d o e n el h e m i s f e r i o d e r e c h o y .ot,ro e n el lobulo izquierdo temporal, cerebral microscopicamnente, , una ant:imezcl'a d e a s t r o c i t o s n e o p l a s t i c 0 f u e r e v e l a d a e n esa p a r t e . . Nerviogliomas: Estos sori, d o s c a s o s d e n . e r v i o o p t i c o q 1 i o m a ; el p a c i e n t e .fue d e 14 anos mujer y el 'otro f u e d e c i n c o afloe y medio hombre,. Esto .fue , e n un taso d e el n e r v i o o l f a t o r i o g j i o m a en un p a c ; i e n t e d e 2 ahok. homhre, e n est.05 dog carjos l a p o s i b i l i d a d d e a c t r o c i t o m a . . f u e c o n s i d p r a d a cm una examinacion m i c r o s c o p i c a . Meni n g i &ma': Forma el seyundo grupo mas g r a n d e de. neop1,asmas intracraniaIek., c o n s t t . i t u y e n ..23.%d e el t o t a l . La edad r a n g o f u e d e 9 a 65 amos, l a ma5 a l ' t a i n c i d e n c i a o c u r r e , e n p a c i e n t e s d e Microscopicamente, 4 son ~ 1 a s i f i ~ a d o s edad entre 2 0 ' 9 . 3 0 aftos. como f . i b r o c i t o s , 5 como anyliomas, 4' d e esos muestr-an a r e a s d e calci$i,cacibn.Esos son 4 casos con s i g n o s c i t o l o g i c o s do m a l i g n i d a d y e v i d e n c i a d e i n , f i l t r a c i , b n e n el hueso. Neuroma acusto: Esos soin seix casos los cuales (4%), todos e s t á n v e l a c i o n a d a s con el oct.avo n e r v i o , el r a n g o d e edad f u e d e 24 a 45 aha's. Desarrol1.0 d e tumoyes: ¡En este gritpo esta;' d o s cordomas, un cranifarygioma; un c y s t e p i d e r m a l y 3 colesteatomas. Ambas cordomns t i e n e n e v t e n s i b n supras.@lar, u'no o c u r - r i b e n un hombre d e . 45' a k o s . y el o t r o e n una mujer d e 50 ahos. La c r a n > o f r a r y q i o m a fue v i s t a e n un h o m b r e d e 13 ahos; esto f u e un tumor con. masa c y s t i c . a a m a r i l l e n s e ( n i ' & a p e s c a d o ) s u p r a s e i a r , , e n l a c u a l f u e en un a r e a d e c a l c . i f i c a c i ' b r t . Esos 3 c o i e s t e a t o m a s fueron v i s t o s en hombres entre 2 C i a 40 ahos ( p r o m e d i o d e 28 ahos) y t o d a s l a s lesinnes supratentoriales. Sarcoma: Estos fueron 4 casos de.sarcoma,, u n o f u e e n r e t i c u l o celular mostrando. e v i d , e n c i a de. - e r o s i b n en el h u e s o , uno f u e un f i b r o s a r c o m a , y l o s r e s t a n t e s . 2 fueron no c l a s i f i c a d o s . Tumores F i t , u i t a r . i o s : Estos, fueron 5 adenomas p i t u i t a r i o s ( 3 % ) , m i c r o s c o p i c a m e n t e . 3 fueron adenomas cromofobe, y 2 fueron adenomas a c i d o f o l i c o c'on e v i d e n c i a d e acromegalia.. El paciente mas. j o v e n e n e s t a serie , f u e de 25..ahos y el ma5 v i e j o d e 38 ahos. .Tumores M e t a s t . a t i c o s : Eston son 6 casos, en 2 d e esos el tumor p r i m a r i o gue en 105 p u l m o n e s , en 2 e n l a b r a s t y 1 en el estomago. En i.1.n. caso fue mi.croscopicamente un adenocarcinoma, el . s i t i o d e el tumor p r i m a r i o n o puede ser a c e r t a d o . T ~ i m o r e sV a s o f o r m a t i v o s : , Estos son 5 casos, 2 d e los c u a l e s son,hemangi ob1 astnmas .y 3 hemangiomas. Discucibn; En or-as series, l a i n c i d e . n c i a d e g1,iomas f u e mas a l t a que e n l 0 5 . o t r O s tumores i n t r a c k a n e a i e s . ~ s t o sf i n e s f u e r o n tambien r e p o r t a d o s por o t r a s a u t o r e s ; Grant ( 5 ) fundo d e ellos que. 'el 48% d e l a 5 l'esiones qLie ocupan un e s p a c i o i n t r a c r a n e a l , s i n ' g r a n u l o m a s . En l a s e r i e . C h a n d r a , los g l i o m a s forman el 36% d e t o d a s l a s lesiones que ocupan e s p a c i o i n t r a c r - a n e a l . La i n c i d e n c i a es más b a j a que otros p o r que' n o i n c l u i m o s granulomas. Zulch (6) da un 45% d e tumores..i.ntracraneales, a s t r o c i t o m a f u e el m a comun d e todos 1 0 c . g l i o m a s . E l pc.r-centaje d e edad d e los p a c i e n t e s con ' ;. . c I c c c e c , 26 a s t r o c i t o m a e n o t r a s series .Fue d e 32 ahos. En otras series f u e s i e m p r e s i m i l a r a l a d e Dastur, el ependiomas c o n s t i t u y e 12% d e l o s g l i o m a s i n t r a c r a n e a l e s eri o t r a s series, como e5 comparada con 10% e n l a s e r i e d e Chandra. E 1 p o r c e n t a j e d e edad d e p a c i e n t e s en otras s e r i e -fue d e 14 anos, m i e n t r a s que e n l a serie Dastur fue un p o c o ma a l t a d e 18 anos. Estos son 12 hombres y 7 mujeres en otras series l a r a z o n 1:ue d e 1.7:l. Meduloblastoma y oligondedrogloma forman un pequeho p o r c e n t a j e d e c a s o s e n otras series. Meningiomas son l i s segunda mas f r e c u e n t e neoplasma i n t r a c r a n e a l (23%), C h a k r a b a r t i , r-eporat como i n c i d e n c i a d e 14% y Dastur d e 13% d e esos tumore!s e n lesiones i n t r a c r a n e a l e s e x c l u y e n granulomas. O l i v e r c r o n a da una i n c i d e n c i a que puede 5er 20%. L a s l e c t u r a s e s t a t i c a s l a fr-ecurmcia con l a cual o c u r r e meningioma E:l promedio d e edad d e esto f u e d e 37 varia considerablemente. ahos. En l a s e r i e Dastur fue d e 26 hombres y 18 m u j e r e s , p e r o e n o t r a s ,fueron mas mujeres que hombres. Neumonas acusticos ( n e u r i l e m o n a s ) o c u r r e n en 4% d e l o s c a s o s e n o t r a s series. E l % d e n e u r i l e m a s r e p o r t a d o por I?ath(l) y D a s t u r ( 3 y B) es a l t o 10 y 8% r e s p e c t i , ~ a m e n t e ) . Zimmerman(l0) r e p o r t a una variacriar; i n c i d e n t e d e 27%, mientr-as Katsura funda que puede ser como un 1 2 % . Una comparable i n c i d e n c i a d e 5% fue r e p o r t a d a por Grant ( 5 ) . E l promedio d e 'edad f u e d e 32 akos, comparable con üastur f i g u r a d e 33 akos. Tumores p i t u i t a r i o s , o c u r r e e n 3% d e otros ca50.5, mientr-as en D a s t u r l a i n c i d e n c i a fue d e 8.7% y e n C o u r v i l l e fue d e 3.4%. E l promedio d e edad e n o t r a s series es d e -7 4.2% m i e n t r a s que 105 p a c i e n t e s e n l a serie Dastur f u e a l t a (38 akos. D e s a r r o l l o d e tumores, o c u r r e e n 5% d e otros casos, como comparacion con un r e p o r t e i n c i d e n t e d e l a l i t e r a t u r a con variacibn d e 3% ( o l i v e r c r o n a 9) a 10% K a t s u r a í l l ) . 'Tumores vasoformativos, o c u r r e en 3% d e o t r o s c a s o s ; el promedio d e e d a d e s d e otros p a c i e n t e s f u e d e 26 anos. Z u l c h ( 6 ) funda en e l l o el I % d e c a s o s y Dastur e n 5% e x c l u y e n d o c a s o s d e granulomas. Sarcoma f u e l a mas b a j a i n c i d e n c i a en l a s series p r e s e n t a d a s (3%); fulch (6) r e p o r t a una i n c i d e n c i a de 3% y Dastur 0.13%. Tumores M e t , a s t a c i c o s , o c u r r e n e n 41.4% d e o t r a caso. E l i n c i d e n t e reporte es 4% por Cushing (13), 4% por Z u l c h í6), 4.1% por n l i v e r c r o m a í9), 4.3% por t:atsur-a í l l ) , y 5.2% por Dastur (B), i n c l u y e n d o granulomas. En o t r o e s t u d i o d e g l i o m a s , .,donde s i e m p r e los tumores comunes y , s i e m p r e con menimgiomas, c o n s t i t u y e n un 77% d e el numero t o t a l d e tumores i n t r a c r a n e a n o s , cuando mas comunmente es el s i t u a d o s u p r a t e n t o r i a l m e n t e . Los mas a f e c t a d o s son los hombres despues que l a s m u j e r e s l a e x e p c i b n a l a r e g l a dada e n casos d e meningioma y adenoma p i t u i t a r i o . La i n c i d e n ' c i a mas a l t a de lesiones m e t a b o l i c a s en mujeres no es s i g n i f i c a t i v a . Como recordamos, l a edad e n t r e 20 y 30 ahos es l a mar afectada c omun men t e. ~ 27 P 33 23 4 3 3 4 wooma e 3 3 TOTAL ZOO &4) .2 2 3 L c c c -r 33 AI margen de la práctica da% El láser -un nuevo medio terapéutico Nuevos experimentos y p r o g r e s o s W.Schweisheirner .. . nEl láser en realidad se halla solamente al comienzo de la investipción clínica practica d e sus posibilidades de empleo dentro de la medicina.)) Estas palabras optimistas proceden de L . Goldman. director del Laser iabordtorium de la Universidad de Cincinnati. y de R . J. Rockwell. fisico jefe de este centro de investigación. Desde el descubrimiento de la acción del laser. este instituto figura a la cabeza en el c a m p de la aplicación práctica del láser en la medicina. De vez en cuando se elevan voces en conma de la aplicación de w e método de tratamiento. concretamente en la cirugia. Es d i p i i de consider;ir I:I respuesta de estos dos investigadores al respecto: ((la verdadera labor de investigación del efecto liser no deniro de la cirugía se halla en sus coniienzos está temiinando)). Sus campos d e a p l i c a c i ó n en la m e d i c i n a , Por ahora el campo principal de la aplicación práctica del laser en la medicina lo constituye la fijación de la retina desprendida dentro del ojo. Pero en muchos otros campos de la terapeutica se experimenta su efectividad, parcialmente con éxito: en la piel, en los órganos interiores. en el cerebro. en la lucha contra tumores malignos. Muchos puntos están en estudio e incluso descubrimientos positivos requieren niás confirmación clinica antes de poder contar con ellos. U íralutiiiwm i ~ o t rIu.wr a2 las Iwiiorrugias gasiricus ~ Las hemorragias de la mucosa gastnca pueden detenerse en un intervalo de segundos con el trataniientn con un.gastroscopio laser. Tal es el resultado de experimentos con animales, llevados a cabo por P r o p i e d a d e s del láser R. Goodale y otros en la Universidad de Minnesota. El laser es un sucesor técnico del máser. El amó- 4 de los que informo en la asamblea de la (Central niiiio LÁSER se ha formado de las leuas iniciales Surgical Association» en Detroit. Este método actúa de «Light Amplification hy Stimulated Emission o1 64 veces más deprisa que el restañamiento por elecR:idi:ition» (amplificación de la luz por estimulo de irocoa~ulación.y la perdida de sangre es mas reduI:] ciiiisión de radiacióiii. L a palxhra VÁSER es. cida. Los experimentos se llevaron a caho en perros ion ;i\iniirmo. u n acróninio dc «hlicr«uave Arnplific, I’ iinrcoti7:ddos. a los cuales se habn administrado h! Stimulated Emission of Radiationn ~aiiiplific:iei6n hcparina para inhibir la coagulación sanguinea. En dc las microondas por estimulo de la emisióri de un grupo de perros (A) se produjeron Úlceras gástncas r:idiacíón). prnfundas y profundamente sangrantes, de unos 3 cm El Maser fue descubierto simultáneiimriitc eii lii- de diámetro. En otro grupo (B)se provocaron unihnr:itorios norteamericanos y TUSOL El primer miser camentc lesiones ligeras y superficiales de la mucosii. norteamericano lo construyeron en 1954 los f i w o s En los perros del grupo (A) pudo detenerse la h e m e , Gordon. Zeiger y Tounes. de la uniwrsidad neoyorrragia cinco segundos después de la aplicacion del kina de Columbia. Unos seis años después. la Hushes laser. La pérdida de sangre se redujo a los dos minutos Aircraft Company hahia Ilewdo a su plena aplica8:ión del iratamicmo en el 84 :O. mientras con la electre pi ictica el primer « m a w óptico». SI I k r . coagulaci6n la pérdida de sangre sólo habia dismiLa tcnipera1ur.i cii el punto S i u l del rii)n de l a w nuido al who del mismo tiempo en el 54:‘:. En los \c niidc en milhmes de Fados. Su cricrgi;: c’i cicii rxrros del grupo (B). con lesiones ligeras y supefiniillones de wcei mayor que la enerpi de I:I luz en cialt? de la mucosa gástrica. se logro asimismo mcla wpcrficie del sol. Para lograr xrnejante conden- diante el rayo del laser al cabo de cinco segundos u c i d n de lucrza. w pro’rcta 1;1 luz de un I á m coil- la dcicnción de la sangre. Mediante la electrocoapu\ c . i i c i i > n a l a tritvcs de una serie dc Iciites. concentrini;iciUn Y* requieren unos cuatro minutos. &de cii unii 5uperlicir dr un di;imetr,>dc media micrzi De siete a diez días después del tratamiento w n :. Schweisheimer, 94 láser se mató a los perros y se investigó la mucosa gastrica. En todos los casos se demostraron procesos de curación. Las exploraciones microscópicas revelaron que el tratamiento con láser no habia producido lesiones en otros tejidos. Estos resultados se corresponden con expenmentos anteriores de Goodale y Mullins. en los que se logró, mediante el rayo laser una rápida detención de la hemorragia despuk de una extirpación parcial del higado o por una lesión hepática. Lo uplicurión del /user m oftulniulogiu Ch. J. Campbell del College o f Physicians and Surgeons de la Universidad de Columbia es u n o de los primeros médicm que ha empleado el laser en oftalmología. concretamente en los desprendimientos de retina. fisuras retinales, angiomas y otros tumores. El y sus colaboradores. al cab0 de unos años llegaron a la conclusión de que «la fotocoagulación con láser promete convertirse en un valioso mét.odo terapéutico. La técnica clinica correspondiente a este método es sumamente sencilla y la reacción de los pacientes excelente. Se han observado relativamente pocas complicac~ones y, en general, no ban podido comprobarse daños duraderos como consecuencia de su aplicación)). Campbell posee una experiencia especialmente amplia en el campo del empleo del láser en la oftalmologia. Valora este método con gran confianza. concretamente en lo que atanie al tratamiento del desprendimiento de retina. En el retinoblastoma considera indicada la fotocoagulación profilactica. Según el. este método es aplicable también de un modo satisfactorio en la periferia del ojo. El tratamiento con un laser de rub¡ durante un tiempo brevisimo (500 microsegundos) y a 6.943 Anpstrom en los pacientes Únicamente ha ocasionado dclores o sensaciones desagradables de poca importancia. No fue necesaria la aplicación de anestesia. En el tratamiento del ojo con laser no puede mocerse Io cabeza. Por io regular. el paciente se halla en decúbito sacro supino plano y el médico lo traía desde arriba. Los pacientes con trastornos perifiricos del ojo pueden recibir un tratamiento ambulatorio y. en la mayoria de los casos. regresan a su l u p r de trabajo ai cabo de pocos dias. Otra valiosa roma de aplicación del láser la constituye el tratamiento de la retinopatia diabética. incluyendo concretamente las hemorragias retinales dentro de un cuadro de diabetes. L'Esperance. del Centro Médico Presbiteriano de Columbia. en Nueva York. ha informado del tratamiento con Iásar de 250 pacientes. la mitad de los cuales padecia de retinopatia diabética. El tratamiento con láser procura la obturación de los diminutos aneurismas que se desarrollan en los vasos de la retina en la diabetes ;i\arvada: de este modo se intentan impedir las hemorragias de la retina. * El Iuser L'Esperance utiliza en su tratamiento el denominado láser verde y no el laser de rubí o el arco de xenón. Considera importantes en este punto dos particularidades técnicas. Por un lado, gran pane del rayo rojo del laser de ruhi es reflejado por los vasos saiipineos de la retina, ya que éstos contienen la roja oxihemoglobina. En cambio, el láser verde de ar_eón Iopra la absorción del 75 de su luz verde. de una longitud de onda de unos 5000 Angstrom. por parte de los pequeños vasos sanguineos retinales. Ademas, con el laser de argon es posible una punieria especialniente precisa y su reducido número de vatios ocasiona una quemadura de menor consideración. En el tratamiento con el laser verde, además de las retinopatias diabéticas. se han incluido también tumores superiiciales. coroiditis y lesiones en el ojo anterior. y está previsto el tratamiento con láser de la fibroplasia retrolental. En los dos últimos años, en Boston se han tratado 329 pacientes de retinopatia diabética de distintogrado con la fotocoagulación con rubi (Escuela Médica de HarGard. Joslin Diabetes Foundation y el Hospital de Diaconisas de Nueva Inglaterra). Los autores Beetham, h e l l o , Balodimos y Koncz (Arch. Ophthal. marzo 1970) califican sus experiencias con la laseroterapia en estos casos como «estimulantes y efectivas). En estos pacientes habia una retinopatia diabética igual en ambos ojos. Sólo se trató uno de ellos. sirviendo de control el otro ojo. El 80 % de los ojos tratados con láser presentaron una mejoria clara, y desaparsieron totalmente los fenóm&os retinopiticos en el 54 "4. En cambio. todos los ojos no tratados siguieron igual o empeoraron durante el periodo de exploración. Camphell aconseja iniciar el tratamiento con pequeñas dosis de láser y aumentarlas si es necesario paulatinamente. Para lograr el nivel de láser adecuado se consideran necesarias. por io general, dos correcciones del ajuste inicial. - El lusm et1 el rruruniimto del &mer L. Goldman. precursor en el campo de la investigación biomédica con el láser, ha investiga& criticamente el tratamiento con láser practicado hasta ahora en los tumores malignos. Considera que o h cen perspectivas favorables aquellos casos en que el tumor es de fácil acceso y no responde a un trata- ' miento con los medios convencionales. €3tratamiento quirúrgico de las enfermedades cancerosas ha llegado. según el, a una «meseta», y el cirujano vuelve sus ojos en busca de ayuda hacia el ingeniero y el fisico. para lograr nuevos avances. Aunque no se dispone de material suliciente para una valoración definitiva. el tratamiento del cáncer y de otros tumores malignos, con láser prosigue con interés y muchas esperanzas. 'P. E. McGuíí. director de la Fundacion para la Investigación Mi- , Schnrislieimer. El /&ur ~ Efecto del láser sobre bs vasos sanguíneos dica con láser en Boston; Massachusetts; observó un . ~erecto favorable en el traiamiento-de-mefanumas~onYahr. Strully y Hunvitt, del hospital neoyorkino láser. Llegó a la conclusión de que «el láser conlitituye de.Montefiore, investigaron el efecto del-láser en las ~. una forma de enefgia-ünican: -En oíros informes arterias de perros en los que habian provocado preMcGuii fue más reservado y critico. Solamente conviamente alteracionq~arleri~oscl-eroti-s,___.,_~ ~. . . sidera logrado el éxito de una terapéutica de #cáncer Se emplean diferentes técnicas quirúrgicas para cuando se ha destruido la última célula cancerosa y anastonmar 10s~vasos.sanguíneos. E n r o d i i s e l l a s s e . _~ la enfermedad no resuige con-los aiibs. Es iodavia ~produce. por lo menos. U M corta interrupción &h. demasiado pronto para pronunciar un juicio definido circulación sanguinea ; esta interrupción podría ocasobre la terapéutica con láser. de los .. ..sionar. en ciertas circunstancias,~~una~~amenaza Son interesantes los experimentos del neurociruórganos de importancia vital. j a n 0 neoyorkino Stanley en el iratamiento de tumoEl nuevo metodo con láser evita una interrupción res cerebrales con el laser de ácido carbónico. Halló de ese tipo. Los experimentos se efectuaron con un que el rayo continuo de este tipo de láser evita el láser de neodimio en la arteria carótida. Para ello efecto del shock. que se ha descrito con la aplicase prccede en cuatro etapas: ción de los láser de rubi «pulsados». La acción del I . ” Debajo del punto del vaso en que se encuenláser de ácido carbónico vaporiza y desintegra iotaltran las inclusiones anerioscleróticas. es decir. en el’.. V: mente el tejido canceroso. De este modo se reduce lugar en que está proyectada la anastomosis, se deconsiderablemente la transmisión de células canceroposita una gota de sulfato de cobre. Mediante l a sas del tumor tratado al tejido sano circundante. absorción de esta.solución se influyen favorablemente Según Stellar. el tratamiento con láser constituye el las propiedades del tejido a la acción del láser. mejor metodo para la extirpación de tumores de di2.” La arteria que debe servir para derivar la re ficil acceso que se sustraen al tratamienio por sucgión arteriosclerótica convertida en intransitable dención o congelación. tro de la arteria receptora, se ((pegan con un adhesivo El ra?o laser conw «bivruri de luz» quirúrgico quirúrgico al punto coloreado de la arteria enferma. L a s dos arterias tienen entonces una pared común. Una investigación en perros acerca del efecto de 3.” Se dirige el laser de neodimio contra el punla irradiación infrarroja con laser (c~ontinuouswave)). to coloreado de la pared arterial. Con ello se produCWI de la piel. musculatura. cráneo. cerebro, higado ce un agujero liso en l a pared común. e intestino delgado. la realizo J.L.Fox. del Depar4.” L a consecuencia es que tras la formación de tamento de Neurocirugia del Veierans Administrala anastomosis. la sangre de la arteria donante fluye tion Hospital de Washington. Una fuerza eléctrica libremente hacia la parte distal de la arteria receptora. de unos 30 vatios, dirigida a un punto de la piel de 2 mm de diámetro. corta fácilmente la piel y la muscu- sin que haya que interrumpir la circulación sanguínea. Los autores insisten en que sólo podrán sacarse latura sin’ ocasionar una hemorragia considerable. conclusiones definitivas del resultado de -te metoCuando se produjeron hemorragias de mayor irnpordo cuando se disponga de muchos más experimentos tancia. impidieron la penetración del rayo de láser Confian que este método sea practicable también ~ en ~ ... . ~ . a través del cerebro y el higado. La energia del laser el hombre y están convencidos de que puede llevarse era absorbida en estos casos por la sangre y no fue a la práctica. posible una penetración más profunda. __ ~ ~~ ~~ ~ ~ ~~ L a curación de las heridas cuianeas abdominales tras irradiación con laser se retrasó en un principio. pero iuvo un curso rapid0 después del décimo dia. Experimentos comyiarativos entre heridas quirúrgic i s de bisturi y heridas producidas por láser no permitieron comprobar (ni aún con la microscopiii) diferencia alguna de consideración. En el empleo del «exalpelo de IUD) Fox pudo comprobar dos dificultades. I _‘I. cuando un ayudante. inioluntariamente. tropezaba con.el brazo del cirujano. se alteraba la dirección del rayo de láser y se produck un efecto imprevisto sobre el animal operirdo. el cirujano o sus ayudantes; 2.”. no podia haber ~rapiismetálicas u otros instrumentos quirúrgic<w en el campo de operdción. porque reflejan la energia 1á5n contra el cirujano o sus ayudantes. Fox se qucmd IJ mano dos \erns de este modo. Sin embargo. la\ qiiem~iduras Silnilron r5pidamente sin complic.+iiimt>>. El rraruniieriro con laser de la piel Se han tratado con laser una serie de trastornos cutáneos de naturaleza no maligna. Los autores que han informado de ello han visto éxitos en general y opinan que este tratamiento debena practicarse en mayor escala. Este tipo de tratamiento ha demostrado ser muy’ electivo para eliminar tatuajes de la piel. Esto se relaciona con la acción especifica del láser sobre los componentes pigmentarios de la piel. La piel normal no resulu dañada con este metodo. Se han tratado de un modo favorable alteraciones cutáneas de coloración intensa (nevus vasculares) y angiomas superficiales. Tambikn ha dado ya buenos resultados esta terapéutica en las alteraciones pigmenurias menores. En el tratamiento de estus casos con Iáscr no se requiere ni narcosis general ni anestzsia liral. Schweishnmer. El lúwi Se ha dudado de si el tratamiento con láser estará indicado en alteraciones cutáneas de esle tipo. Frente a estas dudas, Goldman y Rockwell. con su gran experiencia, abogan por dicho método. Dicen: <<¿Qué puede hacerse para tratar esos nevus vasculares incperables. incurables. deformadores. que alcanzan incluso a los párpados? A muchos pacientes les ha ayudado considerablemente el tratamiento con láser y no hay que olvidar que el instrumental láser de que se dispone hasta ahora es aún bastanie primitivo. Y esto se refiere muy especialmente a los pacientes con alteraciones dérmicas como los nevus \,asculara,. Traraiviento con laser de los órgmos ittrerrlos Existen numerosos estudios acerca del efecto del láser en los órganos internos de animales, concretamente en el hígado. Pero el tratamiento con IRser de los órganos internos del hombre se halla aún en experimentación. Una rama de esta investigacior, st dedica a ver cómo puede llevarse a cabo la extirpación de partes de órganos internos mediante la acción del Iáser. También se investiga la posibilidad de emplear el láser en las operaciones de trasplante de órganos. La irradiación con láser de partes del cerebro es de una efectividad especial cuando se ha levantado la cubierta del cráneo de modo que el laser pueda actuar directamente sobre el cerebro. Las experiencias clinicas obtenidas hasia ahora en este campo sc considera n «esperanzad oras». Jus tiiican la organizi cion de un programa intensivo para desarrollar las técnicas más idóneas. ~ Medidas de prscauciOn en el tratamiento con láser Es coniprensible que una fuente de energia tan «indómita» como los láser deba dominarse muy concretamente para que no Ocurran desgracias. La preocupación principal reside en que la exposición de los ojos sin las correspondientes medidas de precaución --aun cuando se trate únicamente de fracciones de segundo- puede provocar la ceguera y quemaduras irreversibles de la retina o de la lente u-ular. Para proteger a las personas que trabajan con láser se requieren sistemas de seguridad que den señales de alcirrna cuando se hace un uso excesivo del aparato. Se recomiendan unas gafas de un espesos de 4.3 cm. con un vidrio eslándar verdeazulado ) una densidad óptica del 10. Pero por si solas no bastan. En varios estados de Norieamérica. la legislacion ordena ya el registro y regulación de todos los sistemas de láser. Es especialmente p n d e el peligro cuando los dectos del laser tienen lugar ai aire libre. En rela- ción con investigaciones llevadas a cab0 por el ejército de los EE.UU.. ha afirmado M.E. Lasser: «Un observador que mirase directamente el rayo de nuestro «telémetro». correría peligro de sufrir quemaduras de la retina. aunque la distancia entre él y el laser luese hasta de 18 kmw. De un informe de la Western Electric Co. en BufFalo. N.Y.. EE.UU. se deduce que la aplicación de láser. observando las prescripciones de seguridad. puede llevarse a cabo sin daño para la salud. Emplean allí los láser para tratar brillantes. de cuatro a cinco horas al dia. No se ha observado ningitn daño en materia de salud. Es cierto que el operador no trabaja en la habitación en que se ejerce el efecto, del láser sino fuera de ella y con ayuda de una pantalla de \ televisión. Conferencia Anual de Seguridad de los Laser E1año pasado tuvo lugar por tercera vez la asam- blea anual de la «International Laser Safety Confe- rence». que debe su existencia esencialmente a Goldman. En la asamblea de 1970 se comprobó el siguiente e importante hecho: «Las deliberaciones acerca del trabajo con laser han confirmado la idea de que el peligro principal de lesión por acción de los laser amenaza a los ojos. Cuando la fuerza de las radiaciones se mantiene por debajo de los limites que pueden constituir un peligro para la vista. se hallan fuera de peligro los demas tejidos y órganos del cuerpo)). En estas asambleas de seguridad se comentan y discuten los factores de seguridad generales y especiales. encargados de proteger de lesiones tanto a los pacientes como a las personas que utilizan el laser. Se trata de u n asunto de importancia primord?al, Probablemente no carece de justificación el que un repíesentante de la Sociedad Médica de Nueva York exteriorice sus dudas acerca de la extrema peligrosidad del efecto láser. Añade que: «Los verdaderos daños de tipo sanitario producidos por el láser pueden ser mucho menorm de lo que hacen suponer las advertencias de una serie de médicos. Pero. sea como sea. no podemos dejar que siga adelante este asunto, mientras no tengamos conocimientos sólidos acercx de su efecto y de sus daños». La Medicina curativa así como la preventiva lievan el camino de lograr estos conocimientos sólidos. Hay que crear una nueva ierapéutica. Existe la esperanza de lograr con su ayuda éxitos terapéuticos inaccesibles hasta ahora a la Medicina. a O c O c c i O 5 E' 5 F F o cI h n blood f l o w s t A A M,=12.4 & r- M.iO.12 48. T. head E" = 0.8*9% 33.37% U trunk _* basal: i m = 35 Vhr, is=12 I/hr Fig. 19.4. Diagram giving for all compartmcnt~resting sfrtc vulues of mrlabolic h i i i production (,W<,hheat-transfer ~oelticicnlsbetween <Om- PPrtmmU (~csilionbetween units in the right hall of the ñgurei hsai-transfer co6Hicisnls bciwcen skin scyisntr and snvironmenl la1 lempsi'iure TALand iníenriblc svrporative heat l o s ( E v ,marked by outward arrows) Mel~bolic heat productionand evaporatiYS h a t Imarc in kcitlihr. transfer sufficicnu in kcal/hr Perentap listed together with bod E,, is the fraction. assigned to thc pnisvlar skin portion, of the 1Qal additional E, brought into action when exheat must te lost by evaporation of sweat. The ien half of the figurn shorn the distribution ofblwd Rows. The brain is p u l 4 81 40, the COR of the trunk at 210 litcr/hr. AU otha Rows may change according to demand. Their fractions of m u d e (1.) and skin blood 'a. $ Row(i,).wcsruumcdta t e c o n ~ t a n u a n d a ~ l i ~ t c d ~ ~ t i n g v n l u ~ o f i , a n d i . . a r c g i v e n . T h e l i i i k a r r o i r j l o t h s c o r rhead.thcmuaslaofths olihe trunk, and the core ofthe exlremitis indicae that extra heat inpus wcur in shivering and in exercise. Furthermore. in SICIC~Y, it is assumed that 584 dtbtotal heat originatesin ikcorrolthscarcniitiaaFd38./in ibcmus~laofthctrunk.(Cl.eqs.19.~l9.13.)Thssiorapeapcilyofthccomprtmmu cin easily bc ~omputedfrom their ma(y.Fig. 19.3) rind C,, (d. 4. 19.11. After Sioiwijk and Hardy 119.11. ,,,,. . .. . - .,-...,...,..,, .. -,..,”.,. ----.,... c 4 910. I , , , . I .. . .. ., , . * , ... . ,... . O s x s5 + , .. , . , . , . o i w m PJ m ,=, , , ,, . ,,,.. .... ......,... , ..... . ,,.,. .,*.,.."<-e-- - ,.* ..---..._., ",*" - .._..... ~. E .. . . .. . .. ! i ., , . .. -. -,. .. ... ... .. ... P .... .. ~.. .-. I-. I ,. c r- .. r.. ”. .. .. . .. .. . . I . r- _... 1 . -,. --. . .. .,. *. . ~... -. . - ... .. , ,.- .,- ... c .-- CHAPTER 3 PRINCIPLES OF PHYSICAL MEDICINE m This chapter describes the therapeutic and diagnostic application of physical energies in rehabilitation medicine. I t includes thermotherapy (heat and cold), ultraviolefi rays, electrotherapy, massage, manipulation, stretching, and traction. HEAT Biologic processes generate and arc affected by physical energies, one of which is heat. It is the most commonly wed modality in rehabilitation medicine and usually is applied before exercises, stretching, or electrotherapy. It is employed for both acute and chronic disorders, and the physiologic effects are the same whatever the source, varying only in the depth of penetration. Physics' Heat is a part of the electromagnetic spectrum and is a state of particle excitation (entropy). Every atom or molecule above zero degrees Kelvin has excitation and is capable of transmitting energy to another particle either by direct collision or radiation. Energy transfer by collision in solids is conduction and in liquids or gases convection. It only occurs when the absorbing particle has lower entropy (temperature). Heat can therefore only he transmitted from higher temperature to lower temperature. Radiarion is the emission of photons (quanta or packets of energy'. which cross space and when absorbed ran ( i ) increase the particle's excitation state, (2) alter its chemistry, or ( 3 ) be reemitted as heat or light (fluoresrence. phosphorescence ' . The skin is a g o d reflector. fair radiator, and poor ronductor of heat. The absorbed heat immediately encounters tlie high con- . centration of water molecules in the subcutaneous capillary and fat beds, which are subject to physical and physiologic reactions. The specific heat, the calories gain or loss needed to change the temperature of a ,Tam of a substance, is approximately threefold greater for water than it is for other tissue molecules. The subcutaneous water thus beromes an excellent heat storage reservoir or insulator and significantly contributes toward maintenance of relatively constant body temperature. Heat can also be produced in tissue by converting high-frequency electromagnetic waves into (1) microcurrents (short wave or microwave) or (2) shearing, vibrational, frictional. or compressive mechanical waves ( C . S . ) . These are described as diathermy or "deep heat" modalities and may penetrate to muscle. Condurtive. ronwrtive or radiant heat penetrates 1 to 5 mm and is rallrd "superiicial" heat. In summary, heat is electromagnetic energy, which is absorbed by a particle having a lower temperature than a source. The absorbed energy will ( I ) raise temperature, ( 2 ) produce chemical reactions, (3) transmit its energy to another particle, or (4) reemit itself as light or heat. The skin may reflect or absorb the energy, and this last is achieved to the greatest extent by water in the subcutaneous fat and rapillary beds. Physiologic effects of heat'.' Physiologic functions are governed by the eneri? manipulations of spPrialiied niolerules. usually protein. in the reil, its iiiembranes. and extrarellular roinpartiiients. These inolrcules have inherent mechaniral. 75 76 Rekabilitation medicine electrical, and chemical energy that they generate and trarkfer. Adding thermal energy LU this system will increase these transduction processes. Thermal energy in the water molecules of the aqueous solvent acts as a driving force for these reactions and may increaie oscillating motion, charges or dipole separation, or produce electrical changes. Additionally, hydrogen bonds may be made or broken, and chemical ihanges result from alterations in atomic and molecular configurations. These effects are metabolic or catalytic and function in life as the required substrate molecules are available. We may then @astulate the following .9cquence resulting írom the application of heat to cells: ( 1) incrvase cellular catalysis-metabolism requiring ( 2 ) energy molecules (O2, proteins, carbohydrates) producing (3) vasodilation and increased capillary pressures with ( 4 ) transudation and from alteration of membrane configuration or dynamics (5) ionic "pumping" of electrolytes and íiuids. Continuing application or reduction of temperature may result in ( I ) protein degradation creating histamine-like substances. ( 2 ' leukocytosis, and ( 3 ) concomitant inflammatory or anti-inflammatory reactions. The molecular and structural characteristics of proteins such as connective tissue collagen are temperature dependent and elongate with temperature elevation.s- The chemical energy of dephosphorylization of A T P to ADP, with accompanying mechanical work of shortening muscle fibers, generates heat that may produce changes in the helical configuration of fiber proteins, possibly on the mechanical characteristics of the sliding filaments. Protein fractions such as histamina or antigens (cryoplobulins) may be released with temperature alterations. Membrane dynamics fluids and electrolyte are temperature dependent, particularly those of excitable tissues such as nerve. Theoretically, these are conformational changes in the membranes that pervert thr seleitive ionic movement (pumps). The niechanisms of impulse transmission including ionir. electriral, thermal, and light enerpies are correlated. Infrared emissions from live crab nerves have been de- scribed.' The configuratio ):i of protei molecules in end-organ mwnbranes, r 1,: by environmental temper.!ture chani; secretions such as synoviil fluids: I I with tempaature elevatioil In summary, thermal mergy atfe:. structural and chemical characteri! t i molecules, enzyme activity. degradatio:i ucts, and membrane funcilon dong . at the end-plate and seci ,.tory surfa:.( I I ' , ' :'I5 , i .! Clinical eñects of heat Skin reaction locally d u d e s sei: warmth, vasodilation (ery!huna), SWI: reduction in skin mistanc.,, and incns. l a a l tissue metabolism. It heating i r tinued beymd 40 to 60 n.in, core t e r n tun may be elevated and homeosta:i, sponses of distal vaaodilatiiin occur. Usually temperature, p l s q and t pressure are unaffected, as are the ren 31 gastrointestinal systems. h'erve cond ti' velocities and action potentials may ini.r Muscle tone or tension m.iy soften, 1 1 1 elastiiity increase. Ligameiit and ca:r I fibers may similarly gain ei;tsticity, ami tion of joints increase. P a i n will occasiii , be relieved by heat. The exlilanation is 11 bly related to spindle gamm.i afferent rvIi hut as yet this is not a satisfactory exld tion. The anti-inflammatory action of inclwdes leukocytosis, increased cay il pressure, and humoral enzyme effects, acting toward suppmion of the tissue 11 , tion. The amount, rate, and direction of heat gain or loss is dependent on the fcll ing: 1. Source, its temperature artd duration < , I p I i c at i o 2. The optical properties of the skin 3. Con-skin tempeiaturc grslicnt, which i a from 5' to IO" C depending on the I tested: Core temperature a\erager 37' t., C : skin 29" to 35' C 4. The amount of water ml far in the 5 cutaneous capillary and {al beds 5. Hypothalmic and skin ncuial ~ o n t r o l ~ , r .i prui-id? mechanisms mniiitaining COISI temperature, such u retie>: vasomotor re " , . lions d i d to treated areas 6. Respiratory i n d excretor) mechanism i ~ : I I: I: ~ I . . I Principles of physical medicine 7. Ambient temperature and humidity (aged and infants tolerntc h u t pooriy), B. Age sex, nutrition, exercise, hydration, sensitivity, and diseq. Indications Heat is indicated for its ondgeric effect primarily. The usual applications are for musculoskeletal, neuromuscular disorden such as neuralgias, sprains, strains, articular problems, muscle spasms, trigger points, and the host of terms that attempt to describe the vague problem of muscle pain. Simons’ in an exhaustive review of muscle pain syndromes attempted to define the many tums used to describe the problem and reported the pathologic conditions found by a few investigators. There does not appear to be a clear description of the etiology, pathology, or treatment, but heat and cold are recommended among many other modalities. The cause of pain is obscure in the absence of any defined pain end-organs in muscle. The antiinflammatory effects of heat were described above. Spasm of muscle is an indication for heat treatment. The nature of this condition is included in Simons’ discussion but escapes definition. That it is benefitted by heat is often noted subjectively and objectively. I f possible, however, a diagnosis should be made and aspirin or other anti-inflammatory analgesic prexribed, with rest or splinting, before embarking on a program of themotherapy. i Heat before exercises, stretching, traction, or mani$ulation, often enhances the effects and benetits of these measures. The use of heat in obliterative arterial or in arteriolar disease is empinc and should be employed with the greatest d e g m of caution. Wounds and ulcen may be benefitted by topical heat. Cellulitis and abscesses may be ripened to the point of drainage with hot wet rompresses. Open wounds. as heat may have an evaporative drying and vasodilating effect. niay be bmefitted. Tlie soporitic effect of heat is achnowledged clinically. Its explanation is obscure, hut empirically it provides benefit to many ’ 77 patients. Providing this support in a department of rehabilitation medicine should be done cautiously to avoid possible dependency. The simplest modality that may be used at home is often as effective as “sophisticated” apparatus and has the advantage of being easily employed by the patient or his family. Contraindications Heat, whatever its source, should not be u d in acute inflammation or trauma until the initial reaction has subsided, nor in venous obstruction, arterial insufficiency or ischemia, hemorrhagic diathesis, or coagulation defects. In the absence of sensation special care must be exercised. In the presence of cardiovascular, respiratory, or renal failure heat should be used sparingly, if at all. Active inflammatory arthritis particularly with joint swelling, may be worsened subjectively and objectively with the application of heat. T h e use of heat over areas of solid malignanc) is contraindicated, although the possibility of either superficial or deep heat’s affecting a tumor‘s temperature may be questioned. Sources Conductive heating’ Conductive heating is achieved by direct contact with the skin. T h e sources may be ( I ) solids-electric pad, hot water bottle, sand peloids (muds), and poultices; (2) liquids-water, paraffin wax, or compresses; ( 3 ) gases-dry or moist air. The choice is one of convenience and should include accessibility of the part, need for movement, availability of the agent, and the patient’s and physician’s preference. The agents most commonly used in rehabilitation are water, hot packs, paraffin, and moist air. Hot water bottle, heating pad, moist packs, and tub baths are available at home, making these a preferred heat source. Liquids.” Its accessibility, buoyancy, and ease of temperature control make hydrotherapy a readily employed heat source. Normal heat loss with ,hydrotherapy niay be re- 70 Rehabiiit,ation medidin. i duced and u~~desirable te@peraturc e k t h . &chr The tub, p o l , OCN. 'p, . w#th adeqwate hydration. Patients with diffuse musculoskeletal pain may be cmdidaies for this treatment, but a hot tub or shower at home would be equally effective. and whirhi01 are used for palliation (yhulpod), a r u C e , or debndcment (wounds, uicen) .soapq, M6Radiant heot" scptics, and deterguru & be added to the RadiPnt heat is infrared radiation, which water as appropriate buq often am unnccshas a wavelength of.7X) to 12,000 nm and is --safy=-~ul~body immersi& in tubs or tanks above the visible spectrum (390 to :'70 nm). for reant widespread sJrface burns is us& Its depth of penetration is approxiniateiy i o in many centers. The a@dition of camman .to 1 mm b r near (770 to 1500 n m ) , and I salt at the ratio of 0.7 pounds per 10 gallons to 0.05 mn for far (1500 to 12,000 nm). of water bring.l the bath, to isotonic Oonanphotons at longer wavckngth have less entration, and maintcnancd of the tcmpCntUte ergy, thedore. leu penetrability (Table 3-1). with that of the blood b mommendcd. The phriologic effects of radiant heat are Pool t-mpraturc for exereire thm" identical m those of conductive heat. should be approximately '32O C (90' m 106" Sources of radiant h u t are (1) luminous F). Therapy prior to UJcrciSeS or stntchiag or visible .infrared bulbs, which emit near soft tissue injuries or woQnds should k da¡&, infrared, and (2) noniuminous :-adiators, starting at 10 to 15 mid and increasing Up +ch are metallic coih or wire cov~mdwith to 20 to 30 rnin and on alternate days fbr mfractory materials, which emit far infrared. elderly or debilitated patients at appmxiThere may be some visible light in the coils, matcly the same temperaturn. and usuaiiy so with bulbs. Bulbs lor home Compmc~a.These r n i y be turkish towYI, iue are available, but caution must be exerstrips of felt or wool blhkets, or the si1ic;yte c i s 4 against the possibility of bums or Fm. gel pack (Hydrocollator). The latter mains heat longer when heat4 to 150° F and iras OlATHERmY AND ULSRASOUND" a temperature of 122O F 30 min after yPhysics plication. Patients and fimilies can easily be High-frequency currents are generated by taught to UK packs at home. m oscillator that in addition to íi current Panfñn wax. Paraffin. m i n a liqukl after melting at a temperahin; of 120° F, and 4- source r q u i i a a capacitor-or condmscr and an inductance coil. Modifications iipon this ing mineral oil lowcn +e melting tanpesature. It i rapplied dvecqy to the skin, and:& bksic circuit can produce electrcmagnctic (radio) waves that have frequcncia deoften prescribed for arthritis of the hand or fmt. The adherent oil ;Ind wax after its n- scribed as short and ultrashort (microwave) compared to long radio waver. The lame moval makes subsequent massage and ttretchbasic generator coupled to a piemelecmic ing easier. I t s eñectiveness in acute swollen crystal (transducer) is used in ultrasound joint is questionable. E l q r i c heaters or d a i therapy. hle boilers are available for home w.PaThe radio wave, when emitted from the tients using this at home should have a thernioineier available to ensure proper tanpenaTable 3-1. Various ranges of the tures. electromagnetic spectrum Heoting cobinets. Heating cabinets deliver dry or moist heat and have varying acceptRange of ance. Their siee. cost. and maintenance limit Trpr of rodidon wauclrngihr (nm) their use. Exlming larga surface areas to an Lons-wivc infrared 1?,000-1,500 environmental temperatjre higher than that 1,500. 770 Short-wave infnrcd of the body and adding fnoisture to eliminan Visible 770. 390 Ncl. uloivioici 3 9 0 290 evaporation will raia M y temperature. PmFar ultrrviolct 290. 180 found sweating should be compensated €or mr-illatc3 .'I a "Iield' t ' , the i:ou:~If' ancc coil. A. piiiio' pacitor p l ~ and c o ~ ~ t r i q c l e. F'lacii g tor plat 5 indJctaiici: roiled c r 7 . 5 1 uevel 13.56. z7.1 '8 \v3<;e5a re of 2450 cp 3Iicniw;i scribed 8s Y diainetcrs inches, a r f are coiinei to [lie osci The :eii mii.mcr IT,: bui similai a \diirie inilwda ic'? im fields Diutheimy The cui field vary tamce let1 the pla ;a, plied. Un[ rcdUce<l, I rent withi KO ins:ru current. h t l w ''re io11 qriirrator ill!: fiP1 is durtan<.e h l ! eIri:c1 3 t ai 1:inip. ,in,: '1-lie heat rii;itely \r;ives" di1crt"'S tliry heat. r i i ! i ! I Princifirs of phy&al medicine 79 o~illator's antennii, seis up +uoeurrents in a "field'' that dewdopr b e 4 n the plates Of the coupled capacitor or within an inductance coil. A pieroei&uic crystal pia+ between .a+tor plates will subject it to expansions and contractions with each oscillating half cycle. Placing a patient between coupled capaaitor plates will produce capachor heating, or inductance heating where a ;wire is either coiled or laid .on a part. T h e short (22, I I , 7.5) wavelengths are k e d b i the F.C.C.at 13.56, 27.12, aiid 40.68 megicydrj. Micruwaves an 12.2cm long &d hilye a frequency of 2450 cps. Microwavcs are generated off directors doscribed as A, B c he mi spherical^ and 6 inch diameters) and C and D ( d i w r a i 4.5 by 5 inches, and 5 by 21 indies).'The directos are connected and coupled bx coaxial cabk to the oscillator as is the U.S.transducer. The term diothctmy is a mhnomer as the microcurrents do not go thrMgh the bcdy but similar to any current will tnove through a volume conductor along the: lines oí least impedance (resistance in nigh-frequency fields) or across iq surface. Diaihemy" ! i . The curnnts generated inside a capacitor field vary according to the cap-itor size, distance between the plates, mattrial between the plates, and the voltage and {rcquency a p plied. Undcntandably, these vahables c a n be reduced. but the quantificatiod of the currmt within the field or-body il an avcrage. No instrument can accurately :measure this current. Meters on the apparatils only define the "resonance" or tuning of the patient and ;:enerator circuits. The patterns: of the heatirix fields arc different for rondmser pad. iniductance coil. and microwave directors. but 11ie eRect is that they develop +at approxiiriately 3 cm belmv die skin's suirace. Micro-waves" are applied in a similar manner to a Ilmp, and much oí the energy is reflected. The heating patterns v a n w+h different iiirertors hut essenti;illy diñer in the area 1 hey heat. Wtrosnund" is meck~nical oscillating w aSound r n ' ($00, to i , ~ , a o Ocps and 0.15 qn) that produce vibration, shearing, corn" pressjei, and frictional force above the audible range (17,O cps) . The energy is generated by particlt collisions, each with different mws and energy state. With diflerent pSrtKlss collidiag a higher energy is generated tban ir c o n t a i d by each partick, and an n(t&a&e reaction is produced. As the waves ah muller than many particles, they will be r(ftecte43. nKse energy reactions are mechani d an@ predominandy thermal. Coupling or linking uitnaaund to the body ,nuface transmission of the energy. A '?gam ot gap ofi air will diuipate the energy udd void ita dldct. Oil, j e i l i i , and water are u s d as couplingi agents. The energy absorbed by the tissues id tranunitted by conduction. M e d i c implants, except those close to the B k h , are good conductors, and their presence. khcrefore. is not a contraindication to ultraiomd therapy, as they rapidly transmit the h+t and do not reach toxic, temperatures. NontHermal 4ffech. The primary energy is thermal, but alteration oí mem@ucqi brane configuraiion or pwible membrane üeitruction can occur. Trapped gas molecules W y exppnda~d.,coaiesceand with the interQoc reaction .contribute to membrane mpW e . T h e . oD&prarive-nnfaction phenamdnon cFtater. cavitations, which may also Ilt¿r mmbranc or cellular functions. dquip(neni a@ dosage. The generator pduceai high-fri(quency alternating current to dectrudes on &e piezaispric ciprtai. The later may be quartz or barium titanate, which is in the trAnsducer or treatment head. ThP inttnsity is expressed as watts/cm-, \di%h describer tite field of energy under the ttansducer. It is derived by dividing the rnarimal total wattage output by the sinc of the applicator's radiating surfare in cm'. ThJs a machine with 30 w m s total output aid' a radiating surface oí 10 cm- has an areage intensity of 3 watts/cm*. The sound head must br raupled to the area undv trtaiment and moved slowly to avoid local buildup ol thermal reactions, which patienta 80 A'eiabilituiim nic '&ins yili usu;rlly describe iis i.'iarp pain. Thetdosalpe shoiild ' x at imzLkimxl icilerable leveb. This will change along t t e ;¡ne of moveinent of the tmriaducer ;ind cai be corrected by conwmittantly modifyini: tic wattage. TcJerancc will inc:aasc durihg the! course of tre+tmeni, and gmater in tansitiis may be apliiiid. Sessions up to 15 I O 20 n in may be givtn, and several it day. 1:)aily o r .tmenrrof hvo WUons often rrsolve a problei,i within 3 ti3 5 days. Conirai ndicaiions 1 . The previrnisly m<:ntioncdcontraindicetions for heat tliei.apy apply to diathermy, microitienn, tnd ultrauund. 2. M..crothenn will lsuild up higtc timpcrat u i r concentratioi, in edema or on adhesive tape, wet dressing, and over body prominencei 3. The precaution c<mnrerning deep heat to a inalignaiit area is similar to ttwt PRvicusly noted. 4. Vltrasound will w t generate high ternperature in sur~iizlmetallic in>planta. I.ehman'<' repoiti.d that any tfhipentuir elevation w.is quickly coiiductad auay with no tcix :levels resultiilg. The presence oi metal near the skin's surface will cause ;i burn. 5. Bryan et al." reliorted electrorriagnctic radiation ipterfe rence with cardiac pacemakers in t h i , microthemi ftequencies. He noied thik effect for ovens, and this precaution sh,>uld be obwnbd with mimcrothemi diath8,'rmy. Surnmaiy The physiologic efiei,ts of conductive and radiant heat, short-w.:ive. microwave, and ultrasound are thermd. Their indications and contraindications are essentially the same. The consensus is tha. diathermy and ultrasound produce their c'.nical effect solely b>. heat production uittiir tissue. Ascribing an!other eflects to these n odalities is at present not supported bv evidence. Modifying the delivery of these. cnerg:i?s by pdws. Of other hybridizations. does not alter their being essentially thernial axcats. COLI>". 19 Reduction of skin or body temperature is usad i n rehabilitation medicine for (1) local anal[:esia, (2) anti-inflammatory sñect, (3) hypothermia for control of pyrexb, or (4) posible control of spasticity. ' Phisics The physics of hypothermia is identical to that described for heat with the patient and the part treated acting as the heat source and the applied object or the ambient tcmpetature absorbing the calories. The degne oí temperature difference distinguidha hypothermia from cryotherapy. The former lowers body temperatun for extended pcriods of rime (several hours). The l a n a uses extremely low temperarum (near or below zero degrees Celsius) for a short time (reconds to several minuta). The tnnsmirrion away of body t i m e temperature is by conduction, convection, or radiation, depending on the calorie-absorbing object or material and the method of its application. Physiology Reduction in metabolism with lowering of entropy will reduce the mechanical, chemical, and electrical energy of molecules. Undestandably, intracellular and extracellular dynamics will decrease as will that of membranes along their axis or at their endorgans. Details of the specific physiologic reactions can be found ih any textbook on these subjecls,".?*These are affected by the rate, extent, duration, and degree of temperature d u c t i o n . The technic may be to the bady surface or internally by cooling enemas. The reaction to lower temperature ioully is immediate vasoconstriction. and if the temperature difference is signifirant (10' to 150 c lower), degradation or cvoalobulin precipitation ,,.ith hv. . . peieniiama). follow, Systemic effects of hypothermia are direcied to,vard (1) wnse,,,ing errrgy and later ( 2 ) creating calories as they may elevate a lowered core temperaturr. The ronservation mechanisms of the I~ Prinkpie, . skin ase vasoconstriction and reduced sweating. The cnrdiopulmonary mech+nmis are bradycdia, hypocapn&, and hypoknsion. The energy-creating respdnses are notably shivering, where ATP-ADP exothermal reaction creates calories. The inability of infants to shiver contributes ib their poor hypothermic tolerance. Inmeabed fat metaboI i m OCCUR in the liver, t$e greatest k a t generator in the core ana. ¡Fifty percent of basal oxygen consumption 3 in the viscaa, ñski*os and 25% of this is by the have hepatomegaly and prefer highdat diets. The subcutaneous fat actslas an insulator, and when it is absent or deficient, as. in infants or debilitated patients,\intolerance b r hypothermia occurs. Neuromuscular activity is qodified by lowered action potentials and dqayed velocitits. A l o C drop in temperatjre w i l l reduce conduction velocity by 2.5 t o 4 m/m. Muscle tension is increased and b y be due to incrraaed spindle excitability, as well as 10s.ered viscoelastic properties of /theñber mokcules. Analgesia is due to depreQed activity m both endergan and fiber codduction. partsis or paraiyris m a y occur When myoneural transmission is weakened, which occurs at 50 c. The cerebral reactions maf include lethargy, narcosis, and dcpnssiw of neulohumoral activities. Transudation is decreased p that edema formation is reduced, a reaqion to h p thermia that is employed in fireating acutc soft tiuue injuries. The toxic effects of hypothirmia or q w therapy may be tissue da@. Fkfom this occurs, ventricular fibrillatiop and shock as a consequence of hypoten@ion may de. velop. When frostbite or severe hypothermia orcum, slow rewarming with s#temic fluids. anticoagulants, and antibiotics ¡is the appropriate pmcedurc. Using ternperkturn slightly higher than skin or core tirnpdrature is recommended for rewarming. of pit )!rica[ rnrclicinc 01 Indiwiionr As described, cold i:: employecl for ( I ) anti-inflammatory, (2: ;inalgesic, (3) antipyretic, and (4) antii;i>siticity ei'iects. Anti-inflammatory effects. T h e application of any object COO'CI than an inflammtd arca will draw off calo:ies and modify the ~prcgmsof the tiuuc reaction. This applies to ( I ) acute reactions íiom trauma (sprains or strains of soft tis.;ue muscles, tendons, j o i n g ligaments); pliyiical agents, acute burns (first or second degree), 0 1 infections and (2) chronic c a p i l a r and soft tissue inBanamation. An$-inflammatory eliei:ts of cold whether for aüute or chronic diiorders include depresrieg of d physiologic tissue mechanisms. V-nstrictirm, edema, synovial tissue activity, leukocytosis, pr,molytic eruyme ac6vity, and other local 0 1 systemic reactions are cadiiced as is pair. Bleeding IMY also be rrdticed. Tmpcratu-e is lowered in acute Ant- ind superficial ui:oiid-degret burns by the iqmediatc applicaiion of ice and may d u c e the degree of tisrue damage. The use d a cold or a tepid wet compress to a moderately, swollen sprain will often prove very hilpful, Ana[geria. Cooiinp tit:?ar with vapor or ice will reduce pUn úi rridiculopathies, soft tissues, and johts. The niechanism for this edect loas b w t ~ d p u i b t d . I t can often be applied by the patient at home. :An)i'l)ymtic &oct. Tlie antipyretic effect of cooling, using either enemas or cooling mBttmsws or blankets, particularly for rei r w t q tempennur elevation, is often an ~ffective adjuntt. The quadriplegic and paraplegic may pnsent this problem, and coding the patient by conduction will augmrnt aqtibiotic UKi'other medical measures. D e failure of the autonorriic mechanisms to provide adequate tem,xrature radiation places limitations on this technique. The pa(ieht's skin may be incaliable of adequately conducting the temperatiire. and slight gradients should be applied. The patients may Oot have shaking chills or shivering. which ir accounted for h i their altered autonomic sympa-atic mecbanisrns. 82 Reha' iiotion medicine This 11, I ,-ic of slow, g r d . i d &jing is equivalen: that dexribed by Simh Ba50 nirh in I:¡. Epiiome of H>drotheru&' years agcs : the treatment of sun [htat:i stroke. €ic :scribed it as the "St. Vifidnt's Hospital" I ' , itment and covered the patient with wei I 1 sheets. Other :Iimadd*g the I supportive ' ieasures for poshible circ&etory failure, tiii~ is essentially what ir p r w t l y ncornmei: J, ,j. Spariiciiy Lowering muscle empáature to 32' C: : I I affect the sensorimotor.ppthways. Gal--:xia fiber potentials, \<hi& initially ma', :e increased (shivhingl, arc slowed aft?, 20 minutes coolint wi6 ice. Neuromus:,. i.r transmission is iilOwe( and ked.*' When niusck tc4ptrature appri:,? ':es 200 to 120 c:, spsticik will be reduce11 : eliminated for s e v a a l h&rsZ' Applying I.: I for acute "muscle spun!' pmsumes a pt iioiogic terning or "spas*" of murle. Tli< benefits this niay &o& are more likel., . iialgesic as the path@logiq mndition is far i'om certain. <\ Contmindi :oiions 1. Vasciil. ' : Ischemia, with inadequate trans~ii~:: of metabolites to and fmm tissue. ".ay become necrotic when mid is apph d to areas with oblikmtife arterial t > . impaired venous Ohuk~ai. 2. Anestlis .¡a of an area may alovv lbnger more o:ic e x p u r e to be t d h t e d with I t ilting tissue damage. 3. Cold s. .tsitivity or intolerance: The inabili:, of patients w,ith v;UCuli(is as seen . I scleroderma, systemic lupus. diabett!. and Kaynaud's p l r n 4 n o n incluch both vascular and imidunologic f ton that rontraindicate the use 01 ,old. The aged. infants, and ratliei , debilitated individuals 'cannot t o ' . rate cooling. Brief ciituinscribed ryotherapy m a y be tolemtsd. ~ mactions with urtiqaria, . Constii I I lona1 purpura .and possibly coliapsC m a y occur. 4. Indolciii wounds will be further aomproinirir by thc vasomnstrirtive &ect of c o d i , and healing further delayed. i ~ ., Sourcbr other <' haring I tuni oí I w its I Va$or-coolmt or evaporation techriique uses ahyl chloride or fluorimethane sprayed on t h t ama to be treated. Opinions v a n to whether a f r e t should be allowed. A' modes frost accmnplished by holding the sprayT.TmP2 leet fmm the a n a after a 15to 2oaCc spray wñl be tolerated. Repea!.iiig this two or three times at IO-soc inteavals is an adrquate treatment. This should produce analpeia and permit stretching and deep tissue massage, as it may relieve pain in "trigger" points or muscle spasm. k c (packs, bags, or compreasu) cdn he applied to an area for 10 to 15 min, takw off, and reapplied after a 5- to l C 4 n interval. Repeating this t h m or four .times will ohen be effective in acute sprains and equiltior. Planck's t i m a tli r n t that ir severi light or peiiCtrat8 dennis. qu3ntun iral) ch. produces tropy). As thi Stninr Imncnion of a limb in ice water may be tolerated for only 1 min. If repeated with intervals similar io the technique noted for "solids:' it may be equally effective. Cooling pads or blankets are attached to pumps of cooling liquid (saline, alcohol:. The period of application varies with the patient, aystemic tolerance, and pathology being treated; it may be several hours. ,. SUMMhRY THERMOTHERAPY The :physiologic effects of superficial heat are subcutai~a>usvasodilation with elevation of mctlboliun or tempenrun in cellular and i I extracellular compartments. "Deep heat" may elevate muscle temperature with transient metabolic and vascular reaction. The analgesic. spasmolytic, anti-inflammatory, and soporific effects of heat remain the predominant indications for its use. Cold is anti-inflammatory, analgesic, and I capable of producing varying degres of ' maesthtsia. It depresses metabolic activity, produces vasoconstriction, and may r d u c e spasticity. It is often used in acute soft tissue injuries. ULTRAVIOLET RADIATION', Biophysics Is Lhaviolet rays range from 180 to 390 nni. Their optical properties are similar to I lengths disrribec wavcleng is accom rractiom .Asorbin{ a photos r i i t e cal nf other .qroitnd s drugs. or ir the tra rereptors neurouid mitten f pituitary, areas deF melatonic fluid. Th artivity 2 in the OK alands. Physiolog Pimetra o.I nlnl. iiriiip. , 'l'lir ab proirins 4 rhcrniral iannitig, I -idal cWet ' 6 , ri~uro Pri*cipZes of other electromagnetic wavca but d a t a having photons of greater + n e w , The @antu”, of energy of a photon] ¡a direcdy related to its frequency and is kxprcued by the equation € = hn or ene in ergs equala Planck’s constant h (6.62 x IO-*’ U ~ . S C C ) times the frequency per W n d . I t is apparent that the energy of the h a v i o l e t photon is several fold greater th+ that of vüible light or infrared. Ultraviolet rays will only penetrate to the capill+ bed of the dermis. The magnitude of the ultraviolet quantum will cause chem$al (photodrmical) changes compared td i n f r a d , which p d u c a essentially moleculir excitation (entropy). As this energy vanes wid) different wavelengths and molecules, aciion spectra M described that indicate the rnmt ef6cknt wavelength for specific bioi c effactr. T b is accomplished by either rect or indiect reactions. Direct reactions becur when the absorbing molecule change( chemifally or a photosensitizer is raised t o / a h i g h enegy state capable of catalyzing the oxidation of other compounds bdo* returning to ground state. Photosensitized may be foods, drugs, or disease toxins. Th¿ indirect efftct is the transduction of light &e%/ in photoreceptors (retina) into n c ’ r a l signals to n e u r c e n d d n e pathways i d neurotransmitters .in the hypothalamiir, spinal c o d , pituitary, and pineal body. ;These effector areas depkss the synthesis ahd secretion of melatonin in the blood and cerebrospinal fluid. This results in elevatien of pituitary activity and consequent hohonal activity in the ovaries, adrenais. and other endocrine ,<lands. $I 8” Physiologic effecfs” Penetration of ultraviokt is iapproximately 0.1 mm. varying with skin thidknss and coloring. The absorbing substances in the skin a* proteins 0 1 nucleic acid, and the photo,chemical reactions are ( I ) drythema, ( 2 ) ,!;inning, ( 3 ) epithelializa~on,‘(4i bactenoI-ida1 effects, (5) vitamin D, kyntheris, and 6) neiimhurnoral effect. : physical medicine (it Erythema is noted within several h o w after expos* and is maximal at 24 hours I t is d w p -direct or therm& effects on capillaria ahd the possible release of toxins such as histamine, serotonin, and bradykinin. This mpons( is used for. dMaga control; the minimal eryrhemal dose (MED) being the minimal time of exposure to give the faintest reddening effect 24 hours later. Tanning is the increase of melanin granules in the prickle cell layer, which contains keratinmyta: One or two days after photooxidation, mlanocytes divide and secrete melanosome bodies, which contain the melanin granule8 and depasit them into the ,keratinocyte layer. The action spectrum is :between 253 and 296 nm. After 2 to 3 days ‘the tan f a d a as the kcratinocytec dough off. Tanning may provide some protection against ultra*olet radiation. €pitheii<rliz~tion,or carnification, results from accekMed cell division of the epidermis. This may, with excessive exposure, 80 on to desqwamation. The thickened skin with modification of sensory transducer activity may itch less or be less sensitive to pressure and thus be of benefit to orthotic or prosthetic wearers. Bacteriocidal effects of ultraviolet rays ocour in the 260 nm range. The energy slten mitosis or m y produce lethal mutations. ‘ h i s effe.ct can be beneficid in treating Qpen skin wounds or infections. Tllaniiti D, (cholecalciferol) in the skin and subcutaneous tissue is formed when 7~dehyocliolestcrolabsorbs ultraviolet tight. Wunrnan’ describes the better ability of an erperimental gtoup of men in a soldiers’ heme to absorb calcium alter daily ultraviolet irradiation. Csing total body irradiation to modify orleotnalacirr is endoned by odier studirs described in his article. Its use in geriatrir practice should be encournged. The ncurohunioral action of ultraviolet li&t has been described above. The toxic reactions to overexposure to ulimv/olet light are bum, usually from wavek%thi of 520 nm. This is either deliberate RrhPbilitatioh rnrdicitu 84 or inadvertent. thq hitter due tcWns#tiitiond Overcast clouds q d tr? mfkCt& fr4.1 sand, :ommon ccinplihtion in .~ reaction iC conji(dtivitb ~ tivity to uitravioidt light arc n) ~ foil^: I. Pain 2. Edmn 9. Bulb formati+ 4. Fcvn, chills, + a h 5. Conjunctivitis j and/or photofihthdbb 6. Desquamation 7. Infutim 8. Shock, puibld death Chmnic overc&surc lowing: can l a d td &e fol- Gmcn m p Mcthylcnc Mue Coal tar Tetracyclinei RitnRavin Methotrexate Quinine Sullonamide Phenylbutazone Chlorpromsnne Barbiturates. Heavy metah: V I I I Sources The I of I1 cury arc lamps whe: I 1: r sten cathode iimize c, :! new, or mercury VI 11 diñkrent wavekngth ) I cenvation in t l r ult-. i It either under b w : I s - . I where the electroii :I ,I thah the mercury viii , ' i' pressure-hot Tart:'. A I , Rating the pmurii I! 1Cd atmospheres will I . ii without affecting thi: ) : in the low-pressure : 3 $: and require high \ ! I i I' low voltage. The enveiopa ma. , ! I hipti silirate, or (::I ' i r Some m a y be eoateil ' I 1 staks, silicates, bot: ! !! mapesiwn, u k i u i n i ' Thtse reernit (fluores ' ) :I lengths of mercury 1 z , ;< additional broader I n ' k cluding visible rays , ', g i I Rector directs and I: : :I I )ligh-prerrurr h c ! I II broadband spcctrui. i 3 cidal effects.. e#vthei . , I . cooling jacket of :.. (Kromayer lamps) : tion to the skih. Cold quartz m c v radiation from the9.e 253.7 nm (bacterh w k n . air stdimti.: oxide glass (Wood'; WAUICa Di**U,S Endocrine Insulin Thyroxin Epinephrine - RtuiPin Meuboñc Pellagra Eythropoictk pmtoporphvh Porphyria V.xUlitis Scleroderma Lupus-iyriemic, divoid Polyartrriti. hoioia Polyvinyl chlbride In/rrrio"r Herpes Tuberculosis Cardiorcnil /oilup Dtrmaiologic dirtnicr E m i Urticaria sola+ Hereditary xerbdcma Vitiüjo albinijn Epidcrniolysir bullcua Drqs hain Perfumes , .I ' ~ Photosensitizers bf ultmvioleb hhb I ~ I ! , I , . I .., I . , ! I ~. .I jl I. I . I Y 'I , . :; I i , I .I ~, . ,. ' i ~ ~ 18 IC i! I , , '. i: ) , , ,. , . sure cold quartz lanip t&+ rays of 570 to 380 nm, which i-~usehair F e t e d with ringworm to fluore~~:e a bright(-. proferraond modclr are iarget, take higher power, and can cover greater Lamps used for general irradiation; have tuber wound inta coils, and for oridciai or sinus tract irradiation, straight tubes, Suníompr, which are silica glass tubes coated with phosphors, arc u + l l y several bulbs racked in P refkctor and /are available for home or solaria use. spectrum of 280 to 350 erythema and mild b. indications1' The applition and employnlmt of ultraviokt therapy in rehabilitatiod medicine is for ( 1 ) bicteriaidai effect, (2) epithelia& zation, and (3) cakium me")1'sm. Using ultraviolet therapy ad nctively for routine wound c a n will rolving refractory or indolent cubitus or vanfow ulcers After deansing the areas with c a d whiripooi, applying i d ultraviolet four to five times (MED)dail will d u c e bacterial infection and encoura& epithelialization. As the wound theraw should be wound to avoid ovcrexpmun ar& bunting of 6. intact skin IS neccstary. The exfoliative, epithelializati+, and bacteriocidal effect of ultraviolet ys, particularly to an inflamed stump, may improve the resolution of skin reactions such qs folliculitir. Depression of sensation and i n d e a d mkrance for prwure of brace ba&s has been dixusud. The use of general body ina ation to enhance calcium metabolism, pa I ticuiarly in elderly, infirm, confined patiend should be encouraged. It is a relatively +y, inexpensive technic and may help seduqe the problem of osteomalacia, although !the role of vitamin D, per M is not the tow1 answer. The recent developments in dare for the 1 Qo~traln#ictation~ The described toxic ph,>t<5-: i I 7 :I diseases, or drug. d i i h i4dkations for udng ultra%i I( of {wd, \ F?*btrlpt¡on 14 dequires descetion 0 1 tit: .: I! ii . qfsehcy ol the trtatmnts. TI :ii ti " : tqe aource must dways bt ¡{the apparatus has powe. r t i i l i s ::I.¡! I 8 a$v(ys be the same. The <ditii. a'ic I tion of the source to'the p iit 1 Iii : i&&sit)-.' The inwrse sql:ai ,! I;_I :i I! ifthe di$tance fmm the I in1 I:) ti slrfiice is decread by one [.ill 'IC !i of the radiation ir quadriiip ed, hmbert's cosine law stí te I th ' : e l l u g y sttiking the skin .lit z , 1 it i i : 805; at an angle <if;I)'' I N * 1 The application of SIX :!fit li I a q r ' dressings should br r,cl t !IC pmtription. ( : ~ a". ~ I 86 RehabiZitniion medicine . Ssummary Ultraviolet light provides photochemic.al r4ractions in and on the skin, which in r e habilitation medicine are employed lo: bacteriocidal and epithelialization eñects and vitamin D, production. The application of ultraviolet light in tlir case of psoriasis and hyperbili&binemia 01 childhood suggests possibilities for a wideriing application in clinical medicine. ELECTROTHERAPY The clinical applications of electrotherapy pi~sentlyare for ( I ) motor disturbanccq (2) pain, ( 3 ) pacemakers, (4) splinting, (511 spasticity, (6) biofeedback, (7) electrophoresis or phonophoresis, and (8) diagnosis (see p. 3 2 ) . New developments and techniques in medical and surgical management of peripheral neuropathies have impmvcd the prognosis for many patients with lesions previously considered incapable of any benefit. Motor disturbance^.'^^ " Denervated muscle demonstrates histologic changes analogous to atrophy of disuse such as ( I ) decrease in fiber diameter, (2) proliferation of sarcolemmic nuclei, ( 3 ) loss of striation patterns (late in atrophy), ( 4 ) thickening of intraniuscular arteries, and venous stasis, (5) increax in connective tissue (late in atrophy), and after 3 yean, (6) possible dissolution of muscle fibers, with (7) residual fat, blood vessels, and connective tissue in the area. i f reenervation occurs within the f i s t year, a fairly good functional recovery may be achieved. The prognosis, particularly after 2 or 3 years, is bleak. If the atrophy can be retarded in some way, the degree of recovery may be increased. Electrical stimulation of muscle is used to retard these changes. Because they occur rapidly, stimulation should be started at the earliest opportunity and given several times daily if possible. Studies both in the laborat o n and clinically indicate significant retardatioii of atrophy i n treated peripheral nene lesions. In addition to modifying the noted histologic changes. chemical and enzymatic rliariges are also retarded. Extensibility of the muscle is better. 3s is its vascular dpxamics. Principler or incontinerice control have been successful. These technics are limited by the tissue tolerance for the electrodes and the problems of power source. Electrophysiologic splinting. A stimulator to activate the tibialis anticus and foot dorsiflexors at swing-phase to modify foot drop has been used. Similar technics to activate muscles of the upper extremity in quadriparesis are reported. T h e tolerance of t.he skin and patient for these devices is limited and not widely accepted. Sparíiciiy. Tetanizing current for the control of spasticity by attempting to fatigue a muscle U unwarranted. Alternative measures are more effective and less painful. Biofeedback."~ Biofeedback is the term applied to a training technic that attempts to modify autonomic functions, pain, and motor disturbances by acquired volitional control. Using monitors for such activities as EEG. ECG, or sweating and demonstrating the physiologic. activity on a screen or with audioamplification can help the patient acquire an ability to lower his blood pressure or slow his pulse rate, respiration, spasticity, or autonomic functions. That every patient cannot succeed in these endeavors and that some of these functions are beyond conscious control limits the use of this technic. It is a means of expediting "behavior modification" to achieve tolerance or elimination of undesired syndromes. coupling the patient to an electromyograph and having the sight and sound of action potentials presented and using these .stimuli to restore or control motor function is a variation of biofeedback. It is essentially a reinforcement of muscle reeducation when used in treating hysterical paralysis or for paresis following varied neuromuscu~ar-musculoskel~~l disorders. The staff, equipment, and time required for providing this training restricts this procedure to programs designed and equipped for this purpose. Electrophoresis or phonophorerir", Iq Electrophoresir or phonophoresis drives molecules into the skin by ion-transfer with direct currrnt. or by ultrasound mechanically. of physical medicine 87 The necessity, effectiveness, or value of these technics is questionable. MASSAGEU-'] Massage intelligently applied is an effective modality. Fuller explanations and descriptions of technics are available in many sources. Connective tissue massage". " is a stroking move along "reflex zones" to achieve metabolic or vasomotor reactions in the area. T h e evidence that these reactions actually occur remains to be documented satisfactorily. Physical principles The physical principles of massage are to stroke, press, knead, rub, pound, or rhythmically beat the skin and underlying tissue. These movements can be augmented with hand-attached machines, or by machines alone. The pressure can be vaned as can the force of each of the movements. T h e physiologic effects are as follows:'5 1. Skin: Reactions oí hyperemia due to irritative effects. ?. Senmiion-pain: Analgesic and soporific effects are quite often noted. The analgesic effect of stroking or pressure on muscle cannot be explained by modification of an intramuscular pain fiber as none has been described. For the present, reduction of &in pain fibers firing must be considered the explanation for analgesia. 3. Muscle: Reaction to pressure is related to the effect on the vascular and lymphatic systems. Compression will produce an intravascular ischemia and extravascular fluid movement. Whether kneading or deep pressure breaks up "fibrositic nodules" is questionable. The existence of these tender spots is acknowledged and their alteration oí size, sensitivity. arid occasional elimination by massage is noted clinically. What exactly they are and what is happening is unclear as is why they come bark. Light stroking, fingertip massage over a sprained tendon or ligament is often effective but similarly unexplained. 4. I'arrularr The effect on vascular and 88 Rehabilifafion medicine lymphatic disorders is essentially transient and if desired should be accompanied by supportive pressures from elastic coverings, compressive apparatus, or positions favoring drainage when edema is present. Reflex vasomotor reactions following connective tissue massage are described, but this cannot always be achieved. T h e use of connective tissue massage” in these conditions should be restricted to selected patients who after an apparently successful trial are given a course of treatments.“. *’ 5. Prychologic: The relaxing, soporific effects of massage are widely recognized. This may be better than sedatives and often will be the most effective measure in relieving muscle spasm, tightness, or “tension.” T h e explanation of this eñect remains empiric. Suffice it to say it works. Unfortunately, economics force us to w tranquilizers, reiaxants, soporifics, analgesics, or narcotics where massage might be as effective as any of these drugs. lndicaiionr stmtching of muscles fcKi , i pressures above and bel.:>;\ Prior heat, massage, aii8:i effectiveness. A review of the t c i . I exactly what is orcurn:ii: i ,, vague and cannot be i m ( i many instances. The clirii , ! , manipulation in refracti.,,: ; , , and back pain cannot I> ‘1s procedure coirectly ern; ,I, , , (I selected and prepared !I prove its value. Specific descriptions of I( found in references 42 i t u , . . ,.’ ’: , I ,,., : I. 11, , I 1 ~ . ’ c,. # I ! v. , , I I I., I ! , , I), .v. i , I ,,a,,. STRETCHING S t r e t c h i n p 30 atternpi,. articular snft tissues, teriil. muscles by either m r i i i ; means. Its application in i t ’ , problems where motion is i effective. The contraindications a-, tion, sprains or strains, ! I painful musculoskeletal, . , ’ r I ‘!I ‘11 i .)I. , , I , (I,,: , :I> .:, .<I I , ‘ I ’ :. .x’!1 I , 1 1 % I. :, I,; Soft tissue injuries with pain, “stiffness,” and “spasms,” are the classic pathologic conditions for which massage is ordered. Psychologic muscle tension is equally benefitted. Articular pain, with or without swelling, can also be helped, as can arterial or venous i n sufficiency (not when inflamed). Scars may be loosened and capsular “stiffness” (after immobilization) reduced. Massage after exercise, stretching, or vigorous activities is also effective. The technic is the app:li,i ing movement using courlie : , . tiefit’s body movement. K i anatomy of the tight stnu t tendon, or joint capsule ui ; sired movement. Preceding massage and an analgesic ( hance its effectiveness and .: and duydtion of any afier F , Contraindicoiionr TRACTION5’ Soft tissue infection, hemorrhugic or clotting disorders, or inflammatory disease of muscle should not have massage. : si>!, A counterforce of up to ií .! to the ne&, or 100 pounclr used to stretch perianicu1,;ir purpose is to distract verteti;.; 1 1 I . ‘I I r ing neural foramina or pow\ ’ I j I :s,: herniations. Pain in the 1 111 the diagnosis “whiplash” 01 ‘ , , . may be benefitted with t r , a : ~ ’ : I Y i: be manual or mechanical. t1.t :. 3 . spinal muscle tension or pau ,> I e! ficiai. , I , ; <:’ The.indications and coni!: I I i MANIPULATION MANEUVERS Manipulation maneuven include gentle stretching of periarticular tissues and is achieved bv the application of manual pressure and then counterpressure, and sometimes a “click” ir noted. What this sound is remains obscure. It differs from stretching and traction as it is the brief tensing or <li.~ > 1 eases. I ,I,. 1 /,:I. 11 , : t. I’,’~:II~ 18il 1 ~ 8;. ‘ I , Principles of s.milar to those for "stretching" ;u is .th .y-eparation of the patient. ItiJLES TO APPLY WHEN ORDERING I>HYSICALTHERAPYw 1. D o not use physical therapy if medie I { tion, surgery, or psychiatry can be mera effective. 2. Select the simplest, safest, lust corn@cated modality, rquiring the rninintal involvement of personnel. ?. Use a device that allows easy observetion of the treated part. 4. Use home therapy whenever posible. 5. Have specific goals. ' 6. Limit the number of treatments, and if no benefits are noted consider the following: a. Repeat the series. b. Review the procedure to ensum that it conforms to your order. c. Change the dosage or frequency (two or three times daily, 5 or mom days a week). d. Discontinue the treatment. PRECAUTIONS TO BE TAKEN BEFORE THERAPY icd p in i~tbpoksand man a! 1 medicin,, 1! Referral rrg ' t e i d therapist is I , :ommended. ski1 and training of re; , <redphysical VA: I Ti t i.nii patianal therapisYa _ I I'ensqe that ht! pat ' nt will get optima' , nd efficient ciln.. The r role as instruqto. nd supervkir c ' thei. py *des, family, ai !I patiuit is i n m U.. able and; when M 4re i(.i, can save t i t 1 and reduce the costs of I i:atment.l". ** occ OiIAGNOSTIC TESTS Tile mwitoring of ene. L:' transductiori I' :. quir" a scnwr that tar ruansdua the IKI. a visible mni. "1i3 u ~ % y may I e dhmlly r(C0rded from ' ! I S body's surba<e Y iii thmcgraphy or &Ittmohmmetly ( r Ruor.-ccnac Y in the u.i~.viokteffect 0 1 the 18' ions of ringworm. 1a;'osing an energy s onto -he body surface 1 $OB ~"nagriphy where tf .. knrities of di ! Oaue trari6mit different i , t ' nsities of sow( wave: to a sensor that ci ! ~ e r t sthese -ir¡ atoni to visual records Oh-rved reactions to r..,t or cold suct as bli' d prssure change Aanges in thc acdon potentials in myutl I ia gravis, or in newo. sgic findings in mu I i le sdemis are vabaal e diagnostic aids. Bint..ly the reaction of to tleí 'rica&stimuli of var !r ;strength a i d duratia ln can be used to tscl I. I sh the strength duratii,:~ CUM with the: d , : c : 1 e valwa. s4 The: nogroph scans the 1' in nnd wan+ duces :.IC emitted i n f r w d tia in" light, which is re( )r,led on a filni. The di,iails of the technic 8, '; deWribcd i.n denens ': 55. The merits o1 ii:k tshnic are ( I ) its dety-the patieat : : ot exposed to any ioi .zing radiation, (2) i s lack of ail intrusivr component, and ( , the v i d l a . tion it ,tllowa of vascular a d inflammatoq: technic5 An obliterative lesi' 811 can te cad!, reacúor not easily acc&blf 11 radiognphic identifie' without any coot1 ,st requed. Derm hmmetrysa is an e (N lid art of skid resi :ancewhere the cor~:ii.bivityof the skin is 4 e c k d by the &i,:ipe in N m n t Aow wit! any autonomic or -,eiipheral neu:O I I i I. Sensdion: Anesthesia is not a cmtraindication but n q u i m a careful monitoring. 2. Comprehension: Ensure that the pati nt understands what the. usatplent, ikolves and how to signal k any dUcsmfon develop. 3. Equipment: Ensure &at all \run, huting elements, bulbs, switches, dials, and timers are in working order and in the off or zero position when treatmeat is started and ended. Apparatus should be unplugged when not in we. Only use "underwriter approved" equipment. 4. Dueare: Caution as to the dosage for debilitated patients, these with sensitivities, vascular disease (Raynaud's), or edema. ... A description of the technic and application of each modality díscuwd can be found i ~ '8 ! *j ;dying two +res xant voltagd 2") cold skin will )\.uaEe 1 m q o h d @d moist warm skin 1 4 2000 ohms Daklfrom an u t e to Lnaffected a 9 or foii&ing w heat will p.d,le comparadve @$es I,t is painless, r s y to perform, and thej 4uipnient thenia gravis c1icii.s a decremtiit o( . I ' $on potentials after tlie third :o i5fti.i i i 'I. Ius. The pomtials ai? restond tn 1::s :1 the muale and decreased with N: '1.1 c. mggcsting that quanta of transmit-.i . I:dance may be stored with cmlirig ',' Lorn uait testing:'", This ttxhni,: ' ! ' < ' .is +e strength-ánd duration of stini.ii it dicit a minimal twitch of a mrget I I \ I ' ?. The stimuli are applied to eitner i h t 3 1 , .,e or in denervation. to the muscle bel: Recording 'the values on a graph 1) ' 3 . <:E a c w e for each tissue that is difi'e < : i i , til hlues. The details of the method I rforming the test are available in r e t ~ i e ':e 61. The test is relatively simple to ]:>I ,+lo11, qmderately uncomfortable, moderai.i1) itprcduci%le, and nminvasive. It has f i '11 into the +adow of electromyographic ! 111 I , but there am occasions when it may :e I Iployed. Using this technic in the first k. i ii uuks after birth may provide sidequa I : c: :i in pediatric patients with fac.ial pal ', . d not require needle insertions. T- ; , !. ', i 1 1 ' however to pr+:oke a sus RFElENCES I . Momwitz, H.J.: Physics of ticit. In It, 1peutk heat, Baltimore, 1963, ti. Liiht I I I I t:. Licht, Wavcrly Prerr, Inc., pp. 1-23 2. Fucher, E., and Solomon, S.: Phys+Ih+ 11 mpomes to heat and cold. 'In Thir: i 1,. heat, &)timOrr, 1965, S. Lichi and E 1.i t, Wiverly &as, Inc., pp. 126-169. 9. Green, D.:E: A framework of princi 114s ir the diagnosis i.f ringworm has been #dethe unibqtion of b i a n c r @ u ; the r v , 11scribed. i n i p of energy tnndvctiorr in hi iIv8 ;i1 Applying he+: to a patient 4ith ne~+msystem, Ann. N. Y. Acad. SE¡. 2: 1 ti í, murular dised-e produces' alt&qtions of 1974. 4. Stillwell, C. K.: Therapeutic heat. I n €I; .I. book oí physical medicine and rchilii i i i i t ~ 11. Philadelphia, 1966, W. B. Sinnders C ) , , 1: notable sensiti4.y to heat apmu&,,and this 235-243. fact is used in /')any clinics b a +r¿vwtivc 5. Castor, C. W.: Connective tir.sue PCI 1.2 I I: test, where thá patient is e$poaeH to Mist the cñecu of temperature studied ni ii '11, irily sufficient t0,rjiSe Wy Arch. Phyr. Med. Rchsbil. 57::s-1I, I I 7 i . Irquently, tCmp<ltaly e& 6. Genten, J. W.: Eñcct of ultrasound on r n ,ri geration of U p s as visual aguity or reeitcnritiility, J. Phyr. Mcd. 94:?6?-XiI, ! '1. 7. \Yurtman, R. J.: The effects of light 1 ~ ~ 111: apprarance of previously noted sisn $at human body. Sci. Am. pp. 69.2. Jui), ! 'i, may have subsi ied will OTCUT. It ris felt that 8. Sinmns, D. G.: Muscle pain sb-ndronii !, , .). these reactions .ire almost qxclu$iw to paJ. Phys. Med. 54(6):289-308, 1975; .i!41 :: tients w i t h d e 4 elinating distase of'the otn-15.45, 1976. tral nervous sy6i.m. B. Millard, J. B.: Conductive hcntirir ri The rcpetiti\lb stimulation t a t ip 'pyasTherapeutic heat, Baltimore, 1965, S :, !I: ii: sues 1: I 4,a, Ud E. Licht, Wavcrlj PITS, inc.! pp. 2x)251. IO. Zidu, J. ñA.: Hydn>th/npy. In HanU><nkpf p h p i c d niedieine and rchabilitntbn, Phi@. delphin, 1966, W. B. Qiundcn Co., pp. 3 : s 339. I I . Lowman, C. L., and R+n, S. G.: Thcapcu/c u* of pool and tmkk, Philadelphi3 l9:%?, W. B. Sarinder. Co. 12. Stoner, E. K.:Luninot$ and infrared heatii?g. In Therapeutic heat,; Baltimore, 1965, 6. Licht and E. Licht, Waverly Pms, Ibc., i'p. 256-265. 13. Lehnun, J. F.: Diath*my. In Hindbook bf physical medicine andl rehabilitation, Phibdelphia, 1966, W. B. Savndnr Co. 14. Scott, B. O.:Short w& diathermy. In The*pcutie h u t , Baltimore,;1965, S. Licht and $. Licht, Wrverly Prc5, Dic. 15. Mmr, F. B.: Microwav( diathermy. In The*peuaic heat, Baltimon,iI965, S. Licht and t. Licht, Wnvcrly P m r , jnc., pp. 310-320. 16. Lehmin, J. F.: Ultruo>)nd therapy. In The+ putic heat, Baltimore, i1965, S. Licht and E. Licht, Wnvcrly Press, Gc., pp. 3?1-386. 17. Bryan, P., Fuman, S.,' nd Escher, D. J.: laput signals to pacema en in r h m p h l C.vironment, Ann. Pi. Y. Acad. Sci. 167S23- c 824, 1969. .. Iar. pp. 502-537. i 20. Nigbtingte, A.: PhysiIs rnd electmain - i , , phy*ul medicim, Y&, 1959, Tt@ 2 .- .. . Mianillan .? '21.~ Scott, co. P. M.: dall k Cox. j I ! 1. 390423, 1959. 23. Baruch, S.:¡ An epito e d hydmthenpy, Philidelphlli, 1920, W.fB. S.unden CC. '4. Chitfieid, P. O.:Hypo+ennia and ir< &eca on the sensory and pc herd motor system5 Ann. S . Y. Acad. Sci. :+45-44ñ1 1958. 2.5. Stillwell. G. K.:Cltravi,let therapy. In Hind. book nf physiral rncdicibe and rehabilitation, Philadrlphui. 1966, W. $. Siundrrr Cc., p p 340-352. ! 26. Fircher, F., *nd S < + m q , S.: Physiol»g¡c el. f c c u of ultraviolri radidtiun. In Tkr-tic clcctricity and ultrarialet radiation, Balti. T mom, 1967, $ i . ~ t h tani I! Liihi N a v i . , Pres, Inc., pp :!--7-$:' ?7. Scott, B. O. <:Iiiiciil ui.w o í ultravi(di.t rat1 I tiun. ht 1 . 1 i i i i i i i i t i ~V . I ctricity i ~ w l 111:1 , violet radiatiimr:. S. Licht and E. I. cht, 'I\ I rerly Res.,I n r i . pi>. 3:!5 17H. 28. Pnrrirh, J. A,. l'!izp:itni, :. R.,? a i . n , L., an4 Pa I t a h , hl. A. Photc<h<,ri pu>iar$ with < . a i d rii.tho d i : n a>,d Ir,ngw.i., ultraviolet 1iF:hi. Y. Ens1 J. Mei.. l!ll:lC!: 1974. 29. Crcmcr, R . K... f'errynai, P. W . . ; n i R i : , , a d s , P. U.: T h e iirAw m of hgl-t on . I hyprbrlirubiiiaciiia of nfintr, I. u m t I!l94-16397, 195F. 30, Guttmn, E.: Hirtol>li>gy< I depencr;~t.ona i I: repeneation. In Elcarodi bsnol;i .mi elect. . rnyogrsphy, %A H;<mn. Cain.. l!l6l, . L i c h t . n d E. Licht Publii ley, pp. 1'2-133 31, Stillwell, G. K.:Cliniial e , x t i c a l stimulstii, In Therapeutic: electrici y and I ltraviol I ndintiw, Balti,iom, 196 , S. Lich.. and Licht, Haverly :'ress. Iric pp. 1Oi.'55. 32. Pain sympnsiu.x: Sitrg. PIeuml i:61-111973. 33. Sweet, W. H..arid Wcpsic J.: Contri I of pziii by focal electri<;il stimuh ion for auppresii<, Tram. Am. Sciirol. Asso< 93:103-10i, 19ti 31. Taub, A.: Elrctri,A atirnL ation fcr ,.he relibl of pain: two le\rons iri te< inologi<al u:alati.r Perspectives Bicl. M d . l ! ' ( l ) : l 2 5 . l5, ~ 197: 1976. :M. Mrlznck, R., aiii \Vdl, 1 .D.: Pkii mcch; nirmr: a n e w theorv. Si erice 130 91i-9;!s, 1965. 36. Jacobs, A., and I'<:lton,C. S.: Visual ftedba:l. of myo+tric itpur tci I acilitatr n-u:,cle lnxatiom in nomal perron and n;s.titnu w i t . , acct i~]urks. Ateh.~Phyl.Mcd. Rchkil., p1 34-39. fan., 19(i9. 37. Shapimi D.,and Schw,irtz G. E.: Iliofccdba.:i and v i r e d learning: c1,nic.l app i'atioi, Scmin. Psychiatry. 4(:?):l 1-184, 19ri. 38. Harris, R.:Iont<>phora:iis:1 icrapeui:ir electri< ity and ultn?:iolrt radiatia 1, Bdtir>o.e 196;. S. Licht and E L.icht, \%avcrly ,?nI!, Ini pp. 156.17ü. 39. Stillwell, G. Ii.: Elwtric,:l stimulation arm iontophoresis. In Handboo>. of physical medi. cine and mtirbi:itatim. I hiladelphi;., 1965, \V.B. Seunden IZO., pp. Z j3-359. 40. Cyriar, J. H.:Clinical app cation <,I n.irsap.: massage, nianipiilatior, a: d t r r i c i I, New Haven, Conn., 1960. S. L chi am1 ::. Licli Putilirhcr, pp. 1:!2.144. il. Fnnrun. F.: C:.:iissical ",assage tc,.hniqu,i m a s i p e , rminipvlntion P I d trnciio:,, Ne.& Haven. Conn.. I!J60, S. L rht and E . Licht Publisher. pp. i 4 . K <I 43. B i d o f . 1.. S.4 and Elmintime m u u q In Uun&e,rn traction, New! Hawn, h n . , and E. Licht. PublLher. 44. Ebner. M.: C)nmctim tulus m a Hunt ingron, N. Y.,j1976, R. E. 45. Wakim. K. GI: P h y r i d o g i d efft{u;of wugc. In Mu&, iri.Npu¡atbn a g frac:¡? New Haven, b n n . , 1960, $. Li< D aad E. e, Kkk+~fI?ubli rhcr. cupatioii therapy. 1.n Hmtlbmk : :I. medicini and rt~h~biliution, P i ,I I I l%6, W.E, Saviulen Co. 53. Downer, A. H.: Phpicil therap! 8 . 5 1 I , ' Springñeld, Ill., 1974, Charles I 1.1 I I Publisher. 54- R o d , J. C., and Reine?, S.: 1 IF i l , -tic ippiirrtus. In Elecimdiagn~s~.I I t l . tmmyosiapby, ed. 2, New Hsv, I I I 1961, S. Licht and E. Licht Publi i : 55.. Barnes, 11. B.: Thermography a n i 1 ti application, Ann. N. Y.A u d . Sc;. I I: I , 'I. ~ l%4. pp. 204-232. 51. Harris, R.: Tjction. In ~ 52. Martin, G. M.i Racribiig ph+# bpipula- M o+ ,:I ,; ! :. ., 31 I. 56. Licht, S.: !&ctrical skin r e & ~ n c < I I :,i trodiignmii and c l c c t m y o ~ ;1'~ ~ ':# > Haven, COM., 1961, S. Licht aii i . i c I Putdirhr, pp. 412422. 57. Roa, A. S., Ellison, C. W., Mer, i i L V and Tourtdloite, W. W.: Critrr: . ' > I ' '! clinical du@wair ai multiple rcleto' i:i I h r A d . Nruml. 28:(8):21, 1976. 58. Duwdt. J. E., and BommtM, E.: P.%! i of myurhe& gravis by n e w ai:n I! s. ~ 1 8 N. Y. Arad. Sci. 274:174-188, 1973. 59. GilhtI, R. W.: Nenr conduction: >i: 1 i I I smw.0~. In Elcctrodiignoli and ck, :':E,I > nphy. New Haven, Conn., 1961, ! i:: I and E. Licht Pubkhiher, pp. 385-411 60. h i a c e , R. E., and Mcyerr, S I. I ? - ' conduction and synaptic t r m s m S E in 1 I Downey, J. A., and Darling, R. C , :d < I : Phyiblo~icalheir ai rehabilitation r .i i 1 Phillddphk, 1971, W. B. Siunde- (1 D 61. Goodgdd, J., and Ehenitein, A . : ! "I ! I duntion curve. In Electrodiagnosis 11 I, I., muscular distases, Baltimore, 1972, 1' ( I \ i I ¡ ¡ B Wilkins Co., pp. 28-30. I. CHAPTER 29 Th a. b. REHABILITATION OF PATIENT WITH PERIPHERAL VASCULAR DISEASE c. 2. Eli a. 3. b. hí a. b. c. d. e. The term peripheral vascular dixases, as refund to in this discussion, will encompass diseases of the arteries, veins, and lymph vessels in the extremities. The d i m e processes include not only pathologic conditions within the confines of these vnrels but also many conditions due to reflex disturbances in these vessels secondary to sympathetic, parasympathetic, and spinal cord influences. It should be emphasized that this section is not so complete as it might be but will include those diseases in which rehabilitation technics have been or are still employed by some physicians. I t is quite apparent that the'entire complexion of care of obliterative arterial diseases has been radically altered by the success of direct definitive surgical treatment, somewhat eclipsing medical and physical measures. The study of peripheral vascular disease requires essentially the same technics that one generally employs in internal medicine: history, physical examination, and special evaluation technics. There are, however, certain basic aspects of this group of dixases that require special emphasis in the examination and that ma>- be elicited only by a sound history. It is therefore most imperative that a thorough knowledge of the classification of these diseases be known. EXAMINATION The physical examination in peripheral vascular disease must be thorough and general prior to concentration on the affected area. The importance of obtaining a history of trauma, diabetes, and previous venous thrombotic or ca?diac diseases is self-evident. 594 Certainly the knowledge that a malignancy with metasiases exists in a patient with recurrent venous thrombosis that does not respond to anticoagulants is a potent factor governing further therapeutic endeavor. The physical findings of a mitral valvular lesion associated with auricular fibrillation in a patient with evidence of acute arterial occlusion may be of paramount importance in establishing the etiologic basis of the presenting symptoms. Much information may be gained for the specific diagnosis of peripheral vascular disease and for the clinical evaluation of the condition by means of tests designed to measure some physiologic function or physiologic capacity. In addition, specific measurements will enable one to evaluate objectively the response to therapy. Accordingly the use of Mays' test for intermittent claudication, oscillometric readings, temperature recordings, and various tests for vasomotor stability should be employed when indicated. Angiography and venography are frequently used; infrared photography, plethysmography, and the Doppler ultrasound flowmeter may also be used. The treatment of peripheral vascular disease extends far beyond the confines of rehabilitation medicine, but care for these disorders may be aided with the use of certain technics. TREATMENT The scope of treatnient of peripheral vascular disorders within the discipline of rehabilitation medicine may be outlined as follows: 4. f. TI a. b. 5. Pr a. b. 6. C< Therm' HYP~ peated for re1 of col1 tive of and, t< thromt dures degree blood bolizat disease of noa Due most e tion. 'I an inc dent i tabolit rliemii additic blood about tempe by he: is base Diri ant h dectri tically contmlled heat cra#les, rsion beat of diathermy !and chployment Of local heat alwayq inof a cakulated risk. me )ñective beating of &e tissues urlporni 5 at 1times +ter than the mcubolic eñeq so t, witb even moderate heating, then U ?e V0i.a~z+umption lyreat dajger of bur+ Maintenance of +afe M a n tgnprature with application of i + d the heat-absorbing cap&ity b l & l Row. Occhuive apeIdes! this function of b e jrcullrr +tun, and Lht quantity of h u t ic to accumu+e to &e critical pibt tisuC (kruuction. !In addition to t h h n . dilcquate fhiptionof heat, the mneolnitwt of meUbOl¡c@procnram y be dqe*ow by! compouadimg the oxygen req+ den@ of ;Llrcady M O ~ C tissue, as well astby i+ng:the 10cll accumulation oí marWlic end products. ! Indkcdbat Appli(ltion of indirect hehtevokd a gcnernliH refkx vasodilatiqn, e extentiof which is.dcpcndent on the deof +onstr¡ctidn and artepial b l a decarbpensption. An application of the be exdmplified by use of. a the awomen for 20 to 50 d a i m w 3 0 finduction of vasp the 11utremi&aS. T$e Thormothwapy Hypoithormla. puted epiaodler for relief of tive of treatmefit in thrombosis. lht I. most efficient mepos of ccting vam+iad .'&bmbotic idisuu. tion. The local Ne of te perature resiilts io yp.fhojrnio. It is ohiy retcntly that gedan increase of cchiar ac ivity with an inch body @pothernia or "anfñeial hibemaof conccnt ation of acid m i dent inctiop" has gained w e l l i d m w d rroognitim tabolites and himmine-li substanm. b a s in :its use h c a r d i o v a + w nauroiaglc chemical agents are pote t vlrodiiatow. Iq s v Its buc in les dhmatic medical cow addition the rise of the pcrature d thq dit, ns has pot as p t barn fully exploited. blood stimulates medullap ynters M, brin4 In acute *erial occlúsion the applicatioa about d e x vdilaeiony t n c m e of thq of trypoth&ic measuq can be readily s u p temperature and blood fi+ in an wttrimity po+ed on tbe theoretic basis of equating tis. heating of some remot pan of the &XI !-metaboflc requiremqnts with the dimin. sücj is based on this principle f mtkx rrspchse. b k d Euppl. Praciically, however. this Direct heat may be app ed by uy of nidipcutic epproach Ras not been carefully ant heat lamp, conduc on heating with, d*d a n d b daerving. of further study. It electric pads, hot-water bottles and fomtnuis at least udwmlly acctpied that the appli- i . I 596 Rehabililniion medicine cation of heat is unphysiologic and most ill advised. Actual refrigeration of a limb has proved to be extremely useful in securing control of a situation wherein irreversible and extensive ischemic changes dictate ablation but where some other medical consideration mitigates against proceeding immediately. Packing of the limb distal to the point of contemptaied amputation is usually followed by rapid improvement of the patient, subsidence of toxic symptoms, drop of temperature, and abatement of pain. Distal icing is not associated with disturbance of wound-edge healing and secondary wound infection. Hypothermic studies in the treatment of local tumors have established that cold is effective in diminishing edema and effusion and in relieving pain. These responses appear to be operative in the use of ice bags applied to the calf and thigh by some physicians in the treatment of patients with thrombophlebitis and venous thrombosis. Inñammation, induration, edema, and pain appear to be rapidly controlled, so that cold appears to be much efficacious than hot fomentations. An occasional patient treated in this manner may find the cold intolerable so that its application must be terminated. Such an individual, however. is the one who manifests unusual degrees of secondary vasospasm that responds best to paravertebral sympathetic nervounystem blocks. Allernaling lemperalures. The use of contrast water baths, in which the patient alternately submerges his feet in warm and cold water. is now employed to little advantage in the treatment of vascular disorders. With arterial problems, for example, the constrictor of the immersion into cold far outweighs the supposed beneficial effects of alternating the raliber of the vessels. In the patient allergic to cold, however' it is sometimes beneficial to effect gradual desensitization by daily treatments with immersion of the nfferted extremity into water that is progressively rooled. Electrotheropy Muscle siimulolion. Stimulation of muscle with electric current finds no place in the treatment of vascular disorden. Some year3 ago, however, an electrostimulator designecl to prevent venous thrombosis following sur. gery had been introduced. In this approach the calves and thighs of patients on th,: operating table were subjected to rhythmic: contractions in an attempt to improve venou:j blood flow and prevent the static influences favoring venous thrombosis. The apparatus has not found \r-idespreadapplication. Iontophoresis. Ion transfer with histaminit and methacholine (Mecholyl), when carried out with due precautions, is a safe, effective means of obtaining local vasodilatation in both arterial and venous disease. Ulcerations, indolent to other forms of treatment, may exhibit remarkable response to direct ionto. phoresis with methacholine. This type of treatment appears to be particularly helpful in the care of patients with vasospastic disorden, such as Raynaud's disease, with ulcerations of the distal ends of the digits. Mechanotherapy In general, mechanical modalities have proved of little value in the treatment of peripheral vascular diseases. Briefly they may be reviewed as foll0u.s. lniermiileni venous occlusion. In this procedure occluding cuffs are applied to the extremity under a specific pressure for a fixed interval; the pressure is then released for a short relaxation period. The physiologic basis of the treatment U considered to be an application of the observation that venous occlusion is followed by a priod of reactive hyperemia. Several instruments am available in which alternating periods of venous congestion and relaxation are intermittently produced and for which sometimes excessive claims of beneficial results in treatment of ischemic arterial disease have been made. In general. however, observed results are not impressive and have not withstood careful scrutiny of blood flow changes with plethysmographic methods. The recommended rourse of therapy is lengthy, and the g o d clinical results reported do not take cognizance of the natural forces bidding up collateral channels. Pressure-suciion boot. The pa\.ex boot, anotha cise, P suctio ity, w . ber. tempe ulcera with no re poses antiqi Os1 the o! vice exerci the p peutii fit in oscill; seem helps seen maini deper from surfa0 the ri Va ratus fourti iiiflat fashi, wave erall) Cuff trolle in cei insufl the t ing f view to th ment chr01 SY. ployr inect cular dure cardi plied * another example of passive mechanical exer. cise, employs the application of intermittent suction and pressure to the involved extremity, which is enclosed in a treatment chamber. Although early reports noted rise in temperature and beneficial effects on the ulcerations and ischemic neuritis of patients with occlusive disorders, this procedure has no real proved value and for practical purposes has been relegated to therapeutic antiquity. Oscilloiing bed. For practical purposes the oscillating bed may be described as a device that passively administers Buerger's exercises to the recumbent patient. Again, the procedure is far from proved in thcrapeutic value but appears to be of some benefit in relieving ischemic pain. The continuous oscillating movement of the bed does at least Seem to have some sedative effect and also helps control the severe edema frequently seen in patients with arterial disease who maintain the limb in a constant position of dependency in an attempt to obtain relief from discomfort. Reports concerning rise of surface temperature of the limb after use of the rocking bed have been at great variance. Vosopneumaiic compression. The apparatus for this procedure consists of a series of fourteen rubber cuffs that are progressively inflated in either centrifugal or centripetal fashion in an attempt to effect a pressure wave traveling toward the heart or periph..erally . toward the distal end of the extremity. Cuff pressure and compression rate are con,t$led. The apparatus has been employed in centrifugal fashion in patients with arterial ~i i&ufficiency and in a centripetal direction in the treatment of patients with edema resulting from chronic venous insufficiency. A review of results neported lends some support to the emplo:.ment of the apparatus in treatment designed to reduce edema secondary to chronic ilmphatic and venous obstruction. 3yncardial morsoge. The instrument employed in this procedure represents another mechanical device for the treatment of varcular disorders. I n application oí the procedure the ventricular complex of the electrocardiogram is detected from electrodes applied to both arms. From the involved ex- - ~ treinity, to which an inflatable CURhas been applied, an arterial pressure curve is picked up. I n an attempt to augment peripheral flow,' a cuff, complete with a n electronic delay, is assembled on the patient. The time at which the cuff inflates is related to the ventricular complex, as well as the descending limb of the arterial pulse curve, Although several investigators who used such objective means as pressure study in vessels distal to the site of cuff application and plethysmography have reported little physiologic effect, other investigators in the United States and Europe have rendered enthusiastic empirical reports. Massage. Massage is of little or no value in arterial disease, although light stroking or d a t i v e massage brings about a reflex vasodilatation and increased cutaneous blood flow. Heavier massage maneuvers should not be employed, since they may represent a form of repeated small trauma of sufficient additive magnitude to precipitate destructive skin changes. It may be noted that employment of vibrator). devices falls into the same category, even though thermometric and radioactive sodium clearance increases have been demonstrated in the local area of application. Recause of the danger of dislodgment of loosely adherent thrombi, with secondary embolic complications, massage is strictly interdicted in patients with acute venous thrombosis. However, the late complications of this disease (indolent edema, induration, eczema, and ulceration) may be benefited by the judicious application of massage as part of an overall plan to combat the effects of venous insufficiency. In 1939 Disgaard of Denmark introduced an ambulatory treatment for patients with indurated legs, which combines a program of elevation, massage, bandaging. and exercise. Results reported in the United Stales and in Britain lend support to the efficacy of the program and indicate the desirability of more extensive application. Therapeutic exercises Buerger's exercises. I n these postural erercises the limbs are elevated until blanched 598 Rehobilitation medicine and then placed in a dependent positioii until beginning rubor. An interval of rest follows. This alternating filling and emptying of the vessels theoretically increases the arterial blood flow. The procedure is widely employed but is of highly questionable value, especially in the dubious light cast by carefully controlled studies on clearance of radioactive sodium from the calves of patients performing this exercise. Theropeufic wolking. Therapeutic exercises in the form of controlled walking represent a most physiologic approach to treatment of arterial occlusive discase, provided that trophic lesions are not present. The latter qualification itself may eventually have to be altered in the light of some recent favorable reports on the use of exercise as a means of promoting collateral circulation in patients with limited gangrenous lesions. Walking places a physiologic demand on the muscles of the extremities that can be accommodated only by the appearance of collateral blood channels. The patient with intermittent claudication should be encouraged to walk at a slower but regular cadence, up to the point of pain. It does not appear feasible to force walking beyond this point. since the vasoconstriction incident to increased pain is a detrimental factor. Rather the patient should be instructed to accept the rest period required for subsidence oí discomfort and then to resume ambulation. Collateral studies of radioactive sodium clearance from the calf musculature, referred to in regard to Buerger's exercises, were also carried out following periods of active use of the limb. The preponderance of evidence points to greater clearance and. therefore, greater blood flow following anibulation and active exercise. Piophylactic maasurer General. The prophylactic measures related to the care of patients with arterial diseases should be considered carefully. since approximately 307; of patients reporting to the department with potentially serious conditions have self-inflicted lesions caused by improper shoring. misapplication of medica- tions, injudicious podiatric rare, and generally poor hygienic measures. Enumeration of the precautions to be observed by such patients may be found iri one form or another in the various texts on vascular disease, but because of their importance, they bear repetition. Prophylactic measures advised at the Institute of Rehabilitation Medicine are given in Chart 22. Because of the high incidence of trophic lesions initiated by the use of improper footgear, it is pertinent to discuss this measure in somewhat greater detail. Footgear. Footgear, by definition, includes all coverings of the foot, both hose and shoes. Hose. T h e arteriosclerotic patient should use lisle hose, fitted two or three sizes larger than the shoe and manufactured without constricting elastic tops. Lisle is porous and absorbent. Hose manufactured with squaredoff toes are most desirable, to avoid constriction of the terminal portion of the digits and to avoid the tendency toward ingrown nail growth. Stretch hose and nylon do not meet these criteria and should not be worn. Shoes. There is no compromise for comfort, so that shoes must fit properly immediately; esthetics are secondary. Shoe size is determined by a fit that permits enough room beyond the toes (approximately i inch beyond the great toe) on both sides to allow for spread on weight bearing and rmm over the dorsum to avoid injury by pressure and abrasion. It seems most practical to fit shoes in the early evening to allow for the even slight edema that most vascular patients exhibit. The sole of the shoe should be made of leather rather than rubber or a composition material. since the latter materials are poor heat conducton and increase perspiring. New shoes should not be worn for more than from 1 to 3 hours a day for the first week. The preferable style is an oxford manufactured from either kangaroo or Vici kid leathers. both of which are supple and poroiis. permitting ventilation and avoidance of hyperhidrosis. Patients with hallux valgus should be fittrd with bunion-last shoes that are designed with a specific pocket to accommodate the deformity of the toes. The repair of shoes of these patients is . Rehabilitution o/ patient with peripheral uarcular disease mer- ?d . . -8n of .?? , CHART 22 such par n"7ther 1 p ~ ! but :=r repeti- PERIPHERAL VASCULAR SERVICE ,*. a the 2ri :¡\-en INSTITUTE O F R E H A B I L I T A T I O N MEDICINE New Y& Univmity uedierl Ccnta IiiiOUence :<? of im,.XL , .. this CARE OF THE FEET AND GENERAL INSTRUCTIONS includes :id "-m. -,~. ould .,- larger dhout i:oi and qYiared.-qf-tricand -\un nail .es -90 :lot meet *.- iom*_ :mmedi+e is 7: >ugh 'Tinch o-~llon ~.31 over ~ 2 %and ñt shoes :n even .-ients :xmade :rrrposi): : ! i arc 1. Wash feet u& night with fiesoap and w u m water; dry gently by patting with clean wft cloth 2. Apply XI percent rubbing alcohol and allow feet to dry thoroughly; then apply liberal amount of petml.tum, toilet i a d i n , or coconut oil and gently m-e skin oí feet S. Airar, keep f a t mmi; wear wookn sock or wd-lincd hin winter and cotton socks in warm weather; wear clean pair of sock each day 4. Wur bsst-iittiugbcdiodo at nighht; a y hot-water bottle or electric pad to abdomen; never put either d thac d i m t y to feet az lega 'p' 5. Wear shm of aoft luther without box t a r ; bc particuhrly careful not too tight 6. Cut toenail atnight acmn and only when in very good light and only after feet hive been clealucd thoroughly 7. Do not cut corns or callura; ye podiatrist 8. Do not wear circular garten . I --~..spiring. L . :'r,more first ii ~ vníord or Vici : :Y" and . .. ,. ance 1- ': valgus I>-- that rom- ..:::iLnts .. .I is 9. D o dot sit with lqp crosxd 10. Ov&pping t o a and cxcarivc penpiration of toes should be corrected by inserting lamb's wod between than 11. Never uac tincture of iodine, Lytol, cresol, carbolic acid, or other strong antiseptic drugx on feet 12. Call doctor's attention to appearance of troublcorn, ingrowing toenail, bunionr, or ullusa; a b wra, m h o , or blisten n feet or legs 13. f i t plenty of green vegetables and fruits in a well-balanced diet, unless ordered to follow a special diet 14. D o not m u tohacco in any form 599 600 Rehabilitation medicine also quite important, since reconstruction may alter the fit. Resoling, for example, ordinarily results in narrowing of the shoe because the leather is drawn in when the new sole is stitched on. Ideal conditions exist when the shoe is returned to the factory and repaired on the original last. Comprehensive rehabilifafion measures The principies of rehabilitation of the patient with vascular disease vary only in minutiae from the general concept of care oí patients with disabilities. Arteriosclerotic patients with compensated arterial blood supplies usually are able to pursue a normal occupation limited in major aspect to avoidance of exposure to conditions precipitating intermittent claudication or trophic disturbance. For example, a patient employed as a waiter in a bury restaurant required vocational reexploration and counseling because of continuous o w t of intermittent claudication. A young police officer with thromboangiitis obliterans required transfer to an indoor assignment when it was noted that he suffered onset of extreme vasoconstrictor phenomena when exposed to inclement weather. This type of patient, as well as one with chronic venous insufficiency and vasospastic diseases, represents primarily vocational problems so that normal gainful employment may be m;.iritained or restored within the restrictions o1 i.he physical defect. The amputee, however, has a special problem that has been discussed previously. ?he psychologic and social adjustment of the latter patient to mutilatirg surgery and the fitting and adaptation tu the use of a prosthesis are at least as important in rchabilitation care as arc vocation.4 considerations. CHI -. Rl W REFERENCES Allen, E. V., Barker, N. W., and Himr, E. A,: Periphenl vascular direasis, Philadclphin, 1955, W. B. Saunden Ca. Fay, T., and Smith, L. W. Temperature facton in cincer and embryonal cell growth, J.A.M.A. 119:653, 1939. Freeman, N. E.: Influence tcmprature on the development of gangrene in peripheral vascular diseases, Arch. Surg. 40326, 1940. Lewis, T.: Vascular dilordcn of the limbs, New York. 1936, The Macmilhm Co. Knmer, D. W . : Pcripherxl vascular di-, Philadelphia, 1948, F. A. Davis Co. Smuelr, S.: Diagnorir and ireatment of vascular disorders, Biltimarr, 195ri, T h e Williams & Wilkins Co. Wnkim, K. C., and othcn: The influtnct of ryncirdiil musage on thc: p n p h c n l circulation, Arch. Phyr. Med. Rehabil. 97538, 1956. Wisham, L. H., Abnmron, ,i. A,, and Ebel, A,: Value of exercise in periplieral artend diseare, J.A.M.A. 159:10, 1953. Wright, I. S.: Vascular diseases in clinical practice, Chicago, 1952, Year B w k Publishers, Inc. a l tial , tatio somc outli persi vascl sidcr as a the t anatt duce, in tt is no of he tion cific Or plegi; cereb a cei there when quire< GENE Th, plegic retrai: reacq) an in1 with I dysfur lorms tern t the di rtitute mctho ,. I . <_ #- ~ v; ! P c h N V I I ,' m " I E r l 2 O N L .. .. .,. . " ., .., . .. .- .. E 3 "7 -. e N E BO .c o ui P m .OO.. P F .. .2 n 7 ' O *- C cn .? a . . u 3 PI > . u -.-> -- U !! E O - 3 U I C c Y * I- ! 1 I Y E '. . t , . . .... , _.. , n 1 t 8L 1 1 1 . ,, ,. , . <.^ ._-.. ..,, . . .. . I .. "T I , ,. .,~. ."" Ps b.. 4 tt, -T , . . . . I .,. ~,... *.-.--- ) I . - " r i L r. I .. r c * .- ., ,- ~ .. , ,-.- - .--... , ~ __c_ c -.. .. . *- .. .. . .. . 1. o e . r E .. <. . . . .... , .. 6 6 ._ ._ , . .. I . I . ..,. . . I . ., ... . . ..I *- 3 , - o I . .~ . .r -? ci E E P m n m 9 rn z I o rn v) . c , -, . r., . .. I 1.. .. I-. a- *-, nuesItamo8 aaber' que tipo d. , e. . . dato terioaetrioo . ea neoeaari . . , , , .. en.abeU' .. - .-. ti-) - .tdl o&*& ." .. &I oi&.m,a. , y Ist,mas . . es razonable esperar s . . , , , .", arenarios. 7 di e e d v a t e ." . O Q ~ Wd Qa ~ l poder depositado, mieatrss l o s a r t u d e ~ e l t a i i i s pareeea a e r bastantes h e n o s , ya uqe b y lugares p e a "," Iunur Uti8 LC coiy&uolou) necesidhC( un a,k OB un simp-e oryomioecogia forma, g r d o ae f i e x i m i d d a a , a ) eri una etapa mecauica, ,UZ en materlaLes rlo*ogicos. y d e aesilie...o & GU(L y r ~ p , cL- ~ un ~ c60rifw0 ai cual p e r m l t e p r o y e c t o corista u e dos p a r t e s ; eb un mioroacopio d e :uiitaun ~ , e espacimenes tronico d e servo controí e. ouei asil)na i a y ir) un letema &eo- temperdtura U. para r a s t r a e o t r a T ~ un S p r o ~ r a m a o r QB temperatura en especlmen un con- term de tiempo. rieid( 1976), de8cri.e a uw a ,a oryomioscopia i a c u a i e s t a incorporaair etapa uiecanica l'utirte pesa a imtur-impursnr, para yenerar una r e f e r e n o i a grana poteiiciomatroe ae temper-tu-. C i r c u i t w i a ~ e c t r o . A i c 8& . L. a i s & f o o m j e t i v o a e er c i r c u i t o B e ControA e s & a si&: a ) proauclr una dores d e vo-taJe, versión p r e s i s a at! un amp-ificador de t e r m o o o o p i e b)para producir un m-tuje (Le r e r e r e a c i a en Ah forma de una ramp& & i n e a ~OQU un rango proijrambLe d e r i m y caida y &a i a c i r i d a a par& Denteuerae en ai rango u e vo-toje presenta y o ) para comparar 1 0 s termoacop-&ores amp,lficaao en un n i v a de m i t a j e oon u. Vo-thJe d e referwanoia en un c i r c u i t u Qe o w n c o n t r o l y p r o v e e s u f i c i e u t e poaer. en e* estaao c k o r i f e r o para minimizar A 6 Qirerencia e n t r e esos V L t a J e s . L L.~ ,-. I 1 ._ *." . .. .. ..-.. ... I . ... -... . _. n -. c.- .. *. . *-. -_-- 7 , . . j.’ .. r- ^.. I . ! .- .. ?.. ... ,.-~. .~ I I^ .... L . .~ ,... ~. -~. .... . .” . ~. .. . , .... r.. -. ..I .. . .. .. . .._” .~ ,. , .. ,' ... ,. I.- ..I. I ,. *_I ". r. .. .. <. I. * . .1 ,.L ,,.~. C. .. . I.. . r ... ..._. -. ... . *I _ r- ." .. ., . .I-. ...".....I." .. . ... ~ . .~ . . -.. .” .. , I”, . I I . . . . -. I. L ..- .., .~ i t e in- wrm&i dailaao y 1uaPZa ciei paolentu. Uosilnevia tcrmlca eonwarrenee ( teniendo oontroi inlentran circulan LOB orapoa i i e temperatura eon- pJ.eta e n t r e tanto un t r a t a l e n t o y aJuotando p o t e m l a de poslelón y SUS parauetros)nast& optltPiaar e i t r a w a i e n t o actual e a a w e euri&w.o, si. u~-,.Guuu~~ pror@nten ~ mldionQo L a temperatura a i o e ~ Posa ~t o b j e t s r o iie rutureo S~’L campo i i e tcwporatura donp-eta. ev&uaelóii d e tratanisntos propios nu o ~ j e t l v ol a oa;oulaelórr d a t i e n e que eonse&”ir mientras o i I ,.. .. I_ . I . I”. . .- I,. .... .. ... L^. .^- . .. r- ~. ,... . ... .... ...” ._. .- c .. *.- ... 1 "1" .. ñ&Y&:XdNNCIA 'I m'' A p l i c a c i o n e s de l a s Imagenes de NMR en Hipertermia: Una Evaluación de e l P a t e n c i a l de L o c a l i z a c i ó n de T e J i d o s C a l i e n t e s en N o n i t o r e o de Temperatura N o i n v a s i v a . Sumari o. - La A p l i c a c i ó n de l a Besonancia Magnética N u c l e a r (NMR) en t r e s Dimensiones. Para monitoreo de temperatura n o i v a s i v a como también e l calentamieri t o de t e j i d o son d i c u t i d o s . Aunque e l d e l i b e r a d o uso de c a l o r conv e n c i o n a l en imagenes de NMR e s i n s i g n i f i c a n t e , l o s hases f i s i c o s para transferir c a , l o r son r e v i s a d o s y e l p o t e n c i a l de incremento e s mostrado para depender en ambos, e l campo esta.ticomagnetico y e l tiempo de r e l a j a m i e n t o l o n g i t u d i n a l , ( T I 1. De l a d i s c u c i ó n de l a s bases f1sica.s de l a tendencia. de temperat u r a d e l l o n g i t u d i n a l (1'1) y t r a n s v e r s a l (T2) en l o s tiempos de rel a j a m i e n t o , e s t o e s que T I puede s e r un i n d i c a d o r mas s e n s i t i v o que T2. L o s experimentos p r e l i m i n a d e s en e l á r e a de monitoreo r e g i o n a l de temperatura en sangre y agua, son ejemplos que i n d i c a n que l o s cnmbios cte temperatura puecen s e r monitoreados. A1 comercio a. t r a v e s d e l e s p a c i o y la r e s o l u c i ó n temporal, a s i t a n b i é n la. e x a c t i t u d y l a p r e s i c i ó n de d i c h a s m e d i c i o n e s i l i s t a c l a r o que muchas p r o b l e m a s de t e c n i c a s pueden s e r superadms con e l NMR y pueden s e r usados p a r a monitoreo de temperatura en h i p e r t e r m i a . - .~ . -. . . ..., , i n t r o au c c i 5' ,. biempre que la. n a t u r a l e z a de l a resonancia magmetica n u c l e a r (NMX), pueue s e r usada y a t e n d i d a en e l e s t u u i o ae l a . e s t r u c t u r a e l e m e n t a l y m o l e c u l a r de decadas (173), uno en l o s 10 años f u e at e n d i d o para s e r usado con 1Ul~lH para c u a n t i f i c a r l a d i s t r i b u c i ó n e s p a c i a l (4,t>). Porque l o s mecanismos ae r e l a j a c i ó n ae l o s mornent o s magnéticos n u c l e a r e s en campos m a g n é t i c i s e s t a t i c o s envuelven i n t e r a , c c i o n e s t e r m a l e s con e l suso dicho ambiente, e s t o e s de espsc i a 1 importancia para determinar e l p o t e n c i a l d e a p l i c a c i ó n de l a s imagenes de NMH para h i p e r t e r m i a . Donde l a primera. propuesta. d e est e p a p e l e:> para r e v i s a r y d i s c u t i r e l p o t e n c i a l de a.plicaciÓn de ims.genes de NUX n o i n v a s i v a s , monitoreo ue temperaturp, l o c a l i z a . d a , algunos comentprios i n i c i a l e s pueden s e r hechos c o n c e r n i e n t e s a l p o t e n c i a l ue l o s d a t o s usados- en NMR Pars? hipertermia,. S i e p r e que e s mostmdo que los paremetros f i s i c o s meuiaoü con NMR son independ i e n t e s de la temperatura, e s t o e s n e s e s a r i o para determinar s í 'uno de e s o s parametros pueae s e r medido con s u f i c i e n t e agudez y p r e c i siÓn para iliediciones de temperatura, n o i v a s i v a s . Algunos r e s u l t a d o s p r e e l i m i n a r e s en mediciones ue temperatura n o i v a s i v a son usados(ó). - Conclusiones; &s e v i d e n t e que de e s t a s d i s c u c i o n e s , que l a l o c a , i i z a c i ó n de c a l e n t a m i e n t o con NKH no e s p r á c t i c a , usando mediciones ae temperatura r e g i o n a l con Óptimo seguimiento de imagenes de KMR, l a c u a l como e s une. siiiiple t é c n i c a s e n s i t i v a de punto, puede no s e r muy p r á c t i c a . Porque be usos r e l a t i v o s a cambios de agua extra-e i n t r a c e l u l a r , y porque T2 en e l agua d e l t e j i d o e s cercano a un oráen de magnitud mas c o r t o que TL, e s t o e s e x p e c t a t i v o y a que TI puede s e r un i n d i c a d o r de temperatura mas s e n s i t i v a que T2. Porque l a complegidad del, aparpto de imagenes de NMR y su uso r e l a ciona.do con l a s e ñ a l independiente de v a s e l i n e e x i s t e n t e . E s t o i m p l i c a que l a r e l a c i ó n sefia.3. r u i d o y e l s e n s i t i v o r e s u l t a d o de tem peratura. pueda v a r i a r en ur.a p r o p o r c i ó n d i r e c t a de l a poderasa s e ñ a l La s e n s i t i v a . temperatura puede m e j o r a r con e l aumento de l a fuerza. en e l campo, l a meciición de volumenes grandes y v a l o r a r l a s multip l e s mediciones. S e v e r a s preguntas pueden no s e r c o n t e s t a d a s y pueden s e r d i r e c c i g nadas p w ~ l. a termometría no i n v a s i v a usando NMH puede s e r una ap l i c a c i ó n p r á c t i c a . La v a r i a b i l i d a d en l a tempieratura s e n s i t i v a de 10s v a r i o s t e j i d o s en d i f e r e n t e s i n a i v i d u o s puede s e r mostrada. Los e f e c t o s de tiempo de r e l a j w i ó n en l a s r e s p u e s t a s f i s i o l o g i o a s p a r a calentsuniento (como el. incremento de f l u i d o sanguíneo), e s t o e s e v i d e n t e en algunos e f e c t o s f i s i o 1 Ó g i c o s : ' p u e d e n o c u r r i r en v i v o y puede s e r e s t u d i a d o en v i v o . La p o s i b i l i d a d de anomalias c e r c a nas a l a s temperaturas en h i p e r t e r m i a pueden s e r demostradas ( 2 4 ) y pueaen s e r supervisaaas. Es e v i d e n t e que en muchos años f u e r o n n e c e s a r i o s p a r a responder a n t e s e s a s preguntas. - - Una Revisión de l o s Metodos de Inducción kagnética para Tratamientos de Hipertermia en Cancer. .- bario L o s metodos de inducción magnética para predecir poder de absor ciÓn en tejidos son usados para llevar a cabo l a hipertermia en tumores en l a terapia experimental de cancer. La distribución de l o s campos electromagnéticos y asociado con l o s rangos de absor ciÓn concentricos en tejidos (SAH), el desplome de l a abertura coa xial de corrientes de enrollamiento son discutudas. Aplicación de l a ecuacijn de transferencia de calor usada por S a en l a predec ciÓn de la. distribución de l o s campos en e l tejido normal y elevación tie l a . temperatura en el intratumor. La corroboración de esas predicciones por fantasmas, en cuerpos humanos y animales e s para confimar l a tranferencia de biocalor em el modelo en l a elevación de esos metodos de hipertermia. El tamzfio del tumor y deformación son precauciones buenas que se usan en las técnicas de inducción magnética de calentamiento, y s o n revisadas, basadas en las evi dencias pribadas. - - Introducción.dl uso iiioderno .de los metodos de inducción para elevar l a temperatura ae l o s tejidos es revisada en este artículo. dn particular l a distribución de l o s campos electromagnéticos producidos en un lugar paticular y usado en la terapia de hipertermia en cancer. La interacción de esos campos con tejido para un resulptadm espe cifíco en l o s rangos de absorción de energía ( S A E ) , y el resultado de l a elevación de la temperatura en l o s tejidos normales y turno,.res es calcula,docon la ecuación de transferencia de bicalor, que nosotros consideramos. Un pequeño sumario cie experiencias en clíni -- - ca y laboratorio son dados como un medio para corroborar l a predi - cción de l a distribución termal. Aplicación Clinica y Observaciones. - Un número de documentos en clínica humana son usados para descri bir el tejido normal y l a temperatura en el intratumor, la toleran - cia del paciente, toxicidad, y respuesta asociada al tumor con l o s tratamientos de inducción magnética (metodos (3b-47)). Las diferentes relaciones en l a seleccijn de pacientes, sitio tratado, y va?:'.- , ~ * * y - - . . r i a c i ó n en. l a combinación de q u i m i o t e r a p i a y/o r a d i a c i ó n con h i p e r t e r m i a , e s t o s r e p o r t e s impiden una simple comparación de l o s d a t o s de respuesta. E1 d a t o termometrico también e s d i f i c i l de comparar porque e l l a r go g r a d i e n t e de temperatura i n t r a t u m o r a l e x i s t e y que v a r i a con e l tamaño d e l tumor, de fonmación, grado de p e r f u s i ó n sanguínea. Limitando l o s e j e m p l o s de temperatura podemos i n c u r r i r en l a v a l o r a c i ó n del. r a n g o de tenipere-turne i n t r a t u m o r a l e s formadas y una m í nima temperatura tomada \ 4 7 ) . - He sumen. f o s estud.ios t e ó r i c o s de SM..,y l a d i s t r i b u c i ó n de temperatura obt e n i d a con v a r i o s metodos de inducción magnética e j e c u t a d o s en h i p e r t e r m i a son r e v i s a d o s . Los s o f i s t i c a d o s modelos t i e n e n r e s u l t a d o s que también pueden a p l i c a r s e p a r a e l e s t u d i o de o t r a s modalidades de c a l e n t a m i e n t o . Un gran número de e x p e r i e n c i a s en l a c l í n i c a humana son confirmad a s en l a p r e d i c c i ó n d e l modelo y sus s u p o s i c i o n e s d e l concepto de e x t e n s i ó n en l a a p l i c a c i ó n de modelos numericos para l a p l a n e a c i ó n de t r a t a m i e n t o s c l í n i c o s y d o s i m e t r i a t e r m a i , como siempre e s d e s c r i t o en e l t e j i d o . La mas apropiada a p l i c a c i ó n de l o s metodos de i n d u c c i ó n magnética apErecen para s e r e l t s a h m i e n t o en tumores mas e x t e r i o r e s , 6-7cm. d e l t e j i d o en s i t i o s subdiagramaticos, con c o r r i e n t e s c o n c e n t r i c a s . La l i m i t a c i ó n a e l o s metodos de inducción p a r a tra.tamientos en tumores i n t r a t o r a c i c o s son menores, p e r o b i e n d e f i n i d o s c l i n i c a m e n t e . Al volumen s u b s t a n c i a l de d i c h o s tumores puede s e r e l e v a d o a menos de 42 C , y en ca.sos de tumores con diametros de menos de 10 cm. Pequeños e n r o l l a m i e n t o s empaquetados son un medio e f e c t i v r h en e l c a l e n t a m i e n t o de pequeñas s u p e r f i c i e s con tumores con dimensiones mayores que 4cm. en l a s u p e r f i c i e mas s e v e r a a c e n t i m e t r o s a e l t e j i d o d e l cuerpo. PL diametro mayor ( e s menor que 20 cm.) en co r r i e r i t e s de e n r o l l a m i e n t o pueden p r o d u c i r un a l t o SARy d a r d e f o r mación en l a s c o r r i e n t e s c o n c e n t r i c a s . Bsos e n r o l l a m i e n t o s produ c e n un t o r o j d e en l a d i s t r i b u c i ó n d e l SUR, que e s complementario y que e s producido P o r c o r r i e n t e s de e n r o l l a m i e n t o , e l s i t i o de formrción y e l tama.ño d e l tumor apropiadamente tr-t R ado con c o r r i e n t e de e r i r o l l a m i e n t o pueden s e r d e f i n i d a s . - - - I . ..^ ... r. BIBLIOGRAFIA. . ,. . I , . I .I . agrnta such as radiation, chrmotherap). and heat (Elkind ~ n d Uhitniore [ I 21). During the last two decades. radiobiologists in particular carefully studied the effects of hyperthermia on normal and tumor cells since they were familiar with the use o f in vitro assay systems for measuring effects of radiation and drugs. The results of these cell survival studies in the 1970's showed that cessation of ceU division, defined as mitotic death or cell killing, was attained i f cells were exposed t o temperatures in excess of approximately 40'C for time periods of 30 min or more (1131 and Fig. I). 1nthisfigure.thesurvivingfraction o f the heated ceUs is plotted on the ordinate as a function of the time the cells were held at a specific temperature. Note that above about 42.S'c, small differences in temperature, on the order o f tenths o f 1 C, resulted in significant increases in cell killing such that dn increase o f I o C corresponded t o an approximate halving of the exposure time necessary to produce an equivalent level o f cell killing. These results signaled t o the Fig. 1. Cell survival curves, from Dewey et al. 1131. Reprinted by clinician and engineer the importance for measuring accurately mission The surviving fraction o f CCUS grown in a medium at , w the temperatures produced by hyperthermia systems and the ticulnr temperature ii plotted on the ordinate. The absclm need for producing precise levels of temperature throughout length o f time the ccllr have becn exposcd lo the specified tempera tumors. Although the exact details o f mechanisms responsible for the cell killine-b v,hvoerthermia are not known. studies continue to .~ much ImS effective In terms o f additional cell kill if it is suggest that the mechanisms include effect; on cell membranes to0 soon after the first heat dose. The effect is produ and may take Over 72 h t o decay before cell ~enutivity and cell metabolism including intermitosis death [ 3 ] , which are somewhat different than those p r o c f f ~responsible ~~ for returns to original kvels. This thermotolerance may radiation or dmg-induced cell killing (these latter modalities important factor t o consider in the design of clinical p hyperthermia will most likely be delivered in have demonstrated specific damage t o DNA). perhaps fractions. importantly, several environmenta¡ factors have been identified The most important biologi as conditions which will significantly alter the response of ceUs temperature distributions achie t o hyperthermia or which suggest a rationale for combining hyperthermia with radiation. F o r example, h y p o u a (decreased ing normal tissue is blood flow. widely in normal tissues from oxygen concentrations) conveys radioresistance io cells but ' min in fat t o values as high as hypoxic cells appear to be as heat sensitive as are well oxyFurthermore, these values var genated cells. Cells in the DNA synthesis (S.phase) of the cell life cycle are most radioresistant but they are the m m t heat temperature, although little q sensitive cells. While low (acid) pH has little effect on r a d i e is available. While blood flow in small animal tumors sensitivity, acidity leads t o potent enhancement o f heat-induced extensively studied [ I S ] , similar data for human tu cell killing. When hyperthermia is delivered in association with still sparse. It is known, however, that the blood p radiation. potentiated cell kill is demonstrated in exceSS of rate in t u n O l S is nonhomogeneous. As a result, if The CC power density (W/kg) deposited from an external what would be expected by simple additive effects of either IICt thit. uniform throughout the tumor volume, the result modality acting independently, d.c., the two an tint the synergistic. This effect may he a result of inhibition of the tUre distribution is rarely uniform. Thereforqsystems miuw for hyperthermia should be expected t o have appropri repair of radiation damage in cells b y heat during the postimasubstinti diation period. These cell studies have been continued in mice control Of Power deposition which can be altered du , cxtremit treatment. and rats where the temDerature rise was induced b v water - - - ~baths vumed R F currents, microwaves, and ultrasound. Recent results o f 1ppiiuti similar studies in pet animals have shown that the minimum Iv. WHOLE BODY HYPEHTHERMIA napme temperature attained in the tumor was an important correlate in determining the ultimate success o f the hyperthermia treatI f it is accepted that hyperthermia may be a useful t h n a ment [ 141. Although many of these factors are poorly undertic modality for cancer, then there is stili th stood at this time, future unraveling of what appears t o be a myriad of environmental effects will influence the constraints on the engineer and clinician in designing or applying hyperthermia systems. If tumor cells are intrinsically at lower p i i than normal cells, or if blood flow is lower in tumorscompared to normal tissues during heat treatments [ I S ] , these biological facton would suggest a favorable condition for producing ceü fever t h e r a p i a produced whole body hyperther kill by hyperthermia and might suggest a favorable therapeutic the biological variation attained, the difficulty in co gain factor (TGF), i.e., a w a t e r effect in the tumor than in the final temperature. the limit t o the tempera any treated normal tissue. Hahn discusses these biological maintained, and the duration o f the fevcr present real drawquestions in detail in a recent monograph [3 1 and summarizes backs when using toxins. Therefore. certain investigators h i e many of the important effects in I 11. become interested in external means o f producing whole body F o r engineen working in hyperthermia, perhaps the two hyperthermia (e.&, see reviews 131. 141. l i 6 l - I l 8 1 ) . AmoO most important biological phenomena of which they should be the techniques that have been used a aware are thermotolerance and blood flow. Thermotolerance is a phenonmenon somewhat unique t o hyperthermia which has been observed in cultured cells, as w e l i a s in animal and energy, and enclosing the pitimt in 3 ttwipcraiure human tumors 131. This effect is defined as the apparent suit. While interestinc. .nalliaiive rcaultr have. becn < -L~ ~ ~ rrnorted .... wsca thermoresistance induced in cells following exposure to an 1191, there have been no long-tern1 surviv~tsrrported with la-, hican, earlier dose of heat. In other words, a second dose of heat is method. ,. .. ~ ~ ~~ ~~~~ since^ ~~~~ ~ - ~~~ . 78 I I b¡i PERTHERMIA . I I I : : I . ' : SY+EMS umbLr of -ups )r xoducing rcieon :io theniaumuinpo ero-depasite o t n. kuisrn e al. [291. [ 3 I have c&ulatcd tsq~perrturc niformly w i t h h ~ t u r n o t d u r n $ dittbu, for t~o-dimenmo$l modrb of t h e s c i y ~ t c m l a o d 'in temoerature dis ution h u s k t i renilto W a c that both daiices w i l l often haqe traible !L *.”.).un- *,an. Fib 3. A schematk of the annular phased array. (al mis fisure show the two concentric rings with the total o f 16 apertura. (b) An end view rhowing ü apertures and the radiating wavefronts. Reprinted by prmbdon O 1982 IEEE. calculate the temperature distributions for this model, the electromagnetic fields for the hyperthermia system of interest must be found. We use a f i i t e element method ( 3 1 1 which has the advantage that the problem formulation i n c o r p o r a t e the nonhomogeneous tissue regions. In Fig. 5 we show t h e is* SAR contours for both a concentric coil and a n annular phased array model, where t h e SAR (specific absorption rate) is d a i i i e d as the absorbed power density (W/kg). The SAR value is given by where u = tissue electrical conductivity, p = tissue density, and electric field. The curves in Fig. 5 are normalized SO the maximum SAR = 1. Note that the t w o devices give very different SAR patterns, with t h e concentric coil depositing little power in the tumor (SAR 0.2). while the annulpr phased array produces a significant SAR gradient varying from 0.1 to 0.6 in the tumor volume. To calculate the isotherms, the SAR information is used as input to t h e bioheat transfer equation 1321, 1331, which takes into account heat transfer due t o thermal conduction and blood perfusion. We also solve this problem using a finite element technique. In Fig. 6 , t h e i s 0 therms for the two systems are shown for a specific set o f a s sumptions regarding blood flow. The cross-hatched region indicates the tumor area where the temperature is considered to be therapeutic, i.e., temperatures greater than 43OC. Note that despite the large differences in the SAR patterns for the two systems, the final temperature distributions are not too different, e&, the percentage of the tumor region greater than 43’C is about the same in both cases. This is primarily d u e to the fact that the blood flow in t h e surrounding viscera is high and hence keeps the boundary at close to 37’C, therefore. the temperature rise is in the necrotic tumor. Also note t b t for both devices a reasonable percentage of the tumor is n o t a t temperatures the clinician considers therapeutic. Since actual blood perfusion rates in normal tissue and tumor vary consid- üm B 1- Pr ur, th th Cl‘ sean showing a Lrge tumor in visible are the spinal column, ribs, kidney. and m I rg. 4. (a) A o f the CT s u n showing regions and Ihe finite elemat grid u& in the c íb) A digitized model he en he that in the large majority of situations of interest, rlot be able to bring 7 5 percent o r more of the tumor prutic temperatures. There is a need for further m a r c h . pional hyperthermia systems with prti tifying the fundamental limitations of w OF Wi u11 Ih ab bu in E = the th bc lh fe < ha in #th dC o tumor to therapeutic temperatures will still bc very because radiation therapy or chemotherapy will datroY rrmainder of the tumor cells. However, as yet the clinkb ,.annot tell us what percentage of the tunlor volume must (rrnperatures greater than 43O to provide an acceplohle dini* rrsponse. It is important to emphasize that when the hyprlr n d o nincludes normal tissue, the combination of hcrt na bt i ? normal ~ tissue, the interaction hclwcen thc vill produce unacceptable daniagc in the norm Iciit to putting more radiation dose into norm a w already treated lo their tolerance limit. If ¡in l m ! in in b< 1; la tu 1:. I’ 9 Y1 tb Ih of trvedom. VfI. ,lilt .I:,;,< lNTtHSTlTlAT H~PER I11LHMI.A T SVSTqM5 n '. t 1 I 1 Fii 8. A dmgram of the dcaipn by Ihc Dartmouth hypcrtharr,,h for an interstitial antenna. The fieurc show the crthetn. and fiber optic thermometry probc. IMAAH SYSTEM .,,% .,. .. *'< ., Fig. 7. Diagram of a radio frequency needle electrode hyperthermia B I Y :' Y system from Astrahan et aL [43]. Reprinted by permission. number of groups have been investigating the use of invasive systems, particularly interstitial ones. An interstitial system is one where the power is deposited through energy sources that can be inserted through (or a s part of) hypodermic needles or catheters. Physicians have developed quite sophisticated techniques for placing catheters in most locations within t h e body, either during surgery or under ultrasound or radiographic control. Presently, three types of interstitial systems are under investigation: RF needle electrodes, small linear coaxial microwave antennas, and ferromagnetic seeds. In the first case, usually two parallel planes o f stainless steel needles are implanted near the tumor boundary [ 4 1 1 - [ 4 4 1 . An RF voltage (typically 0.5-1 MHz) is applied t o the two planes o f needles resulting in currents between them. These currents heat the tissue due to its resistive properties. Temperature may he monitored in the hollow needles in order to control the power. Recent developments permit switching the powerbetween pairs of electrodes in order t o provide better temperature control 1431, and inserting flexible cathetfr electrodes which are less painful to the patient. F i g 7 is a block diagram of a typical system as described by Astrahan et ai. [ 4 3 1 . Manning et nl. [ 4 5 I and Cosset et al. 146 1 have reported some very promising clinical results with this type of system. The use of linear coaxial microwave antennas was first proposed by Taylor (471 and has since been refined b y a number of groups [481-[521. T h e advantage o f a microwave antenna compared t o RF electrodes is that a single antenna will radiate power into the surrounding tissue. However, the physics of the problem dicates that most of the energy will be absorbed quite close t o the antenna. Therefore, for tumors of clinical size, it is necessary to implant a n array of these antennas [ S I ] , 1521. From an engineering point ofview,theseantennas are interesting because they are immersed in a conducting medium, and hence, conventional antenna theory must be extended for this case [ 5 3 1 . When compared t o interstitial RF needle electrodes, the microwave antenna arrays have the advantage of being able to be placed farther apart, and hence, fewer of them need t o be implanted. However, compared t o the RF needles, it is more difficult to control the energy deposited along the length of an antenna, which has a natural resonance length. At our institution, these antennas have been used t o heat both superficial tumors 1541 and &epseated ones. The deep-seated tumors have been located in t h e abdomen and the brain. A diagram of the antenna used at the Dartmouth-Hitchcock Medical Center is shown in Fig. 8. The catheter is a slight modification of the one used for interstitial radiation therapy. This catheter becomes part of the antenna design as described in King et oL 1531. The length of the tip hA is chosen t o optimize the radiated power patterns taking into account the catheter, tissue characteristics, and antenna radius. In order to provide feedback control, the temperature at the antenna is monitored by a fiber optic temperature probe that is n o t af- i & I1 I n C V n 1 Fig. 9. A diagram of the microwave system dcvcluprd a1 Dumw# used l o drive an array oCinterstitial microwave rntcnnm t 1 I I I t Fig 10. A schematic of a ferromaenetic implant system for heath deep-seated tumors. fected by electromagnetic fields [ S S ] , [%l. In Fig. 9 a bloc diagram of the system is shown. Its major feature is the usem p i - n diode switches t o control the average power to each 11 tenna using pulsewidth modulation. The power to each ai tenna is controlled by a feedhack algorithm using the tcmpen ture information from the thermometry probeshown in F i g 8 Stauffer et aL [ 57 I , I58 I have proposed the use o f fern magnetic seeds as an interstitial modality. In this concep illustrated in Fig. IO, the ferromagnetic seeds are deposited i the tumor volume during surgery. The patient is then pl8m in a large concentriccoil, e.g.,as in the Magnetrode 1221, 123 I f the frequency is low enough (<2 MHz). then it can be show that more energy is deposited within the tunior volume thi in the surrounding nornisl tissue. There is no major advantal of this system compared to other interstitial systcmg i f t e m p ature must be measured invasively. However. several resear( groups are trying t o design seeds whose magnetic propcrtk change such that at higher tcniperaturcs thc magnetic perme bility sharply decreases. snd hcnce. the seeds arc self-regulatif in temperature [ S S ] , 1591. While this systciii has yet 10 I tested in thc clinic. if is bring tested in sninials snd appean 1 have excellent potential. Its advintage o w r the R F and mitt, wave interstitial systems is that after the srrds arc implant: skin incisions can be closed. and hcnce. the implants u n I left in for extended periods with less risk of infection. I i . , : , , r . ., I : '' I 3. :IS, : 1r.11 Iri ' ' . "' ' I: Recently, we set uce iwrmai tisue tempera I i-e urixceptible niorbidity ''I : -ti , t~iii m e t f r ; at limits that I ) 11 unicceptable rkk. ' i ' i ,t: tiam: not commented on t i II ' asan , , [ 13) \\ c , l>ruc?.L “<rllul*, I 1 I “ p ” o d . s :\ S>l...i<’l<>. >r#,l I.. I (;i~Tu<,cL. r,’\piin\c. t o ‘i>,iitii”rti<<“r \>I Ii>pc.tI>i.ril>i:,2 n d ,adi:,- t!on.”Rodiolra>.. vol. 123. pi>.463-474. IP77. 1141 M . W.I>cu.hint.D. A.Sim. S. Sip.iri.10. and W. G. ( onnor. “Thc importance of minimum tumor icniprraiure in drtrrniininp carly and long term responres 01 rpontanrour cminc a n d felinr tumors to heal and radiation.’’ Conccr RES., WI.4 4 , pp. 43-50. 1984. 1151 C. W. Sonp. A. Lokrliina. J. Rlicc. M. Pallen. and S. H. Lcvitt. “implication of blood flow in hyperthcrmic treatment ufrumors.” IEEE Tmns Biomed. Eng.. vol. BME-31. pp. 9-16. Jan. 1984. (161 P. M. Corry. O. H. Frazicr. J. M. Bull, and B. Barlope. “Methods for induction oí Systemic hyperthermia,” in Physicnl A~ppcetsof Hypenhrnnin, G . H. Nussbaum. Ed. New York: Amcr. Inst. Physics, 1982, pp. 587-599. (17) J. M. Bull. ”Systemic hypcrthcrmia: Background and yrinciplcr.” ’ in Hypenhennw in Concer Therapy, F. K. Storm, Ed. Boston, MA.: Hall Medical Publishing, 1983. pp. 401-406. [ I S ] L. C. Parks and G . V. Smith, “Systemic hyperthermia by extracorporeal induction: Techniques and results,” in Hypnlhermio in COnCCr niempy. F. K. Storm, Ed. Boston, MA: Hall Medical Publishing. 1983. pp. 407-446. 1191 R. T. Pettigrew. I. M. Gall, C. M. Ludgate, D. B. Hom, and A. N. Smith, “Circulatory and biochemical eifectr ofwhole body hyperthermia.”Br. J. Sur~.,voi. 61,pp. 727-730,1974, (201 R. Cavaliue, G . Moricca, F. DiFilippo, L. Alae, C. Monticelli, and F. S. Ssrtori. “Hyperihennic perfusion 16 years after its first clinical applications,” Henry Ford Hosp. Med. 1. vol. 29. no. 1, pp. 32-36.1981, 121 1 J. S. Stehlin, Ir., B. C. Giovanclla, A.E. Gutierrcz,P. D. de Ipolyi, and P. J. Greeff. “15 Years exverience with hvnerthcrmic oerfusion for treatment oí soft ti& sarcoma and malignant melaenoma of the extremities,” From Rodúrl. Ther. Oncol.. vol. 18. J. M. Vaeth. Ed., pp. 177-182, 1984. 1221 F. K. Storm, W. H. Harrison. R. S. EUiott, A. W . Silberman, and D. L. Morton, “Thermal distribution of magnetic-loop induction hyperthermia in phantoms and animals: Effect of the living statc and velocity o i heating,” hf.I. Rod OnroL BioL m y s , vol. 8, pp. 865-871,1982. 1231 F. K. Storm, W. H. Harrison, R. S. Elliott, and D. L. Morton, “Physical aspects of localized heating by magrietic-loop induction,” in Hyperthermia in Cancer Theropy, F. K. Storm, Ed. Boston, MA : Hall Medical Publishing, 1983, pp. 305-314. (241 P. F. Turner, “Regional hyperthermia with an annular phased array,’. IEEE Tmns Biomed Eng., vol. BME-31, pp. 106-114, Ian. 1984. 1251 F. A. Gibbo, M. D. Sspozink, K. S. G a t s , and J. R. Stwart, “Regional hyperthermia with an annular phased array in cxprimental treatment of cancer: Report of work in progress with P technical emphasir,”IEEE Tmm Biomed. Eng..vol. BME-31, pp. 115-119, Jan. 1984. I261 I. R. Oleson, “Hyperthcmia by magnetic induction: I. Physical characteristics of the teshnique,” Inf. 1. Rod. Onml. Biol. Ayr., vol. 8,pp. 1747-1756.1982. I271 J. R. Oleson, R. S. Heusinkveld, and M. R. Manning,“Hypcrthermia by magnetic induction: 11.Clinical experience withconcentric electrodes,” Inl. J. R o d Onml. BioL P h y s , vol. 9 , pp. 549-556, 1983. (281 M. F. Iskandcr, P. F. Turner, J. E. DcBoiv, and J. Kao, ”Twe dimensional technique to calculate the WI power deposition pattern in the human body.” J. Microwave Power, vol. 17, pp. 175-185,1982. 129) K. D. Pauhcn, I. W. Strohbehn, S. C. Hill, D. R. Lynch, and F. E. Kennedy. “Theoretical temperature profiles for concentric coil induction heating devices in a two-dimensional. mi-asymmetric, . Phys., inhomogeneous patient model,” Inf. J. R a d O n ~ lBiol. vol. 10, PP. 1095-1107, 1984. 130) K. D. Pausen, J. W. Strohbehn, and D. R. Lynch, “Theoretical thermal dosimetry produced by an annular phaed array type system in CT-bared patient models.” Rod&. Res., vol. 100, 1984. 1311 D. R. Lynch, K. D.Paulsm, and J.W. Strohbehn, “Finite element solution of Maxwell’s equstions for hyperthemil treatment planning,” J. CompufationolPhyr, accepted for publication (32) M. M. Chen and K. R. Holmes. .“MierovasculPr contributions in tissue heat transfer,” in Therm01 Charocrerisfics of Tumors: Applications in Defection md Trearmenl, R. K. lain and P. M. Gullino. Edr. New Yoik: NYAS; vol. 335, pp. 137-150, 1980. (331 R. K. J a b , “Bioheai transrer: Mathematical models of thermal Systems,” in Hyperrhermio in Cancer Therapy, F . K. Storm, Ed. Boston, MA.: Hall Medical Publishers. 1983. pp. 9-46. _ 1 in tissue: An adjunct to tumor therapy.“ hled. lnsrmm,,y~if4j; ,,. pp. 16-21.1976. ..,.<( .=, 1421 E. W. Gcrncr. W.G . Connor. M. L. M. Boanc. J . D. Da. P Mayx. and R. C. Miller. “Thc patcntial ufloc~irtd adjunct to radiation thcrapy,”Rodidoby. val. 116. 1975. 1431 M. A. Astrahan and A.Norman, “A localized currcn thcrmia System for u x with I9biridium intentiti Med P h y s , vol. 9 , no. 3, pp. 419-424,1982. 1441 1. W. Strohkhn. “Temperature distributions electrode hypcrthcmu systems: Thcoretio J. Radiar. OnmL BioL F i ~ y rvol. , 9 , pp. 1655 (451 M. R. Mannin8, T. C. Celar. R. C. MiUer. J Connor, and E. W. Cerner, “Clinical hypcnh phase I trial employing hypcrthcrmia alone with external beani or intersti1i;il radioihcnp pp. 205-216, 1982. (461 I. M. Cosset, J. Dutrek, I. Dufaur. P. Jsnoray. E and D. Clarke. “Combined interstitial hyperthc therapy: lnstitute Gustave Rouuy technique results,” Inr. 1. Rod& OneoL Biol Phyr, vol. 1984. (471 L. S. Taylor, “Electrumagneiic ryrinpc,” IEEE 7hm. Eng..vol. BME-25, pp. 303-304, Mu. 1978. 1481 L. S. Taylor. “Implantable radiaton fur cancer thcnpy wave hyperthermia,” Roc IEEE. vol. 68, no. I. pp, 1980. (491 G. M. Samaras, “Intracranial microwave hyperthermia duction and temperature control,” IEEE Tmm. Biom vol. BME-31, pp. 63-69, Jan. 1984. 1501 D. C. dc Sicyes, E. B. Douple. J . W.Strohbehn “Some aspects of optimization oran invasive for local hypcrthcrmia treatmcnt of cancer? PP. 179-183.1981. 1511 jl W. Strohbchn, B. S.Trcmbly. and E. B. Douple. “Blood 6: ’.: effects on the lemperaturc distributions from an invasive m-: ~: wave antenna array uscd in cancer tlierap)..”IEEE zíons Bo*.8,,;::. ,&U Eng.,voi. BME-29, pp. 649-661, 1982. (521 B. S. Trembly, J. W. Strohbchn. D. C. de Sicycs, and E. Douple, “Hyperthermia induced by an array of invasive m i a P wave antennas,’* J. Nnf. Concer Insr. mono^.. rol. 61. pp. 4Vl499.1982. i in’ I531 W.P. Kim. B. S. Tremblu. ”Thr - ... ...~~. . c*c . . R. .. and 1.- W.Strolihchn. tromnpnetic field of an inrulatcd m t c n m in a conducting o< PI diekctric medium,” IEEE Tianí hlicmwir nmry Te&., he an MTT-31, pp. 574-583. 1983. 154) C. T. Coughlin, E. B. Douplc. J. W.Strohbchn. H’. L. ~:atonJ:-:: B. S. Trembly, and T. 2. Wong. “Interstitial hyprrthcmi ’ :. combination uith brachythrrapy,” Rodidom. vol. 148. R ”: 1 *%’! &, ~~~~~ _”_. ?QL?QQ l.,I_. OP2 -1- ~ ~ 155 J D. A. Christensen. “Anew non-prrlurhinF tcnqvr~lurcPI& using semiconductor hand edgc shift,” 1. Bior>v.. vol. 1. 543-545,1977. SiJr~iicaIEle trot ect nology: Quo Vadis? rtm.r.-nir dnielopmenl of the moderii el<.cl Its tecwsurhr Is ouniiied. The UP o f the tie< mnipiinil to ,>IhnIkmil knkor: (he pl:iwna rc Ihi w&i<rim c f the (he&.:docbpde is humr:~ porrlians i si:nd<Wtic de:uorqety arid the .,n iiimmd, ilono wlUi a unimiry df wmc curre, &eclion m d wavefonri &encra<ing technique in ~!ttnontntn of e l ~ t i o s u r g bgnmtow. l 1 INTRODUCTION HILE the u x o f ,electricity in tlicrag o t ssrvati\t,Iy dates back to the 161ti cm ilation f o r the application oEelectricai i :tiiii+s wiis hid hy d'/monval 3 c e i i t u i reIiorti:d his expeiinien tal observaiiiin rn: : 1 aliovc 113 kHz coiild be passed 1lirou:h h u t i:vMence o f pain or nsuroniu+wl;i W h therinal i:ffcsts were noted [ Z ] . I i wwtniteil an alcc:tricai appwtus that , I r I m t niodernti: voltages: he camductad r ':til oxpenrnentr with ar imalr and is,olatId ~urat:iona131. Siimiiltanwudy, Teda a:;< Wion coil systcnis w h r h produced m1.c 11: N.ii(ebchmidt. ir 11191, dsmonrtrs':% :in8 t:l'l'wti of h$i-lrequency currcnts t ',I ':lculat<iiy diseaires a i d waa amoris : h( <$ medicine ccmy[II.thercal cnts in surgical ater. In 1891, ilternating cur. ir human body . t h u l d i o n , al. 9 3 , ü.4rsonval uccd large curiher of phyaiowe and muscle idin developed iigher voltages, he efficacy of eating articular irst to use the iliucript icceived July 30 l984:1cvired Ssp I:/ :r11.1984. 1,: author i.1 wilh lhe Ik{imment of 171,:cir ..I i d Compuisr 113.524. O0 i E" r . .. Technicalnote n i +) Digital temperature controller for low-temperature light microscopy i M. R o s e n t h a i Division of BioEnginesnng. MRC Clinical Research Centre. Harrow. London HA1 3UJ. England W. F. Rail’ ARC lnslifule of Animal Physiology. Animal Rtaaarch Station, 307 Huntingdon Rosd. Cambridge Cü3 Wü. England KeywordkCircuiC Control system, Cryomicroscopy, Tempersture Med. & 8iol. Eng. & Comput. 1984. 22.471 -474 )5 over the range 0.25 to 4 250’Cmin-’ and allows the specimen temperature to be held at any desired temperature between =: -150 and +40cC. PERATURE light microscopy or cryomicroscopy is a tool for examining the deleterious erects of freezing awing on biological milterials (LUYETand PRIBOR, LER et al.,1976 MCGRATH rr al.. 1975; RALLet al., 2 M e c h a n i c a l heater s t a g e need exists for a simple. reliable cryomicroscope REID(1978) described the construction of tiie mechanical hich permits a high degree of flexibility. Cryoheater stage. Briefly. the stage consists of a machined brass design can be separated into two parts: block through which cold gaseous and/or liquid nitrogen circulates (Fig. I). The brass block is attached to the “y mechanical stage which is mounted on a light microsubstage of a light microscope. Heat conduction between the scope and couples the heater to the specimen block and the substage is minimised by a thin piece of an electronic servocontrol system which allows the Styrofoam and the use of nylon screws to attach the block to specimen temperature to track a programmed temperathe substage. A slide-heater assembly (Fig. 2) is placed on top ture against time profile. of the block. Electrical insulation is provided by a piece of (1978) decribed a cryomicroscope which incorporated clingfilm (or household plastic wrap). ust mechanical stage and a motor-driven potentiometer The beater slide is constructed as follows. First, a thin film ce temperature ramp. We now report a of chromium metal is vapour-deposited onto one side of a ign which couples Reid‘s mechanical glass microscope slide (75 x 25 x 1mm). Then a l2mm wide gitally generated reference temperature. section in the middle of the slide is masked and a thick layer gn permits programmed cooling and warming rates of copper is vapour-deposited on the chromium. The resistance across the chromium section of the heater slide should ideally be within the range 150-25OQ. A foil copper/constantan thermocouple (No. 20108-1. Rdf Corp.. Hudson, New Hampshire, USA) is placed on the uncoated side of the slide and sealed under a 22 x 26mm coverslip using a clear histological mounting medium (e.g. DPX). Electrical contact between the slide heater and controller is made by attaching a thin sheet of copper foil to the edge of thermocouple \- coverglass 1address Amerrcan Red CJOSS Blood Research Labomtorrss, ,”*‘ecelved 13rh Sepremner and in lrnnl form 7th November 19H.3 l%IE %al 1% a Biological Engineering Computing September 1% 471 ‘., f i g :. \ t ! t , w \ l ~ h e\olt:,gc I uliciii.i:iL. u:.igr;im h c t w c i . i i i t i c Iir.:it<r-\liJc (u) to produce an accurate amplified version of the iher- mocouple voltage ( h ) to produce a reference voltage in the form of a linear ramp with a programmable rate of rise and pdii and the íacility to hold the ramp voltage at any preset level (c) to compare the amplified thermocouple voltage with the reference voltage in a servocontrol loop and provide sufficient power to the stage heater to minimise the diíTerence between these voltages. bier slkie ct7mple1e sysl jiiiiction ihcld in liquid n i t r i w n at 196 )is ampliíicd h! A l w i h J t a slide tempcr.iiurc or +JO I V output. Thc amplifier cmplo!cd fin this task is Inicrsil lCL7M)I. Hhich is a monolithic chopper am with a stable offset koltapc ttempcraturc cw < O-I/iV c - f ) . The programmed ramp voltage is derived írom a 34 upidown counter clocked by a variable rate astable 3-digit BCD digital-to-analoguc convertor. The cl can be any of 10 preset values to yield the desir of coolinglwarming. The user can sei the upper and lower l i cool/warm cycle by using two sets of BCD switches. The siage temperature can be held i either of these limits. A temperature ‘hold’ posit obtained in the following manner. I f the cool/warm (upidown) is in the warm position, one input of gate A high. When the output of the BCD counter is equal setting oí the upper limit switch, the output of magnit 3‘ ani 10‘ gal eqL ma hiF 3.2 A ami volt slid1 refo to II In was the Iran: heat, ad@ over: lider temp I I coi . - relircncc 3 Electronic circuitry 3. 1 G m , r u l schiwi. The design objectives for the heater control circuit are as roiiows: !!IC ihcimi~c(>uple andem. must Th heate lLl2 Whei ihan SWitCI the to & lyi l prod i perioc hold geld iempe gain c 4 op4 4.1 Fig. 3 Schemafic diagram of rlie hearer controlcircuit ; 1; o Fig. 4 Circuit diqrants oii*oseri-oconrrolloops rlioi supplJponer I O the slide hraier b ’ P, We durin@ @!Ter 11 We amhient !e\;! \vhi!e t i e su5stay is coo!ed and final preparations made before controlled cooling and wmni::~ 4lternati\el>. specimens can be sealed between two covzrglasses and cooled Ie.g. quench frozen) belore transfer onto a precooled heater slide and then examined duriii- warming. red ra:C I. to, I:? nbulki nite!). 31 ,¡tic i) 2 s$...ch 4 is held II te.'hc ign: d e .\ servocontrol loop uiis achieved by comparing the lmpliíied tlicrniocouple voltiige with the programmedramp idtape in ;iniplitier A 3 :ind supplyingsufficient power to the \lids heatcr to eniiblc thc stase temperature to track the :eference \olt:ige. Two methods were used to supply power :o the heater in response to the output of A3 (see Fig. 4). in the initi:iI system (Fig. 4dI.a DC supply for the heater ras used. Thc operator sclects the total voltage available to :he heater uith an extcrniil potentiometer. A buflered :nnsistor driver then controls the Dower dissioated in the beater. To achieve proportional control, the gain of A3 is idjusted such that at 'hold' temperatures there is minimum uvershoot. The resultant pseudoproportional control provides good temperature control at a particular brass stage temperature. but the gain of A3 and/or the heater voltage must be readjusted ifthis is changed. The Iatest circuit (Fig. 4h) couples a 50V AC supply to the hater. Control is achieved using a zero-voltage switch ich triggers a triac ina proportional-controlmode. he voltage at point 0 of Fig. 46 is at a lower voltage e bottom of the internal ramp of the zero voltage the heater is on. and when the voltage is higher than of the internal ramp the heater is ON.Voltages at point between the bottom and top of the internal ramp bursts of power to the heater. The internal ramp adjusted to give optimum stability of the stage at a temperature. This circuit arrangement was found to better stability over the whole range of brass stage atures without the need for further adjustment of the f A3 or thc supply voltage. 4.2 C~litir~irioii re.m REID (1978) has described the use of aqueous salt and sugar solutions with knoun melting and eutectic temperatures to examine the capabilities of particular heater assemblies. Such calibration tests permit measurement of the difference between tlie temperature of the specimen and the temperature of the stage thermocouple. temperature gradients in the horizontal (across the field of view) and vertical directions, and the rates of cooling and warming under various conditions. Operation of the cryomicroscope ucticd ciiiisiderurii>iis 9r I W have examined a wide variety of biological material Cering and thawing over the past five years and can following practical advice. ve mounted our cryomicroscope stage on a Wild roscope equipped with phase-contrast optics. The kness of our machined brass block assemblies (9 or 1 requires the use of a long working distance conThe voltage of the thermocouple in the slide-heater ly is continuously measured with a potentiometric er. Recorders capable of steps of 100 per cent zero event markins are particularly useful. Records oí rance o í a variety of specimens during cooling and h3\e k e n m:ide on time-lapse videotape. 16mni m and or ZSmm photographs. buildup oí írost on the brassstage and spewimen slide 'n interfere with observations. especially when low xioling :ind warming or entended holding periods .red. O n e wlutiiin is to cnclnse the brass stage land the niicroicopc ifnccesaryl in a plastic hag and h.y urth <Ir> .¡ir <iri i i i r o p ~ Entry port>in the ha)! .W tilc iiiCid~~ip_ o h:llllpie~. i adling .ind cirientaiiiin <,í\ample>on ihc rlidc ib hesi ishcd uheii iiic bra>, ?iage I I J t amhient tempera~ c i m t r ~ ~i .Itkn rni.tint.1111the ,.implc temperature ai I6 Biological Engineering 6 Computing Oneexample oíacalibration test isshown in Fig. 5. F'irsta small drop of a I 5 per cent weight NaCl solution was placed directly on the centre o l the heater slide assembly and a coverolass placed on top. The controller was adjusted to maintain the temperature of the sample at ?O C and sufficient cold giaxous N, was then passedthrough the hrass tag^ to cool and maintain the substage at -60 C . Thc controller was then adjusted to cool the specimen at I C min and a series of photographswere taken us ice and eutectic salt cr)stals grew into a field of view approximatel) 400Iim from the thermcuiuple junction. Ice cr\it.ih appeared uhcn tlic i d thermocouple indicated .I tcmpcr:i[urc <\¡ - 9 5 í. 1 1 . i ~ i d i Thc pubihhed freeiing p<i;nio1 tk,i, September 1984 - ~ ' 473 wiiition I* - ii ( iHt~i, <I <I:.. i L h ? i . u I , i L b nJir.i::. .i timpcrature dilTcr<:ncc< i f 1 5 (' hcturcn ihc t h c i n i < u ' i i p ! r . and the ohscr\ed lield oí l i e u . O n continued coding !he quantii! oficc gradual¡) increases 1Figs. Sh and, I. and upim reaching a thermocouple temprature oi -23 5 C- small dark crystals of eutectic salt INaCI~?H,O)and ice formed between thc large ice crystals IFig. Sdi. A puhlished eutectic temperature of - 2 C I D A M rt u/.. 1962) indicates that a constant temperature dillerence of 1.5 C was maintained between the thermocouple and sample during cooling. The controller was then adjusted to harm the sample ai 1 Cmin- and the crystalline materials melted at the same temperature ai which they formed. The constant temperature difíerence (1.5 C) therefore permits the accurate determination oí the temperature oí this sample horn the measured thermocouple temperature during controlled cooling and warming. ' Acknodedymrnts-We thank Professor Heinz WolR lor providing research facilities and J. Baker for consultations on the circuit . IiEI. rR4NZhCTlCNS ON tllOMEOICAL ENGIKEERING. VOL. RME.34. NO. 5. MAY 1987 c9 375 A Whole Body Thermal Model of Man During Hyperthermia hyperthermia procedures complained of pain at particular areas of the body outside o f that being treated by the regional applicator. Significant increases in cardiac output during regional hyperthermia have also been described [3], [4]. These clinical findings illustrate the need for a whole body thermal model o f map, adapted for hyperthermic conditions, which can aid in predicting the hot spot locations and @e extent of cardiac stress. Several mathematical models have been formulated to describe whole body heat transfer in man [5], [61, [7]. One o f these models has been applied to hyperthermia [8], [9], [IO] but the simulations did not include surface cooling with sprayed water and a circulating water bolus which may be used by the clinician to decrease patient discomfort during a treatment. Also, the effects o f nonlocal, or “aberrant,” energy deposition were not considered. INTRODUCTION Aberrant heating is especially significant when frequenHE use o f hyperthermia as an adjuvant cancer therapy cies below 1 GHz are used to treat deep-seated tumors. has been documented by many research ‘groups [ 11. Results from a three-dimensional block model o f man [ 1 1 1 Recent studies have shown that hyperthermia treatments’ are used in the present study to determine theoretically the administered in conjunction with radiation therdpy and magnitude of nonlocal heating during regional hyperchemotherapy can be effective in reducing tumor size and thermia. ultimately eliminating the tumor. This laboratory is curThe objective of this investigation is to quantify the rently developing a system which utilizes electromagnetic systemic physiological response to regional heating using energy in the radiofrequency (RF) range to induce hyper- a whole body thermal model of man. Theoretical calcuthermia in humans. The applicators being considered for lations of R F energy deposition throughout the body, acimplementation of the hyperthermia treatments are the counting for aberrant energy, are input into the model so miniannular phased a m y (MAPA) and the annular phased that the effect o f this phenomenon can be observed. The a m y (APA), which are manufactured by the BSD Medi- various cooling methods needed to maximize patient comcal Corporation. fort and minimize increases in cardiac output, thus inThe development of a safe clinical hyperthemiia pro- creasing patient tolerance for torso heating, can then be tocol requires a priori knowledge o f the effects o f R F evaluated via this model. energy deposition and surface cooling conditions on regional temperatures, blood flows, and evaporation rates. I. OVERALLHEAT BALANCE EQUATIONS It has been reported [2)that patients undergoing clinical In this model, man is subdivided into 16 body segments: head, neck, two upper arms, two lower arms, two Manurcnpt rcccivrd September 10. 1986; revised December 1. 1986. This work was pcrfomed hy the authors as pan of their employment by hands. thorax, abdomen, two thighs, two lower legs. and lhc US üovcrnment and as such h i s piper ir not subject to US copyrighi two feet. All o f the body segments are considered cylinPmtecti<in.The opinions in this paper am solely those of the authors and do no1 n e i c i ~ n l yrrlieci official HHS opinion. Mention of trade names of drical in shape, except the head which is assumed to be c o m m c ~ c ~ npnrlucir I d r r i nul constitute cndorrcment or mcominendstion spherical. in addition, there is one central blood comfor “IC by HHS partment. Each body segment is further subdivided into C , K . Cham) rod R . L. k v i n afe with Biomedical Engineering and InrtNrncnidi!<inBranch. üiuiriim of Research Services. NiH. Bcthesdn. four concentric layers; namely, core, muscle. fat. and hlD 208’4: rnd the Vcprninent in¡ Biomedical Engineering The lohnr Hopskin. Thus, there are a total of 64 body elements plus one kin5 Unirrrwiy Schrwl <>¡ CIcd~cinc.Biliim~rc. M D 21205 central blood reservoir. Each body element “ i ” ( I 5 i M. I. Hdyminn 13 with Dcpnnrnent of Elecincil Engmcenng. Florida 5 64) is characterized by a temperature ifi 1, volume Iniematwnr~~ k v r r w ~ . FL u t 9 9 V(i),s u r f a c r a r e a S ( i ) , d e n s i t y p ( i ), specilk h e a t c ( i ) , IEEE L o p ‘iiiinhcr $ b ~ l ; ! : d Ah:ifnwf-A whole body thermal model or man hrs been developed the changes in re;ionil t e m p n t u m and blood llowr during hyperthermia treutments with the minhnnular phased array (MAPA) and :,nnular phased army (APA) applkatoorr. A model al the thermoregiilstory response lo r q i o n i l heating based w the experimental and ounierical studies ot others b u bmi lncorpontcd into thls study. Experimcnidly oblained energy de*position pittrrna aitUn a human leg erpwed la lhe MAPA were in@ into the model and the mulla were compured to those based upon a thmretical depoaltion pattern. Exposure o í the abdomen to the APA WM modeled with and without the oberrnnt energy depositlon that k M been described previously. Results or the model reveal that therapeutic heating ( 742°C) orextremity roil tisuc sarcomas is possible without signiíkant systemic heating. Very high bone tempcrutureo ( > S O T ) were ohtiined when the erperimenbI uhuirplion pattern was u d . Ciiculiiions show that rystemk heating due IO APA exposure is reduced via evaporative spray cooling techniques coupled with higb-velocity amhicut air Bow. 10predict T r . -. 1.30 4 42 0.01 16 0.060 I .m 1.01 1046 6.97 0.0016 0.050 1.w 10.46 0.001I 0.400 1.36 6.81 0.0013 o 1w 7.52 om28 o 800 1.10 9.11 0.w11 0.100 11.41 3.21 I .w 10.46 ... ... ... ... thermal conductivity k ( i ), electrical conductivity u( i ), basal metabolic rate Qb(i ), basal evaporation rate Eb(i ), and basal blood perfusion per unit mass o f tissue wb(i ). The blood compartment is characterized by a single temperanire Tb, volume density pb.and specific heat cb. Values of these physical propenies were obtained from the literature [7],[i2] (see Table I). The energy balance equations for the body segment “j” ( 1 c j c I6)are I) core: v,, - 3) aT(4j - 3) at = Q d 4 j - 3) - Q m d 4 j - 3) + + Q,(4j - 3) - E(4j - 3) + Q d 4 j - 3) + Q,I 2) muscle: C(4j - 2) aT(4j - 2) at 3)far: C(4j - i) W(4j at - 1) 0.0 0.61 0.81 O 79 C(4j . 0.0 0.39 0.0012 -1. 4) 1.86 o01 4.27 0.0 . 10.55 1.0 14.22 0.81 . 5.19 c.0 0.11 skin: + Qmet(4j) - E,pny(4j)+ + Qd4j) - E(4j) - Q,, where C ( i )= V ( i )* p ( i ) * c ( i )and Qconv is the heat transferred to the tissue by convection with the perfused blood (see Section 11). Qcodis the heat transferred between tissue layers by conduction (see Section 111).Q, is the rate o f metabolic heating (see Section Vil). is heating by muscular work (see Section VI-B), Qñ is the rate of electromagnetic energy deposition (see Section V), E is the evaporative heat loss from the element (see Section VIII), Qpnl is the heat exchange between the lungs and the blood in the pulmonary system (see Section X), Qcnv is the heat loss from the skin layer to the environment via convective heat exchange (see Section IV), and ESP”>, is the heat loss from the skin layer to the ambient air via externally applied water on the skin (see Section IX). Each body element is also characterized by a “setpoint’’ temperature. The set-point temperatures are determined by the method described by Stolwijk [SI. Under steady-state conditions, with thermoregulation turned off, zero RF-energy deposition, and basal metabolic and evaporation rates, the 65 energy balance equations (see (I)(4), (9)) are solved simultaneously under a set of thermally neutral ambient air conditions (29°C. 20 percent relative humidity, O. 1 m / s ) . The resulting set of 65 temperatures are the set-point temperatures. 11. CONVECTIVE (VIA PERFUSION) HEATTRANSFER TERM Convective heat transfer occurs between the tissue element “i” and the blood which perfuses this tissue according to the equation Qcon,(i) = p ( i ) * v ( i )* * (Thgn(;) - (ph * 4;)* c h ) Th.nil(i)) (5) I \RN\’ rt Lil’ rllERM.AL MOIIEL OF MAN DURING HYPERTHERMLA ’>. here h e sul>~cripts“in” and “out” represent the prop- cilies iolthe Iilood entering and leaving the body element, r:,\peciively Assuming complete thermal equilibration kctween the iissue element and the blood leaving the eleI,. cnt: Tb.o.(i) T(i). (6) 11is also assumed that blood enters each tissue element at ~;t,csame teiiiperriture (¡.e., there is no preartenole heat i:r;insfer with the arterial blood) so that = Tb.in(i) (7) Tb. 311 L ( i )is the length of element “i,” and rl and r2 are the radii at the midvolume and boundary of element “i,” respectively. WITH THE ENVIRONMENT IV. HEAT TRANSFER The ambient air conditions (temperature, velocity, and relative humidity) are inputs to this model, as are the conditions for heat exchange with a constant temperature water bolus which surrounds the area treated by the applicator: Q...(j>= W j ) ‘I’liUS, Q d i )= d i ) * v(i)* ( P b * 4 i ) * c b ) * (Tb - T(i)). * (T(4j) - T,) + H d j ) *So‘) * (T(4j) - &)l. (8) ‘The temperature of the central blood compartment is calciilated by assuming that there is no postcapillary heat tfitnsfer with the venous blood and that the venous blood i i well mixed in the central blood compartment. The heat belance equation for the blood may then be written as (14) H i s the heat transfer coefficient between the skin element and ambient, while i f b is the heat transfer coefficient between the skin element and the water bolus. H( j ) is determined via the following expression [51. H ( j ) =(H,(j)+ H c ( j ) * 3 . 1 6 * v o 5 ) * S ( j ) (15) where H, is the radiative heat transfer coefficient in W / m 2 . “C between the skin and the surrounding surfaces, i f , is the convective heat transfer coefficient in W / m Z “C between the skin and the air, v is the air velocity in m/s, and S is the surface area of the body segment. The water bolus heat transfer coefficients are estimated as . * ( T ( i )- T b ) - QWl. (9) ’rile value of u( i ), a function of local and body skin tempcratures, is determined by the thermoregulatory model ilcscribed in Section VI. 111. HEAT TRANSFER BY CONDUCTION Heat is assumed to be transferred by conduction within a body segment in the radial direction only. Axial coniliiction between adjacent body segments (e.g., between the hand and lower arm. head and neck, etc.) is neglected, and azimuthal symmetry is assumed within each element. The heat conduction between two radially concentric body r:lements is modeled by the equation (10) = G d i ) * ( T ( i )- T(i + 1)) where Gem( i ) is the effective heat conductance between (issue elements “ i ” and “ i 1.” The effective conductance between two adjacent tissue elements is a funclion of their geometries and thermal conductivities and can be determined by the series addition of the individual conductances of each tissue element based upon the dislance between the tibsue boundary and the midvolume radius of the element. Consequently, &(j) = iO*Hc(j). (16) Values of H,and H, for the 16 body segments were obtained from the literature [5]. V. ELECTROMAGNETIC ENERGY SOURCETERM The RF energy deposited within a body segment “j,” Qdep( j ) , is assumed to be subdivided into the four tissue layers based on a volume-electrical conductivity product weighted average, i.e., Core: QoId + G ( i )= 4ñk(i) l/rl - I/r2 G ( i )= 2 ñ k ( i )L ( i ) In ‘rhere k ( i ) IS r./rl for a sphere (12) fora cylinder (13) ihr themiill c~inductiviiyof element “i.“ (17) Muscle: Skin: where VS( j ) = V ( 4 j - 3 ) * o í 4 j - 3 ) + V í l j * o ( 4 j - 2 ) + Ví4j - I ) * o í l j - 1) - 2) vía¡)* o ( 4 j ). Experimental values of the subdivision of RF energy within a human lower leg were also used for the case of MAPA exposure. . Vi. MODELOF HUMANTHERMOREGULATION A. Conrrol of Skin Blood Flow The expressions used to describe human thermoregulation were obtained from a model developed by Stolwijk 151. Based on this work, the vasodilation and vasoconstriction o f blood vessels in the skin layers depend on an "integrated" whole body skin temperature signal, the hypothalamic (;.e., head core) temperature, and the local skin temperature. The skin temperature signal for a body segment "j," represented by the parameter ERROR(4j). is calculated for the 16 skin elements as follows: ERROR(4j) = T(4j) (211 - Ts,(4j). All positive values of ERROR ( 4 j ) are summed to form the parameter WARMS, while all negative values of ERROR(4j) are summed and set equal to the parameter COLDS. Each ERROR ( 4 j ) term is weighted according to the factor SKINR ( j ).which is proportional to the density of temperature receptors on the skin o f segment '>." WARMS c ERROR(4j) * SKINR( j ) J-1 COLDS 16 = - c ERROR(4j) * SKINR( j ) J=I ERROR(4j) + SKINV(j) * DILATI(p(4j) * Y(4j)) 1 + SKINC( j ) * STRlC (27) where wb is the adjusted basal blood flow (see below) and SKINV ( j ) and SKINC ( j ) are weighting factors which are proportional to the density o f vasodilation and vasoconstriction effectors on the skin element "j." respectively. Based on published reports 161, 171, regional blood flow depends on the local temperature as well as the central command described in (27). The relationship used in the present model is that the basal skin blood flow is doubled for every 4.5 "C increase in local temperature above the set point temperature of that element and halved for every 4.5 "C decrease in the local temperature. Therefore, * 2,0ERRORí4j)/4.5 . (28) others [6]. A first-order exponential equation was denved which predicís the change in skin blood flow as a function not only of skin and brain temperatures, but also of time. ERROR(4j) < O. This is the same approach used by Wissler [6] to model the delay in human cardiovascular response. For the time (23) step "n" * ERROR(I) - 5.0 * (WARMS - COLDS) (24) DILAT SWEAT + 29.0 * (WARMS - - u., u, w,- I - W", = exp ( - A t / r ) (29) where , .u is the desired skin blood Bow predicted by the original thermoregulatory model as a function of skin and brain tempekture only (which represents the perfusion after infinite time), A? is the duration of the time step, and r is a time constant. B. Control of Muscle Blood Flow Muscle blood flow can be increased by either a central shivering command, based on Stolwijk's themoregulatory model, or a local controller, which was not included in Stolwijk's work. All of the hypenhermia simulations (25) assume that the patient is at rest, so any muscular work is due to shivering. It is reasonable to assume that there is no shivering in the basal case or during a hyperthermia treatment. Thus, in this model the muscle blood flow depends only on a local control mechanism. COLDS) As reported by Sekins et al. [13], the blood flow to (26) muscle during a hyperthermia treatment depends on the * ERROR(I) + 7.5 * (WARMS - COLDS) = 320.0 *ERROR(]) wh(4j) The skin blood flow model described above, which is in(22) dependent o f time, was modified according to the work of STRiC = 117.0 .-- >O The parameters WARMS and COLDS, together with the head core ERROR value, ERROR(]), are substituted into three control equations to determine the efferent command signals: = -5.0 44)) 44j) =44j) 16 = where STRIC is the vasoconstriction command, DILAT is the vasodilation command, and SWEAT is the sweating command. DILAT and STRlC are positive valued parameters used to calculate the deviation in blood flow from the basal condition in the 16 skin elements: CHARNY <I al: THERMAL hlOl>FL O F H A N DURING HYPERTHERMIA local muscle temperature. but not in the same manner as the skin blood flow model described in Section VI-A. Muscle blood flow remains at a basal level until the local muscle temperature reaches a “critical temperature” of 43 “C. Once above this temperature, the blood flow to the muscle seems to increase linearly with time according to the expression wh(4j - 2) = wh(4j - 2) + B(fh) - rO(4j- 2)) * rh *( (30) - 2 ) - E((.) * [Ter - T0(4j - 2)) * r. * SWEAT * 2 . 0 E R R O R ‘ ~ i i I . * . O C. Controlof Other Blood Flows The blood flow rates to the core and fat layers of the 16 body segments are kept constant at the basal level during the course of all simulations. Cardiac output is determined by summing all local perfusion values. Blood flow to the thoracic core element is assumed to be equal to the cardiac output. VIL METABOLIC SOURCEHEATING The effect of local temperature on metabolic heating is included in this model. Based on data from the literature [15]. the rate of metabolic heating in an element is assumed to increase approximately 7 percent for every 0.5”C increase in temperature above the set point of the following element Qmet(;) = Qh(i) I I ~07ERRORl,i/O.J j ) )* (32) VIII. EVAPORATIVE HEAT Loss TERM Heat is transferred by evaporation from the 16 skin elements to the ambient air according to the thermoregulatory control equation f«r total sweating (see Section VI-A). The rate of sneating is assumed to double forevery 1°C increase in local tsnipcraiurr ahwe the local set point [SI (H(j) W (3.1 where PSbnand P ., are the vapor pressures of water 11 mm H g at the skin and air temperatures, respcctivel/ which are functions of temperature and, in the case I): ambient air, the relative humidity. In this model, seg ments which are covered by the water bolus cannot lose heat to the environment by evaporation of sweat. Heat is also lost by evaporation of water from the lungs (¡.e., thorax core element) to the ambient air. The evaliorative heat lost via this route depends on the ventilation volume and vapor pressure of the ambient air. Mitchell [16] relates ventilation volume to overall metabolic rate as follows: -M * 0.0023 * (44 - Pa*) (35) where Elung is the rate of respiratory heat transferred from the lung in W , and Qmc,,body is the total body m,?tabolic rate in W , i.e., E- = Qmt.wy 64 Qmet.~y off. The perfusion is held constant once the basal level is reached. (331 where SKINS (j)is próponional to the density of swra glands in the skin element of segment “j. “ The heat Ics from a skin element to the ambient air is limited by t:i, following relationship [5] .(31) where r. is the elapsed tinie after the R F energy is turned I E(4j) = Eb(4j)+ SKINS (j) E,, (4j) = (Pskln- Pur) * 2.14 *< where wh is the perfusion to muscle in the RF-heated segment “j,” B ( q , ) is an empirical factor, T,,is the critical temperature, To is the steady-state temperature of the heated muscle element prior to R F heating, and th is the elapsed time after the RF energy is turned on. Upon increasing the blood flow to this heated region, the local temperature drops and eventually falls below the critical temperature. At this time, the muscle blood flow is held constant at a new steady rate. w,. The resulting temperature profile is the “Type 11” response described by Roemer et al. [14]. Once the RF energy is turned off, the muscle blood flow remains at the elevated rate w, until the muscle temperature falls below 39°C. The muscle perfusion subsequently decreases with time according to the equation wh(4j - 2 ) = w((4j .5 = Qml(i). i-1 (36) IX. EVAPORATIVESPRAY COOLING Whole body cooling can be accomplished by spraying the skin surface with water. The rate of evaporative cooling depends on the skin temperature and the air velocit;d and temperature according to the expression: EmY(i) = h, * SPRAY (A * S(j) * (P,ktn - P,) (37 I where h, is the evaporative cooling heat transfer coeffi . cient in W/mm Hg m2 and S P R A Y (j)is the íiraction of the segment surface area which is wetted. The heal transfer coefficient was obtained from Cooney [17]: . h, = 14.7 * > 0.50 m/s 11.2 * voZM u < 0.50m/s v h, = where v is the air velocity in m/s. (38) (39) X. PULMONARYHEATEXCHANGE In the pulmonary system. the heat transferred ktween the blood and lung is assumed to be governed by ani equation of the form the cardiac output) and ature. Tungis the thoracic core ternper- the hone and XI. METHODOF SOLUTION The changes in tissue perfusion and heat lost by evaporation, both of which are dictated by the response of the thermoregulatory model, are substituted into the governing heat balance equations ((1)-(4), (9)). Similarly, the various heat transfer terms described in Sections 11-V, and VII-X are substituted into the appropriate energy balance expression. The coupled 65 first-order ordinary differential equations are solved for the temperature in each element as a function of time on a VAX’-I 1/750 computer using a finite difference method of solution. XII. RESULTS A. Extremiry Heating In order to evaluate the thermoregulation of skin blood flow, immersion of the forearm in a hot air chamber was simulated. It was necessary to use a nonzero value of 7 in order to fit the experimental data of Johnson et al. [it?]. With r equal to zero an unrealistic response was obtained as shown in Fig. 1.The change in skin blood flow upon immersion was therefore recalculated with a nonzero value of 7 and compared to the original, time independent model and also to the experimental data of Johnson et al. (see Fig. 1). Blood flows obtained with 7 set equal to 12 min were in good agreement with the experimental data. A simulation of the thigh heating experiments presented by Sekins (131 was performed using the first-order skin blood flow response and the muscle blood flow response described in Section VI-B. Power of 200 W was deposited into the thigh for one hour, starting at time zero. A& at 5°C was blown over the thigh during the heating period as well as IO minutes prior to heating (not shown) in order to match the conditions of the experiments. The energy was subdivided into four tissue layers according to the theoretical method described in Section V. The muscle temperature and blood flow predicted by the thermal model are represented by the solid lines in Fig. 2. Inspection of Fig. 2 reveals that good agreement is found between the numerical predictions and experimental data when 6 is kept constant at 1.0 ml/minz/ 100g/OC. Experimental data were not available for the time after 20 min of heating due to limitations of the Xet3’ washout technique employed by Sekins 1131. Figs. 3 and 4 display the temperature profiles within a lower leg during simulations of MAPA exposure. Power of 200 W is deposited into the lower leg at time zero. This energy is subdivided into the four tissue layers in two manners: according to the volume-conductivity product weighing described in Section V, and based on experimental data. Experiments by Charny et al. [I91 measured the time rate of temperature rise in an amputated human leg during RF-induced hyperthermia. The specific absorption rate (SAR) values calculated from these data revealed that 14 percent of the total deposited energy is in IO percent is in the fat. The energy depositions computed by the two methods are Compared in Table 11. The rate of blood flow to the hone. which is not under thermoregulatory control. is based on t w o different literature values IS), 171. In these simulations. the leg is surrounded by a 25°C water bolus which is built into the MAPA. The water bolus is removed from the lower leg surface at the end of the one hour heating period. The ambient air is at 30°C. O. 1 m /s velocity, and 20 percent relative humidity. Fig. 5 shows the effect of lower leg MAPA exposure on whole body parameters given the conditions of Fig. 3(a). The whole body response is similar for all four of the cases shown in Figs. 3 and 4. In these simulations, the RF energy is deposited only into the lower leg segment. Based on the calculations of a three-dimensional block model of man [ 1I]. there is some aberrant energy deposition during MAPA exposure of the lower leg, mostly in the thigh and foot of the treated leg. However, this aberrant energy deposition does not significantly change the whole body response to MAPA exposure. B. Abdomen Hearing Hyperthermia treatments in the abdomen were simulated via a IO00 W deposition into the abdomen segment. This power was subdivided within the abdomen layers by the VS product weighing method. Fig. 6 displays the whole body response to APA exposure without evaporative spray cooling. The simulations shown in Fig. 7 calculate these parameters when the patient’s limbs are sprayed with water during the heating period. As in the case of lower leg heating, the power was turned on at time zero and turned off after one hour. In Figs. 6(a) and 7(a) the ambient air velocity is 0.6 m/s. In Figs. 6(b) and 7(b) the air velocity is 1.0 m/s. Air flow can be maintained at this high velocity by a 12-inch diameter fan blowing 150 cubic feet/min. Based on the three-dimensional block model of man [ i l l , RF energy directed at the abdomen with an APA operating at 70 MHz will be deposited into the body segments in the relative amounts shown in Table Iii. The effect of this aberrant energy distribution pattern on whole body parameters is shown in Figs. 8 and 9. In Fig. 8, there is no spray cooling, while in Fig. 9 the. patient’s limbs are sprayed with water during the heating period. The air velocity is 0.6 m / s in Figs. 8(a) and 9(a), and 1.0 m / s in Figs. 8@) and 9(b). In all of the simulations of APA exposure the abdomen is surrounded by a 25°C water bolus, which is removed from the abdomen surface after the heating period. The air temperature is 30°C and relative humidity at 10 percent. Previous repons by the authors investigated the effect of applying ice packs on the extremities during APA exposure [20]. Results from the current version of this thermal model show that the evaporative spray cooling method is a more effective modality for reducing the extent of systemic heating. _" 381 c H + R ? i Y <I ril T H F R U A L MODEL OF MAN DURING HYPERTHERMIA Skin BF Response t o Immersion 30 n.o I A A 11.5 15.. 12.5 I... 1.5 C Y v> 5.0 ... 2.5 0 I I I I I 1. 2c J. 4e W W Time ( m i n ) Fig. I . Thwrcticai calculations of forcam skin b l d Raw rcsponsc to hot air exposure with a zero and nonzero lime constant. Expcnmentll dam are fmm Johnson [IS]. Muscle Blood Flow Response,to 200 4a 44 -u P E 41 4. 0 t- 3. I o I .V?. ?rp 30 lime (mini 1 200 U To Lower Leg w/theo O r f w 280 U To Lower Log wiexpt O r f I 86 Y . I I I I* n Y I u I I w w I 1 1 . 8 8 I a. (2) -O : EEz3 Y O I e 2 e Y U W O . 1 1 . 8 0 R TIme ( n i n ) n E O I- u o I I 18 2e I Y I I I u w O. I I w 1 R TIme (min ) (b) (bi Fig. 3. Tl~eorctic.l calculations of tempsnturc profiles within a lower leg exposed to 200 W via the MAPA applicator. The power is sobdivided into the four layers by the V-S weighing method of Section V. (a) Bone blwd flow is zem [71. (b)Bone blood flow is 0 . 6 5 mi/min/ 1Wg [SI. Fig. 4. S a m conditions as Fig. 3 extcpi power subdivided according to expnmenul rrsultr 1191. (a) Bone blood Row ir zcm and (b)bone blwd Raw isO.65 ml/min/100g. XIII. DISCUSSION The whole body thermal model presented here is most useful for comparing the effectiveness of various surface cooling conditions to reduce the adverse effects of systemic heating, namely elevated cardiac output and local temperatures. Due to the lumped nature of the model, regional averages are calculated rather than exact “hot spots.” Given this limitation, there are certain trends which are evident. In the case of lower leg heating, the extent of systemic heating is slight. Core and brain temperatures increase less than 1°C during the one-hour heating penod. The thermoregulatory system causes an increase in blood flow to the muscle and skin regions o f the leg. These perfusion changes result in a 30 percent increase in cardiac output above the basal level. Whole body sweating an changes in skin blood flow also act to dissipate the heat. hus, the thermal response of an extremity to regional heating is controlled not only by local thermoregulatory mecha- 4 nisms but also by central thermoregulation. Thermal modeling of an isolated leg neglects the significant effects of hypothalamic feedback control. The average temperature of the muscle element is approximately 41.5% which is slightly below the therapeutic range for hyperthermia. Considering the lumped construction of the model, this result indicates that therapeutic heating of a tumor within the lower leg can be accomplished but there may he some elevation in the temperature of the surrounding normal tissue. Since block model calculations have not been able to provide sufficient detail we have estimated the division of energy deposition into the four tissue layers by assuming that the electric field within the MAPA applicator is parallel to the tissue interfaces. According to boundary relations, the tangential component of the electric field is necessarily conserved across the tissue boundary. Thus, the SAR in each region is proponional to the electrical conductivity of the tissue. Under these conditions, only 4 W of the total 200 W assumed deposited into the leg are THARNY II 0 1 THERMAL MODEL OF MAN DURING HYPERTHERMtA TABLE II COMPARISON OF THE E'IEROI DiSTRtBUTtON WITHIS A LOWER LEG CALCULATED B Y THE METHOD IN S t X T I O i v AND OBTUSED BY EXPERIMENT - Percent energy inlo leo_tissue by V-S product weighing Percent energy into leg tissue fmm a p t . 2.0 90.5 2.5 76.0 bone muscle fat skin 14.0 I... 5.0 --E \ 10.0 IS.. - I*.. I... o) L Q + 7.. .. Nhole Body Response t o 260 U Leg Heating I.. e LL U o O Y o . a E W I m I- 1 . 2 . w u m e4 TI e* m..- o. Tlne lrnin) Fig. S. Calculations of whole body response IO 200 W lower leg heating. actually deposited in the bone. Yet this assumption still results in a notable increase in bone temperature to 4243°C (Fig. 3(a)). The effect of nonzero bone blood flow is to decrease the maximum tempe ture in this region by approximately 1°C (Fig. 3(b)).+ Experimental results obtained from studies with amputated human leg "phantoms" [I91 have shown that the deposition in bone is significantly greater than what would be found if the electric field were parallel to the tissue interfaces. When the thermal model is used with the experimental values o f energy deposition, the calculated temperature profiles are quite diffeent. Assuming zero bone blood flow results in a maximum bone temperature of 62°C (Fig. 4(a)). Given a perfusion of 0.65 ml/ min/ 10g. the bone is still heated to a maximum of 57°C Fig. 4(b)). -These calculations reveal that the bone temperature may significantly elevated during MAPA exposure. Again. the limitations of thi. model must be emphasircd. The 7 6, Tine ( i i n ) (b) Fig. 6. Calculations of whole body response to loo0W abdomen heating with no spray Cwting. Cd Air velocity PI 0.6 m/s. (b) Air at I .O m/s. bone temperature is most likely not spatially uniform. This tissue is heterogeneous in composition and its thermal and electrical conduction properties are anisotropic. However, localized "hot spots" o f elevated temperature may exist inside the bone which approach those predicted by the thermal model. Due to patient considerations, it is not possible to monitor bone temperatures during a clinical hyperthermia treatment. But experiments with the unperfused amputated leg phantoms measured similar bone temperature increases for a power deposition of 200 W. It should be noted that rJdially shifting the leg a w a y from , u , hcsd ncck tho= - sbdomcn upper arms forearms hands upper legs lower legs feet o. E o I- x 1 ~ 111 1- N-1 I Y I 1 1 I -- -.. L o I. CL *.... E o g ... ... ... 1.. I- e." --- a + Ih. b. .. I t c<- e I. m m - n .L ~e Y - 0 o O ..- 4 A I Tine (nini *- (b) Fig. 7. Same conditions as Fig. 6, b u t with spray cooling. (a) Air velocity *- 0.6m/s. @)Airat I.Om/s. rY ~ ..' I P c - ,... . the central axis of the MAPA reduced the energy deposition in the bone by over 60 percent [19].The maximum bone temperature under these conditions would be reduced from 61.6-Cto 49.3-C for the case of zero bone blood flow and from 57.0"C to 47.0DCfor the case of nonzero bone blood flow.Two cases of abdomen eating were considered: the deposition of loo0 W into the abdomen core element only, and the deposition of loo0 W into the whole body, which was distributed according to the data in Table 111. In both cases, systemic heating was found to be significant. Figs. 6-9 reveal that high-velocity air flow (1.0 m / s ) coupled R 2.0 1.o 20.0 37.0 14.0 5.5 I .5 18.0 0.8 0.2 with external application of water spray on the patient's limbs are helpful in controlling the increase in cardiac output that occurs during abdomen heating. However, thorax core and brain temperatures initially rise to high levels in both cases. Without aberrant heating (Figs. 6 and 7 ) , these regions cool off by several degrees after approximately 15min of RF heating when sweating becomes the principal mechanism for heat loss. When aberrant heating is assumed (Figs. 8 and 9).evaporative spray cooling with high-velocity air flow is effective in keeping the calculated brain temperature below 40°C. As shown in Figs. 6-9,evaporative spray cooling removes up to 200 W of energy, which is about 10 times the energy that can be transferred to a circulating water bolus around the abdomen. Exposure to high-velocity air flow during evaporative spray cooling appears to be the most effective cooling modality. Simulations in which the patient is exposed to these surface conditions prior to heating indicate that precooling does not affect the extent of systemic heating. The assumption of 1 kW deposition directly into the abdomen core increases the regional temperature to 42Mac, depending on the cooling conditions. When aberrant heating is assumed, the abdomen core reaches a maximum in the 40-42OC range. These results indicate that treatment of a tumor in the abdomen core with an APA applicator may significantly elevate the normal tissue temperature in this region. The effect of the aberrant energy deposited into the other body segments, such as the neck, upper arms, and thighs was to increase the average temperature in these body segments above 40°C. even with spray cooling and high-velocity air flow conditions (see Fig. IO). It must be noted that these numerical results could not be compared directly to measurements made during clinical hyperthermia treatments. There is little published quantitative data on whole body effects during regional hyperthermia. The core temperaures cdculated for abdomen exposure to the APA applicator are. however, in good general agreement with those of others 131.141. Similarly, the muscle temperatures calculated for lower leg exposure to the MAPA applicator agree with published * CHARNY CI 01 THERMAL MODEL OF M A N DURING HYPERTHERMIA .. -t I 385 a,.- j -F --11.. .* I... O ., Q u I E O I- I.. I... ,___. ...- rn 1.. a *.. n t.. a o.. m L O t -* O Li. 0 o O <II Tlae ( m i n i (b) Fig. 8. Calculaliona of whole body Esponse 10 Iüüü W healing with aberrant deposition and no SPRY cooling. (a) Air velocity 0.6 m/s. íb) Airs1 i m/s. . .< 1 c m I 'a U t It.. I... -re-------\ ____.___... .-._.--.. ................ I I I I I 1 <"I h i or1 <I1 I I I 8 -t -g ._____ ...". .._ .. 1 M 1.. '.., \ rir dnn ,.- u -u -- 1 . 1 1.. L I.. TI o O d Fig. 9 . Sime conditions as Fig. 8. but with 'pray cooling. (a) Air veloeity 0.6 m/s. (b) Air ai I m/s. clinical results [21]. We are pursuing collaborative work which will be necessary to further validate the results of this model. CONCLUSIONS Results from this study show that the aberrant energy that is distributed throughout the body by an APA applicator will cause significant systemic heating. The best conditions for limiting t h c estent of the systemic heating are evapontive spny cooling with water on the patient's limbs and exposure to high-velocity ambient air. Under these conditions. the calculated cardiac output during an RF exposure of 1 kW is increased to a value approximately 2.5 times the basal level. While brain and thoracic core temperatures remain below 40°C during the treatment, the average temperatures in the neck. upper arms and lower arms exceed 40°C. Simulations of exposure of the lower leg to a MAPA applicator indicate that then is negligible systematic heating. but the effect of energ) deposition in thc hone is potcntiall) dangcroii\ I lEFt THA<SACTI<>NS 386 “ . Average Temps w i t h No Aberrant Hea,t O V LlIOM1~1~IC4L F I G I I F F R I S G . \O1 RUI: U NO J ‘!*Y lVS7 Average Temps wlth Aberrant Heat I. - U n E 0 3 s I- .-. __.,--- r----__ _--.-.--._________ ,,-,.......__...-...-r _-_-_-_I. n Fig. IO. Calculated average tempcratures in three segments under the conditions of(sj Fig. 7 @). Fig. 9@). ACKNOWLEDGMENT The authors thank Dr.J.-L.Guerquin-Kern for many helpful discussions about whole body heat transfer and the related physiological effects. 1141 R. B. Roemer. 1. R. Oleson. and T . C. Cetis. “Oscillatory iemperature response 10 constant power applied to canine muscle.” Aner. J. Physiol.. vol. 249. pp. R153-RIS8. 1985. [IS] R. L. Levin, and M.I. Hagmann. “A heat and mass transfer model for computing thermal dose during hyperthermic lrealmnl of extremities,” in 1981 Advances in Biocn#inrrrin#.R. L. Spilkcr Ed. New York: Amer. Sac. Mcch. Eng., 1984. pp. 13-14. (161 J . W. Mitchell. E. R . Nadcl, and 1. A. 1. Stolwijk. “Response io REFERENCES weight loss during exercise.” 1. Appl. Phyriol.. vol. 32. M>. 4, pp. [I] C. M.Hahn, Hypenhermia and Conccr. New York: Plenum, 1982. 474-476, 1972. I21 P . F. Tumer, BSD Medical Corporaiion Hyperthermia Tech. Note 1 17 D. O. Cwoey, Biomedicol Enginruing Principlcr. New Yo& 12, Snit Lake City, UT, Aug. 1985. Marcel-Dekker. 1976, pp. 114-117. I31 B. Emami. C. Perez, G. Nussbaum, and L. Leybovich. “Regional [I81 I. M. Johnson, O. L. Brenglemann. and L.B. Rowell. “lnienctions hyperthermia in treatment of rccumnt deep-seated NmOrs pdimik w m lofnl and reflex influences on human forcam skin blood Row, nary repon.” in Hyprnhennio Oncology 1984. Vol. I . 1. Ovcgaird J. Appl. Phys.. vol. 41, no.6. pp. 826-831. 1976. Ed. Lnndon: Tiylorand Francis. 1985. pp. M)S-M)8. [IS] C . K. C h y . 1. L. Guequin-Kern. M. 1. Hagmnn, S. W.Levin. 141 F. A. Gibbs, M. D.Saporink, K. S. Gates, and 1. R. Stcwan. “ReE. E. Lack, W. F. Sindelir. A. Zibell. E. Glatstein. and R. L. k v i n . gional hypenhennis with an mnuluphased n m y in ihc expcrimnul “Humin leg heating using a mini-annular phiwd amy.” Mtd. Phw., treatment of cancer;’ IEEE Trans. Biomcd. En&. vol. BME-31, pp. vol. 13, pp. 449-456.luly/Aug. 1986. 115-119. Jan. 1984. [201 C. K. Charny, R. L. Levin. M. 1. H a p a r m . and E. Glatstcin. 151 I. A . 1. Stolwijk and I. D. Hardy, “Control of M y temperature.” “Whole boay thermal model of man during hypnhermia,” in Pim. in Handbook of Physiolop-Reocrions Io Enrironmrnral A ~ ~ D. I s , Nonh American Hypenhrrmia Group Ann. Mrer., 198% H . K. Lee Ed. Belhesda, MD:Amcr. Physiol. Soc.. 1977. pp. 461211 1. R. Olesan and 1. M. Hamlsan. “Preoperativehypnhermii and 67. radiotherapy for extremity samma: Initial msults.” in Pmc. Nonh 161 E.H.Wissler. “Mathematical simulation of human thermal behavior American Hypcnhennia Croup Ann. Mcn.. 1986. using whole-bcdy models.” in Hear Transfer in Medicine and Bid- 1221 1. R. Olesan and 1. M. Himlson. “Pmopraiive hyprrherrnia and op. A. Shitzer and R. C. Eberhnn Eds. New York: Plaum, 1985, radiothcnpy for extremity s1rcom: Initial rcsultr.” in Pror. Nonh pp. 325-373. American Hypcnhennio Croup Ann. Men., 1986. 171 R. O. Gordon. R. B. Racmer, and S. M. Hoivath. “A mathematicd model of the human tcmpcratun regulatory system-transient cold exposure response.” lEEE Trans. Biomed. Eng...vol. BME-23, pp. 443-449. Nov. 1976. I81 1. A. 1.Siolwijk. “Whole body heating-thermoregulation and modeling.“ in Physical Aspcm of Hypenhrnnia, G. Nussbaum cd. New Yo*: American Insi. Phys.. 1982, pp. 565-586. 191 R. 1. Spiegel, D.M. Lkffcnbiugh. and I. E. Mann, “A thermal model o f the human body cxposed to an electromagnetic field.” Bioelerrromag., vol. I , pp. 233-270. 1980. I101 W. I. Way. H . Kritikos. and H. Schwan. “Thermoregulatory physCnleb K. Charny was horn in While Plains. N Y iological responses in the human body exposed to microwave radiain 1961. H e received thc B.S. dcgree summa cum tion,” Biorlerrromag.. val. 2, pp. 341-356. 1981. laude in chemical cnginccring from the State UniIll1 M. 1. Hagmann and R. L. Levin, “Aberrant heating-a problem in versity o f N c w Yo&. Buñalo. in 1983. regional hypcnhemia.” IEEE Tranr.’Eiomcd. Eng., vol. BME-33. He is presently a cundidate for the Ph.D. dcpp. 405-411. APT.1986. gm in biomedical cnginccring at The Johns Hop 1121 M.A . StvehlY and S. S. Stuchly, “Dielcciric propcniesofbiological kins University School of Medicine. Baliimorr. subsiancc~-tabulated,“ J. Microwave Power, vol. 15. pp. 19-26, MD. His thesis rercnri-h is on regional and whole Jan. 1980. body heat trannfcr. 1171 K . M . Serins, “Microwave hypenhcmia in human muscle,” Ph.D. Mr.Charny was n mdpicnt ofthe 1980 Kodak disrcnaiion. Univ. Washington. Seattle. 1981. Scholars Award. L -HARM n al: THERMAL MODEL OF MAN Dqai\ I IHYP i - rL p'" . t I 387 1mplicr:tion of Blood Flow in Hypei-thermic Treatment of 7'urnors ! lishmciit aid Inigressive growth of malignant tum , x s is pilsjiiile w ! m thc supply of e s x : n t d nutrients is adeqiU.tely nlsintaineil t u o y h v ~ c u l anetworks. ~ The morpho1oy;c;il chi.;icreristics o f i a s d a r bed and the olood tlow in tuniors ha\: :>em itudiei b) a number o f investigators [ I S ] [ZO] . h i 115 tte uiitid stage of tumor growth, the tumor Cells ar: sapporrcl by the nutrierits supplied from the host m u l a turz. As tli: :ulnar mass iricieases, the adjacent venules(srnd hmt iis'ues hecome dilated and tortuous. Subsecnilotitelial CEUS (cells that make up the inner part of'Zaviileh :f h:ooil v e s s l j ) &ifthe altered host venules start to prdifeiatt:. perhaps J ) die influence o f angiogenesis factors (substaices which stimuiete tiie development arid growth of hlcoii vewlh:, froin the tumor cells as described by Folkman et xi. [21] and othcr investigators [2?]. Numerous sprouts g i w out of the hypertrophic venulesandgrow towards the tumi~r Tbe sprouts or their brariches eventually fuse, giving Bsc l o I ~ ~ o p sThe . grcwing sprouts or caiiillaries penetrate iiit<i ihe periphery of tumor and anastomose with the aiiteriot eriti of host capillaries, and then blooa begins t o perfuse tluoudi Ihe new vessels. Although most of the new capillades in tumors appear t o form from host venules as described .i')ov.:, necv;isciilarizations may also be possible at the artwioli.r site of host c:apillaries. It is gs:,ieraily helievecl that the vascular pattern is characterirtic for : x I i type o f tumor, although striking variations in the vaIcu1í.i pa:teriis can he seen, depending o n the stageof tumor grow t in the siime type o f tumor. As the tumor mass increases, 111 irc tumor capillaries are formed and elongated. The hastily for iicd new tumor capillaries consist o f a singlelayered endotlsha. wall wiih no external basement membruie. in niany tyl1i.r of tumors, tha vessels are a sinusoidal type (a form of thui-u;died blood channel with irregular sh:ipe) with interrupted lin:iig of endothelial cells. Between th,: gaps ofendothelid cells, neoplastic cells often protrude into the hIBen o f car>&iiies :.rid obstruct the perfusion o f blood. I t has been ob- : . -'' tic.ularly in the large undifferentiated tumors. One of the other striking features of the tumor vascular network is the prerenu: of to~tuous,giant capillaries, as large as 50 pm in diameter. . The wall o f such vessels is composed only of endothelial cells with some fibrous supporting tissues. These vessels are usually '- located at the periphery o f tumors and contain venous blood. these vessels may be considered as venous capillaries. -- Thus, Arterior-venous shunt is also a common feature o f tumor vasculature pattern. Occasionally, matured vessels are found in tumors, particularly in the slowly growing and highly differentiated tumors. These vessels are composed of intact and complete endothelial linings with normal basement membranes rand are supported by fme strands of collagen fibers. It should be noted that not all tumor vessels are newly formed vessels. It is of interest that the host vessels are resistF- ant to neoplastic growth and are rarely invaded by the tumor cells, but often are incorporated into the tumor mass 1231, [24]-[26]. The incorporated host vessels do not increase in -number, although the length and caliber may increase. Portions of such host vessels incorporated into the tumors eventually disintegrate together with the tumor vessels, particularly in the necrotic area of the tumors. YIn summary, the vascular network of tumors is rather different from that of normal tissues and consists of: I) capillary sprouts, 2) sinusoidal vessels with interrupted endothelial linr i n g , 3) blood channels without organized endothelial lining, 4) $ant capillaries, 5) matured capillaries with basement mem-branes, and 6) host vessels. The relative proportion o f the above components in each tumor Is characteristic of the tumor c ype as well as the stage of tumor growth. I ... I F , ! . Skin 16'c ~ - - - - FS 2. Cha water bit the use 0 Heating t i m e (min) 1. Changes in blood flow in the skin of SD rats huid with wale bath. The blwd flow meanired at the snd of heatingwith the ux D radioactive microsphsrei. The average and SE. of 8-12, meesun muairem Fip. ,,, the skin 1361 -1391. ments PIC shown. nounctd ch It43Y un md Ip tively. At 1 I .- BLOOD F m IN TUMORS Once the tumor vascular network is established and blood tarts to flow into the tumor from the host arteries, the mass of tumor increases progressively. As mentioned earlier, the .number of host arteries or arterioles seldom grows, whüc the umber and length of tumor capillaries fed by the m e host -arteries increase as the tumor grows. Such an increase in the capnetwork and an increase in the demand for blood in '-:cess o f the capacity of host arterioles would result in a deh e of arteriolar pressure. At the same time, the extravasu. lar pressure in the tumor increases as a result of the prolifera*n of tumor cells within a limited space. An increase in the I travascular pressure exceeding the arteriolar pressure results iíiregional vascular stask and necrosis. The limitation o f diffus$n length of oxygen and possibly other nutrients is believed be another cause of necrosis in the tumors (27). 'L-Whether the blood flow in tumors is smaller or larger than that in normal tissues has been an enduring question. It has I n been suggested that the blood flow through the inegul b constricted, dilated, and twisted vascular network in tumors is sluggish and retarded as compared to the blood flow in t h - normal tissues. It should be emphasized that the blood fll Iin tumors vanes with the type of tumor and the stage o f tukor growth or size oflumors. Furthermore, the distribution of blood perfusion in the tumors is quite inhomogeneous. Usuad- the blood flow i n the well-vascularized peripheral area is p d e r than that in the inner area of the tumors [24J. The - I P reported blood flow in various tumors and normal tissue varies enormously [ 191. We observed that the blood flow ii the skin and m u d e of SD rats was 7-8 d / I O O gimin an 4 5 ml/iOO g/min, respectively (Figs. 1 and 2). The blwi flow in the 0.3-0.7 g of Walker tumors of SD rats was abou 50 ml/iOO s/min, whereas that in the 2-5 g tumors was onl: 10 ml/lOO dmin (91, [281. The tumor blood flow in th' spontaneous mammary carcinoma of the moux was onl! 1-17 ml/iOO %min [IS], 1291, while the blood flow in th outer side of lymphosarcoma of the dog was as large as 1831 ml/iOO g/min and that in the inner part of the tumor wa 121 ml/iOO &in (301. In this context, the blood flov in lymphoid tumors appears to be relatively larger than tha in other types o f tumors. For example, the blood flow in thi lymphoma of the human was 38.4 ml/ioO gimin, while thi in the anaplastic carcinoma of the human was 11.4 ml/lM g/min (311. The blood flow in the Novikoff hepatoma of th~ rat was 2-5 ml/iOO g/min and that in the normal liver wa 80 ml/lOO dmin in the rat [32] or 47-120 ml/lM) dmin ii the dog [33], [34]. In humans, the blood flow in a liver car cinoma was 12 ml/lOO &in, while that in the normal live was 29 ml/IOO dmin [35]. It appears that the blood flow ii the neoplastic tissues is generally smaller than that in the cor responding normal tissues, although ample exceptions ma) exist. v-u~R By ~ y ~t The most commonly used normal tissues to study the e: fect of heat on vascular function have been the skin and mu! cle mainly because it is relatively easy to heat those tissues an to measure their blood flow. We have investigated the c h a n ~ e in the blood flow, vascular volume, and vascular permeabilit, &fold in d kidiute thi heating. The ped auad, in F nu was 7 &Owl 101.0 mlll 4S0C fa the rkin SU 31.5 d/10 about 4.fol blwd flow lt heltUig con blwd flow though the was still sbc 120 min. H h e skin bla oí OUI rnves minat43'~ Thc bloo nun (Fig. 2, c i t a d to R ~ value. al 30 and 10 alnw uvely. The i uhich was t L 1 ' ~ 11 44OC. Ur the muscle I 4 4 O C for up 11 rlrii 11 icr~::ise .I 1 . t.cwd !lo\< . , I tlii I1 1 ~ ~ 1I C,: : IZí :'I I. .~\bc~iit ! . j . f i ~ l.i o c .~E r the r n u i e blt < i t!w,, i ( i t s ~h \ I { : d after ile:itiig at 4:)' i o i cui) rriiii. <) >bseivib iiai the hloodíluu ,:. ::le $.:P. 2nd i" i i ~ e of riie 1'isc;ier rlt 1:.iezsed by 9.fold it) i>i Iifztiiig at 41.5% for 1 1 i :4(i], l)i.l:$,: et al [ d i / reFu:ts I : I? ü - i ' ~ . iir.arz.iw ir blood flou in the $ 2 n d a 1 0 i o i ~ l~I.,C,.:J;P U,t..ood ti. '.I the re)iiluaJ t i s i e s . : *e foot of die \ V . j t ~ i rrar iipon hL,.iriiie at 4 1 y fcr 1 h Tkr &ive obsarva:icir: . i f ?O-fold inarexv3 ..I the sloii blood :law A t -U"Cis strikiiirl:,,;;:eater tliari tiir ircrease,in the b i o a ~f h v we obserred in the skin o f S1) 01 Fisclier rats Iieated:;~~ 43 O or 43.SoC as d:scriberi above. D i i i son eta/. [41] fiirtl.cr re?urted that the tlood flow in thc s k i t of Wistar rats stxtati IO ,.lecrease aitcr he.itirig for I h a t J?"':, while w e observea vu de:line in blot>d flow in the skim vf Sí) rats after heatin: tkr 2 !i at 43'C (Fig. I). Steviart and Ileg,,: 1421 ~&orted that heatine at 42.5'C f i i r I h iriireaseil the 12 JEEZ TRANSACilClNSON LIlOMEDlCALfN<iI~E>.XING. VOL. E M F 3 I . N O I . JAIII'hRY 1 9 1 ~ the blood flow in Walker tumors heated at 43'C was similar vascular damage and hemonhagewere ohserved afirr heating ; I to that in the tumors at norniothermic condition. 43'C. Endrich er ai. (541 measured the velociiy of KBC's in it,: The blood flow in certain types of tumors appears to in- rhabdomyosarcoma grown in the transparent chambers in rat!. crease, at least temporariiy, upon heating at relatively low !em- When the tumors were heated at 40*C or higher temperaturei, peratures. Sutton er aL 1461 and Bicher et aL (471 reported the velocity o f RBC'$through the capillaries steadily declined that the blood flow in mouse tumors increased upon heating Stasis and petechial hemorrhage in venules and capillarier oc. at temperatures up to 41-42OC for 30-40 min, but decreased furred when heating was continued, resulting in a decreare ~fi when the heating was prolonged or the temperature was raised. the number of perfused capiliaries. The circulatory damage by Vaupei er al. [48] also reported that heating at 43°C for 20 heating at 4042'C for 60 min was apparently irreversible. A min or at 44-C for 15 min increased blood flow by 5-100 similar transparent chamber device was used by Reinhold er a¿ perceni in 60 percent of DS carcinosarcoma o f the rat. Further [SS] in their study o f heat effect on the circulation in the heating caused cessation o f blood flow in these tumors. In 30 rhabdomyosarcoma of the rat. Impairment of microcirculation percent of tumors studied, the blood flow decreased from the accompanied by severe necrosis was observed following heat. beginning of hyperthermia, while no significant change m ing at 42'C for 3 h or at 42.5OC for 162 min. Dudar and I& blood flow occurred in the remaining 5 percent of tumors. In I441 studied the heat-induced vascular changes in VX2 car. the same DS tumor, blood flow was found to be impaired cinoma grown in a rabbit ear chamber. Both the RBC velocity upon heating at 42.5OC for 100 min by Van Ardenne et al, and the total blood flow slightly increased when heated at 1491. Stewart and Begg 1421 reported that the blood flow in 42.S'C. Such an increase, however, lasted only for 10 min, and the tumors of the SAFA mouse increased slightly during the the vessels were completely occluded thereafter. Table I Jiows first 30 min of heating at 42.5'C. returned to control level the heat d w which induces vascular damage accompanied by by the end of heating for 1h, and significantly decreased 1-2 a decrease in blood flow in various experimental tumors stud. days after heating. These investigators also reported that a ied. similu decrease in blood flow occurred 1-2 days after heating in three other mouse tumors. Rappaport and Song [40] ROLEor BLOOD FLOWIN THERMOREGULATION observed a slight increase in blood flow at the end of I h heatAs described in the preceding sections, the results to date ing at 43.S°C in mammary carcinoma o f the Fischer rat. The indicate that the response of vasculature in tumors and normd blood flow, however, drastically decreased 1-24 h after heat- tissues to heat stress is markedly different. The reported dab in& Dickson and Caldenvood I411 noticed that the blood on the response o f vasculature in tumors and normal tissuts 10 flow in the Yoshida sarcoma grown in the foot of rats did not heating can be graphically compiled 89 shown in Fig. 3. Upon change significantly during heating at 42'C for 1h. The tumor heating at 41-43OC, temperatures commonly used in clinical blood flow, however, decreased when the heating was pro- hyperthermia, the tumor blood flow either undergoes no sip longed for more than 1h. It was of interest that the tumor nificant change or s l i t l v increases. uuiallv smaller than 2. -< blood flow feu almost to zero when measured 1 h after heat. fold. Indications are that ;he tumor v&kature is quite vulner. ing at 42OC for 1h, and then gradually returned to the pre- able to heat so that severe vascular stasis. occlusion, and hemheating level 12 h later. The effect of heat on the vasculature orrhage are prone to develop at 42-43'C, at least in experic and blood flow in the BA-1 112tumor grownsubcutaneousiyin mental animal tumors. In contrast, the blood flow in normal the scalp of the rat was studied by Emami er d [50]. About tissues, e.g., Uwi and muscle of rats. markedly increases upon *- a SO percent reduction in the blood flow occuned after heat- heating by as large as 20-fold. Although the heat.induced in. ing for 40 and 30 min at 41 and 42OC, respectively. More pro- crease in skin and muscle blood flow starts to subside after c nounced and long-lasting reduction in blood flow occuned heating at 4445°C for 30 min, complete vascular stasis ap ,. when heated at 43 or 44'C. We observed that the functional 'pears to occur after heafug with much greater heat dose (Figs. intravascular volume in the SCK tumor o f the mouse progres. 1and 2). The magnitude of increase in blood flow by heat in sively decreased for several hours after heating for 30 min at different organs may be different, The ratio of blood flow at 41-44OC and began to recover from 1day post-heating [9], resting stage and the maximum blood flow in different organs [ 131. [Si], (521. Histopathologic examinations o f the heated of human is known to vary considerably 156). ,SCK tumors indicated congestion o f vessels with blood ceUs, According to the bioheat transfer equation [IO) -[12], the stasis, occlusion, and hemorrhage. differential response of blood vessels in tumors and normal tis --The tumors grown in transparent chambers have been used sues would greatly affect the temperature distribution during to investigate the heat-induced vascular changes by other in- hyperthermia. Guy er aL 157) graphically showed that tumor ,-vestigators. In squamous carcinoma grown in the transplant temperature would rise higher than normal tissue temperature dhambers in the cheek pouch of hamsten, Eddy ef uL [53] when the blood flow in normal tissue is preferentially innoticed temporal vasoconstriction during the first several sec- creased. so that the blood flow in the normal tissue become l n d s of heating at 41-4S°C, followed by a dilation. During greater than that in the tumor. Fig. 4 shows our representative observations on tempera. -*ieating at 42'F for 30 min, parts of a few vessels became static. When examined 1-24 h after heating, relatively mild ture changes in the Walker tumor 256 grown S.C. in the leg of &asis, diapedesis (passage of blood corpuscles through intact SD rats and that in the muscle adjacent to the tumors (391. esse1 walls), and petechiae (a minute red spot caused by an The heating was applied with a water bath at various tempera%cape of a small amount o f blood) were evident. More severe tures. I t can be seen that the muscle temperature rose rapidly ,picC! a 2 - . ..- a Fb. 3. R and thr icmpn dati Io, tumors I . Chi or SD n 118 4. at lempo with 11 Reprcn: \iii . 9 : ti;: 1::: tl¿i il" 4:!.0"('/30 ri J j 4:!.5"<'/40 ri 1 arid then declined si&$fic.intb? within sev. $al minutes of heat.. ing at 424i'S. A p x 4 nily, die blood So ;;inthe heated mu,.. c k increased ar d ffii.4 the rote of heat dii $ationwas acoelcr.. ated, resultiiig in ffie (licreaie in tempera.)re. The higher tl:e teniperature iisi!d, %e ioiinvr the declini ti tanperature c,i:.. curre(:, inG:atiig m 1icrias? in blood f W occurred sooncr with .in inctias:. in iH.:iippiicd teinperat b~After the initid drop, the n i w l e t:irg eratux gradually .rlcreased, espeoialiy .C increase in . i e musale temper.* at ,45 and 4ó'C 'Cui.,~eciin~l ture could IY: üttrbui:d tc the hegkinii 4 of retardation af blood flow ?II the r.ipicle k8eatedat suc,i:high temperatures as sh( wn ir. liil5. 2. ap weii as ths rise «: $xdy temperature. Nt:vertheiess. the riiiSle te:r:perature w. :I about 2OC lewcr than :he teiiiperaturc,,#fheating water i i : die end of 30 min heiatkg. The tempcr3tire ciunge in the Walker tumor wiis quite differixt frorn $at in the niuscle d,.ting heating. When heated with 42 or L 3 ' C wkr, the turn temptranire rose to abaut O.!;OC be1o.y thc water temper;t$re, and remained at airnost th? same 1:mpel-atures throi.+out the heating. When heate'.l at 45 ( r 46"C, the tem.,(rature of tumors rose, irnrnediitely dr~ip~iecl, and then sOOii rose again to about 0.S"C below thc water bath temperature. Apparently. there was a short..;.ired ircrr.rse in the tumor t;lpíid flow within a few minute!; of her!.$ at 45 and 46'C, jrhich was followed by a retardation of I/iood !low, as the .levation cif tuanor temperature iiemora~;~tecl.The absence Of any indications of drop of u:niperatuit aftur the initial tis in thc tumors heated at 42 01 431 ' :. .s in .igreerrient wi:h h e Observations by us [38] and 0the.p (451, as previousl) described, that the :uinoi's remained I Oclwgad at 43'C. blood flow iri %'&ir The most úiiportiu.t c;~serv..tion in this , i d y WES that the temperature of 1-Z g tuinofi 10% signii taiitly higher than that in die iidj¿cent r t ~isrle temperature ,bring rhe heating. The above ,muh co 111: be :.ttribiited m; @ l y to the lack of apprec:iable iirid s w t 41 ed ir.crease in bli mad flow in the tumors (during heating. I1 should be rtresse<:,.howevcr.that the temperature 'af sniaüq H';ilki:r turiiort dii: not rise ai high 11 thdt Ui the larger 1un.c).s, which may be ai ,tiiiuted to the relatively large Kood 113 u. a i d thus, the resu iririt swift clearance iif heat. It IL ipp:ii<:ni thd I :iii:ii ti<>,,d [L:tt tn :uc:i)rs rid sur. lEEE TRANSACTIONS O N BIOMEDICAL ENGINLERINC. VOL. BMF-3I. NO. I , J A S C A K Y 1 . ,... TABLE II BFR FOR WALKER TUMOR O F RAT 1391 - .,... Room ?emu. Blood ~iou*l .BFR *.. __ Muscle Turnon ~ 0 . 9) 7 Tumon (>2.0 8) - 10.26 48.08 15.66 4.69 1.52 43T - Blwd now. BFR ZBAS 55.55 14.02 0.49 - ,,95 * mUlOO dmin. rounding normal tissues is the primary factor which determines whether the temperature .in tumors can be raised higher than that in the surrounding normal tissues. Table I1 shows that the blood flow ratio (BFR) for the Walker tumors o f 2-3 g and surrounding normal tissues (blood flow in tumor/ blood flow in normal tissue) is greater than 1.0 at normo. ._.. thermic condition 139). However, the BFR becomes only 0.49 upon heating at 43*C, owing to the remarkable increase in blood flow in the normal tissues without a concomitant in--crease in the tumor blood flow. Preferential heating of the tumor could then .be expected to occur in the 2-3 g Walker '-tumor. A further decrease in B F R and thus preferential heat-. ing of tumors might be expected i f the vessels occlude, and thus the blood flow declines in the tumors during heating. It d a s often been observed that the vascular damage in tumors progresses after heating 191, [40]-[42], [58]. It is conceiv-able, then, that the BFR in certain tumors may be greater than 1.0 during the fust heaíing, but becomes smaller than 1.0 durng the subsequent heating. The BFR for the Walker tumors lmaller than 0.7 g was greater than 1.0 during heating, which may account for the relatively low temperature in the small tu' 7 0 1 s during heating. I t would appear that preferential heating *. f *::mors with matured blood vessels may be difficult because slit.': ,esselo may react to heat as the nomal tissue vessels do ..mi :he.blood flow increases. It has been proposed recently to vasodilators to selectively increase the blood flow in normal tissues so !hat tumors can be heated preferentially [59]. Because of the uneven distribution o f blood perfusion in tu31% the temperature distribution in tumors during heating c.n be expected to be considerably heterogeneous. Recently, - G u l h o et al [60] reported that the temperature gradients y-+e larger than 1C ' in locations only a few millimeters in dist ice from each other within the same Walker tumor o f rats, .~ '' and that the inhomogeneity o f temperature was exaggerated w g hyperthermia. The heat damage in the peripheral area o tumors has been reported to be rather difficult to achieve. l k relatively good blood perfusion and efficient heat disipation may be incriminated for the failure of hyperthermia to driage the peripheral area o f tumors. Jnfortunately, in the treatment of tumors o f internal organs with most of the presently available microwave or RF hprthermia units, a considerable amount o f heat energy is de isited in the superficial organs, i.e., skin, and underneath cumeous tissues. It is then probable that the blood is puued to -@e heated superficial organs during heating, resulting - in a del ne in the blood flow to the internal organs. Therefore, in ..-e hyperthermic treatment of neoplastic tissues located in the internal organs, the blood flow in the adjacent normal r . . . .." - C. .- ?< F. I - I- ~ <, , tissue of the organs may not increase as niucli 3s that =hiii would occur by more localized heating of the o i g a n i i i u b . ever. inasmuch as the blood flow in the neoplastic tirruex t j internal organs w i l lalso decrease when the bluod is pulled I the heated outer organs. the ratio of blood now in the tuino, to that in the adjacent normal t i m e s may still beconic sinalle1 than 1.0 during heating. OTHERIWLICATIONSOF VASCULARCHANGESm I HY PERTHERMU The preferential damage of tumor vasculature at tern. perature bearable for normal tissue vasculature and ensuing changes in microenvironment in the tumors would have pro found implications for the hyperthermic treatment of tumor% The intratumor pH is intrinsically lower than that in normal tissues, due probably to high glycolytic activity in the tumors and inefficient drainage of acidic metabolites of the glycolysis, such as lactic acid through the vascular system. We 191 a n d Others [47], I481 found that the intratumor pH further de. creases upon heating. Such an increase in acidity, accompanied by an enduring hypoxic condition [61] and a decrease in nu. tntional supply as a result of vascular damage, appears to bc the cause of additional cell death in the tumors after hyperthermia Observed by US [Sl] and Marmor and Hahn 1621. The development of thermotolerance may also be impeded in the hosüle milieu in the heated tumors 1581. In the use of hyperthermia in combination with radiation or drugs, in addition to the interaction o f heat and radiation 01 dNgs at the molecular or ceilular level, the potential implica. tion Of environmental changes consequent to the vascdpr changes in normal and neoplastic tirsues should be taken into account. It is a weil-known fact that hypoxia reduces the response of tissues or ceils to radiation. When heat is applied prior to radiation, the increase in blood flow, and thus an en. suing increase in PO, in normal tissues, may enhance the response Of the normal tissues to subsequent irradiation. In contrast, the hypoxic environment in the tumors due to V~~CIIIM damage [Si] may render the tumor cells resistant to radiation Suggesting that irradiation should be applied prior to heat when the heat dose is sufficiently high to cause vascular dam age in the tumors. The possible increase in drug concentratioi in normal tissues by virtue of heat-induced blood flow and vas cular permeability and the possible decrease in drug concentra tion in neoplastic tissues as a result of reduced blood suppl) due to heat-induced vascular damage should be investigated Hyperthermia at relatively low temperatures, e.g.. 39-41'C however, may increase the blood flow in certain types of tu mors, and thus may increase the response of tumors to radia tion. Such an increase in tumor blood flow miy also increav the dnig concentration in the tumors, making !he combineG use of drugs and hyperthermia complicated. ACKNOWLEDGMENT The authors would like to thank P. Evans for help in the manuscript preparation. 11, p. M. cow, REFERENCES E, Tilchcn, Bulogic, ,, ,nd E, p. "Ullmsoud-induced hypcnhermia for the V c i i m n t ni human su. i,:: ',, , . >cpt 1964. 11. I Pctsnon, "l'urnor b l w i flow campar-d with tionn.il I¡,:~\K !.load How," in Vimor Blood Circul'iiior H. I I'cbxsw. I h l 1979. ch 5. pi>. 103 -I 14. penhemin on v a c u i j r 1unc:ions o: uil t U m ~ . nnt.Iclinimiinicii[ioi." J :'or. Cor~rrInrr..,vol.M).pp. 711-71.1. M J ~1978 . .:' W.Song, M .S/Kang. J. <i. Rhcs. ani1 S H. L.EI~II. "Emrr.i! fiypenhemia on hscular function in nixm.il iind neopls:.il: i i \ ~ . w ; ' ~ n n N.Y. . &od. SO . vol. 335. pp. 1147, biz. IW. : ' . W . Song, 1. G.!Rhee. and S. H. Lebici, 'Blood fl<iwin wnnd ! i i w c s and cumon iiring hyperthermia." J h a t . Cuwerlnrr., v(iI h.4, pp. 119-124, . 1980. I:. W. Song, "Ph ,iological faclon in hypenhcmia of IIIIIMD.' ?'hy.iicol A S ~ ~ C I SHyperthermia. O. H. Niissbaum u.. Mcd l'hyi. Monograph . Amer. Ass. Physicists in Med VJU2. pp 'I Jd2. f . l I w 1 . Phys.. vol. 9.11983. J A. Dickson and :S.K. Calderwod, "Tcliiperntiirc range anti siirctive sensiiivityiifiumon io hypenhcnniu: Acriiical w i e w , , ' 'hn. N . Y . Acad. Scl.. vol. 335. pp. 180-205. Mar IYXO. 1 Steward and A. Reg& "Blood flow changes in trmspImtcci n w u ~ etutnoun aad &in aftL.1 mild hyptnhemia." 81. 1. Rdi,,i IYM. 1411 A J. Milligan. "lnttrtinal hlmd flaw in Chincse hainrrío during liyperthemiia." R,idi Res., vol. 91. p. 318. Aug. 19112 T.q. Dudac. "Micmcirculamry flow rerponrt 10 Iiyperthemiia," in J I s r Annu. .Ucri. Rad Rei. Soc.. Sam Antonio. TX. Feb. 1983. Ab9 AC 5. p 8 I' M.Gullino. "in8,ne; 01 bimd $uplily on themil p p c n i e i and mciab<ilium 0 1 iijammii, i..arcinomu." Ann. N.Y Arad Sci.. v o l . 335, pp. 1-21. M u . 19811. C. U.Sullun. "Dircilsrion of i h r M i c k 'Effcct of hyp:nhcrmm om vahcular function tn ~iirmaland neoplastic tiisues' by C . W.Song. \ l S. . Kang. and I. (3. Rhcc." Ann. N.Y. ,4cud. Sci.. i.01. 315. pp. 13-47, 19RQ. (Discusrion: pp, 45-47,) H I. Bicher. F. W . tlbt.zel,T. S. Sandhu.S. F m k i . P Vmpl. M I> O'Hara. . and T . Würien. w k t r 01 h y p n h e n i . 1 lm normail arid tumur niicnXn~~r0nmcni:' Rudiuluq? *"I. 137. p,,. Si3-%10 1441 K. K. lain and he Ni,. u, . u- IYXO i'.biup;l. !N Slulitr.Klea>er, ICC. R l . i n z . rod f , K~lliouuski. 'Hliwú t i l w I ; ~ - L C. ) ~ y g c n 4-J pH <Ia<tnhuitiinin n~rli&(. ndni t ~ m w d $ p m I ~ L I ~ I I I Ch < Iy p : n n c r m ~Haric ~~,~,"t,~.,..i.........' C b n p W. Son# Was born iu Churchon, Korcl, in 1932. He received the B.S. degree in biochmisuy from Seoul University, Seoul. Korea in 1957 and the Ph.D. degree in radiation biology fromlhc University o í Iowa. Iowa City, in 1964. From l9ó4 10 1969 he was at the Medical Colk p of Virginia as an Assisuiit Professor of Radiobiology. 101970 he pincd the Dcpiruncni of Tbenpuiic Radiology. University ofhfinncmu. MiDntipoliS. as the H u d Of tlu Radiation Biology Section. His cumnr research inlcrerw PIC the effect of ridiarion and h y p + m m i a on vueular funetiona. ndiasensitiz.. tion of tumors, and rabiobiology of tats1 bady irradialion and bone m m w IraIISplinislion. - I A n N Lokshinv WLI him in Morciw. U.S.S.R., in 1932. She rcccivcd ihc M . D &egret Imm & Second Mavou Mcdicil 1nsl)lutc in 19% che Ph.D. degree Iwm the Bnnknko N C U ~ U I . aspects and role oí various thelhlsl derri.“ Slruhlrnihrropw. vol. 159. pp. 73-81. Fcb. 1983. 1491 M. M. Von Ardsnnc, G. Bohmc. and E. Kelly. “On IIK opiimiulion of local hyprrhermy in t y m b a d on L new rpdioím)ucncy procedure.’’ J. Caner Res. Clin. Orno/.. vol. 94. pp. 163-184, Junc 1979. 1501 B. Emmi. C. H . Nurrbwm. N. Hahn. A. J. Piro. A , hitsfhilo. and R . D. Quimby. “Histopithological study om lhc efíecw of hyperthermia om micmrusulaiure,” Inl. J . R a d Onrol. Bioi. Phys.. vol. 7. pp. .343-Y8. M u . 1981. 1511 C. W.Song. M. S. KMg. J. G. R k . and S. H. L v i t t . “ V s r u l u d a m a g e d dcliycd cell duth in tumors after hypnhcnnin.” Br. J . Cancer. vol.41. pp. 309-312, Feb. 1980. (521 M. S. Kang, C. W. Song. and S. H. Levin. “Role of vpxula~ function in rrspoose of tumors in vivo lo hyperthermia.” Canerr Res., vol. 40, pp. 1130-1135. Apr. 1980. 1531 H . A. Eddy, “Alteration in tumor micmv8sculature during hyperthermia.” ROd¡010#?. vol. 137, pp. 515-521. Nov. 1980. 1541 B . Endrich. B. W. Zweifach. H . S. Rcinhold. and M. Inuglietu. “Qumliutive studies of microcirculatory function in rmlignmt tissw: Influcacc of tempratwe on microvascular hcmodymicr during tlu culy wulh o í the B A I I12 m $aIcoma.” Inl. J . Rod. Onmi. Bioi. Phys.. rol. 5. pp. 2021-2030. Nov./Dec. 1979. 1551 H.E . Rcinhold, B. Blachicwicz. 8nd A. Berg-Blok, “Decrease in tumor microchubtion during hyperthermia.” in Conccr Therapy by Hypcrlhcrmio and Rodidon. C. Sueffer. Ed., Baltimore. UD lad Munich, W. Germany: W h i n 4 Schwancnberg, 1978, pp. 231-232. I561 S. Mellmdcr and B. lohansson, “Control of re~lismnce.exchange and capciuncr functions in the peripheral circulation,” Pharmecol. Rev.. vol. 20. pp, 117-196, Sept. 1968. 1571 A. W. Guy and C. K. Chau. “Physical aspects of localized heating by radbwivc md microwaves,” in Hypcrrhrrmio in Cancer Therapy. F. K. Storm. M. Boston, M A Hall. 1982. ch. 13, pp. 279-304. 1581 J. G . R k , C. W. Song, and S. H. Levin. ”Cbingcs in thcrmo rensitiviq of mwx mmmary carcinoma following hypcnhcnnia úi vivo.” Comer Res.. vol. 42. pp. 44854489, Nov. 1982. 1591 C . F. Babbs. D. P. Dnvitt, W.P. Vwrhccs. J. S.UcCsw. atid R. C. Chan. “lhmrriical fsasíbility of vasodilafor cnhinccd local tumorheating.”Europ. J . ConecrCIin. Oncoi..vol. 18, pp. 11371146. Nov. 1982. 1601 P. U. G u l l h . R. K. Iún. and F. H. 0i~th.m.“Tcmperatu~ gradients and loul pxíusion in munrmry cwinom;’ J. Naz. Cancer Inn., vol. 68. pp. 519-533, Mar. 1982. 1611 C. W.Song, J. G. Rhee.M d S . H. Leviti, ”Effcnoíhypithmnii on hypoxic cell fraction in tumor;’ Inr. J . Rad. Oncol. Bioi. Phyr.. vol. 8, pp. 851-856. May 1982. 1621 J. B. Mannor, F. J. Hilerio. and G . M. Hahn, “Tumor erndicnfion and cell survival &r localized bypahennip induced by ulmsound.” Cancer Res.. vol. 39. pp. 216&2171, Junc 1979. I gcry INtiOle. uur«u.in I’i6Y. Fmm 1965 to I979 rhc we5 with the Thcnpo i i eRadiology Dcpanmnt. Burdcnko Ncumrur. g q Institute, where rhc worked on ih ndb rhenpy cliaicil &IS o í brain tumwa. In 19a1 S k emigind to thc United StMer. knd abc L -.a“ now with che Dcpinmcnt of Thcrapcutic Rdml. ogy. Radiation Biology Section. University oí Uinnsroia. Mmneapolii. Her current rescuch intcrerts the effect oí radiation and hvwnhnnii on vascular functions. .. CE IIi I ck , .. 1 su tb Juow G. R k was born in Seoul. Korea. b 1947. He receivedthc M.S. degrrc in p h y s i o h fmm th Scaul Naiional Unirorily in 197s inp the Pb.D. dcgtw in b+ysical ~ i c n c efrom r & Univcrsitv of Minnesota. Minnemolir. in 19%). m di1 CCl tul ab <* F Minnsroti. where nar in i tumors, human I 1 i Msrrba P a i l a was born in Minaupoli wht lhe with a minor in niiunl rcicnccr from rity of Minnerai. Mintmapolis. in I Shc b u w d c d on various rrs &e Univuity of MinDsou ria= cold hvdiaesr riudiu. mil cl wb 5Kl lhC mat. now working on vascular hyprthcrmi8 ~ a l y ~ri i b that bme ~ pian ir en H thai %yatour H. Lcvln was born in Cltiugo. U. u 1928. He icccived the M.D. d c p e fmm thc UniversiIy of Colondo. iknver, in 1954. In 1979 he joined che University o i Minnesota. Minneapolis, as Pmfc.w>r and Head oi the ikpanmeni of Thvrpeutic Radiology. His pioeipi arc- of re-b iotemt include the rok of ndE iriotiUicnpyiachebctmcntorbrcutcv~cr.id Hodgkin’s dixrrc. He has lcerured c i l c ~ i ~ ~ l y on lbnc.lidother topics in radiation w d q y in major cities fhtwghout thc United .Que< iad Europ. Dr.Lcvifl is th+ Past Prcridcnt of the Amcricin Sorirty ofnicry>cutic Radiologists and he ir the cumnt President of the Radium Society of America. con( 1’ tirsu: bctw ciihe -3 1 - lirrUl inter: 31 2 ii i 1 Is SI Ma tn m XStiOi Th l’”W, hcnr i Fig. 1. Basic antenna design. Schematic of thaintcrstitul microwave antcnna used m these experiments The antenna fits into I blunt-ended nylon catheter TABLE I left right I.7m 2.8Cni 1.21.Ocn 0.50.5rn 0.1- O.7m 111 O.HCrn 1.20 1.X" 0 . 9 ~ ~ 0.5m 0.3tn 0.4- 44.l.C 0.9tm 0.3ci 0.3m 16.1.C 43.V.L 0.8W 0.6- r 44.1.C Fig. 2. Bi ihennis four-ant IC"MI. pom'cr d optic tern] Both the YSI thern hciped m brdin. Recent lhernionie TlCxinp te tw pruhca We prob tach icmh ====== .*, Lb.9 I .* , ~ ~. , .~ - Bureau of Stantiardsi iiicriiir, therriloiwter over the tempcrature range 3O*Sl0C (+(J.i)?'C aLriiracvj. Both the mercury 1hermometi:r a n d tt:riperiiiiire probe, were iriirticrad in .I tariable temperatu!c . < i r a l a : irig \r i t ' r bath I1li:nnorniu #. 420) for calibr~tr.' 1 1 ~ r o c e d i i r ~ sT. m m r a t u r e \:orrectionr wcre made ror each he 1 s iridicxtc.1 lq caiibratiiiii data. . . .. . Stereota.njc m a r i i p t i l a i m weIe u r d for catheter insertion. p$obes .vi>:: rigidly held I>)stereor&yic &ctrotl* he 19 cqxrinieiits iisiiig <.ne antenna. tlie nylon . . .. - . .____ 4atheter (Best Ind.) m'~ guided into tlie posterior occipita! ].....--.ny~rb h e and advaiiced pxrdlsl 11) ihc c o r t e a l surfice at a deptli nging from 0;4 to I 3 cni. rherind Astribuiions wen: niapintern I!S .il(~iigthe entire length crf the inserted Lqnper.~it'ir:probe was advanced 3f each location l..-*;:Zi-= h I mm increments perpenriicu~arto tile ionpirudin:ii axis of . .... ~. ..._~~ ~ .--+,z ~ ~~~ . . I , f .. . A '. In contrast, in t: ,, .,' i <"-I l. h Rece hnor Plexúig torprut b e p', Each te ,, :,, ,:, I 1, , . ,,, ' ,,, , 8 , , ' ,, . 11 . I , , ,.I ,, , .I ,[, , . experiinents iising an array o f t w o o r as, the riylon catheters viere inurted into the arietal lobe orihogc:id t u the s u r f a a <of the brain. In exyeri. +ants utilizing tNo irlicrwave antennas, the catheters 'were ipserted parallul tu .lie sagitral Sirius and were separated by I : ~ ~ ~ ~ ~ ~ i < 1.0 ' ~cm. ~ In ~ nine r p expc,rinierts. . ~ ~ ~ I an B array ~ . o f four antennas was :quare wnfigiiratiun with an antenna at each , :. I ' ' LI t i l ~ i i t tends wtiich domer. The dhgoni.1 rcprdiion of ioippoing antennas W I S : '. I: :.hi[ 2 tliwiigli the 1.5 cm and the si'je ierigth of separztjim was ;ippruxUii;lteiy 1.,1cm. In enperin:~nts iisirig multiple anterinas. the YSI 1 < I , i i i i p iitrcontiolled dherniistor probes w l e inserted into the posterior occipit.ii 1; ! I I b . ' :..IO l'ur iniiltilolx and advanced awimicirly, perpendicular tcl the axis of'the I .! I $ I ISP iherrni:i. antennas. Thermal h l d h r w < : carefully mappad in 211 experi. I I k. I ' : Lh r:mpxahmts by mdklng [ipI<: parses ;st .;.iryjng deprhs in the I 'r ni, trcJi,iwn:. h i n . Teii>peraturr ~ , , ~ r c i n e nuirt: ~ < , taken a t I : ~ > i r iii:r,:. i , ' 1 ',h t ! * ~ : . i ~ .11 , n ~ m i s diiiriili r,s.ii p ,>, I.: .I?C:J:LJI: ,:.itrthui,iir,: ".<,e JIS, ~ , ~ e 5e.o O 0 va Y O O I 5.0 3.6 4.0 OIüTANCE Ismi I o <.O P.0 2.6 6.0 4.6 c I vu < ThwnIalol 1i.m h 3.0 5.6 4.0 CHBTANCE Irni 6.0 4.6 This f í u n shorn the temperaturn dinributions (upper graph) nmrded from Uuec YSI probes in a pass thmugh the bnm papcndicuhi to the longtudinal uir of the antCMIs. T h e onentitions of the thermistor probcs and the four micr?wave antennas are depicted in the lowu graph. The tract ofthc middk tempmhlrr pmbc (YSI 2-roüd <r*ngIes) WU pund on the cortial edge of aniennas Ai and A2. Anothu temperatun probe I-oprn quaies) was poutioned d o r r t to nntenna A4. The third probe (YSI 3-0pen cucles) was inserted through the medial third of the fourantenna m y . The distance between the thermistor probu Was 0.4 cm. A sin@e fibu optic (LI-solid circle) probe was passed in a pLne pimilei to the antennas in the center of the array. The x-axis scale is the same for both p r a p k and i s bued on exact Itcteotaxic coordinater.The y-axis in the Iowa graph is a rclitive scale of distance. Fa 5. (Ya ." ... . . ... .". ..,,. ..~ ." .I I , I ,.- ,I ... . ." .... 0 - . I." 60 ANfEOIM ) f f- POSTERIOR Fi.7. Irotheims generated by a four-antenna m a y m the right hemisphcrt of a developing dog with I histol~icallyconfumed @oarcoma Temperatures wm mcesurcd in bofh horizontal (huh marks) and ve-1 (crmes) pbncs to the four-antenns array. Three horizontat p h n a are shown at depths of 1.2 cm, 1.0 cm, and 0.7 m The antennr phament was similar to the piacemen: represented in Fig. 6 (h, = I .O cm,hB = O 5 em). Maximum NFP was 20 W. Fir. 8. This low power *w (30x1 üiurtratcs the orientation ofa YSI :humistor piobe tract (large solid arrows) to an antcnns (Al) in a horizontilly a t section. The uact ofthe Luxtron ñber optic probe (L1)was &o urüy idcntüied in this fku. ferent antenna design (131. However, the temperature distributions were not symmetrical around the antennas, as predicted by the theoretical calculations which assumed uniform blood flow in the brain. The lesion invariably extended farther mediaily into the white matter tissue compared to the lateral extent of damage into the cortex. Two factors could account for this observation: 1) brain tissue perfusion is normally lower in the deep white matter compared to gray matter, and 2) heat dissipation is greatest near the cortical surface o f the exposed brain. An additional factor o f potential importance m accounting for asymmetrical temperature distributions in the brain is the difference in dielectric propc ties of gray and white matter. Due to lesser water conten white matter has a lower permittivity and higher conductivit and hence, a higher specific absorption rate of microwi radiation at 915 MHz than gray matter [ 141. The thermal dosimetry data measured during interstiti microwave heating of normal dog brain reflect the variabilli of brain tissue. The inüuence of cortical sulci, ventricles co taining cncbrospind fluid, and large venous sinuses. in ad< tion to the variable cytoarchitecture in gray and white matte result in complex t h e d distributions. Temperature maxin were not necessarily found in the center of the four-antmi array. The maximum temperatures at a depth equal to h (brain surface to junction) were most commonly observed or near an antenna nt the edge of the square array. One pro lem with using interstitiil antennas in the dog brain was th surface heating to damaging temperature levels was MI m d y observed. This could be due to absorption of excess¡ energy at the tissue-air interface. However, it should be notc that these antennas were specifically designed for herüi larger regions o f tissue at greater depths than can be atiemptc in the dog brain [l3], [ I S ] . An important advantage of usil multiple antennas was that less power was required by e a antenna to generate therapeutic temperatures in large r a o i of tissue. This was in part due to the additive effects of il overlapping electrical fields. Hence, the amount of eneri deposited around the insertion o f the antenna and cathei into the brain was reduced and caused less tiswe daniage the point o f insertion compared to experiments using a sing antenna. The problems associated with thermometry meesuremen in electromagnetic fields have been previously reported 116 ,u r 19hd . , c v o C~I ~~l . L: 0 C h L I Z I : I ) ... i1Yi~ERTIIFR!dlA A N D BR.AIN TUMORS 61 . micrographs ale 48üx. The problem o f heating of the temperature probes b y r heating, the thermistor. probes were oriented at right O I the microwave antennas. Temperature recordings fhe histdogic.tl rerultr oi t h w c\pcrinitiits are iiiipurriiit rerpeit;. L , , r !p!~:,,I,+.A C v i d c n c e d r thermal h r n + threshold in the normal dog brain using microwave heating for 60 min occurs between 42.0 and 4 2 2 ° C . Second, these temperature threshold values for damage are similar t o those reported by our group using ultrasound heating in the normal cat brain [ 181. It should be noted that the difference in normal body temperatures between dogs (38.3'C) and humans (37.OoC) may affect the thermal thresholds for damage in of these parameters in vivo needs further study. The results o f locally heating brain tumors in an experimental glioma model with the MAAH system show the biological feasibility of using this system to heat human brain tumors. The potential limitation of the present interstitial r n i c r i v s c heating system is die in3bil;ty to prtsisely tun. treatment potocoia (up to wven day protocol haa been app seated tumors 1201. The ult of with prbnuy central nervous been reported [2i]. hhuy results from Ph therapy and interstitial centmi nervous system [ colkrysr lowed that ptiepts momdiothcnpy had an owrail r with a 71 percent e thb study showed that elinid tQ using intentitid heating 00 frequency and microwave ippiicators. niir ACKNOWLEDCMEP~I The authon wish to thank Dr. D.DI Bignu for g QO sly iuppiyiq the purifid SR-R$V, E. Jkfich and E.% x m i o i iechniul udrtuice, E. Mñlemiui fo hirtolrqjcd prep tion, P. Richey for graphic design, and P. Home foi mkrorcopy. 111 I21 I31 I41 INTRODL.C.Iicjv ~ ALIGNANT brain tumors caiirwi. ;,re.:arly be erkctiveiy managed with convent1on;il t!~er:::ie~rtic moc$liries. orary clinical manageniw; w t i s i , 1 s c'f a szqbentiai of surgery. ionizing radi4tio.1, iiid :hdmoil erapy . ommon hrain t.un:or id a ~ . i l d i ~die . d i l b 1 stoiii.i I, has an irvariably i a t d tim: c w r e , rrriiy dstiii: n two years despite t h t ros: asresrivc $ i n i d id on this fact alone. ,the ir nt o f intracraiiial hypertlici-rhia Jrc xcll j~ustihd. rthennia as an experuiimta! t; :atmeill for' braiii s based on a sound bioph, skd rat:x& [ I ] . F$rther. development of intracrat$id 11) iiwtherma, yhilr e 1iioenginei:ring prohleiri. may r q i s e i i t mie ! o f the amples of hyperthennal tre1tr::ent o!' d?episeated on. The brain, :situated within i!ie cranial vault. is a . t terfaces) cannot be preciszl)m d e r i n d , 3 uver mort: than a p p r o p a t e l v 10 c m fr+m an face, While t h e b % @ s u11 re:vesents an i pedi. vasive Iiyperthermal't~ieri,p!, this sdid, $able. ribed platform offers c c m ~ l i r a b l e advdntages techniques are utilized. rthennal techniquey ap;ili,.~bIe to úitratranial I received Lbrch 25. 1983; W v i s d heating !the ftlirc wain v ill: ironinvamp iilti~ioaicdevices. lliing eJectroi-iri:ne+ teci n i q i c i , Silbeigian rlr al [41 have remrted heating tlii1rabbii h r x i with .I t<mirii.asive nignetic iii.iuctah device. Sipiaras ?t d [SI rep x t e d Iitatinp the cat brlin w r h aii iniasivt micr i w ~ i .device. ' i n dl cases. regardless 3f whether iniai:va o r not::o\as.ve heatin8 was utilizsd, üssue temperalures were 4 a s u l r J by masive :&hniqws. CliniOal attempts !ut in1 :acranial hypqtherniih (for expenniental $rain tiirxi; $erap:. j h a w beenrerbrted by Heimburger ?r al. [tlJ using a i *$terni u!trdsound w$tmand 1)) Samaras ?tal. [ S I , [?] u<:iig $11 imp:anicd microivjve antennasystem. In oqder i o rstio+üy administer intratrmial Iiypeitiiermia f ' x brain tumor thet;ipy, :here are foil:. basic problems that niust beisolvcd. I'liey are 1) heat dclivmy 2) temperature ni(asurc::ierit 3) telnperatuie cqitrol 4) pretreatmest dtrd p'st:rcacment cstunation of spatial thennal fieid distribyiions. In Gis paper. specific alutions for the first thrce items will be ,derribcd; $e lasi (alii! most difficult) iteni will be dixusseii. ri:cognizi&g th.it no practical solution presently :xists. I Parted in tiart b y the Amerbcan Cri PDT-LOS. in part by the h'NCDS 11,. and in p:tn by the Whit& Fa from tho Dean. Schi,irflof \fe mtogy. ;mi tho ~ i v i s i o of n N:ui author is with the Neurooniulogy RCY. ,LIC., :Labomto es, mmenl Of Radiation Onwloyy. Cnivcriit,i , :' hlaryland S$oril " ~ ~ ~ + ~ ~ i i m $10 o wz .i 2 i l I . De o; i I + i b , ., ! ' . Ii 1 " HEAr DEUVERY F u n h e l i t d l to Wery tivperrhermal t b r a p y i8 the problem of deliFring heat k1 thi: target tumor, while sparing the riinoun/ling noiinai Tissue. Ulriascknd. m n p a r e d to electronuignetil radiatnin, Las superWi: penctratbn depth iii aiolopical tissues. and #itq the ;ippropriate insrhimmtnitiuii, precise focusin# at (depth rnhy b e Jbtainad 121, 131. Howeyer, ultnwinic intracranial hyperthwmia is not ncihinvasiw; since ultrasound dbes not iien@irate the skull weii $ section of the skull niust b( surgically iemoved h r each idírasonic traniducer eniploybd iri the trea#ment. Furrhermore, p the contemporary absence'of noninwsee thermonieiry, "nohinvasire" ultrasonic heating ' still reqiiirh inviisive tissue ii)nperaaire measurenic:nts. Silbetman et 01. [4] :ire irivestigatitlg the feasibility of using magnetic loci)) indimion for norrinvasive intracranial hyperthermia. While this b.mt delivery tcahniqua is t ~ l non. y invasive, it still rcqidres úivüsiw tissue temperature measurenient. burthennarc, unlike ultrasound. i t suffers from a crucial habiiity t o &cur the hcat-produdng energy (in order to spare normal ti$e). and relies soMy on the hope that differential heat tr&sfer between turncmr and nomial. nonrepairin$ n e v o c s tissue will result in preferentiíii tumor heating. The consirairits on an; h p i a n h b l c Intracwiiil I i a i d s - ~ I ! '1. 4 1 !I ~ j 1. ' ~ , ' ' aver> device include rnininial size t u miucr brain tisue damage upon implantation. maximal rigidity io increase the accuracy of positioning. eiicapsulation i n ni~iitoxic, nonreactive material. a reliable spatial energy deposition patiern. and a simple means of altering spatioleniporal heat delivery. O f all the modern methods of inducing controlled hyper. thermia, electromagnetic radiation in the microwave spectrum appears to be the most appropriate for invasive intracranial heating. We have previously reported the results of in vivo dielectrometry in felines [SI. Measurements of the conductivity (mS/cm) and the relative permittivity (unitless) of both gray and white matter in the brain were measured;in the range of 0.5-1 .O GHz, the uncertainty in the measurements was on the order of 1.5 percent. Figs. 1 and 2 show the frequency dependence of the conductivity and relative permittivity of feline gray and white matter over the range of 300-1000 MHz: values at 1 1 0 0 and 2450 MHz were not measured. but were estimated by extrapolation. These Same figures also show an estimate of the depth of penetration (O) (dis. tance to reach about 63 percent attenuation) using a simplified approximation 191, [IO] of the form IS M I, I5 I. 1 .3 4 5 51119l.O 1.1 where w radial frequency (rad/s) c speed of light in vacuum (3 X 10'' cm/s) relative permittivity (unitless) a conductivity (mS/cm) E, free space permittivity (8.84 X lo-" mF/cm). The results of this calculation serve as a useful index in the design and selection of implantable microwave antennas. Antennas for invasive heating of the brain have been reported by Strohbehn er d. [ill and Taylor 1121, and are of a monopole (sleeve) design constructed from m a l l , semi. rigid coaxial cable. We have studied the heatinn Datterns of this monopole design in both static phantom, live, and freshly exsanguinated feline brain. The antennas can be constructed from semi-rigid coaxial cable with an outer diameter of ap proximately 0.7 mm, which satisfies the requirement of minimal diameter so as to minimize tissue damage upon implantalion. However, this design is not very rigid and tends t o bend " -6 and buckle upon insertion. -. i n an attempt to improve the rigidity of this device, we heuristically developed a new design-the c0-l slot rad&or r (shown in Fig. 3). The coaxial slot is f i e d with a high thermal conductivity, low electrical conductivity adhesive [I31 io preserve structural integrity. The energy deposition patterns of various design lengths (d = 10.8, 14.4.21.1.and43.7 mm. respectively, where d is the distance from the tip o f the an-1enna l o the center of the slot) were empirically studied in static phantoms [I41 encased in a thick wail styrofoam conT a i n e r , sealed with cellophane and warmed in an oven to 35°C. Each candidate antenna was operated at 2 4 5 0 MHz with the u same net power: equal color contours (corresponding to - _- Fig. 1. The frequency dtpcndenEs of conductivity (mSlcm) mht permittivity, and CaiNlated pcneíration depíh (cm) for feline 0 matter over the frcqumw nnge from 0.3 to 2.45 GHz.Conductiv and permittivity at 11M) and 2450 MHz wme estimated by exkq lation. o* * conductivity, eg = relative permittivity. and Dg dog ofpenetntion. Fg. 2. The úeqwncy dependma of conduqlivity (mS/cm). reht Pe~iitivity,and cilnibtcd pmetralion dupth (an)for feline wh manor over the üequcncy nryrfiom 0.3 l o 2.45 CHr Conóucti* at 11W and 2450 MH2 were estimated by extrapolation. vu N ductivity, ew = relative perminmCy,D, depth ofpcnctntkn - .- I- - - Te wsu -. @Co-cC - L 2.45 A* h . o / q ; N*4,6.8 >Lo= 12.25crn . .. T.lb"( E. 2 I cimrit C."IC<*" 3. A schematic d L g n m of the ndbting portion of a c o u n l ! antenna The design warempirioinu detcnmcd. The lenpthd to in the text is the dhtence üom the centcr oi the dot to short-circuited end af the antenna. For operation at 2450 M Fig. ho = 12,25 A functionalantcnru the coaxial dot compkl r i d with a high thermal conductivity, low olwcttiu~conduce! material 1W*andis encaPaiMed thinTeflon sheath to PI- conlact between the copper outer conductor and b n i n t i ~ u e . approximately 38'C) obtained from a liquid sheet piar over the "split" phantom surface immediately followin¿ 20 s heating yielded the patterns shown in Fig. 4 . We seleci the pattern obtained with d = 10.8 mm (which conespor to an eighth wavelength in Teflon at 2 4 5 0 MHz). as oppoi 1 F :tie ideiiticd anattvii. al locatitin of t h . k I i ~ i ?:',Ir: br ii!:.E:..arriinaticin <if the t<vu patterns shows an i - c r t : ~ : J ra.lid heitiiig gatteni for tb? dot design comp(re,t -o í t e sltr\c deign. T i e a x d heatid;: 1:atterns appear to b cornprat~le. Therefore, the rr~xial slot radiator ilt:.;ipn k ca'Jse Jf it$ mi&nal radial sit-, improvzd mechadca: ri:idii: , and unp.oved heating patttjii.. appears appropiat,! ti): :.titrasraiiiai heat ilelivery. In p r k r to m a t this device witti a nontoxic materel, either a q f i m spray or a thin:w;il Teilon tube [16] can b e usad to qicapsulate the coax+J hi.. Oiir experience withthe device is that, io the absence of ioniwti\e t c j i ; n i ii influences, the $palia1 heati@ pattern is relatively reprodurib k , although variations, probably due to mechanical L b r i c i tkin technique, occur. A single antpnna may be useful for heating residual tumor once the bulk of the tlll11or has been surgically removed lo decompress thetbrain. However, in order to heat brger tumor volumes, a sinde antenna operating at 2450 MHz i s totally inadequate. Foe a "no blooQ flow" case, the devlce 1ieat.s an appro,xiniately &ylindrid vdunie (to temperatures exceeding 4 1 O C ) of radial gimensioa 0.6 cin and axial dimencion 2.2 cni; ir^ the case o f @e sleeve design, the radial dimensbn is on the order o f 0.35 c k . Therefore; at best, the slot des$n operatirig at 2450 MHz can only heat a 2.5 cm3 volume to ttmperarures above 4i°C, whereas the sl(eve design would o d y hear approximately I cm3. There are IWD possible approaches to increasing the volume of heat tissue; one approach ir to increase the number of ariteniias, and the other is io change the frequenay o f microwave radiation. Fig. 7 showsjthe frequency depenuence of the axial dimensioq (2d) of thd dot design and tht frequency dependence o f ithe effective penetration depth (Deff). The effective penetrition depth i s 60 Deff = o.8 [ogt*y] + 0.2 &hit.] where the assurpptionr are btirig made that 80 p s c e n t of the brain p a r e n c h h a is gray matter and 20 percqnt is white matter, and thbt, furthermore. this weighted average is a reasonable estirbate o f the material properties thlt the iadiation üluminatesJ At 2450 MYz, D e f f = 13 cm and M = 2.2 cm; at 300 MHz, Deff = 30 cm and 2d':= 17.7 cm. It shoul~be noticed Deff/2and 2d correspond tb the radial that at 2450 "2, and axial dime$sionr of the, cylindrical volume k a t e d above 41OC (when the integrrl fhcrmistor temperature is maintained at 45'). and one c w l d , by linear frequency scaling. estimate the anllogous volwhe zit lower fnquencks. It is also noteworthy that axial dimen$iorr greater than 10 em are prob. ably not useful b the human brain. TEMPERATUREMEASUREMENT Tissue temptrature measurement during eleairomagnetic heating requireb the use of special themomewy systems. Temperature mtanurement ih high intensity microwave fields can be accomplished with sniall. nonmetallic (anü thus ininirnaily perturbing) sensors su<lh a s the fluorooptic probe [ 181 ilimiiistors. except for the B ~ i ~ r n p p~e n[ i')I arid tiicrmis. . ., 66 I¡ 1.1 KKAUAI r i o v o x rn1.>\!1 nIcAiL ~ . X G I ~ ~ I . U I V\ G( 8 1 . n l i t 3 1 ,YO. I , J A N I : A H ~ Ip, , ,.,!Al: ‘C ... .. ..... ..”. I . . -... .. .. .. .. .............. . ...................... .*.*.................. ............ ............=......... ......-..... ... .u1 Fi. 5. The quniiequüiinum tempemtun distribution oi the iIS wavelength dot antenna d e n i m p h t d m a kctimmwnack thaired feüne brain. The antenna was o p c n t d at 2450 M k with a control system thit mainbind the intern thmninor at 4S +/0.1’C. Temperatures were meuuiad with a mlibrsted Luxtron lOWA thmnometer and I miuomanipuhtor. The figure depicts tempemture measuuIcmenb made dong the i n t a m axis ai v ~ o u s rsdisl distances (0.3,O.S,0.7S.i.O, and 1.2s an). -” .. ,~. L . .... .......... .... .........a ...... -. .......... P -_ I I _ I- . -. n m was u d . Step I: I f lei( - .~ > 0 5 . then Al = K1 + K4;else KI = coordinates of the tuniiir margin is k i w u n . ilic íi>llo~<i questions must be answered. K 4 = K4 + K 7 . I ) What tissue (malignant and nornial) irniperal Step 2: I f I q I > I .O, disable the inteser controller by be prescribed for treatment of ihis patient? by settinp oi = O and proceed to Step 4. If Ici I < 0.5.proceed 2) What duration o f time shuuld the tissues be exposed to Step 4. these prescribed temperatures (using the siiriplifying PSS Step 3: I f lai I > 161- I I, then K3 = K3 - K6; else K 3 = tion that a constant spatial temperature distributi K3 + K6 and if luil > lot-I l. then K6 = K6 - K9; else out the treatment will be used, and noi con K6==K6 + K9. required fractionation schenies)? Step 4: I f I q I > 3.0 or I q 1 < 0.6, disable the derivative 3) Which array of implanted antennas will most cl controller by setting 61 = O and proceed lo Step 6. approximate the prescribed spatial heating paitern S t e p 5 : I f 16,1>16,_,1,lhenK2=K2+K5:elseX2= implies selection of the length or frequency o f opere K 2 K 5 and if lo, ¡ > O , then K S = K5 K8; else KS = K5 each antenna and the anatomical location of each anten K8. At the present time. our knowledge of the medical p Step 6: If any K-value is now less than unity, then r e s t tion (temperature and time) to achieve biological cffec that K-value to unity. is, at best, vague. However, in order to minimize Step 7:Calculate the generator control value (CJ and tissue damage, it is essential to maintain the temp begin a new measurement/control cycle. outside the tumor volume below 42'C. Furthermore, i n our implementation, the values o f K7,K8, and K9 are tumor temperatures should be above 42'C, normal t normally unity. We have found that the initial values o f Ki, temperature far from the heated site will be about 2loC K2, and K3 primarily affect the time required to reach the heat transfer in tissue does not permit spatially sharp tem target temperature; this effect becomes more pronounced ture transitions; uniform tumor heating is not practica as the time for a measurement/control cycle is increased. (considering the heterogeneity of the tumor structure) The generator control value (G) is a digital word bounded probably even desirable. by the bit length of the computer being utilized, and further In order to select the most appropriate aria bounded by the bit length o f the digital-to-analog converter it is necessary to be able to predict their re being employed to drive the generator. i n our application, a 10 pattern, which requires knowledge o f their ener bit converter is used and, furthermore, the analog generator pattern, the effect o f tissue thermal conductivity, a transfer function (input voltage to output power) is h@ly effect of tissue thermal convection (i.e., knowledge nonlinear. We have found that this control algorithm does not three-dimensional blood now vector at any point). S t require a linear correspondence between G and output power, et 01. 121 J haveattempted to mathematically simulate but heuristically seeks the value of G necessary to achieve the n o d brain.. Probably the greatest difficulty in a stable tissue temperature. However, it is necessary to adjust the resulting heating pattern is the absence of d the maximum possible value o f G so that it roughly corre- edge of the direction and magnitude of blood flow a1 sponds to the generator input voltage yielding the maximum location in and around the tumor. In our laboratory, w power output. Furthermore, it is pNdent to provide a maxi- systematically attempting to empirically determine the sp mum output power limit that will not damage the particular heating patterns for various array confiurations in normal antennas being used. tumor-bearing canine brains. The objective is For applications utilizing multiple antennas with multiple database which may then be employed to ascer sensors and either multiple microwave amplifiers (or a singie tivity of the various simplifying assumptions used m generator with a time multipfexing scheme), a single sub- theoretical formulations of Strohbehn er al. (211. Fur routine realizing this algorithm may be employed with an NX more. localized blood flow estimation (using thernlal clearance .~ 22 input/ourput matrix containing the parameters for each of and brain blood flow manipulation using hyper/hypocap& the N "channels." Because of the adaptive nature of the is expected to elucidate the level o f influence of blood flow algorithm, compensation for mteractions between ChaMelS on spatial themal distributions. will occur; however, the degree o f compensation is directly -". related to data processing speed (throughput lime), so that CONCLUSIONS .. a slow machine wiu result in poor compensation. Intracranial hyperthermia can be accomplished by invasive and noninvasive means; tissue temperature nieasurcn~entscan, at present, only be accomplished by invasive techniques. Practkal solutions for three of the four problems under- This paper has presented practical wiuti»ns to some of the *-. lying administration o f intracranial microwave hyperthermia problems of accomplishing invasive intracranial microwave have b u n described. The fourth and final problem involves hyperthermia. In order to proceed witii the development --' the pre- and post-treatment estimation Of spatial thermal of this approadi, it is essential ilia; we gain an entpiricnl field distributions in the tumor and mounding normal and/or theorctical understanding of hon iniracranial heal tissue. This is the problem of thermal treatment planning transfer processes operate. and dosimetric quality assurance. In other words, given an individual patient whose tumor has been radiographically R~RENCES localized so that a reasonable estimate of the stereotaxic K1 - ..- 1_- _.. -- K 4 and if 18il > I&¡-,I. then K4 = K4 - K Y ; else - + I. ,! - . . , ?'! , , , -.,o\ lilO\I~OICAL ENGINEERING, VOL !/ BME-33. NO 5. MAY 1986 411 i ~i $ 2ti fication ~ of Thermal Model for Human Tissue MORTEN KNUDSE.N AND . ..\ .itai>le m o d d xtrueture ufspntbl and temporal tempr- ' iirsuc, exposed to electromagnetic heating ~ t s r t ; ,,,' I, d i n g , is drrrlopd. This model. denoted the control . , ; I ~ r 11 t ~ for tlirrmiil dariniriry In hyperthermia cancer therSI,, i OW>: ,-t:ci~l riintrol model parameter v i h e s for various types I I...tnt!,:. r i e i . i i L~ISUP arc determined from apriori knowledge about l ' l l r l po\tuon and puniniewrs. The control model parameters for , :,\\LO, u t ,!stiinnted froin patient treatment dntn through the use ifirsrion technique. The resulis indicate that the conitre is adequate. With the available #priori k w w k d g e detirmiiwd control modd parameter values do not I .II,:I r:t,roduí,i the rrprimentnlly ntinuied values. Accord.tn C I C I I¡fie , ation bawd anexperimental data is recommended, if 1-1 I. ~ I U J, , N I in human I. INTRODUCTION I 1 it.'::hl \ I , models o f human tissue play an important p . 1 ~:n .!ypcnherniia cancer therapy, in particular for ~ m . ~ p i,i.i:c:d it simulations of hyperthermic treatments [I].: í r r thl> .hn aiid Roemer [ I ] have divided the field of I , ' I I I , I ~ ,iwnietry into four areas: comparative (evalua- T . rent heating modalities); prospective (individt:r( treatment planning); concurrent (feedback . I . ! rljl :!urmj; a treatment); and retrospective (post-treatI ' 1 c! ilti (tion o f the therapy). The ultimate goal of pro[', , ' i i . c incurrent. and retrospective dosimetry is to t cwitrol, and estimate the complete temperdture i,,, I i n ::if: iuinor and its environment. This requires very ; 1 h ! '. rrtldels containing detailed and accurate iiifor11.' i i v i h i : t patient inatomy. electromagnetic and therI: : i h iie iiaranieters. and physiological response. The ' : ; ~ I ~ I ! , :d iwdel building approach is mainly theoretical t' '; / i r I:. ' t h.xe mathematical models are developed from 11) la i s and relationships. is however. also a need for a different type of I!' : ~ . l vhii li has a simpler structure and does not require i i ~: ~ s : i n i i .ition prograiiis. To predict and control the ( ' ' ~ I I L V ~ I ~i ~ n , a. few selected locations in the tissue the :I LII infi'rrnation is: which heating and cooling input .ire +red to obtain desired steady state temperI : ' , ! . : > iii th: specified locations. and how fast can the tem)i ~ . : i u r . ' ~ hci changed? To contain this information, a low w:I t Jn$'?r function is most appropriate. The model is 1'. ,111 or :ornp;irative. prospective, and concurrent do>:~:~'irj. bi I ;IS the immediate application is for design of , I I.. :!Ef ipili '8 ~ 8,. I I in. Ivns. :rq~' PCCIWLI March 7. i9n5: September K ~ L L I V I, with the Inslilulc of Elcctn>nic Systems. Aalborg Uni- I /U , Ikpanineni of Oncuiogy and Radioihcrdpy. .'(I -tc -1 ('. 'ir Kcw.1n6. R.diurmrsrionen. Airhur. Dcnrnsrk. 1 , It ILIC '.uiiihi.i X < i O ' I * l l ' JENS OVERGAARD feedback control algorithms, we shall denote it the control model. Experimental modeling-the alternative to theoretical modeling-is very suitable in building the control model. Experimental modeling o r system identification contains two steps: first, the structure of the model must be chosen, and then the model parameters are estimated from measured input-output data. As theoretical and experimental modeling are complementary to one another, both methods shall. however, be utilized. 'The purpose of this study is -to develop and verify an expedient structure for the control model; -to determine theoretical values of the control model parameters for different types of homogeneous tissue; -to estimate control model parameter values from treatment data for various patients and tumor locations; and -to determine i f the control model parameters can be calculated a priori from known anatomy and tissue parameters with sufficient accuracy, or i f they must be determined experimentally in each case. In the following, the applied hyperthermia system is firsf described. A theoretical tissue model based on the one-dimensional bioheat transfer equation is developed, and the computer simulation program and the chosen control model structure are presented. Next, the prediction error identification method is adapted to the current problem, and the method is applied, first to input-output data from the simulation model and then to data from 24 clinical treatments. Finally, the model structure and the calculated and estimated model parameter values are evaluated and compared in regard to accuracy and usefulness. 11. THEHYPERTHERMIA SYSTEM In the hyperthermia system used for the patient treatments (Fig. I ) , power is applied to the tissue through an inductive applicator, and surface cooling is provided with a plastic bag with recirculating distilled water. The system is further described in 141. The effect of heating and cooling will decrease with. distance from the tissue surface. and the combined effect can cause a temperiture maximum in a fairly superficial point (maximum depth 23 cm; see Fig. 2). The tumor is assumed to be located between +I and x2. By manual adjustments of heating power and cooling water temperature. two temperdtures. e.g.. T(.rl) and TLr?), can be controllcd. I n a new version of the system. a microcomputer per- , T' = 7' - Thi h the increase in temperature in relation to hlood trniperaiure y IW/(m . "C)]is thermal conductivity of tissue p, c, and ph Ikg/m'] arc densities of tissues and hlood and q, [W . s/(kg . "C)]are specific heats of tissue and blood m [m'/(s kg)] is flow rate of blood per unit mass of tissue S(x) [W/m2) is the absorbed power density. The gain as defined in [SI is . COOLING Fig I.Block diagram ( i one-channel f hypenhenntii ryricm where X Distenc. lrom surfor. Coolins ~ H W I Fig. 2. Temperature distribution in tissue along an axis through the middle of the applicator. P = Al, [W] is the absorbed EM-power A [m2] is the applicator area 1, [Wlm'] is the average transmitted EM-power at the surface per unit area. where For a plane wave C(x) = ( I / A L ) L [m] is the depth where the plane wave power is reduced by a factor e. Simulations and measurements on phantom material 141 show, however, that although the decay is close to exponential, the plane wave approximation is unacceptable. instead an empirical expression is used Fig. 3 . Cantml plant. io is transmitted EM-power. T. is cooling water lcmperature. T l x , ) and T(x,) are tissue kmperatures in depths x, and x2. (3) where the constant B and the actual penetration depth Lh forms feedback control of two tissue temperatures 161, are determined from phantom measurements. The surface cooling gives a boundary condition [12]. To design the controller, a reliable model of the thermal process is required (see Fig. 3). Ill. MODELS A. Theoretical Model Modeling of the process (see Fig. 3) consists of two steps: calculation of the local power density from the ap- plicator, and calculation of the temperature distribution in the tissue as a result of the generated power. The bioheat transfer equation is a widely used mathematical basis for thermal tissue models. Although it is known to have several limitations, it has proven to be quite useful for obtaining the major features of the temperature distribution in relatively large regions of the body [13]. As the power density variation around an axis through the middle of the applicator is small in directions perpendicular to this axis [4], a one-dimensional approximation is considered reasonable. The results of this study can give some further evidence of the validity of the applied assumptions and approximations. For a semi-infinite homogeneous volume of tissue the bioheat transfer equation takes the form where k [W/(m2 . "C)] is heat transfer coefficient between cooling water and tissue T, ["C] is cooling water temperature. Using the Laplace transform the following solution is obtained: B + . +. -Y 1 where x [m] is distance from surface t [ S I is time T = T(x.I ) [ "C] is tissue temperature Th I "C] is the temperature of blood entering the region - I + - Y k -1 -L :+ - a (5) 419 KNUOSEN A N D OVERGAARD: IDENTIFICATION OF THERMAL MODEL FOR HUMAN TISSUE where s is the Laplace operator, u = Y/P,C,. Tb . and L'= j z (6) PbcbPim A s LJm] is the depth where the cooling gain is reduced I(...-S & T 1.ST T. Fig. 4. The control model. All model paramnen am lunciions of depth. by a factor e (see (8) below), we shall denote it as the penetration depth for surface cooling. Note that the heating gain is the steady state increase in The steady state solution (s = O) is temperature T' per unit power input, when the cooling water temperature is equal to the blood temperature. T(X) = K,(X) (T,- Tb) + fo + Tb (7) In block diagram form, the structure is even more eviwhere the cooling gain is dent (Fig. 4). For homogeneous tissue K, and Kh can be calculated Kc(x) = (8) and (9) i f the tissue parameters and the applicator from -, gain is known. The time constant can be approximated, I+' kLc using (IO), to - and the heating gain is Kh 5=-- Y B - Kh - p,c,L,,eXiLk. B (12) .. I+- The initial slope of T(.h f ) as response to a unit step input fo(s)= l/s is Iv. PARAMETER ESTIMATION To estimate the model parameters o f the control model a corresponding stochastic discrete time model is used [E]. + ~ ' ( n I ) = e,T'(n) + e2Tf(n- n , ) $. Simularion Model The time solution T(x, r) can be obtained from ( 5 ) by inverse Laplace transformation. To obtain a more general program, capable of simulating inhomogeneous tissue with temperature dependent blood perfusion. a numerical method is needed, and a simple finite difference method has been chosen to implement the computer simulation model [ 6 ] . In this study. only homogeneous tissue with constant blood perfusion is simulated. C. Control Model + OJo(n) + (1 + 6,q-I) e ( n + I) (13) e-"' , e2 = k,(i - e-&"'), e, = kh(l - where: O, = e-&'') and T' = T Tb.TE = T, - Tb.AI is the sampling time, and n indicates the discrete time as f = n . Af. n , = round (To/Af)represents the delay. e ( n ) is a white random sequence, and q-' is the backward shift operator. The last term in (13) represents system noise. Using the one-step predictor structure [E], 191 - - ~ h ( n+ I ) = B I ~ ' ( n + ) Bz~:.(n n , ) + O o ( n ) + &4e(n) The principal requirement on the control model is a c(n) = Th(n) T'(n) (14) simple structure and few but significant parameters. A first-order transfer function plus a time delay for cooling the estimate o f the parameter vector 6 = {81~~&8,)'minimizing the error variance E{&, e)) is determined. As effect meet this demand: the identification is carried out after completion of the I treatment, only nonrecursive identification is considered. T(x. s) = [K,(x) e-"'""'(T,.(s) I s 7(x) Estimation o f the noise parametere, requires more SamTb(s)) + Kh(x) fds)] f Th(s). (1 1) ples than are obtained during a patient treatment; therefore, 6, ,values are assumed a priori. in the Appendix it The four control models parameters are is shown how the remaining parameter vector is dctermined for Og = O and 8, = 0,. In both cases the delay n, ["C/(w/m')l heating gain: Kh is determined by a separate minimum search. cooling gain: K, ["C/Tl To evaluate the identified model the model output T,,(~I) = B $ : ( n ) + Tb(see (18) i n the Appendix) shall be plortime constant: r [sl teú together with the measured data. and the root nrean time Jeliiy: r,, [si. q u i r e tRMS) rnodcl error - + . - . ! 1Ro TISSUEDATAUSEDIN THE SIMULATION Paa;&r 1lLIH tym __+ 3.5 , I¡' 0.44 0.029 @.O015 It' 0.44 0.8 , 10'' 0.9 m.02~ 0.0034 3.5 . 16' 0.M 0.6 . 10'' 0.9 o. o29 0.0091 3.5 . 1)' 0.64 0.6 ' 10.' 0.9 0.029 O.OU64 4.0 . it' 0.57 1.0 . IO*' 1.0 0.031 0.0085 4.0 , 10. 0.57 1.0 . IO" 1.0 D.031 0.017 2.0 . 1I' 0.20 0.011. IO-' 0.06 113 0.010 3.5 ' Y shall be calculated. v. IDENTIFICATION OF SIMIJ~(TION MODE& Based on input-output dam from the four control model parameters seven differenttypes of An experimentally coefficient between id[W/m2 TI, is The power density is calcoiated as . From measumments on phantom cm applicator, values of B and applicator on skin surface: B 10 mm water layer: B rial with a 6 x 4 I 0.1 Lh B 0.5 3 0.1 Lh B .& L. 3 In the simulations, a 10 mm water la er is assumep. For identification of the simul~tio I&) and T&) are step functions. A s 'good requires weak correlation between t& inputs, the steqs are not simultaneous. TlMf Iminl 'k e; KNUDSEN AND OVERGA4RD. II>ENTIFICATION OF THERMAL MOUEL FOR HUMAN TISSUE IHI I I, , 5 O W 20 40 30 50 M P I W jmmj DEPTH lmml O ' 10 7 3 7 -E 3 8 O o i ..- 1 0 m 3 0 4 0 5 0 DEPTH Imml Fig. 6. Estimated contml model panmeten: heating gain Kb,time constant T. cooling gain K.. and delay Y<, four the simulated tissue types listed in Table I . vcmus depth. (Only discrete time-delay valuer T ~ ,= n , ' AI c m be assumed.) VI. IDENTIFICATION BASEDON PATIENT DATA The patient data come from treatment of six patients with seven tumors; see Table 11. Each tumor has received from three to six treatments. and a total of 24 treatments have been analyzed in this study. The recorded data consist o f tissue temperatures measurrd along the central tumor axis in 4 depths I cm span, in and on both sides of . .~ .. the tumor, skin surfwe temperatures in 2-3 locations, and p w e r delivered to and reflected from the applicator. .As the cooling water temperature has not been recorded, it is estimated From the surface temperatures, the temperature of the water reservoir, and information of water circulation. The sampling time For the tissue temperatures vanes during the treatment (30-200 s). so to comply with the idcniiticati«n algorithms. nioditied datasets with constant lime intervals are generated by means of linear interpolation. The b l w d teniperaturcs are assumed to be equal to the initial tissue temperaturcs. The results of rhc identilications are presented 35 p l i m o f thc cuntrd model pariinicten venus depth. For a m - T A B L E 11 ANALYZED PATIENTS AND I' 65 ' P'iMrY fvmr III* 1 ~ 1 tmr TUMORS '' q'"b'"fanewr i"tC.1 hii:010w 'a'on adc"oc4rc'noma 'OlDn IdF"OWCl"OM rnf*lt.I?I *2 o E 65 F '"W'W1 irmpn "ode > " 2 i 4 Cn 74 M n e t t node >,<.a 61 Y 1"q"in.l' I i V " "OO. id", C. 65 I 'ngvln~l d ~ i i I t n 1,'4* cn iarynX i m i r n o i d C.rclnOm .bdWe" M I > g n . n l in1,nm Mcl alignaninelmom ""e 1i F weiit 70 M "CCL nodi 5iii6 CI ,.<.I C. breast I ~ ~ Q C I I C ~ ~ M L 1.r""" CD,d.<illld c,~c,*,,~l parison the corresponding simulation parameters for four representative tissue types are replotted as well. Thc heating gain and time conhiant is recorded for six conbccuiivc trcatrnrnrr o f a tumor in Fig. 7 í 3 ) . The mean and >tdri,l,trd f 'h/0 5 1 O zc Y '0 5 IO O 20 30 40 50 40 50 DEPTH lmml Kh'B . ,E -- 1 I I 4 , U e 7 0 3 z 0 a g 2 I ' O 0 '0 20 30 40 50 10 O DEPTH I mml *. L_ - r. -.-. Lr c .__ r- 20 30 DEPTHImmJ Fig. 7. Estimated heating gains and time constants for patients. (a) For six consecutive treatments of tumor F. (b) Mean and standard deviation foi tumor AI (three treatments). tumor B (six treatments), and tumor F (six treatments). deviation of Kh and r are recorded for three different tuW e mors in Fig. 7(b). A s the temperature probe depth vanes -E between treatments the mean is based on linear interpoI 3 lation of individual values. The average rms model e m r for all treatments is O.1o C. 7 The estimated values of cooling gain are mostly unree 2 liable, as they do not decrease with distance, and even z negative values are obtained. I n these cases estimation of J 1 heating gain and time constant is repeated with heating i ! power as the only input, ¡.e., the cooling gain is a priori t Y .assumed to be zero. The difference between the estimated I heating gain and time constant values with and without ' 2 3 4 5 6 cooling is typically less than 10 percent. TREATMENT NUMBER The model parameters have also been plotted as a funC- Fig. 8. Hating gains V C ~ S Utreatment S n u n i k r fortumorü. (Depths 5 mm: O. I5 mm: x.25 mm: O . ) tion of treatment number. Fig. 8 shows the heating gain for six consecutive weekly treatments of a tumor. The time constant shows a similar lack of trend. sponding output temperatures TM of the identified control Finally, Fig. 9 shows the patient data versus time for a model. The rms model errors are 0.21", 0.15". 0.20", typical treatment with manual control, and the corre.. and 0.16" for 5 , 15, 25, and 35 mm depths. ,-. e í>il>\f * A h 0 OVERGi\ARI> I0I:NTIFICATION O F THERMAL MOOEL FOR HUMAN TISSUE I 04) IS 30 45 15 30 45 rc O TIME (min) .. í:i,g. 9. Iiipul power 1.. cooling waler iemperature J. mcarured tissue lcmP:atun:s Tíx) for the founh treatment of t u w r F (depth x = 5 mm: El, IS mi: @. 25 mm: X . 35 mm: +). and control model output lemp : ~ n : svM: VIL DISCUSS~ON AND CONCLUSION 7 he@$ is a good agreement between the control model oiit iuts and the simulated or measured tissue temperatiirm, as :ieen in Figs. 5 and 9 and from typical rms model t:lmv values of O. 1-0.2" C. Accordingly, the simple conCrol mcdel structure appears to be adequate. The results in !;ect.on V show that blood flow variations have a considi:rable effect on the model parameters but, nevertheh!, the linear control model fits well for real tissue over il large temperature interval. An explanation may be that i.he blood Row in most of the treated tumors may not have e:rc:edt:d the blood Row in resting muscle [IO]. 1 he csi.imated values of the heating gain and time constai,t show large variations. For consecutive treatments of the same tumor the standard deviation of both parameters is tipically 20-60 percent (Fig. 7 ) . There is no trend in i,he panimeter values for a specific tumor as the treatment piuyesses. 111 mosi cases. the cooling water gain and the time delay could not be estimated froni the patient data. This was due lo the wriations o f the cmiling water tetriprrature being tu« small and corre1atr.d w i t h power input. and t o the re- 483 cording of the cooling water temperature being inaccurate. In future systems where the cooling water teniperature shall be used as a computer control variable, both problems will probably vanish. The question is now,'which method should be chosen to determine the parameter values: a calculation based on a priori assumptions about tissue parameter values or an estimation based on experimental data? Using the first alternative. the model parameters can be determined as a weighted average of the parameters for different types of homogeneous tissue, using the curves in Fig. 6 or the expressions (8). (9). and (12). It requires a knowledge of the tissue composition and values of all the parameters in the theoretical model. In addition, the theoretical model structure is crucial-Le., the applied bioheat transfers equation must be a valid mathematical model. The advantage of this method is that it is easy, and that it requires no treatment data. This is important for prospective and comparative dosimetry. The disadvantage is the lack of accuracy. The results in this study seem to indicate that the theoretically determined parameter values may be off by a factor of 2-3. There are indications that insufficient knowledge of the applicator gain contributes significantly to this lack of accuracy. For example, measurements of power distribution in phantom material show large variation in B (3) for different water layers, and the applicator efficiency seems to vary as very hot applicators have been experienced during some patient treatments. Another crucia1 parameter is the blood perfusion; the physical interpretation of the blood flow rate m in ( I ) is questionable, and the values given in the literature show large variations. Accordingly, - . an accurate a r>rioridetermination o f the control model parameters studies of the validity of the applied a priori assumptions. The experimental method only requires that the structure of the control model is reasonable. The structure of experimental models is generally far less crucial than the StNcture of theoretical models. Consequently, the method has two distinct advantages: it is accurate, and it requires no a priori knowledge of patient anatomy, tissue parameters, applicator gain, etc. The main disadvantage is that it can only be employed during and after treatments. When the purpose of the model is to determine the parameters in feedback control algorithms (concurrent dosimetry), the identification must be performed on line in the beginning of each treatment. This constitutes a selftuning or adaptive controller. as described in [ I 11 and [ 121. I f further studies reveal that time dependent control model parameters are appropriate to reflect variations in blood perfusion, a recursive parameter estimation must be performed during the complete treatment. In reference to the stated purpose nf this study the conclusion is -the stmeture o f the control model i?i adequate: -the niodel parameter values for homogeneouh tksue, determined from <I priori assumed parameter \slues hy identitication o f the siniulation model 2nd by an.d)tical calculaii~iii. b h o u good ~ i i u t u a lagrwtiteni. hiit \ t i t t i ihc : .. ., . -- IIII 4k-1 IY.\P,\A< IIO,, ,>L. h l ~ ! \ ~ l\ Ii ~I lV~, , I ~ I I . ~ I ~ , .\,>I W I t i i\ I ) 5. V A \ l w h available II priori knowledge. they do not accurately re- and thc gradient vector and H w i m matrix a f t produce the experimentally estimated values: N 2 -for the analyzed patient treatments. the heating gains c(e)= -- C (T'OO - r;,(w~ ( 1 1 .e) N.=i and the time constant have heen estimated. The results show large variations even for consecutive treatments of N 2 the same tumor. A reliable estimation of cooling gain and H(e) z R(e) = 2; ~ ( r i .e) +'<ri. e). time delay requires a more vigorous variation of the coolN.-i ing water temperature. The parameter vector is then determined iteratively from -approximate values for the control model parameters can easily be calculated. If. however, an accurate model 0 . = 0 c..). - (W, + p , E ) - ' G , . (20) is required, an identification in each treatment based on experimental data is recommended. E is the unit matrix. Small values of p give fast convergence, as p = O corresponds to a Newton iteration, and P APPENDIX = m to steepest descent. PARAMETER ESTIMATION I f the noise sequence e ( n ) is Gaussian, a maximum An estimate of the parameter vector 0 = {ol&&}r in likelihood estimation is obtained by the Markov method. the discrete time model (13) is determined for two special' In both methods. the delay nl is determined by a separate cases of the prediction enor method [ 9 ] . The two cases minimUm search as the integer giving minimum Vahe O f correspond to two specific u priori assumptions about the the performance index. noise. ACKNOWLEDGMENT -9, = O gives the simple least squares method, where 6 can be found analytically. Significant parts of the work behind this study have been Introducing the signal vector In particular we are grateful to done in student projects. . . J. E. Duhn who constructed the identification program. {T'(,,- 1) T : ( ~- - 1) lo(n(15) - a performance index, equal to an estimate of the mean square error, can be written N N 1 1 &n) = - C Nn=i N n = l p(e) = - C - ~ y n ) ) * . (16) A s v, is independent of 8, the value 6 minimizing (16) can be found analytically as (17) 6 = -H-'Gío) where the gradient vector is and the Hessian matrix is H=B4 = 0, leads to the Markov method. iTL(" - Tf(n - '1 A s the signal vector - I ) 'o@ - I)}' (18) is now a function Of the be determined analytically. 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"Hypenhemis cancer therapy: Modelling, parameter estimaiian and ciinin>tof icmperatum disiribution in human tissue." in Proc. 1 1 t h IFlP COMJS.ysr. Model Opiirnizolion. DO. 709-716. 1984. 171 H. P. Schwan and K. R. Foster. "RF-field interactions with biological systems: Electrical pmpenies and biophysical mechanisms." Proc. IEEE. vol. 68, pp. IW-113. Jan. 1980. IS] K. J. Astmm. Inirodurrion IO Srorh,~riii.Conrrol 7hto-. New York: Academic. PP. 162-179. ~ 8 0 . 191 "Maximum likelihood and prcdiriion emor melhds." AUIOmarira, vol. 16. pp. 551-574. 1980. [ I O ] I. W. Strohbehn, CI o/.. '' Blood Row ciiecis on ihc i c r n p e r a t k dirtñbulion fmm an invasive m i c m w w mtcnna a m y used in cancer therapy." IEEE Trons. Bioinrd. E t q . . vol. BME-29, pp. 649-661. 1982. ( 1 I] M. Knudrcn, et 01. , "Hypenhem)ia system with self-iuning coniml of temperature disirihuiion in I~SSUC:' in Proc. 4rh /ni. S?mp. H?. perrhermie f l ~ l c o l o ~vol. y. I . London. England: Taylor and Fnnc i s , 1984. pp. 691-694. 1121 M . Knudsen and L. Heinzl, "Two-pin1 coniml oficmperaium profile in lissue." submitted to In,, J. Hyp<.rrhrrmio. 1131 R . B. Roemec. "Thermal modelling." in Prrir. 4rh /ni. Symp. H y perihmnic flncolop. val. 2. London. England: Taylor and Francis. 1985. pp. 293-298. .. N vz(n9 e) REFERENCES elW(n - I, e) (19) -. KY1Jl)'ihN A N > ,.>YBRGt\.4Rl> I1)ENTIFICATION OF THERMAL MOI>EL FOR HUMAN TISSUE >lwtm linudsen received the M.S. degree in dectricil engineering from the Technical Umversity of Denmark. Copenhagen, in 1963. From 1965 to 1968 he was with the Selva Lab- 485 Jens Overgaard war born on November 27. 1945. He graduated from the Univcrjiiy of Aarhur hirdical School. Aarhus. Denmark, in 1971. Fmm 1971 to 1976 he trained in clinical medicine and in cell and radiation biology. Fmm 1976 u> 1977 hc was a resident in ndiation medicine at oniiiry. Tcchnical University of Denmark. From 1968 lo 1969 he was a Systems Enginem at General Dynamics, Rochester, NY. and from 1969 to Massachurenr General Hospital. Boston. MA, and 1971hc was implcmentingcomputcrcontn>lin the was a Clinical Fellow in radiation therapy at Harpapcc industry with Measurex Corporation. Santa vnrd Medical School, Cambridge. Cumntly he is Clan. CA. Since 1971 he has been an Associate Headof the Seclion of Expcrimental Oncolow and Profcisor of Control Engineering at the institute Radiotherapy, the InstiNte of Cancer Research. 01 Elzcironic Systems. Aalborg University, Aalborg. Denmark. His lnain Radiumstationen. Aarhus. H e has participated in clinical and fundamenial i i i t c ~ ~ shave t s been modeling. identification and contml o f energy pmduc- research in hyperthermia and cancer treatment since 1969. ¡rig and distrihuting system%and in recent ycan of cancer hyperthemia Dr.Overgaard is President o f European Society for Hyperthermic on. sirlenis. cology. and was Chairman of the organizing committee for the 4th International Symposium on Hyperthcmic Oncology, Aarhus, 1984. i " . l . 1 . .".. ^. I . ,._. *-., d. k. 4. i r o i t s k i i , A. Gustov, ,,>rt>aChev, L. Siz'minh. ! , >' 'lechkov, E. A ' Aransher+v. OladyshMina, I , I; i:obrynina, A. i i i . A. Odintsov > . :i ' . i' f.idl. ctiermometry bas : ) : I e! e;tromagnetic : frequadcy raage of tile , i n t e r n a l i n t e 4 i t y of the r a , i i q e d s s i o n s of ure of $&adiating La3ers: is being tmEe +es i t possibte ; t o -sure to the penetrat:.q depdh o f the contea4 at wavelengths 'froca 1 t o 30 to '1 O.& .lo, and qor layers with 4 low water is tw wavelendth in a vacuum . Thus f o r o f tw human bddy a t a wavelendth of 30 cm - t e :e.i .t Corky/Sdent a wavelength i .: oi n antenna, a r I:,. :nta t antenna is 1 i I r ,vid d b y a quarter e - . , .c:ic ~ , f the antenn 5,: I'-i u r f ~ c z boundary is a ? ':ir: f the antenn 1.t :'I. ' ~ 'h iadiometer i s a fcsquency o f 9 Fti :; .gial , modulated w i 8: ' . b i g o : 3 p a r e m t r i c t i :,irim tc.ic amplifie 01: ; Y based on a 0 . 1 . i i r c u i t which oh' ' : f a t i . n time constant pi' :'o a K;P = 4 potenti (If t'.e radioueter t. if. I I . .#O i i . v m t i g a t e p a i ,[l . 'Fie mx;t valuable ab!' ll'itmi! :BLues o.f dept 1':i:uea : y is achieve I! i f w : ,of the powe 1*?i !. ( ! r ? o . : . Variation I: (3 i' :I ?,eral degre ;"l1 * l 'tliai: ) oven taking 8i' '': 'h? :-<,<'ired accu 0 : :'?(luce by an ii.Liiai:i i n . This í ' X : O : ';md ~ from t (:uLt :I> guarantee I 'iii:.t,zai. n '? ( I d i f f e r s í thi ~ .-.-~ ...,.,- -._ ';'n rk:, ~idiopliysic Ir-,'l.':;ll Ill 3t:itute of t 3 'r'?kii:x.k-i,No. 3, twiq Resejarch Iqstitute I p d i c a l radiot:hepmonieter which dtgloped; The rad&thermmetríc co)npleX coni t , and radic-emissím c a l i b r a t o r s . line. b t c h i n g t o t1.e human body lancing( loop of simi1.aa size^. The ion w k f f i c i e n t R at. the antenna/ ge 4 d de*& on the nature of the: tkssues. The ch provides d i m c t amplificas given i n I'igl. 1. The infrequency é.r+ifier contween the nlo+lator and 14 type. The, quadratic ion of the ra(liorPter. engineering, ha@ two rom O t c 30 dB and outr. The fluctfution thrarihof 4 sec is 0.025"C. depth temperpure i s used that of d e t e h i n f n g the an +O.icC. This l e v e l i c u l t i e s ahd above a l l undary on the measure25 range r(su1t i n an Researcb r e s u l t s have mation formulp does not ake i t possi)ie t o e i i e of R on th& temperature o f reflection from the [3]. But i t is q u i t e of the bodf p a r í s being ¡ . S . II. Kirov aaslated from W d i t s i r i r z i r t e d S'pdember 28. R. and the ' i a Fig. 1. Block diagram o f the radiometer. 1) Antenna; 2 ) c i r c u l a t o r ; 3) modulator; 4) c i r c u l a t o r ; 5) parametric a m p l i f i e r ; 6) t r a n s i s t o r a m p l i f i e r ; 7) quadratic d e t e c t o r ; 8) low-frequency iinit; 9) KSP-4 p r i n t e r ; 10) n o i s e g e n e r a t o r ; 11) attenuator; 12) minicomputer; 13) power unit. A method i s proposed i n [4] i n which t h e e f f e c t o f R on t h e r e s u l t s o f t h e measurement o f temperature i s s i g n i f i c a n t l y weakened. For the sake of s i m p l i c i t y l e t us assume that t h antenna does not have loss and d i s p e r s i o n . I n that case the radiothermometer r e g i s t e r s nitudes which a r e p r o p o r t i o n a l t o t h e e x p r e s s i o n T, - T,R + TnR, where T, i s t h e average temperature,whereT=R i s t h e r e f l e c t e d s i g n a l from the antennalbody boundary, and TnR i s s i g n a l a r i s i n g from r e f l e c t i o n o f i n t e r n a l n o i s e from the same boundary. It i s apparent t h e expression t h a t i f t h e temperature o f the input elements o f the radiometer and theavera temperature of t h e o b j e c t b e i n g measured a r e kept equal (Ta Tn), i . e . , i f thermodynamic e q u i l i b r i u m i s maintained, then t h e decrease of t h e useful s i g n a l by an amount TaR w i l l be During t h e mcasurement t h r . Lempercompensated by i n t e r n a l n o i s e r e f l e c t e d from t h e boundary. a t u r e o f t h e input d e v i c e s and one of t h e c a l i b r a t o r s is kept approximately equal t o the average temperature o f t h e body. E r r o r due t o mismatching under these c o n d i t i o n s Of approxi mate thermodynamic e q u i l i b r i u m does n o t exceed 0.1"C. - i lbo r a d i o emission c a l i b r a t o r s were used t o c a l i b r a t e t h e s i g n a l : water heated t o tem- 1 ,' peratures o f 33 and 36'C and contained i n thermostats of the Ti.-150 type. A f t e r recording o f t h e c a l i b r a t i o n t h e antenna w a s p l a c e d on t h e area t o be i n v e s t i g a t e d and t h e radiometer 4 s i g n a l was recorded. the the method described above was t e s t e d by means o f measurements, using a radiothermometer and a mercury c a l i b r a t i n g thermometer, o f t h e temperature of human t i s s u e e q u i v a l e n t s . Their r e s u l t s coincided w i t h an accuracy o f ?0.loC. I n l i v i n g tissue w i t h a temperature gradient the radiometer measures an averaged temperature o f t h e r a d i a t i n g l a y e r s , which, f o r t h e head, i s 1-1.5OC lower than t h e depth temperature. This was confirmed experimentally by radioand electrothermometer measurements o f c r a n i o c e r e b r a l temperature during ventriculography. We have been using t h i s new noninvasive method f o r a number of years i n c l i n i c a l p r a c t i o t o i n v e s t i g a t e average depth temperatures. The r e s u l t s o f t h e examination o f 300 p a t i e n t s s u f f e r i n g from i l l n e s s e s o f t h e nervous system and i n t e r n a l organs t e s t i f y t o t h e valuable d i a g n o s t i c p o s s i b i l i t i e s o f t h e radiothermometric method [ 2 ] . LITERATURE CITED 1. 2. 3. 4. 80 A. B a r r e t t and P. Myers, Science, V. S. T m i t s k i i , A. V. Gustov, I. 12, 669-671 (1975). F. Belov, e t a l . , Usp. F i z . Nauk., (1981). V. S . T r o i t s k i i , V. I. Abramov, I. F. B e l o v , e t a l . , R a d i o f i z i k a , 24, No. 1, 118-121 (1981). V. S. T r o i t s k i i , i b i d . . 2, No. 9, 1054-1061. g, No. 1, 155-158 I z v . Vysch. Uchebn. Zaved.. , 405 iEEE TRANSACTIONS ON BIOMEDICAL E f f i l N E W f f i . VOL. BMI-33. NO 4. APRIL I986 Aberrant Heating: A Problem in Regional Hyperthermia MARK J. HAGMANN, MWBER, IEEE. AND ffi RONALD L. LEVIN a mannequin filled with tissue-equivalent phantom material. The measured rate of energy deposition (specific absorption rate, or SAR) in the neck war found to be 2.2 times that in the abdomen when the APA was positioned for abdominal heating [7], [SI. The local SAR in the neck was reduced to 30 percent of that in the abdomen when a and 580 MHi. The local ntu of rnerl(y saline-@led bolus was placed around the neck of the mane h n t . and thlsb oftan exceed that In the omen. TIN P*<m düir nequin 171. In clinical tests made with the APA, a salineihcrnnt healing Is dependent upon the WiitioM of Ue arbs OIÚl2p. filled pillow is usually placed under the patient’s head and ~ h c r n nheating t appears te hc much les# prososirrd fer tre4tmcnt neck to d u c e neck heating and improve patient comfort of the thigh or upper arm than it is for tr(atiMn< d the .Mown. [8]. In other tests, when a helical coil applicator was used to heat one thigh of a mannequin filled with tissue-equivI. INTRODUCTION alent phantom material, the deposition measured in the PERTHERMIA has shown considcrnble pmrnise cmtch exceeded that in the thigh [SI.Another phenomefor the adjuvant treatment oficancer, but ii is esen- non that could not be evaluated without realistic threetia1 that the heat be delivered to the tumor region with a dimensional modeling is the localized surface heating that high degree of precision [l]. IQeaiiy the tanperanire has been measured near the tapered waist of a female throughout the volume of both the tumor and the sur- model when heated with the APA [71, [IO]. rounding normal tissue would be known so that one could Numerical sotutigns obtained using block models of determine the degree of uniformity of treatment to the tu- man have been used in the evaluation of biological hazmor and also estimate the extent ‘of possible damage to ards from exposure to electromagnetic fields [ i l l , [12]. the normal tissue. In practice temperanire p m k are used These selutions have predicted several experimentally obfor measurements at only a few iltracavity or intet)tliiai served phenomena including selective heating of the neck locations. The degree of sampling may be somewhat in- [I21 and head resonance [13], as well as the enhancement creased by moving a probe locrted within a peicdta- of energy deposition due to the ground and reflectors [ 141 neously placed catheter [Z] or by using temperatun probes or by one or more other bodies [15]. having multiple sensors [31. We believe that quantitative treatment by hyperthermia 11. METHODS requires the use of electromagnetit and thermal modeling In this paper we have continued to use the 180 cell block for estimation of the temperatuniat locations other than those where the probes are located. This is particularly model of man as shown in Fig. 1, which was developed important when frequencies below 1GHz arc used M treat earlier by one of IS (Hagmann) [ 1 I], [12]. The cubical deep-seated tumors, since depositbn is not as localized at cells of the model have various sizes and are arranged for such frequencies. Others have used two-dhensional-ekc- a best fit of diagrams of the 50th percentile standard man. tromagnetic modeling in attempts;to characterize the en- A partial correction for dielectric inhomogeneities is made ergy deposition in a cross section:of the body duriig hy- by using a volume-weighted complex permittivity for each perthermia [4]-[6]. Realistic three-dimensional modeling, cubical cell based on the partitioning of 12 different types however, is needed to explain the phenomenon of aber- of tissue throughout the body. Thus far, we have considered only idealized applicators rant heating. which we define to bC energy dapasition eutside the region intended for treatpent. Abermnt heating in order to highlight the effects of aberrant heating. We of the neck has been observed in measurements made have made the appmximation that the incident electric when a BSD annular phased array (APA) was uced to heal fKld has constant magnitude and orientation within the expose4 volume and is zero elsewhere throughout the Minurcnpt received (kioober 29. iQR4: *vised S e p ~ e r n b a18. 1985. body. Thus, deposition of energy throughout the rest of The ruthon un: with the Biomrdicrl Enginunng and Immrnoniition the body occurs only by means of scattering from the exI4rrnr.h. D i \ i h n uf R s x a x h knicsa. National initiiuies of Heiihh. i k. posed volume. If the incident electric %Id is nonzero outiherdr. M D : O N 5 side the volume chosen for treatment, then aberrant heatIEEE~ . ~ ~* up m h c XJO~ISS r A b w l - A 100 cell block ntvdel of myI b u ka und to cuepte the pittern of energy deposition w k n r&-frwtfCnicy ip)l*itglire used for irutment of cancer hy hyperthqmia. When the iLdohan ir exposed with p o h r h t b n praliel to the h of the hody at g*lWneics from 10 to ó0 MH.,ipproKimma)y M c.mal ol tb toW ene r g l ir deposited outride of lhe ahdomen. Whb I r r l i o n ir InurW to u much u W p e r m 1 at several resonanbs whkh 9cco1 betweCa 1W r rm‘nmC-RH w U.S. Gokernrnsnt work not protected by U.S. copyrixht Y a E F R T O W K I (11HZ. > Fig. 2. Whole and regionrl SAR for plane-wavc crposurc head dotted. lower a m dashed. mean solid. Fig. 1. Realistic block model of man showing regions ing will tend to be more pronounced than is shown in the present calculations for idealized applicators. For example, when the APA is positioned for abdominal heating of a phantom-filled mannequin, the aberrant neck heating is significantly increased i f the water bolus about the abdomen is deflated (71. Since the water bolus serves to confine the incident electric field to the abdomen, the incident electric field at the neck is greatly increased by deflation of the bolus and so the neck heating is increased. W e have not attempted to address the issue of local deposition since a block model with much greater detail would be required before the values o f deposition at various points could be obtained with accuracy. The volume average deposition was evaluated in the head, neck, upper arm, lower arm, upper torso, lower torso, upper leg, and lower leg, with these eight body regions defined for the model as shown in Fig. 1. The lack of symmetry in solutions for exposure of one thigh or upper arm required that 1 6 body regions be used since the calculated values of deposition were different in the left and right halves of the model. Fig. 2 shows the frequency dependence of the average and local SAR for exposure of the model shown in Fig. 1 to a plane-wave having Z polarization (parallel to the length of the body) and a time-average power density of 1 mWlcm2. The phenomena of head and arm resonance, which are apparent in Fig. 2 , have been described previously 1131, 1151. Resonances are also present in the following figures of this paper which pertain to exposure with idealized hyperthermia applicators. The calculations for each figure were made using a total of 96 frequencies from IO to IO00 MHz in order to illustrate the pronounced dependence of energy deposition on frequency. 111. RESULTSAND DISCUSSION A. Abdominal Exposure Fig. 3 shows two different block models that were used in order to determine the possible effects o f limb positions on aberrant heating. In pose I , which is the same as Fig. 1. the arms are down at the sides and the feet are together. In pose I1 the arms extend outward from the sides and the centers of the feet are 100 cm apart. The cubical cells in which the incident field is present have been darkened in Fig. 3. Calculations were made for three different onentations of the incident electric field. The Z polarization, with the incident electric field parallel to the length of the body, approximates the AYA. The X and Y polarizations correspond to anterior-posterior and left-right onentations, respectively, which approximate exposure with parallel-plate (capacitive) applicators [ 161. Figs. 4 and 5 show the frequency-dependence of the fraction of the total heat dose that is delivered to the exposed ponion of the abdomen using poses I and 11, respectively. The two figures suggest that aberrant heating is strongly dependent upon the positions of the limbs and is generally most pronounced for the case o f Z polarization. The frequency-dependence shown in Figs. 4 and 5 may be summarized as follows. Below 60 MHz, the fraction is not sensitive to frequency, and for Z polarization, approximately 60-70 percent of the total heat dose occurs outside of the abdominal region. Aberrant deposition is most pronounced at various resonances between 100 and 500 MHz, where as much as 90 percent of the total energy deposition occurs outside of the abdomen. These resonances are dependent upon the positions of the a b s and legs. At frequencies well above 500 MHz, the deposition is localized due to the high absorption in tissue. Microwave applicators are known to provide localized treatment, but the relatively shallow penetration of tissue generally restricts their use to treatment of superficial tumors 1171. Deep-seated tumors can only be treated at microwave frequencies by the use of interstitial or intracavity applicators (181, [IS]. It should be noted that the block model solutions are likely to have appreciable error at frequencies equal to or greater than those corresponding to the extreme right-hand side of the two figures 1201. Table I gives the ratios of regional SAR to that in the 407 HAGMANN AND LEVIN: ABERRANT HEATNCl Fig. 3. T m poses used fot exposum of abdomen. TABLE I APPIIOXIWATE RATIOS OF &GIONAL DEWSlTION TO THATIN THE ABDOMEN 8 I a C r 1 6 - e 4 - I E AT L O W PLEQUENCIES FOR .".--...U p p a r Arm L w a r Arm Upper Torno upp.r X Lar., E O I 2 - '1 r R f A O B I # LO, Le, ,111 .45 .34 .47 .o1 TABLE 11 2 3 . I 5 6 78) 2 102 FRIPUfKI <fWZ > 3 4 ABWMEN 1 B.d, Ils*ion Heid Neck U p p e r Arm L o r i r Arm u p p e r TOI.0 u p p e r Le> 8 0 7 1 .iP 2.47 .I1 .64 .16 WORST-CASE RATIOS OF REOIONAL DEWSITION TO THATIN THE POR ALL~ E Q U E N C I EAND S POLARIZATIONS Fig. 4. Fraction dcpsiiian in c r p w d volume for pose I. i a z POLARRATION 1 L-ir Le, PO'< 1.1 3.1 4.4 5.9 4.1 1.7 1.6. I I1 ?O.. 1.0 3.1 4.b 4.4 1.9 1.9. o 45 ! I ? I I I) f x r O I D R exposed pan of the abdomen at IO MHz with both @$es for the case of 2 polaritation. The rdtios are all much lower for the other polarizations at frequenc¡es,below 60 MHr The large dilfcrcnce bctueen b a l u e h for the lower arm in the two pose6 is attributed to the difference in distance fmm the applicator. The SAR in the legs is also significantly different in the two poses. Table I1 gives the worst-case (maximum) ratios of regional SAR to that in the exposed pari of the abdomen for all frequencies (10-io00 MHz) and all three polarizations. In all except two cases which are noted in the table, ~ 2 polarization, and in the two the worst case O C C U ? ~for exceptions the valuer for Zpolanzations were only slightly less than the worst case. The values in Table 1 1are considerably greater than those in Table i, showing the pmnounced effects o f vanous resonances. Worst-case values are significantly less for pose II than for pose I in the upper torso, lower arm. upper leg, and lower leg. Fig>. 6 and 7 shou the ratio o f average SAR in the neck to thdt in the enpo\ed ponion of the ahdomen for pose> I 1 o Y I n E II S n ! i P O S E O n E a N 6 a I FIZOLWCY CHHZ. FREOLKKV <nH1.1 Fig. 6. Ratio of heating in neck to exposed abdomen for pose 1 polanutionr: X dotted. Y dashed, Z solid. > Fig. 8. Ratio of hating in lower innIO exposed abdomen for pose I poIafiutianr: X dotted, Y dashed, Z solid. I L F I E W E I C Y < U r n .> FREWEKV < M Z . > Fig. 7. Ratio of hating in neck to exposed abdomen for pose 11polan. utians: Xdoncd, Y dashed, Zsolid. and 11, respectively. It may be seen in the two figures that, as noted in Table 11, for the worst cases of frequency and polarization the average SAR in the neck is somewhat greater than three times that in the abdomen with either of the two poses. The two figures also show a pronounced difference in the frequency-dependencein the two poses. For example, the maximum ratio occurs at 300 MHz with pose I and 170 MHz in pose U. Figs. 8 and 9 show the ratio of average SAR in the lower arm to that in the exposed portion of the abdomen using poses I and 11, respectively. Tables I and 11 show that, either at 10 MHz or for worst-case conditions, aberrant heating is most pronounced in the arm. The two figIIRS each have a maximum near 150 MHz where arm resonance may be seen in Fig. 2 for plane-wave exposure. A second resonance near 300 MHz is just visible with pose I1 but dominates the lower frequency resonance with pose I. Fig. 9. Ratio of heating in lower ann to exposed abdomen for pose I1 polarizations: X doltcd. Y dashed. Z solid. B. A m Erposure Fig. 10 shows the block model used for evaluation of aberrant heating with exposure of the right upper arm. Calculations were only made for the incident field polarized parallel to the axis of the arm. Table I11 presents the worst-case ratios of regional SAR to that in the exposed portion of the right upper arm for frequencies from 10 to 10oO MHz. Aberrant heating appears to be much less pronounced than was found for exposure of the abdomen. Over the entire frequency range used for the calculations, the average SAR in each region outside of the right arm was less than 30 percent of that in the exposed region. Over the first decade in frequency, from 10 to 100 M.Hz, all regions except the right lower arm have values of average SAR that are less than 8 percent of that in the exposed region. Fig. 11shows the ratio of average SAR in the right lower arm to that in the exposed pari of the right upper ,,, , 409 i4 ',,;Y,6Ir11 .&P.ID LEVIN: ABER.RANT HEATING Fig. 12. Block model with thigh exposure. Fig. IO. B l o c k model with ann exposure TABLE 111 WoiIST..CAsE RATIOSOFREGIONAL DEPOSITION TOTHAT IN T H E UPPER A R M FOR ALL FRWUENCIES Bod, R e l o p i Heid ? L e í , > Heid ( R i g h t 1 Neck ( L c f I ) NrcL ( R i g h t 1 L e f r U p p e r Arm L i f t L o w r r Arm R i g h t Lower Aim L e f t Upper Toiio R i g h i U p p e r Torso . ., L e f t L o w e r Torso R i g h t L o w c r Tali0 L e f t upper Leg R i g h i Upper Leg L t f t Lower L l g R i g h i Lower Leg . , .. RIGHT RltiO .14 .14 .19 .12 .12 -18 1.16 .os .I3 .o4 . O8 .o3 .os .o1 .o3 II I L o Y E R , I. ... ... n R II S n ! E X P O s ..I ... -... E Q " i .... lhg. I I . Ratio oí healing in h g h i lower n m IO exposed hghi upper a m . .. ii,imi'oir - .. . <. TABLE 1V RATIOSOF REGIONAL DEPOSITION FOR TO THATIN ALL FREQUENCIES R.ti0 Body Region Head ( L c f r l Head ( R i g h t 1 Nick ( L c f r l Neck ( R i g h t 1 L e f t U p p e r Arm R i g h i U p p e r Arm L c f t Lower Aim R i g h t L o w e r Arm L e f t U p p r r Torso R i g h t U p p r i Torso L i f t L o w e r Tor10 R i g h t Lower RIGHTTHIGH Torso L e f t upper Leg L i f t Lower Leg R i g h t Lower Leg .I3 .I3 .41 .44 .a1 .34 .10 .53 .16 .35 .22 .29 .35 .14 .38 nounced than for exposure of the abdomen, the possibility of greater heating in the lower arm than in the exposed upper arm certainly needs to be considered in clinical applications. . . .. . WORST-CASE the block model in Fig. IO. The ratio has a max- iriuni of 2.16 at 330 MHz and a value of approximately I:) 8 from IO to 100 MHz. While the exposure in regions cI,stant from the applicator appears to be much less pro- C. niigh Exposure Fig. 12 shows the block model used for evaluation of aberrant heating with exposure of the right thigh. Calculations were only made for the incident field polarized parallel to the axis of the leg. Table IV presenfs the worstcase ratios of regional SAR to that in the exposed portion of the right thigh for frequencies from IO to IO00 MHz. Aberrant heating appears to be much less pronounced than was found for exposure of the abdomen, but is more evident than for exposure of the right upper a m . Most of the large ratios in Table IV occur at frequencies of 200 MHz or greater. For example. the ratio of average SAR for either side of the neck is less than 9 percent of that in the exposed part of the right thigh for frequencies from 10 to 170 MHz. Over the first decade i n frequency. from 10 to 100 MHz, the ratio of regional SAR to that in the exposed portion has a maximum of O.19 i n the right lower torso and does not exceed 0.16 in the other regions. Aberrant deposition may present a problem in treatment of the thigh at frequencies of 200 MHz or greater, but the extent o f that problem appears to be significantly less than that for treatment of the abdomen. IV . CONCLUSIONS When radio-frequency energy is used to induce hyperthermia, much of the heating may occur outside the region intended for treatment. Such aberrant heating is likely to go undetected during a treatment session since there are PractjFal limits on the number of temperature probes that m?y be used. For this reason we would strongly recommend that patient complaints regarding heating in varibus parts o f the body be taken seriously. Our results suggest that aberrant heating may generally be minimized by avoiding the use of frequencies in the resonance region which occurs from approximately 100500 MHz. In all calculations made for exposure of the abdomen, arm, and thigh, relatively low and stable values o f aberrant deposition were found at frequencies below 60 MHz. Another possibility is to use microwave frequencies for which the deposition is highly localized due to shallow penetration o f tissue. In some cases there may be a conflict between minimizing aberrant heating and other important factors. For example, when treating a portion of the human arm, efficient coupling of energy to the arm would be expected to occur at arm resonance. Since arm resonance is a manifestation o f the interaction o f the fields with the arm as a whole, the deposition is not well localized. As a second example, for the case of exposure of the abdomen, it appears that aberrant heating may be minimized by the use of other than 2 polarization. Parallel-plate (capacitive) applicators would provide these polarizations but are known to cause excessive heating o f the fat layers f161. The azimuthal polarization obtained with the Magnetrode would also be likely to limit aberrant heating, but this applicator is also known to provide little deposition near the body axis [Zl]. It is suggested that mannequin-shaped phantoms would often be more appropriate than phantoms having less realistic shapes for the experimental evaluation of radio-frequency applicators intended for use in hyperthermia. Since our calculations suggest that the positions o f the limbs will alter aberrant deposition, it would be best for the models to have arms and legs in positions typical of those during treatment. ACKNOWLEDGMENT The authors are grateful to Dr. E. J. Glaistein, Chief, Radiation Oncology Branch, COPIDCTINCI, for continued support and encouragement. Dr. Glatstein first suggested the phrase “aberrant heating” to describe the phenomena which are discussed in this paper. The authors also appreciate the assistance of R. O . Creccy o f ROB/ COP/DCT/NCI. REFERENCES [ I ] 0 . U. Hahn. “Hypcnhermia lor Ihr cnginccr: A shon biological primer.” /€€E Tmnr. Bioiomrd. En*.. vol. BME-31, pp. 3-8. Jan. 1904. 121 F. A . Gibbs. Ir.. M. D. Sapozink. K . S. Gates. and J . R . Sicwan. “Regional hypcnhemia with an annular phased a m y in the erperimentnl treatmenl of c.ncc~. Repon of work in pmgresr with a tcchnical emphasis.” IEEE Tronr. Biomed. Eng. vol. BME-31. pp. I 15119. Ian. 1984. 131 V. A . Vaguinc. D. A . Christensen. I . H.Lindlcy. a n d T . E. Walston. “Multiple sensor optical thcrmomiry system for application in clinical hyperthermia.” IEEE Trans. Biomrd. Eng., vol. BME-31, pp. 168-¡12. h. 1984. 141 . - U. F. Iskander. P . F. Turner. J. B. DuBow. and I. Kao. “Twodimensional technique IO C B I C U I ~ ~ Cthe EM power deposition pattern in the human body.” 1. Miernww POMI. vol. 17. pp. 175-185. Sept. 1982. I51 P . M . Van Den Berg. A . T. De H m p . A . Segal, and N . Prnagman, “A computational d e l of the clcctmmP@tctie heating of biological tissue with application to hyperthermic cancertherapy.” IEEE Trans. Biomcd. Eng.. vol. BME-30, pp. 797-805. Dec. 1983. 16) O. Arcangcli. P. P. Lombirdini, G. A . Lovisolo. G..Marsiglis. and M. Piatelti. ”Focusing of 915 MHz electmmagnctic power on deep human tissues: A mathematical model study.” IEEE Trans. Binmed. Eng., vol. BME-31, pp. 47-52, Jan. 1984. (71 P . F. Turner. “Electmmsgnctic hyperthermia devices 8nd methods.” M.S. Ihcsis. M p . Elm. Eng.. Univ. Utah. Salt Lake City. June 1983. 181 -, “Regional hyperthermia with an annular phased amy;’ IEEE Trans. Biomrd. Eng.. vol. BME-31, pp. 106-114, Ian. 1984. 191 M. I. Hagmann. R. L. Lcvin. and P. F. Tumer, “A comparison of the annular phased a m y with helical coil applicators for limb and torso hypenhermia,” IEEE Trans. Biomed. Eng., vol. BME-32. pp. 916-927. Nov. 1985. [IO] P . F. Turner. ”Hypenhcrmia and inhomogeneous tissue effects using an annular phased array,” IEEE Tram. Microwave Theory Tech., vol MTT-32. pp. 874-882, Aug. 1984. I l l 1 M.I. Hagmann. “Numerical studies of absorption ofelcctmmagnctic energy by man,” Ph.D. disaenation. Dep. Elec. Eng.. Univ. Utah, Salt Lake Cily, Dcc. 1978. I121 M.I. Hagmann. O. P. Gandhi. and C. H . Durncy, ”Numcrical calculation of clectmmngnctic energy deposition for a rcslistic model of man.’. IEEE Trans. Micrownvr Throry Tech.. vol. MTT-27. pp. 804809, Sept. 1979. 1131 M. I. Hagmann. O. P . Gandhi, I. A . DAndrcs, and 1. Chattcjce. “ H a d ~ ~ S O I I ~ P CNumerical C: solutions and crperimcntnl results,” IEEE Trans. Microwvc 7ñeory Tech.. vol. MTT-27. pp. 809-813, sept. 1979. 1141 M. I. Hngmann and O. P. Gandhi. “Numerical calculation of el.%tmmsgnetic energy deposition in man with ground and reflector cffects.” Radio S d . , vol. 14, pp. 23-29, Nov.-Dcc. 1979. 1151 O. P. Gandhi. M. I. H i g m n n . and I. A . D’Andrcs, “Pan-body and multibody effects on absorption of radio frequency clcctmmgnetic energy by animals and by models of man:’ Radio Sd.. val. 14, pp. 15-21. Nov.-Dec. 1979. 1161 0. M. Hahn. P . Kernahan, A . Msninez. D. Pounds, S. Primas. T. Anderson. and 0. Justice, “Some heat transfer problems associated with heating by ultraround. microwaves or rndiofnquency.” Ann. N.Y. Acnd. SO.. vol. 335. pp. 327-346, Mar. 1980. 1171 C. C. Johnson and A . W. Guy. “Nonionizing clenmmagnetie wave effects in biological materials and systems.” Proc. IEEE, vol. M). pp. 692-718, lune 1972. 118) I. W. Stmhbzhn, B. S. Trembly. and E. B. Douple, “Blood flow effects on the temperature distributions fmm an invasive rnicmwave antenna array used in cancer therapy.” IEEE Troni. Biomcd. Eng., vol. BME-29. pp. 649-661. Sept. 1982. 1191 I. Mendtcki, E. Friedenthsl, C . Botrtein, R. Paglionc, and F. Sterzsr. ”Microwave applicators for Iwalired hypenhermia trestmenl of c a w r of thc pmstatc,” Inr. 3. Radiar. Onml. Biol. Phys., vol. 6. pp. 1583-1588. Nov. 1980. I201 M. J. Hagmann. O. P.Gandhi. and C. H . Durney. “Upper bound on cell size for moment-mcthod S O I U ~ ~ O ~ S . ”IEEE Trans. Microwave Theory Tech.. vol. MTT-25. pp. 831-832. Oct. 1977. . 41 I HAGMANN AND LEVIN: ABE.RRANf HEATING í.2 l . l 1. W. Stmkhn. .'ThcarctieaI IcmDeratUre distributions for solenoidai-type hypnhermia syrtems."Med. Phyr.. vol. 9. pp. 673-682, Sept.-Oct. 1982. ". in%in Medicine and Bioloev Societv forthe Washinston. DC and s . ~. ~. . .Northern . ..~~.. V'&nia chapten and a member o f & Executive Cornminee forthe Warhington. DC chapter of the IEEE. ~ o n n i a LWIO ~. ~~ was born in ~ h i ~ e i p h i PA. a, on January 14. 1951. He rcccived the S.B. (wiih honon) and S.M.degrees in 1973, and the k . D . Mark J. Hagmno.(S'7S-M'79) was born in Philadelphi8. PA. on FebNary 14. 1939. He received the B.S. d e g r u in physics fmm Brighnm Young University, h v o . UT. in I-. and the Ph.D. degree in electrical engineering fmm the Unkenity of Utah. Salt Lake City. in 1978. His doctoral thesis focused on numerical evaluation of the absorption of electrnmagneticenergy by man. Subsequent to receiving his doctorate, he served as a Research Associate and Research Pmf w r at the Univcnity of Utah. He was a Visiting h f u r o r in the Department of Electrical Engineering at the University of Hawaii. Honolulu, fmm 1981-1982. Sincc 1982 h e h u workedasa Senior Suff Fellow in the Biomedical Engineering and Insmimenution Bmnch of the Division of Research Services of the National Institotes of Health. Bethud.. MD. His general research interests include numerical pmndures for electmnugnetics. elcctmmagnetic imaging. biomedical applications of micmwavrj. and clcctmmagnetic biological effects. Cumntly, he ir in- in bo<h thCOretical and experimental sNdies regarding elenmmagneüc applicmn for use in hyperthermia. Dr. Hymann is a member of the Bioclsuomgnctics Society, the Radiation Research Society. and Sigma Xi. He is Chairman of the Engineervolved degree in 1976. all in mechanical engineering, from the Massachusetts Institute of Technology. Cambridge. Hi<dDMnl thesis dealt with the numerical madcling of the water and solum transpon pmccsses associated with the cryoprescrvation of biological cells al low mmperaNm. Subsequent to wxeiving his doctoram. he served PI a Research Fellow for I LIZ yenn in the Biophysical Laboratory of Harvard Medical khwl, Boston. He then was an AssiaUnt h f e u o r for three yean in the Siblcy k b l of Mechanical and Aemspace Engineeringof Cornell University, Ithipa. NY. Since 1981 he h u b a n LI Biomedical Engineer in the Biomcdiul Engineering d Rem h Branch of the Division of Research Servicwi of the National InstiNIa of Health. Bethe&, M D and an Adjunct AuiMint Fmfesror in the Department of Biomedic8l Engineering of the Johns Hopkina k h m l of Medicine, Baltimore, MD.His gcnenl research interests include bibheir and mass transfer phenomena and p h a r m n ~ ~ k i ~ Cumntly. tic~. he is invalved in both hyperthermia and cryobiology research. Dr. Lcvin is a member of the Fadiation Research Society. the Cvobiology Society, the American Society of Mechanical Engineering. and the American InstiNte of Chemical Engineering. He h u just completed a tern as Chumun of the ASME Technical Committee on Bio-Heat and Mass Transfer. . i I1 I I -0 TI<\\54CTt(*\5 O \ Hll'\'l I,I< 4 L 1 \(iI\l I HI\<. \ lit H"I 31 I J \\l ANI Usable Frequencies in Hyperthermia w i t h ( . Thermal Seeds WILLIAM 1 ATKINSON. IVAN A BREZOVICH. ANO DEV P. CHAKRABORTY Abm-Tmperatun distrlbutions are cornpuled for tluur models ~ M I U I I C to~he heated by muslnnl p w c r seeds. and from that. the katlnp power wbkh thc lmphnts have lo produe 10 achkvc clinicdly acnptahk rcmpcmlum In lhc I u m r u e ohlained. Calculations of the hear produced by thermal d a exposed Io an ekrtromagnrtk inducilon liehi showed it lo k drongly dependent on the pcrrneahiiity o t the m t e r l i l . on th &Id trequency, on Ihc seed di.mcter, md on tbr orlentition of the implints wiih respect to Ihc Rrld. II ir recommended <bat, o t k p a m e i e r r permltling, the impinb be oriented puaUel lo lhc id&hi and that the liehi frequency he ippraxlmitely 200 kHi or lower. Under I h m conditions. implants wlth diimcien M rnaü .d 0.25 mm produn iumctent brat for M y clinkcsl i p p l b t l o n without un$= heiling by eddy currents Rowlng within the patlent. The uu of frequenck above the mommended puis n m i n rrsirktions on the Implanl gcomdry and on the -mtk p n p r t k i o t their milerial. Nndles orknlul perpendicular io the Reld produce emugh heat to reach therapeutic iemprraium only within a n i m w range of parameters. I 1.~NTRODUCTION N local hyperthermia, one usually aims at elevating the temperature of the tumor to a therapeutic level while leaving the temperature of surrounding tissues essentially unchanged. Superficial tumors can be heated by a variety of techniques, e.g., resistive heating with external electrodes [ I ] , 121, microwaves (31, and ultrasound [4]. Such techniques, however, may pose problems in heatingtumors, the main one being the overheating ofhealthy tissues. Thus, in certain situations, some invasive method of heating might be preferred. Invasive methods now under consideration are heating with implanted electrodes [SI -191,implanted microwave antennas [10]-[13], and thermal seed heating [141-1 161. In the last method, the tumor is heated by implanting into i t ferromagnetic needles (thermal seeds) and by applying an electromagnetic induction field. The induction field can be generated by a coil encompassing the tumor-bearing region. There are huo distinct categories of seeds, namely, constant temperature seeds and constant power seeds. Constant temperature seeds are made from a material with an abrupt transition from the ferromagnetic state to a nonferromagnetic state. They produce significant heating power below the critical temperature and only little power above it. This *at property implants are at the Same temperature, and thereby some degree Of automatic CQmPenStioti -,.. for inhomogeneities in the thermal properties of the tissues is achieved. Various nickel alloys have been suggested f material of the implants [ 171. [ 181. Constant power are composed of a material with the critical puint Car the clinical temperature range, and they iherefiwc p in a given induction field a constant amount nf pow gardless of their temperature. A typical material for seeds is stainless steel W30. Comparing the temperature patterns obtained by ih types of thermal seeds, the pattern produced by the stant temperature 'hpiants can be expected lo be homogeneous, and thus ir the superior of the two. T quuements for the material of constant temperature are, however, very stringent. The needles niusi be of producing sufficient power to reach the desired ture, and the transition from the ferromagnetic to ferromagnetic state should be sharp. Therefore. c temperature seeds may not become available for lar clinical trials for wme time. Constant power seeds. o other hand, can be made of a wide variety of materials. less steel #430, e.&, can be purchased in the form o having any desired diameter. We will therefore restric present investigation to constant power seeds. For the construction of a thermal seed hypert system, it is necessary to know what magnetic the seeds must have and at what frequency and the electromagnetic induction coil should o questions are addressed by means of a theoretic In Section 11, the unavoidable heating by eddy investigated and shown lo put certain restricti frequency and intensity of the induction fiel 111, temperalure patterns are computed. and from heating power which the seeds have to be capable o f p is determined. Section I V explains which combinat induction field frequency and magnetic permeability o implants are able to produce the required power. Secii summarizes the findings and gives specific recommendaiio for the optimal range of induction field frequencies. 11.EDDY CURRENT HEATING OF T i s s u ~ ~ wen the tumor.bearing region is placed into an el magnetic induction field, tissues are he;ited by currents flowing within the tissues, as well as by the th currents originating from the hot seeds. In this section. ihe formertype ofheating be examined, It has been demonslrated that for frequencies up io thc r" 10 MHz Manuscript rcceivcd March 1.1983:~evi~cd juty 30, 1983. ~ h i ~ ~ ~ region, ~ k there is essentially no attenuation of thc was mpporicd inpnrt by theComprehensiveCaneer Center Coresupporf magnetic field within cylinders of mus,hequivalenl m i i r ? ¡ Grant CA 1 3 1 4 * a n d a m n t fmm the Friends of Lebanon, Birmingham, having radii lo or maller than of tlie ~iuman l r AL. The authors arc with the Department Radiation oncology, uni. [19]. Starling from this reSUlt. i t call bc sliiIU11 by eienientíW methods that in a cylinder, the rate o f licit production per versity of Ahbama in Birmingham,Birmingham, A L 35233. ..I c 0018-9294/84/0100~070%01.00O 1984 IEEE .nil T,?I:?)blood te:!ipar)i'i:i a t point ,?('C) m y h m e t r x h l W d ;low rate (m'/kg-s) p density c' tis+< I kg/m') ph density I:: h l w d I k g h ' ) Ct, specific k a t o! h o d (J/kg°C) K thermal ciindqctiiity o f blood(W/m.°C) H', power gctierdted by metabolic processes per unit tlssue voisme(W,m3). 11% ahere J the 1' idd dn &stance &e edd, pmduct d e r th pt*nl Since we will only cunsider cases in which the rate of yeit produced bq the ihrnooeeds is much larger than the etabolic, heat pi'uduation rate, we can ndgiect the term on e righthand . ' sIdz of (2). in addition, we will assume that *e temperature (or' the blood as it reache1 any point in the $s.me voleme will be normal body temprpture (37OC). Thia *sumpti+ implies that each volume elemmt of tlssue is per%sed by blood ves+$ not connected to neighboring voiume dements. Equntior. (21 is therefore a betternpproximation for e r spetfused by capillaries than by larga veins and arteries. us, deftning x AT(?) = T(í)- T,(r) Where now Tb(8= 37'C, (2) becomes V 2 ( A T )- u2(AT) = O (3) whereby (4) ip the blood perfusion constant. It is understood that AT = 47x8. In derlving the sobtion to (3), the r-W wll be trken darallel to the directbn of the inplanis. If the needier are long compared tu the cross-sectional dimenlions of the a m y , the z.depbndence can he neglected and the biohsat equation becomes (5) The temperature solution to (5) will, be repraented as a linear su#erposition to N l i e sources coincidiq with the axes of the neadbs in the array: u where r, is the distance between the point of hterest and meedle i . and K,,is the hyperbolic B e w l function of order Zero and o f the :scconü kind. By considering the thennoseeds 4s line sources. ni: are neglecting the fact that wme of the qumor tisue has beeh replaced by metallic implmts. Sinif rhc. thermdl prcpei:iec *>fthe impianrr .ire very diWerr.nt f r ~ m @o\r (11 the tissue>, tqw~iilll) in the:: ;a&. ul: h u t iocivci. tiuns will not be exact. However. the error should be very where small since in any clinical situation. the total volume of the implants will be small compared io the tumor volume (les I< =( than 5 percent). The expansion coefficients A i in (6) can be d,, found from the condition that the power emerging per unit length of each needle has the same value P. Using Fourier's r law of heat conduction, the power emerging from implant r > = { dfi i can be represented as P = -K t o ( A T ) . di (7) for r < d,, forr>df, for r > df, and I,,, and K , are hyperbolic Bessel functions of the and second kind and of order m = O, I , 2, -. Noting 1211 where the surface integral is taken along the needle surface over one unit length of needle. Doing the same procedure for all needles yields N equations for the N coefficients AI. To carry out the integral in (7),we assume a cylindrical and that upon integration over @ all terms coordinate system with the z-axis coinciding with the axis cos [m(@ @ti)] will vanish, we gei of needle i. Writing the gradent operator explicitly and substituting the expression for AT,(7) becomes - Substituting(ll)and(l4) into(8)gives Q where ri is the distance from needle j to the point of interest. where i = 1 , 2, '-, N.Upon solving the ensuing set of e having coordinates r and 9,and u is the radius of each needle. tions for the expansion coefficients A, and substitution of In our coordinate system, Ai into (6), the desired expression for ATis obtained. The power per unit length of needle is shown in F (9) as a function of the blood perfusion for 3 X 3 , s X 5. a r j= [r2 + d j ; - t d l j cos (@ -@#)I 7 needle mays evenly spaced throughout a 4 cm2 where dG 1s the distance between needles i and J and @uis the needle diameter being 1 mm. The blood perfusion the anguh coordinate of needle j . The dependence of normalized io that of resting muscle mo = 4.50 on the partiwlar orientation of our coordinate system with IO-' m3/kg-s and the thermal conductivity is fued at thd respect to ti.^ needle array d o e not lead to any ambiguities for living muscle K = 0.642 W/m."C (231. The h e a t i n g p M of the results. As we will see later, all terms containing was computed for a temperature elevation of l*C at a @ drop in the integration over @. midway between the central needle and the nearest needy The first integral in (8) can be computed by use of the reia- aiong a diagonal of the implant array. lsotheml plots tion I2 I] vealed that the temperature at this point is close to the m i d mum temperature in the central region of the tumor. The com a puted heating power can therefore be considered as the pow¡ Ko(w)=-nK1(~) (lo) required to elevate the temperature of the coldest point h ar the tumor by 1"C. and by intcgralion over @: It can be seen from Fig. 1that the power required by the needles increases with increasing blood flow. In addition. closely spaced needles require much less power than needks ( I i ) spaced far apart throughout the tunior. The above invesiigb tions were repeated for needle diameters ranging from 0.1 to 2.0 nun. It was found that the power levels differ at moS The second integral can be evaluated with the aid of the exby 0.1 percent from those computed for the 1 mm diameter pression [22] seeds. Thus, for all practical purposes. the heating power ir independent of the diameter of the seeds if the minimum Ko(wij)=Io(m<)Ko(m>) + 2 I,,,@r<)Km X (w,) tumor temperature is to be elevated by a given amount. m=1 As an example of the temperature computations, tempenture distributions were obtained for a 4 cm square array of 1 (12) mm diameter needles spaced I and 2 cm apart (Figs. 2 and 3). COS ím(+ -&)I x - - ,/ -. CI / /' needles are capable uf producing cnuugli h e l l range of permeabilities and induction field ire fact. in some applications. even noní'erroniagn 6 = I ) could be used. v:h: ' 4-60 - . 3: fíhHzi 10' 3x10' Hating power p r o d u d by uicrmal seeds oriented pmuel to the induction field. The ppnmacr #~= F a 2 w h m the ridbra is pressed in millimeters. F@. 4. (a) ItkHZI .m Hating Power p r o d u d by thamai rcedr oriented pcrpendic. u k to the direction of the induction fieid.(=) seed diameter = 1 mm, (b) seed diameter = 2 mm. Fig. 5. It can be seen that the heat production is gcneraily much higher when the needles are parallel to the magnetic field. In this case, there is a large nnge of frequencies and permeabilities for a giwn seed diameter in which the amount of power required for adequate tumor heating, computed in Section 111, can be attained. The power drops for both orientations as the frequency is increased. It can be seen that PI depends strongly on the value of 8, and therefore upon the permeability for a given needle diameter. The dependence of P, on the permeability is much weaker than for Pa. Note that in the perpendicular orientation, 1 mm diameter seeds produce sufficient power for adequate tumor heating only with a narrow range of permeability values and only for close (1 cm or less) needle spacings. On the other hand, 2 mm diameter V.CONCLUSIONSAND DISCUS~ON The heating power required by thermal se quately heat tumors was calculated from a theoretical Computations also showed that themuseeds can p sufficient heat over' a wide range of induction field f cies. The usable frequency range for a given t was found to depend on its permeability, and since quired heating power depends on the density of the arrangement and the rate of blood PerruSion of the on the particular application as well. When designing a hyperthermia apparatus, o in principle, make it operate a l any desired frequenc magnetic permeability of the implants. on the uth is rather difficult to control. It therefore seems induction machine should operate at a frequenc permit the greatest flexibility in the choice oí jí. shown that induction field frequencies of about 20 lower would satisfy this condition. In the parallel arra 1rnm diameter needles with jí > 8 would produce power. Needles with larger permeabilities would b of producing more power than needed, and th diameter implants could be used or the magnetic sity could be reduced below the level assumed in th tions. A lower induction field intensity would mak thermia treatment more comfortable since !here wo less eddy current heating o f the region exposed to the lion field. This would be especially advantageous in the t ment of obese patients. We have shown that needier oriented at right angles induction field produce substantially less power than oriented parallel to it. While the perpendicular arrang may be capable of producing sufficient power to heat t in certain situations, the margin of extra available would be generally very slim. It is therefore likely many situations, the needles would not be a sufficient heat. In the computations of the power produce seeds, the product of the field intensity time was assumed to be fued at a certain val lo assure that healthy tissues would n o t be unduly he by eddy currents flowing within the patient in the case the chest or the abdomen were exposed to tlie indu field. In the treatment of tumors of the extremities. Iiowev the relatively small radii o f the exposed bud) regions and I resulting decrease in heat generation by cddy currents should make it possible to use an induction field value. Therefore, the reduction in the heat g thermal seeds, which was shown to occur at high field fw quencies, could be compensated for by 3pp intensity. Thus, in the treatnieiit <iflesiuns a wider range oí induction field frequiiicies iuiild be used than in the treatment of visceral tumors. Finally, we want to niention that tlie relir production of the thermal seeds at high ind REI~ H E N C E S L r r r n . S. Wapnick. V Picone. G Vaih. m d N. ~Uinicd, :ndic;uion by rarliiilnequcncy rhcr.<py " J . 4mrr M u d . 235. pp. 25-2''. 11.1) 1976. .s. "Use of tí ticid\ 1.0pmducc h!pcrrhcmiii i n animiil in Pioc. lilt. S y n p i:unrcr Ticrop> b:, H)prrihcrtniii ond ihingim. DC.AUK. 1975. p p 226~227 u n . A. W. Cuy. i:. G . W m x . B. J. lklitcur. and 1 U. <c. "Eviluation o(. a micmwwo c o r i l i ~ tuppiicicoor." I. Mrd.. vol. 51. pi!. 143-146. 1970 mor. D.Pounds. 1'. U . Postic. mil<?.M. H;ihn. "7'rcaI. aiprficial human nrnplmm hy hypcnhrrmia indueill hy 1," Cancer. vol. -I). pp. 1%-XlO. 1979. 1 mdC. V . McClihc. "A tcehniquc for Iocdizzd hcaiing An adjunct to tumor ihrnpy." Mrtl. Inrtrurn.. WI. 10, J.ri.-Feb. 1970 tu.J , M. Hcvczi. kl R. Manning. . i d E. J Orimsk. cry of intersliiial lhcrrnoridioth~rapy." in P r o ' . i d lm ncrr Th'licrnpy b.y lf>perthermio,Drug.<. ,ind R o d , h t r O. Junc 1980. pp. 5115-507. rnning. T. C. Ccw. and E. W.Genier. "inierstiiiil ¡ahcrapy." in P i o í 3rd Ini S y v C a m e , i h r r q ? by d a . ~ r u . r~i n. d a d . F W ~ C O I I ~co. ~ E JUW . IYXO. p p . rovieh d I. H. Young. "Hypenbrmia w i t h implanicd ." Mcd. Phyr.. vol, 8. pp. 79-.84. Jan --Feb,I9H 1 Y. I. A. Brrzouich. W. I. Aikinrm. I> P.ChiiLribody. ni. 1. l n g m . and R . 8. Mclilvein. "iiypctthmrnia with I: in v i m and i n vivo c<,mla~ions." lm. J. B ~ O Iin . Piiy.t.. vol. Y. pp. 373-..3112. i ~ 8 ~ . W.S m h k l i n . E.Bowers. and J Wilrh. "Cancer nhcnnin using M inrriive rnicniwavc iysteni." ver. vol. 14. pp.181-186. Jan. . E. 1979. Boweri. J~ Walsh. and E ü. Duuple. ,'An wave lystem for locally-inducd hyperthermia for 1, Mirmwavr Power. vol. 14. pp. 339-.3.50. . Fellow at the Compo Brmingh.tm imm IY h"iBi,i.aer~Pn,p.. vol. [SI 1963. w vol. L14. rp H72?..H'25, "Conthou@meamremen: o f utcnc x m . , a ~ : ~ g e dl.'fer!i enti and VC?, b microcomputer," Am& ,I.PI:)<io:,lol. 245, pp) H 1 7 8 8 1 S 2 , 983. [91 G . .A. Mook, O. ran Asscnddft, and \?.,G. Zljlslrii. ' % w e Icq:th dependenq of the appatmphotom, 't: derentiinitioii iof b W d oxygen aaliration," Ciirr. Chlm. .4<:u vi I 26, pp. 170179, 1969. -, . Dk*cbic Ptoperties of Süüd Tutioiu D1irin.g Nombtbemb end Hypertbcmiia ROE%RTPELOSO;DhVlDT.TVMA, A N D :xAKI~SH K.. ] A D , %bsrdr-D*lcctric p m : p e u oí five rat munrncy i:ircinomlu, O n e R t ~ i w n i , ~ r l R t / m ~ r k w c r e m e u u iYai ld mL;8t37ind43"C , over a I)quency of 1 MHz-I GHE. N6 -4gnlficmt di1Tmrncn were w~ad in the ~uisureddielecmc prq<:rlics xtf normal mid neoplaati: h u e s , praai)mrbly due tn the hi@ ,vat= ccmtunt of luth types of twirs. ---7 L lNTRODUCTION Recem research hps indicated that loo;iiiz?d :.iyper:hei mia can be induced el'feqtivdy in mrnc tumolS ')) rudío tlcpuency currents (RF) arid dy microwave power I W V ) a i a m O n i of cancer t e a t m e n t [i]-[31. Sinci: the theniial energy ahsoiied by a t i g u e from tin RF/MW source depeml. r.por; its electi ical propertbs, characterbation of these propc' :irs i)! numml ind eltecneoplas@c tissues is kmportani fix using ti :SI r~i:th,>d,i lively [ 4 J . Alth,ougb a number of invcsti@:o.s !),:,veniiasimd ,in)<:I va:.iwui ,101the coqiplex dielccttic constant (e* E' mal tiss(ies over ii wirte frequency range [5 , [ 6 ] , the '.lui:. on ncoplas(ic tissues are scant L71-l I O ] . We ' h < : r e ? , ~m::asi.red re - - Manuwipt rcceimd Ftbruary 16, 1982;revised 'darct~ 7. l!l44, This work wa) supported bi( a Research Career De% 'p m e 9 A'wd A .id a NitionaiGcknn Foiindk1wn Grant to R. K.lain. R Pclojo is with the +piirtmentof BiomediCJ 1:n &m:t rinl:. ( ' a r m :pie MeUun L'hivarsily.I'iitrairgh. PA 15213. D. T. Riirna was with tho Department of Eleu c I E r $ini:crmg.1:arne@eMeIon University:Pitirburgh. PA. He is no d c c t a r d . R. K. hiin is with :hs Delt.irtmen1 of Chemical ni in5 e W I ~ ]',C u w c i e MeUun Chiirrulb. F'ili~Ourgh.PAlS2I3. ! <l,.I ... r i i - i the dielectric constant 3nd cbnductivity i n i'irro of a variety of neoplastic tissues from the rdt over a frequency range of I MHz- 1 GHz at 37 and 4 3 T . Frequencies within this range are used for the heating of tumors [ I I . EXPERIMENTAL APPROACH We used, in this study, the shielded open circuit coaxial tine method developed by Bussey [ 111. The use of an open circuit h e eliminates the need for accurate determination of aample length, allows one sample to be measured over a wide frequency range, and permits instantaneous access to the tissue sample. The coaxial sample holder (outer cylinder 31.6 mm X 7.0 mm and center conductor 3.0 mm X 6.3 mm) and its contents were uniformly heated by a lucite water jacket surrounding the sample holder. The temperatures of the sample holder and the tissue weremaintnined within * 0 S 0 C o f the desired temperature [ i 21. The amplitude and phase angle of the reflection coefficient of the coaxial sample were measured using a General Radio oscillator (GR 8601A) and a HewlettPackard network analyzer (HP 8407A) for frequencies helow 110 MHz, and a HewlettPackard oscillator (HP 8690A) and network analyzer (HP 8410) for frequencies above 110 MHz, in conjunction with a phase magnitude display unit (HP 8412A) anda transmission test unit (HP 8740A). These measurements were substituted in the transmission line equation to obtain the dielectric properties ( 111, [ i 2 1 . The instrument precision in determining E' was 7-10 percent for frequencies less than 50 MHz, and 2-7 percent for frequencies .greater than SO MHz. .For €".the precision was 1-2 percent for frequencies less than 5 0 MHz, and 2-15 percent for frequencies greater than 50 MHz. Distilled water was used as a standard to calibrate the system. Propanol (Table I) and freshly excised rat muscle tissue (Table 11) were used to cornpare our measurements to the available data 113 1 -[ 15 I . The spread in the available data was about 15 percent (owing to different preparations), and our measurements fell in this range. Dielectric measurements were made on five rat mammary tumors (Walker 2 5 6 , MTW9, MTW9A. NNU, and 13762), one rat glioma (9L),and rat muscle. AU tumors were grown subcutaneously in rats and were excised seven days post implant. Average water content of these tumors was approximately 80 percent (Guiiino, personal communication). Since most of the neoplastic tissues were kept frozen until the day of measurement, we also investigated the effect of frozen storage on the dielectric properties of rat muscle. The difference in dielectric constants o f freshly excised muscle and previously frozen muscle was found to be less than the experimental error within the frequency range of the study [IZ]. RESULTS Shown in Fig. 1 are the dielectric properties of six tumors and rat muscle at 37'C. Temperature coefficients, calculated as ( E ~ V - e430)lE3p X (i00/6"), are given in Table 111. The difference among the various tumors in values of E' at 37 and 43OC was within the experimental error, and there was no clear Qend in the effect of temperature on E' (Table 111). On the other hand, ail tissues exhibited a temperature coefficient of about 2 percentl'c except for the highest frequencies (>IO0 MHz) where we have established a large uncertainty. The temperature coefficient for E" is in agreement with the reported value for normal tissues [ 161. DISCUSSION In order to explain and condense the data acquired on tumors, -. two sets of equations with five parameters were used to fit the experimental data. The first was the Cole-Cole equation ( 1 4 1 , [ 151 and the second was a set of empirical equations. Since we could not fit the data well t o the Cole-Cole equation ovel the frequency range 1 MHz-I GHz, we opted, for convenience, to s t h e data t o the following expressions: I- - 18.6.0.6 lo 16.1 lS.7-16.6 23 18.1.1.0 50 18.L.l.C 17.7 17.6-17.8 7s 18.1.1.86 17.7 11.0-18.4 1 w 18.1.2.31 11.1 17.1-17.6 zoo 17.1.3.64 11.3 16.9-17.6 16.8 14.9~10.1 P?oP.nd zoo 17.0,l.O 400 lb.2.8.S 24% 18.3 17.9-18.6 14.1 14,s-16.3 10.7.8,s 'Oo 8w 11.3 11.3-11.& 7.6.7.1 6.S.b.8 lwo cOMsA lo 200,1260 lS 109.S26 161-196 so 91.282 75 80.18s 104 92.llb 19.5 75-83 73.S.152 63-72 56.30 *oo S3,Sl.S sz.s.33.s IW log E' = a log E''= ,3.8 s1.54 d +b log f + e log f C +log f /bW4 3 .. , Here, a , b, E , d , and e are empirical constants, and ' frequency in Hz. The empirical equJiions fit the dala t o b d than 1 percent, and the Cole-Cole modrltoabout I O F ' $ ; [121. L.I 1 .. 112 1 26 J 51 1 55 1 18 - 1 11 1 97 1 61 1 91 L 12 -1 27 -1 O0 8.8 .I .5 .2 .4 .6 i.1 i .9 .o .7 I .2. 1.4 1 O2 '.E1 - 1 81 - 1 01 I 58 1.9 ,.o, 8.Z ! I, F !EOllliNi:Y :a> .L. .o .91 1 91 L 8s L I1 1 54 1 57 oi 0 100 IO IHHiI .I .6, .f . 91 1 .6' 35 .& . i , ' 94 , 67 ! 51 z 28 .28. .l' . 43 .5,, .4: ,.3: 39 '.4. I1 O0 .or - 1 80 I P '?,S* I :#¶A U A.4 I' i l l(I I':lll(4 i I" " !j . 'I '1.) , I Ir,? I ! . I ! .! I .I o 12 a14 o 75 o a? iE 51 I1 '/I !1.1 !1.7 -.(I .9 L2.l -.9'O !2.7 -.94 -.9.¿ L. . I L, r.c IV are t,he I i e i t S i t p;irain:terI,.alitci I. r ¡ u iry urcinomas--WZ!i6, MiW9. HTW$ i hlN!l, , ~1.1 e rat It. i r d r a t muscle ;it 8:;l mi! 83 :he values for ,111siii r e o p i a r t i c tinucp a r i ~ l : ,L those of musc,e. a iiii,hwalcr conicl! riir I.: 5 expected since. witliiii this f r c q u r i c y 1inre I E ;I'IltiLnt ir the o r i m a r v 1,lctor. H o w e w i . k I f ' u 11. !!I ITable I.",,, 1 1 Qr P. 14 I , I IT. . i, , UUllii o, Cancer I n i t i t u ' e . I Iiom Qr R. J i e l i o r r IYu>ptt 11 r REFERENCES 111 E. R. Atkinson."Asersment of current hyperthermia technology," CuncerRes.,vol. 39,pp. 2313-2324.1919. 121 R. K. lain and 1.' M. Gullino. Eds., "Thermal characteristics o f 1umors: Applications in detection and treatment:' Ann. N.Y. Awd. Sci., vol. 335, 1980. 131 R. K. Jsin, "Biohest transfer: Mathematid models of thermal systems," in HypathmmO, F. K. Stonn,Ed. Boston. MA: Hall, 1983, pp. 9-46. 141 S. M. Michaclson snd H. P. Schwm, "Factors governing the u r of mrrowvPvelradiofrequency energies in cancer therapy." A h . Radirrt.Biol.,vol. 9,pp. 323-409,1981, 151 C. H. Durney, C. C. Johnson, P.W. Barber et al., Rodiofrcquency Radiation Donmete Handbook,2nd Ed., USAF School of Aaospace Medicine. Brooks AFB, TX. 1978. Rep. SAM-TR-78-22. 161 E. C. Burdette. F. L. Cain, and 1. Seals, "in vim probe measurement technique for determining dielectric properties at VHF through microwave frequencies," IEEE Trans. Microwave Theory Tcch.,vol. MTT-28, pp.414-429,1980, L71 E. C. Burdette, J. Seals, R. L. Magin, and S. P. Auda, "A priori determination of power absorption in hyperthermia bared on in vim dielectric measurements: presented at #e 3rd Int. Symp. Cancer Therapy by Hyperthermia, Drugs. Radiation, Colorado Stale Univ., Fort Collins, CO, lune 21-26.1980. 181 1. L. Schcpps and K. R. Foster. "UHF and microwave dielectric properties of normal and tumor tissues: Variations in dielectric properties with tissue water content,'. Phys. Mcd. Blot.. vol. 25,pp. 1149-1159,1980. 191 K. R. Foster and J. L. Schcpps, ''Dielectric properties of tumor and normal IIIWCL 11 radii) through micrnwavc ira( J.hiUroupvePower.vol.16,pp. 101-120, 1981. W n w C. M. Hahn. P. Kcrnnhsn, A. Martinez. D. Pounds, s, T. Anderwn. and C. Justice. "Somc hcat'usnifq asvlciated with heBtinp by ulirauiund, miuowsvrr pn frequency,"Ann. N.Y. Awd.Sd..vol. 3 5 5 . p ~ .321-346 H. E. Buswy, "Dielectric mwsurements in a shielded coaxial Line." IEEE naris. Inrrrum. Mcor.. vol. IM.2 124.1980. R. A. Peloso. 'In vitro dklcctric properties of rveta tiuues during norma and hyperthermia." MS. th MeUon Univ.. Pittsburgh. PA. 1981. S. K.Garg and C. P. Smyth.'Minownvcabwrption structure in liquids. LXI 1. Thethreedielectricdirpr of the normal primary alcohols." J. Phys. Chem.. YO. 1294-1301,1965. K. S. Cole and R. H.Cole, "Dispersion and abmrpti trics. I. Alternating current characteristio,"l. Chem 9,pp. 341-351,1941. R. Pethig, Bioelectric and Electronic PropertiesofB terials. New York: Wiley, 1979. H. P. Schwan and K. R. Foster. 'RF-field interact' logical systems: Electrical propertiesand biophysical Fmc. IEEE.vol.68,pp. Iü4-l13,1980. T. E. Dudar and R. K. Jain, "Düfmential response of tumor microcirculation l o hyperthermia." Cirnnr Res. pp. 605-612.1984. R. K. lain, F. H. Grantham, and P. M. Gullino, "Blmd heat transfer in Walker 256 mammary carcinoma."l. Na hsr.,vol. 6 2 , pp. 927-933, 1979. .. i ?, , , .’. A Sufvey of Computer Simulations of Hypertherm¡a Treatments i . JOHN W. STROHBEHN. SENIOR MEMBER, IEEE. ANO i,%,.\, \ , , y , Q - ROBERT B. ROEMER Abrirnct-Tbis paper i ra m k w of lh. ru<.-o~-lh.-anof a ntw area of comparative thermal dosimetry is the r.oniparaiiv in hyperthermia: computerid simulations of hypenhermia ireat. tion o f ihe abilities o f different Iieatiiig moddiiies mrnls. OIK of the more dliii.?ult problem in hyprrthcrmh is the figurations to properly heat clases of tumors. Cal determinilion of the complete temperature field thraugbout both tufor this application can be done using mor and nonial tiuue. Thearetical methods of rstimiting temperawhich contain only the most significant milto ture diitribuüonr are needed lo help address Ibis problem. In Ibis paper we divide this &Id into four areas: comparative, praspec~ivr, physiological features of “typical” patients and the concurrent, and mrwpctive. We lhen summirim the malheoutiral characteristics o f the power deposition patterns. formulations of both the ekclromagnctic and ultrwnlc power deposifor prospective thermal dosimetry (individual pat lion probkms and the beal transfer problem. This is followed by ment planning) detailed infonnaíion is needed fur m i e w of lbe numeriul lechulqua available for calculating the power d e W o n In the tiasve M d then tinding the resulting temperature dar patient’s anatomy and expected blood perfusio distribution. The paper concluda wüh i *riplion of a IC& ol so that detailed tower deposition patterns can be i p p l k m k drawn from the current Iiterilurc. and used to determine a complete temperature d 0.NE of 1.INTRODUCTION the more difficult problems in clinical hyperthermia is the determination of the complete temperature field throughout both tumor and normal tissues.me temperatures a areta-s only a limited number of locations d ~ i n clinical heating, the temperatures in the +majOutrof the tissue ?e.g& w h o m and it is therefore..difficult .to.a$.gs the efficacy of the equipment and treatment protocol ut&ed. Similarly, when planning hyperthermia treatments it is desirable to be a L k t o . & k u h e temperature fieid to be d=a in a particular patient so that ihe treatment can be optimized. To a t i k m i to g y h these it is possible to use mathe. matical models of the patient anatomy, thepower deposition pattern in the heated tisue, the physiological response of the patient, and the the‘rmal interactions in the tissue to calculate complete temperature fields in the heated tissues. The purpose of this paper iS to review the state-of the art in this rapidly growing field. While analytical methods are appropriate in same situations, we restrict ourselves tu numerical methods because they are more appropriate for clinical problems which normally have irregular boundaries and inhomogeneous tissue properties. Computer simulations of hyperthermia treatments have the potential to become valuable standardized tools in four aspects of thermal dosimetry [I] : comparative, prospective, concurrent, and retrospective thermal dosimetry. The goal for that particular patient. The goal o í these sim to optimize the proposed thermal treatment by d the power deposition parameters which niaximize peutic effects of the tumor temperature disirib minimizing normal tissue damage and patient stress. Cona rent thermal dosimetry (feedback control during a treatmg ~involves calculating complete temperature fields d ment and adjusting PO r deposition paranieiers (and o variable quantities) to op . ize the actual treatnients as lined above.locations In present lications,while measured coyitrolled, the goal at discrete are ap \ treatments is to control the complete teniperat Retrospective thermal dosimetry (post treatment of a completed therapy) has as its goal the calc complete temperature field that was atiain ment, based on knowledge of the‘measured te selected locations.. These data are needed for meanin clinical evaluation of the efficacy of hyperthermia as a tr ment modality, as well as for evaluation of th performance and of the heating protocol utilized. Most hyperthermia related simulation studie either been generalized parametric investigation tial of hyperthermia 12) -[I I] or have emphasized the probkrr. of comparative thermal dosimetry [I?] -1261 one., two-, and occasionally threedimensio idealized patients, dong with equally simplified power de. position patterns. Although no work has been reported thr: attempts to utilize detailed anatomical daia thermal dosimetry, some work has been repo Manuscript received June 2 3 , 1983; revised October 13,1983. This deposition patterns alone [27]-[32] iiiclud work was mpponed in part by the National institutes oiHealth undw Grants DDS CA 23594. CA 17343, and CA 2 9 6 5 3 , and by the National detailed patient models, and one paper has c;Uc Science Foundation under Grant ECS 8025818. ture distributions for detailed anatomies (331 1. W. Strohbehn is with the Thayw School oí Engineering, Dutconcurrent dosimetry, no published work is mouth College, Hanovcr. NH 03755. R. B. Roerner is with the Department of Aerospace and Mechanical attempts to control the complete teniperature Entineering, University of Arizona. Tucson, A L 85721. to controlling the measured temperatures). e, k * wic u here where E ir the speed of sound in the tissue. Values h r may be found in the literature (5 11. Equation (12) is a scalar version of ( 6 ) for the mr In homogeneous tissue V*E= O and (5) reduces lo the stand- field. Therefore. !he same general analytical or nu ard form for the wave equation. i r . , the vector Helmholtz approaches can be applied lo the ultrasouiid prub equation. However, in patients there are large variations in the EM problem. Since most effort in the ultrasoun the dielectric constant, e x . , between fat and muscle, and as applied io medicine has been for diagnostic hence often this term must be retained. When operating at the concentration has been on calculating tlie fields lower frequencies, ¡.e., in the resistive current range, k’ == ferent sizes and shapes of transducers. Most of 11 iowp. Since we expect significant gradients in E or H over culations have ignored the attenuation in tlie me . l / R i . factor that is critical in hyperthermia. Finally. a rn distances of the order of the body radius R,,, if ik3 I 4 then ( 5 ) and ( 6 ) reduce to ference in applications between the EM problem and t problem is that in the latter case the impedance mim V~E:V(V. E)=O (8) at interfaces between some tissues, e g . , air-niuscle or bone, is so large that almost all o f the energy ir refl V’H = O. (9) these interfaces. Since significant heating can occur interfaces (e.g., mode conversion of ultrasound at 1)ie Note for typical values of Ro (15 cm) and o (0.5 mholm), this approximation is valid for frequencies up to about 10 bone interface) knowledge of boundary location especialiy important. MHz. For this situation we are essentially dealing with Laplace’s eauation. The other critical information necessary in solving the 111. NUMERICALM~~~~~ FOR sOLVING THE B~~~ electromagnetic problem is knowledge of boundary condiTRANSFEREQUATION tions. Particularly important are interfaces where E changes ‘Ost realistic hyperthermia problems “quire abruptly. It is well known that at such boundaries the p a r a e l solutions, and fmite differences or finite element component of the €-field is continuous and the perpendicular are the methods of choice of most investigators. F component obeys the relation ference methods generally require less storage and E time to run and are easier to program for s e:EIp = E ; E ] ~ . (lo) but data entry for the boundaries of complex g (7) Good discussions of the development of the ultrasound equations from fundamental principles can be found in many sources, ex., [~i1-[53].AS noted above, the quantity we need for hyperthemia is the intensity of the ultrasound wave. As in the electromagnetic case we wu assume $1 are of he fom p(t) = p,-iwr, ln this fom, the average intensity at some point is given by properties when finite element methods. At present. the c method *O utilize depends on the individ background, interests, and the Of PI addition, future developments will perhaps advance of applicability of both the dkect discrete Fourier methods [SS] and the weighted residual methods 15 are presently quire fast for problems with 11011 properties and simple regular geometries. I= IP1’/(22) (I ’) For steady-state problems, the elliptic bioheai = acoustic impedance, equation is solvable by finite difference methods de where p E acoustic pressure equation. For On basic equations for acoustic or ultrasound waves are nonlinear, for the standard heat be lineanzed sionai problems, efficient tridiagonal routines are a but under reasonable appro~mations they 1521. Under these assumptions, a wave equation can be (551. Simüarly, successive over relaxation (SOR) (point, line, block) are efficient for t\vo.diii,ensiuiiaI pr written for the pressurePi.e., as is the alternating direction implicit (ADl) te This latter method can be made more effici V2P + K2P= o (I2’ i f an optimal set o f cyclic paranteters can be dete where the complex wavenumber K may be written as experimentally [%l. The AD1 method is not 3s exs tended to three-dimensional problems as are SOR ni K=k-jol (13) but splitting methods can be extended to hmriic t l t ~ > ~ lems [ S S I . Most current finite element iiietliiid (FEXi) and (I ir the attenuation coefficient in the medium. Under niques use triangular elements, stJndard orderins rcilini most situations of interest in hyperthermia, ¡.e., in media and banded direct matrUr solvers. but tliir is a rapid11 de, ne ’.o~st“ case I I40 . ITL€ lHANSACTIONS(JN HIOMFDI~~\LINCl?rl:EHI~(..VOL H X t I 31. NO. i . j A S t ' 4 ~ ~2 'S.! operating at 27 MHz (741. Once the fields were f m d . they calculated the temperature distributions using a finite differ- .,POr absorbing media, die local intensity can he calculated ,r cnce method. ~~~o~=Kl*(ro~l* At this stage in the development of hyperthemid. much of the numerical analysis is oriented toward increasing our under- where K is a scaling constant and is the local standing of system performance (comparative thermal dosim- velocity potential. in this situation. gr(ro) can be etry), and homogeneous models with regular boundaries from the Rayleigh-Sommerfeld diffraction integral may be sufficient. In this case, finite difference formulations are usually quite adequate. As efforts move into activities *(ro) = gsk-"" dS such as treatment planning, where it is desirable to calculate isotherms for a specific patient, nonhomogeneous models must be implemented. In this situation many investigators which treats the transducer as a collection o f feel there are strong advantages to finite element formulations o f spherical waves. in this notation we have since the basic algorithm is structured to account for both X = wavelength. S is the physical aperture of the tr internal and external irregular boundaries. The use of fmite and $(so is the aperture (source) weighting funct element methods for EM problems is relatively recent (771 weakly attenuating media (the acoustic amplitude (791, and further work in this area is needed. is attenuated by approximately 1 percent p The strength of the FEM for clmically oriented problems of travel) the effects of attenuation are satisfactoril is that anatomical and tissue complexities are accommodated by means of the exp (-w') with r' being the path in a general way in the basic algebraic formulation, such that tissue and a the amplitude linear attenuation c from the user's viewpoint, complex problems are not signifiWithout attenuation there are several efficient cantly harder to solve than simple problems. The FEM, in calculation, eg., (831; however, the problem is more conjunction with graphical systems for inputting data, eg., if attenuation is included. Criffice and Seydel (841pe from CT scans, and outputting absorbed power and temperathis integral numerically using a twodimensional su ture data, should lead to systems that can be used in the over the face of the transmitter. The rapid variation clinic to facilitate specific patient treatment planning. How. dkr phase term forces the summation increments to ever, techniques for preprocessing the data and for automatismall with correspondingly long computation times. cally generating finite difference grids for situations with et al. (as] and Swindell I 8 6 1 have independently dev irregular boundaries are under investigation for the fuiite method for accelerating these calculations by difference formulation. The disadvantages of the FEM compared to fmite dif- wards from the point of interest (ro) and summin ference are: 1)greater complexity in the algorithms and pro- tribution from all points of the transducer fac gramming, and hence a greater development effort; and equidistant from r,, . For layered inhomogeneous material, reflection, 2) greater computational overhead. Because computers in tion, and mode conversion effects can be included. Re hospitals tend to be moderate-sized and smaller than those and refraction d o not usually appear to play signi used in research settings, attention must be paid to developing in soft tissues because of the similar acoustic im efficient algorithms. velocities of most such tissues. Mode conversion can in cases where the boundary conditions are known or can portant at bone surfaces [87]. be approximated with specific values. imolementation of the ~~. fmite element technique-to the vector EM problem is straightV.SPECIFICAPPLICATIONS forward in principle. However, the fact that the fields are in COflhfaDefieDevicm general complex leads to potentially large matrix storage A. problems. While there are techniques for handling these One of the more common regional hyperthermia systm problems, eg., automatic bandwidth reduction or sparse being evaluated in the clinic is the Magnetrode (Henry Me& matrix techniques, to date these algorithms are just beginning Electronics, Inc., Los Angeles. CA) (88]-(9i]. which is bir to be applied to the EM problem as it relates to hyperthermia. cally a circumferential copper electrode centered on the ksi When the applicator is launching a propagating wave, e%., axis of the patient. * y - . . ..*' .. ,,.., .._ *.- ~~ might o Hill et a die mon sorbed F model. I die isott p i d and et al. to ,, t I 7.5 CM 15 CM Fig. 2. The finite element grid used for calculating the imthems for the concentric coil heating 1921 IO cm SKIN SURFACE 5 cm 7.5 em VISCERA MODEL: BEST C á S E 15 ern Fig. 3. A n example of the isotherms calcuhted for concentric coil heating for the case shown in Figs. 1and 2. Viscera model: skin heldat20'C. blood flowintumor=O;Uivircera,27 mUiOOpm~min;inmurcle-fat 18mViOOgm.min 1921. c rn) Fig. 6. Onedimensional model for patient PnatomY and tumor used in uniform power deposition airnulition 1151 Recently Lynch, Paulsen. and Strohbehn (unpublished) approached the EM problem using a fmite element model, by extending a model o f Lynch [82] for a circulation problem. The basic equation reduces to a scalar wave equation since in a two-dimensional model it is assumed that the electric field from the annular phased array is tangential to the long axis of the patient, and hence there is only one component E*.Their results look very similar to those found by Iskander et dusjngthemoment metbod.Theyused the powerdeposition values in the bioheat transfer equation to solve for the temperature distributions. The same finite element grid can be used for the EM and thermal problems. The results are presently being prepared for publication. More cases need to be run with these types o f models (using either fuiite element or moment methods) in order to evaluate how well the model describes the phased m a y and to answer auestions about what types o f tumon the annular phased array can heat effectively. 'O- 5) --Y 45- $ 402 w. 5 ''- C.Uniform Power Deposition One interesting question is how effectively would a hyperthermia system that deposits power uniformly in tissue heat up tumors under various blood flow conditions. Halac et al. [is] analyzed. a one-dimensional inhomogeneous model of the abdominal (Fig. 6) and pelvic regions subjected to a uniform power deposition field. The tissue temperature distributions were found using an SOR algorithm. Fig. 7 illustrates such a profile for a 7 cm annular tumor model located in position one. The assumed tumor blood perfusion pattern had three regions: a highiy perfused periphery where the perfusion was set equal to the normal tissue perfusion (W.DR = WN), an intermediate region where perfusion was one-half of that value (WIR = wN/2), and a necrotic core with no perfusion (WNC = O). AU normal tissues had the same value of tumor perfusion (WN). The results of the analysis are given in a compact format in Fig. 8 for the annular tumor perfusion model for three tumor sizes (the three columns) and three blood perfusion magnitudes (the three rows). Within each rectangle results are given for the tumor located in each o f the five positions indicated in Fig. 6.The results are given in terms of the range of absorbed power levels that give acceptable tumor temperature distributions, as indicated by the size of the vertical bars. For absorbed powers below the value at the bottom of a bar no1 enough power is absorbed to heat the tumor to therapeutic temperatures. For Fig. 7. RADIUS k m l An example oftempcrawre dirtribution in the unirorm, depoaition sixnulition [is]. this simulation, the lower acceptable imperatun WIU cl as 42OC. Conversely. for absrbed powers larger than the at the lop of a bar, too much power has been applied either 1)significant portions of the tumor are u n a c q hot, (this upper allowable temperature was chosen as 6 or 2) a nomal tissue limiting condition was reached. TO! late clinical conditions, the.temperatures in the nwmal m and fat tissues were not allowed to exceed 44"C, since a this temperature there is a risk of tissue dani3ge and Maximum applied power in such cases is denoted as m limited (ML) or fat limited (FL). Similarly, since to) patterns in human whole body hyperthermu suggest that organs may be damaged if a significant volume o f vi tissue is heated to temperatures above 4,' C, a limi; that no more than a 1 cm thick band o f viscera tissue exceed 42OC was applied (VL). Finally. tile total 1 absorbed by the patient was not allowed to exceed 2 k sulthg in power limiting (pL) cases. This is a practical ' "L.-. ................ ux>. < 0- r L . . . , . ! > I ! VL Y, YL L. Y L . . ................. , . . . :~.!::: .. < I l l , 1:111 .I : , i - ' :4 . :. .. I.. .... I..._ T . I , I . ; ' F.UU3E- ! j i I ! , . , . c [&6]who analyzed a 6 cm diameter by 20 cm lone uniform tissue region whose axis was the same as that o f the 16 cm diameter transducer which had a radius of curvature of 20 cm and was located 10 cm from the skin surface. Figs. 9 and 10 show the SAR pattern and the resulting temperature fields calculated using an SOR routine for two different blood perfusion levels and for two different frequencies. In these computer generated figures, the ten gray levels are evenly distributed between the highest SAR (or temperature) and the lowest. The gray levels do not vary monotonically with data values, but were chosen t o give contrast between adjacent isotherms. in all figures, ten gray scale levels (10 percent increments up to the maximum field value) are presented. in the lower part o f Fig. 9, the SAR distribution for the transducer operating at 0.5 MHz is shown. in the center, the temperature distribution for a blood perfusion rate o f W = 10 kg/m3/s (a value that characterizes viscera) is shown. In the upper part is the temperature map for W = I kg/m3/s. It is apparent that the value of W has a profound influence on the steadystate temperature distribution. The temperature distribution is much more spread out for the lower blood tiow and although it cannot be determined from the figure, the maximum excess temperature reached is h o s t exactly twice that found for the higher blood flow. Fig. 10 shows the same situation as Fig. 9 except that the frequency has been raised to 2 MHz. The SAR is seen to be much more tightly focused, and the steady-state temperature distributions bear little resemblance to the SAR. in the case o f low blood flow, a large evenly heated volume is located within 2-3 cm o f the skin. The temperatures in this region are approximately the'same as those found at the focus even though the SAR, as demonstrated by the lower figure, is much smaller than that at the focus. The existence o f this region o f superficial heating could limit transducer design and operating parameters. Scanning will not necessarily remove the superfiiial hot spot since the superficial heating pattern is quite wide and significant overlap of power deposition will exist in that region, but not in the region heated by the tightiy focused beam in the tumor. Fik 9. Lowa: absorbed power density due to foaircd US opcrniiw at 0.5 MHr Middle: temperalure map m high tissue. Upper: tempmiure map in low pafurion tiuue 186 VI. SUMMARY The use of the computer to calculate power deposition and temperature distributions is reasonably recent in hyperthermia, but the field is now receiving increasing attention. To date the large majority of the work has been oriented toward comparative thermal dosimetry, though the techniques required for prospective thennal dosimetry are now appearing in the literature. Good two-dimensional models for treatment pia+nning should become commonly available in the next few years. The areas o f concurrent and retrospective thermal dosimetry are just in their infancy. Since numerically they require the same types o f algorithms, they should move forward together. For two- and three-dimensional models we see no fundamental problems that should preclude algorithm development. There are two major problems limiting the progress in this field. First is the lack o f adequate data to put into the simidations. Clearly, blood flow is the most important physiological 1 Fig. 10. 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Woads. ”Theory. mearuremcnt. and application of thcrmnl propenier of biomstcrids.” Annu. Rei.. Bioph.vs. Biorng.. vol. 4. pp. 43-80. 1975. 1611 R. B. Roemer. T. C. Cctas. J. R. Oleson. S. Hslsc, and A. Y. Mailwhich. “Ciinipamii\r F I A I U I I I I I ~ 01 h>prthrmir modsltiicr: I . Numrricrl a n i l y u > 01 Ihcrnirl daw & Rudi<ir Re.,.. 118 hr. puhlnhed “Comprraiw C I ~ I U ~ I N I D 01 hypenhcrmis hcrlinp tics: II. Appliciiion of Ihc srccptrhlr p o w c r rubmitied for phliiaiion. IV82 T. C. Celar. A. M. Flctcher. and R . H Rirmci. “What ¡nist lion c m k obteincd from imnsienl icrnpcr~lurcEYrvCs:’ in p* 3lsr Annu. Mrrring Radmr. Res. Srw..San Antiinto. TX. 27-Mu. 3. 1983. A. J. Milligan snd B . S. Msroud PmFhpour. “Mark+ predictions of tumor and n n m l tirsw b l n d flow during h w Ihcrmia:‘ in Proc. 3lri Annu. Mrrriny Rodiur. Res. Sw., 4 Anionio. TX. Fcb. 27-Mat. 3. 19x3. P.Vsupcl and W. Mucller-Klicwn. ”Heal rusccptibiliiy ofblood flow.” in Proc. .<Is1 Annu. Mcrriiiy Rudiirr. Rrs. Sor.. 27-Mar. 3. 1983. C~ICS.” -. 27-Mar. 3. 1983. H. H. Pennea. “Analysis of iissuc and m e r i a l hliuxl lcmpniq in the resting human forearm.“ J . Appl. P h w o l . . vol. I, 9+122. 1948. ASME J . Eion<d J. C. Chata, “Heal transfer to hlood VCSICIS.” Eng.. vol. 102, pp. 110-117. May IYXO. J. 1. W. Ligcndijk. “The influence of bl<rdfiov in large rrui. A. R . Miichell and R. Wail. ThrFinire ElrmrniMrrhodin PDifferenrid Equotionr. New York: Wilcy. IV71. R . F. Hatringion, Field Compumiion by Momrn York: Mamillan. 1 9 6 8 . C. H. Dumcy. “Ekciromrgnciic dorimeiry for models o and animals: A review of iheoreticsl and nunurical tech P r o c . IEEE. vol. 68. pp. 3 3 4 0 , 19x0. P. M. van den Bcrg. A. T. de Hmp. A. k g s l . and N. “A computational model oí the elccmmagneiic hcsti logical tissue with application IO hypcnhcmic cancer IEEE Trans. Biomrd. Enp.. 10 be published. A. Tinove and M. E. 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Lynch, “Comparison of spectral and iimr-stepping W proaches for finilc clement circulation nrohlcnis.” in Ocruni ! h o e . . B O S I O ~ .MA. 1981. pp. aio-xii. I. Zemnnek. ”Bern behavior within the nearficld of vibrU*, piston.” J . ACOYII. Str. Amrr.. vol. 49. pan II. pp. IXI-Iqi 1971. C. P. Griffiicc and J. A. ScyJell. ”Spherical WWC drcompuri. approach to ultmronic field ~ a k ~ l i l i i m s . ”J . Nondrtnuw Evol.. vol. 2. pp. ?11-247. IWI. E. L. Madre”. M . M . GcwJsitt. and J . A. Iagiehrki. ‘‘Cimllw I - W ~ V C Sgenerated h) l o c u r d i&dtiiion.“ J . AFOISI 5.’ Amrr.. vol. 70. pp. ISü8-IS17. IV81. ous t .- ..-.. ...... i f .' $,rript ~ . m ri Ud, , I i May 30,, 71984. ,, , I,, 112; , 'wlxd t:la,rtriwl ~aurcr,E,P,. , I , cf currerit.lav&ng 'r.ri!,torv. I'lius. the icnip:it.rure rue would be well below that i , t otliei ~ I ~ t r ~ ~l hdeey :(lit1 ~ . nut consider the .>.is -3.r thickness and width, and its electrical and thermal paranirters. D.c.ni" .MO .*ni."O .i.C?& they calculated the temperature distribution around thc dirpersive electrode and evaluated the effects of these changes on thermal performance. Due to their use of symmetry in the two-dimensional model, they could not show the leading and .c,i,, trailing edge effects. The main objective o f this paper is lo develop a reasonably realistic three-dimensional human thigh model that can 1)show not only the leading edge effect, but also the temperature rise L.nl I 5 W n e and fall characteristics with respect to time, 2) explain other experimentally observed phenomena, and 3) become a tool for evaluating dispersive electrodes, predicting their performance, Fig. 1. Frontal view of the cylindrical model with 17 levels. Level 1 is the uppermost section of the left th$ and designing better and safer dispersive electrodes. is the lowest. The x axis points in the lateral directio axis points in the inferior direction. T h e small interior r METHODS rents a full-size square dispersive electrode locatcd be and IO. A. A QlindncalModel Fig. 1shows the frontal view o f our cylindrical human thigh model. Fig. 2 shows the horizontal view o f our model, one crow section of the cylinder. The x coordinate points in the right-to-left direction, the y coordinate points in the superiortoinferior direction, and thez coordinate points in the anteriorto-posterior direction. A s shown in Fig. 1,the model has 18 levels and 17 layers. A level is a two-dimensional cross section and each level has 242 nodes. Two successive levels form a slab layer and each layer has 240 hexahedral and prism ele. ments. The f i t e element method [8] allows us to use different shaped and sized elements to model the boundary smoothly, whereas the fmite difference method requiresidentical elements everywhere in the model. A s shown in Fig. 2, we compres the elements in the top and bottom parts of this cylinder in order to bring out the details of the voltage distribution and power dissipations. There are 4356 nodes and 4080 elements in this model. To calculate current densities and temperature rises, we must fist determine the voltage distribution. To fmd the voltage distribution throughout the model, we solve Laplace's equation: 4 v2v=o. This equation is subject to the following boundaw conditions: 1) rigid (Dirichlet) boundary condition-voltage values are specified on the boundary B, ,and 2) natural (Neumann) boundary condition-the voltage change in the outward normal direction should vanish on the boundary B2, ¡.e., ... whereB, +B2 forms the complete boundary: In electrosurgery, the rigid boundary condition occurs at both the active and dispersive electrode sites. Fig. 1alsoshows one square dispersive electrode located between levels 5 and 10. The voltage value at the active electrode site depends on the electrosurgical unit used, its operational mode, and its control setting. It is typically several thousand volts. The dispersive electrode is grounded through the electrode cable to the electrosurgical unit. However, due to the radio frequency signal and high magnitude of current used (up to 1A),inductive voltage drop occurs along the electrode cable. Thus,,the mlw. value at the dispersive electrode site keeps changing depend@ on the amount of current collected by it. The natural boundary condition states that current euuid enter or leave the model except at the active and dispersive dec. trodes. However, current can travel in any other direction .) long as it satisfies the above restriction. Therefore,heat dircip tion and temperature rise occur not only at the active and dk persive electrode sites, but also within the boundary and 6 ternal elements. The human body is so complex that it would be difiicult 10 model it geometrically and physiologically in real detail e K í with 100 O00 elements. The shapes o f the internal organsad the outside surface boundary are irregular and complex. Tb resistivity values and thermal characteristics change from OW to organ, and from tissue to tissue. Skelctd muscle is hiehi, anisotropic. At low frequencies, tlic resistivity measured trAn>verse to the muscle fiber direction is higlier tlian that m a d , ' II .I .. . I : !. s . I I ~< I I: . L . 'n). tenti&l value after t h e n itera.io IS. :ind k- is the 0ve:rrelo.a ion is facti) ~hiChsp:edsuptherae,ifo,nvergt:nci:. Without u i i g ~ :ni- I : \>'IS 0'1. o¡., -:I?: I ,i.\",! 1 im I . ,. , .iv,!iiiLiii> ' .I:. , ,,. , . , I , , . .., . , : , . . , : I . I 11' :We ioptheiterationifanyo'tli:fi>Uowiggconditionsiiri~~: I ) t& number of itetptions ~xc:eds500,2) the iteratiw E ~ U tion ,!is diverging, or !) changes OF aU nodal voltages bete ein sum.js$ve itsrations &e lesi thir. a prespeciiied error raiw. Onl~~hena>nation8)ismet,<io w e proceed tothenettrtep, w,wteminpte the nhcle process. we dietenninekhe vollag< distribution, we calculbte the density throyh each :lele:nmt using If "4 move the eleftrode 1o:ation forwatd or backwarcl a .ong the jy$nder, or if we employ e1ei:t.rodes of different shapes and size$ the tdal tmoe&nce b:twean the active and diqwsive elecirades changes, which result3 in different current an4 p , w r s thniughout the m d u t i i . However, an actual dlectro. set u*t is able tadeiiver &noit constant power fo@a'vide in the impe@ance valua. Therefore, the total p w e r in the whde model n i u t be a constant regarale IS of inipedanceualue, ¡.e., :s .s- rof 11 d c ! m . : ~ .s ~:ir ~ I n is iillii.l-:I' VCl. Power = 1 C I ( ' )vo Y slf (81 wht+e;Vol(') is the vplume csf tli,: element i. We use the con. 4 ; ¡:¡. '¡:u. cL,e?!, ient Sta4 total power value o f 105 \V which is the typic4 piwer > :' +.,>:,I.. i , r ~.i:-age delibted by an eiectrbsurgical unir with the 50 percent coiitiol ' o :,tbr: v i ' real sett g(h@fpower)?ndpursciitmode [19]-[20].Weailjust p.,! >., EO PO r'densffies unda differmt conditions to satisfy the conu)) :,! by stad dower ,requirement. rile C. hermination of the Teniptrtdure DlsMbution T) (ietormine the temper2ture distribution. we mwt ,olva the heat equation b c aT * l V a T t P at (9) whse,p, u themarrdensit),,~t : k specific heat.1 the tjhermal con&mtivlty, and Pthe energy ipteration due to Joulean ieat. ing.iw@ch has units of power per anit volume. For innct mides, P isberely the overal power deriiity discussed above.wlulc foz surtkk nodes expos4d to ra,iiati*mand convection prccr oses. P ii+lqdes, in addition to thi! p w m density. power lost t i l the env&qunant due to radiation iind convection. The r d h tivn le>b!P,hJs . m i t i .tipiwer per un¡! area. It is calculated b y P, = e,o(r' (10) - T:) where es is the emissivity of human skin (0.97 [Zi]),o is the Stefan-Boltmann constant 15.67 X IO-' W/(ma . K')], and T and T. are temperatures in Kelvins of each node and the environment, respectively. The free convection loss P, has units of power per uiut area. It is (11) P,=k,(T- Te) where k, is the free convectioncoefficient (23 kcal/fm' .h.K) [U]) which is equivalent to 2.68 W/(m' .K). We scaleP,P,, and P, to obtain the total power for each node. Our model used in determining the temperature distribution is the same one used in determining the voltage distribution as shown in Figs. 1 and 2. However. the temperature model is homogeneous in contrast to the inhomogeneous voltage model. We use the Same values of the mass density, the specific heat, and the thermal conductivity for all elements because there are not any e marked differences in thermal parameters from one layer to theothers 1121-[14]. Nevertheless,an inhomogeneous temperature model would be better. We select the massdensity value pm of 1000 kg/m3, the specific heat c of 3400 J/(kg .K), and the thermal conductivity I of 0.36 W/(m . K) to model more accurately the thermal properties of the skin and fat,and muscle layers that influence most the temperature distribution around dispersive electrodes [i2]. The heat (Laplacian) equation in Cartesian coordinates is We can approximate each term on the right side o f (12) in terms of temperatures of neighboring nodes and distance to them; for example, aaT(x,y,z,r) ax' - where the constant a = I/( prn<.) 15 t h C thcrni»nietric O%. tivity or the diffusivity. T(x..v.:.f + A l ) is the temperature Of the same node after m e A I , and from (13) and we define ky,,kya,k Z l and , k Z a siniilarly. In setting up (14)for every node, we must give s p e ~ Ea. sideration to surface nodes, because they do not have neighbors used in (14). in (14). there is only one u T(x,y , z, I t A t ) . By solving (14)for ail nodes, we daar. mine the temoerature distribution after time A l . For thetea perature distribution after time n A i , we successively detenni the temperature distribution by solving (14)4356 times,+ ing future temperature values as present temperature vpl a, and repeating the whole process 11 times. When the electrosurgical unit is turned off. the power&% in the medium becomes zero and heating due to current plas comes to an end. However, node temperatures continm change with time due t o conduction. convection, and rada% effects. If weturn on the electrosurgical unit again before% around the dispersive electrode cools off and becomes s t a b w which is often the case during electrosurgery. t h e e i e t m d e ~ even hotter than before due to elevated temperatures from* previous usage of the electrosurgical unit. Our model sim& these effects of the electrosurgical unit during the course of^ simulation. We implemented our model on a T1-990/12time-sharingcomputer and wrote the programs in standard FortranIV [I% A minimum run time for solving the Laplace and heat tmrufq equations for a specific electrode and its location in the& sharing computer environment was IO min. It took 6 s form iteration in the solution of (3), a simpiifid representation d a -. - T(x,Y,z,r) T(x - 1 ,Y, 2. f) T(x + 1.Y, z, r)- T(x,Y,2 . 1 ) Ax I Axa A% where A x , and Axa are distances between the node of our Laplace's equation, using the Gauss-Seidel iterative mnhod interest and neighbors in the x direction one level above and It took 12 s to dciermine the temperature profde after tlmc one level below, T(x t l , y , z , r)and T(x - l , y , z , r ) a r e t e m - Ar by solving (14) based on the present temperature dinri perature value of these neighbors, T ( x , y , z , r )is the tempera- bution. We used a At of 6 s. ture value of the node of our interest, and xo is the average of Axl and A x 2 . D. Experimenral Setup Therefore, for each node we can represent (9)as Fig. 3 shows the experimental arrangement used on humu subjects. The subject controlled the activation and deactivati3 T ( x , y , z , t + A r )= T ( x , y . z . t ) of the electrosurgical unit by a foot switch to avoid possol + A r . a { k x l [ T ( x tl,y,z,t) bums during experiments. Since we wereinierested in thetan perature distribution only around the dispersive e1ectrode.n - T(x.~.z,f)I used a second dispersive electrode as an active electrodt + k,l [T(x - 1, Y , z , 1) - T ( x , ~ , z , t ) l supply RF current through the body to the test dispersive elc. + k y l[ T ( x , y + I , z , t ) - T ( x , y , z , r ) l trode. Due to limited skin temperature change, we nieawc. temperature with eight 34-gauge epoxy-coated copper-coo +kyz t T ( x , y - I , z ,f ) - T ( x . Y . z . ~ ) I stantan thermocouples. Each thermocouple could monfio + k r i [ T ( x , Y , zt 1.1) - T ( ~ , y , z , t ) ] the time-varying temperature chmgc of a specific point U& the dispersive electrode without removing the dispersive cki + kr2 [T(x,Y,z 1.1) T ( ~ , Y2 ,,r ) l } trode. However, it was quite diíficult to get spatial t e m p t-. Ar (14) ture rise information under the dispersive electrode usingtk PmC mocouples. Thermography could overcome this problem 12I: . . / I :, . .. . .. ., 111 ,..,,:: 3 .. ~ _ . 1 I /r ___* _* ---- *_ _* -7 .____ -..--- .-_ c.__ (h I kg. 4. (,L) Calwlated current Uur sil es across lhe righthalfaf die square vn in Fig. I and the adjacunl surface for three hyyars. irt cli pointed by the x and Y. axes u c mity valiics are tiorrnslirci to the lpwest curra$ density undd Llie lispcrsive ,:la:trodc. n i . lop curve tlectrode with a contact qrxi 01' 130 cm:' was located between levels 5 and 10. It a i n t ~ i i r : dfive layers tind consismi of 84 iiodes and 65 elementi. #: the i sinulaticm progressed. we used .lifferent locations for act$ie and dispersrve eleqtrode!:,;ind d i f ikrent electrode areas and :;t.apes, 'Pig. ,1 shows the i:ílculatcd dirrent density across the. iighi half of t.he dispersive uiectrode .iad the adjacent surface, :irid the temperature rise around it which exceeds the normalskin temperature of31"C. The cur. lent density across the lefi hail is symmetrical to that of the light half. The rnaximuth traiisi'erse current density ratio oí 2.00 across the disperrivei8:li:ct .ode occiirs at the second layer ,if the disperbive electrode [.hf ratio betwcen Ghe current den.dies when r/r = 1.0 and x/r = O along the middle curve in Fig. 4(r)]. l ñ e rnaximunr ratio betwecn the higheat current density [upptr left and right cr'rners, when1 x/r = 10 along the iop curve in Fig. 4(a)l a& r:hc lowest current density [center of the fourtb layer. w h e ~.x/r = O along the bottom wrve in Fig. 4(a)] wlthm the dispersive electrode is 3.14. Overmyer o/. (41 calculated 3 ratio o f 2.9 for the circular electrode without allowing diflerei't la) err, which is reasonably close T O our result of 3.14 arid 2,110. However. they did no7 consider .he leading edge effect. Our result also indicates; i h a f 1:liere is a maximuri current :lcnriry ritio of 2.12 ilonl: t h ! dispcrsi.ve ekcirude iii the y d i r e a i o n , the miiu betwecii r h . i u r r c n : d.~ri~:!!, uf t i e <enter oí the leading edge [the first layer, when xJr = O alorig thc top .y '* curve in Fig. 4(a)] and that of the ínurth layer [when xJr = O p . tribution along the characteristic bottom curve at in the Fig. dispersive 4(a)]. Theelectrode current density shows that disthe peripheral region withonly 26percent ofthe total dispersive electrode area collects 45 percent of the total current,while the remaining 7 4 percent of the area collects 55 percent of the current. Therefore, nonuniform temperature rise occurs under the dispersive electrode. Fig. 4(b)clearly shows that the leading edge and side area exhibit higher temperature elevation than the trailing edge and center area. The highest temperature gradient occurs at the leading edge corners, and there are also temperature rises away from the dispersive electrode site. The ratio between the hnhest and lowest temperature rises under the dispersive electrode is 5.52 compared t o that of 4.00 obtained by Overmyer et al. [4]. B. lime-Dependent Temperature Distribution Fig. 5 shows the temperature rire characteristics from our simulations and temperature cooling characteristics from both simulations and measurements from a male subject whose measured data points best match those from simulations. Variations in the maximum temperature rises among seven subjects were + l " C for the full-size electrode and t3'C for the small-size electrode. Female subjects consistently exhibited higher temperature rises. Fig. 5(a) shows results for the fullsize oval electrode and Fig. 5(b) shows results for the small-size square electrode. In experiments, we used Johnson and Johnson ovalshaped electrodes with 130 cma area for the full-sizeelectrode, and we cut this full-sire electrode into a 6 X 6 cm square electrode around the dispersive electrode's connector to determine the details o f the temperature rise and fall characteristics. While the electrosurgical unit was on, the temperature rise with respect to time was almost linear. Howeve1,the slope of temperature rise tapered off due to effects of radiation, conduction, convection, blood perfusion, and blood circulation as temperature under the dispersive electrode increased. Using the fullsize oval electrode, the temperature rises after 0.7 A of RF current for 1min were 2.47'C from simulation and 2.4"Cfrom measurement, and temperatures after 2 min of cooling were 3225°C from simulation and 32.15"C from measurement. It took more than 20 min for the temperature under the dispersive electrode to return to normal skin temperature (31°C). Temperature rises after 1min using the small-size square electrode were 39.65"C from simulation and 40°C from measurement, and temperatures after 2 min of cooling were 34.52'C from simulation and 3 5 9 C from measurement. At this p i n t , we applied another 0.7 A of RF current for the next 1min, which resulted in maximal temperatures of 42.36-C from simulation and 4 1 3 ° C from measurement. If we allowed 2 min more for cooling, the simulation predicted a temperature of 36.38"C while the measured temperature value was 36.7"C. These re. sults indicated that our model could be a useful tool in predicting temperature rise and fall characteristics under various conditions. We also modeled a 130 cm' full-sized figure-eight.shaped electrode. Fig. 6 shows isothermal contour maps after 1min of current for an oval electrode and a figure-eight-shaped elec- 1 p , ...., - r 3% O w 1 orr Tm., mm (81 D (b) 4 w. Fig. 5 . Temperature rise and cooling characteristics. Solid h i simulation, X indicates meawremcnl. (a) T;ullYze owl (b) SmiUlizc quare elccuode. ,"?. 6. Iwithnmal contour map showing the tcmperature rise from w mal skin 1cmPerature of 31'C after 1 min of RF cunent lor (11 b full-rize ovd- electrode, and (b) Ihc lull-sue fwurc-cwhiJuld Fig. electrode. e. trode. The maximum temperature rises for these e l e c t r d were lower than that of the square electrode. The areas wilhp 33OC isothermal contours (2°C above the skin teinpernturc' decreased, and less than 40 percent of the total electrode im had a temperature riseof 1"Cormore. In F i g . ó ( b ) . t h e r e d leading edge at the center ofa figure-eight-shaped electrode a lower temperature rise than other iionrecessed leading d P Fig. 7 shows three isothermal contour maps after 1 mb P! heating, 1min of heating and 2 n l i n of cooling. 2nd I min.' heating, 2 min of cooling, and 1 ,nit] of Iicntinp. again. .,. :: Wr: Wc ' WllJ i thy 1)i F (C) 8, Inoüiermal coqlour map for the sniaiisize oval electlode after min of heaüngi 1mirl of ,waling and 2 min of c+m.nwi (4) I min of heating.2 min 01'ciinliig. md 1 min ofadúiiiorüheatii. m) thp dispersive electrode depcnds not only on the h@hest temp$"ire, but alto On the rhcrmal characteristics of underlying ti** and the dispersive electro(e applied, and the dqration of tq14which this elevated temper&ture is maintained. Webelieve t*t;l:he burn temfleraturc for the permanent tissue damage in t# (high ,area is over 48°C. Th$correspondswell t o m e results odShahaiíd Webster [3] and PeQiee [ S I . C; 4ffectt of t h e b c a t w n of Dlsperuvr oddilctiVe Eiecmdes !Fig. 10 shows the effect of inoving the square dispersive electrode along thd y axis in our model. The activeelectrode l*ion %Itillfilledithe entire IWd 1and the square electrode ofcqpied 6 levels. We coiild nqt place the dispersimelectrode s@r(ing at level I &e to the codflict between the twodifferent qrkhlet boundaw conditions. When the electrode v a s placed smrting at level i f , its tiaiiingi edge touched the end o f our &dci. which has 18 levels. When the dispersive elearode war l@<ic;ltedI<IOclose 10 the active electrode.the temperature under ¡I;hrc3iii~.quite hy?h d u e to the coiicentrired cunehr density f /- Sloltlnp Lnil Fig. 10. HQhert temperature under the dispersive elccirodc tion of its loution in the cylinder. I,, Fig. 11. Isothermal contour map for the íull-size square electrode Y it was placed starting at level 13. (d Fig. 9. lsothumal contour map ior the small&e figure-eighthped elcsirode aftex (a) 1 min of heating, (b) 1 mm of heating and 2 min of cooling, and (c) 1 m m of heating, 1 min of waling, and 1 min of additional hating. at the leading edge and heat conduction from the active electrode site with its very high temperature. As soon as thehighest temperature hit its minimum when the dispersive electrode was placed starting at levels 3 and 4, it started to rise as the electrode moved farther away from the active electrode. W e can explain this effect in terms of imposed boundary conditions on our model. The model had finite extent. The electric field distribution which determined the current density was disturbed because the Neumann boundary condition required that no current exit through level 1 8 in the y direction, however, the dispersive electrode had to collect the same amount of current no matter where it was located. Fig. 11shows the isothermal contour map when the electrode was placed between levels 13 and 18. Due t o the Neumann boundary condition at the entire level 18, current was concentrated more at the leading edge. Therefore,the temperature rise at the leading edge was higher than that with normal dispersive electrode location (between levels 5 and 10). At the same time, the current density at the trailing edge was smaller, resulting in lower temperature rise at the trailing edge. Compared to Fig. 4(b), Fig. 1 1 shows more concentrated current density at the leading edge, higher temperature elevation higher temperature gradient in the y direction. We con this unexpected result an artifact because of our mo extent. However, human limbs also have finite di Our experiments yielded higher temperature rises and leading edge effects when we placed the dispersive elear on the lower leg or on the lower ann. iherefore, as long I dispersive electrode was placed reasonably far away from active electrode but not close io the end of the extremi temperature rise was minimal and the exact dispersive el location became a factor o f little importance. To test the validity of our active electrode assumpt changed the active electrode from the entire level 1to nodes in level 3 in order to simulate the sharp active el used in electrosurgery. Calculated temperature around electrode area was several thousand degreesCe1sius.w be enough to make tissue around it evaporate. Fig. the temperature distribution around the dispersive electrodr which was placed between levels 13 and 18. If we e x a d both Figs. 1 1 and 12 closely, there is no significant differem<. which supports our modeling of the active electrode, Up until now. calculated current densities and ternperalui: distribution characteristicshavebeensyniiiietric iii thex mrd; nate due to symmetric or centered active electrode locatiom If the active electrode location is skewed with respect lo tk dispersive electrode. which is often the case iii our experinimt’ and actual electrosurgery, the teniperature rise oí the two si*’ of the electrode will be different. Fig. 13 sliows the ¡sothem.*contour map around the dispcrsive elrctriide loc;ited bctum I 'I * Icro1: . .......... . l'al : l ~ :I .. 7.' ........... ~ ,'.l,:xim,.m tkrqer:,we ........... .... l,r .IS. ... ..... ziii.: Sari.* *IIciroi:* .... Fcpir. Wt1-rtmio.c awtioa. -, squaw .l.Elll<(i I unibtord I I( ">Z Y ",2 2.:": Y ",Z I.!'*C IY "J 1IL.C Zi nz .- :.~.í OM1 *bstW* / L Y I I l t dCSi., Rinp ibclmd. ~ lar ri1g were ideptical. lii O L I s i x AaticDx WI vtri:i: current qensity iiiideii :.he C.spersiw el i&cd that curreht density tn :very eleincni 1 1 1 to iii.Le the currbnt density unier tke dispmi ,J elbctrijdeuniíottii However,, we cc~uldnqt reniiwe r i h t i v : ! ! , Ygh :went . . . ....... ..... .deiisi'.yat the IeaPingedge outbide th- dispersiv: eledtro' e. The ........ mixiinurn tempaature rise fdi the q u a r e i:!e:iiode w i t h unihi current density wiis I:l7'C. 'Ilús ternpei; lure lis':isonly .... Wi' or' that of the quare sl+:trode wiLlico1 i.rifdrm :urrent ........... Liaisiry. I f the leading edge Sfect outside thr dispers;veelec. xr?dc were removed with the iddition rifaz.withd miieq the .......... tetnp,:rature rise would have become even I~,wiv. &i.>rher conceptually superior disperiivc el?cmde !; a ring alictiode. We b o w thar reaiperaiure r i m < I any di.-pasive iel4Ct;ode are highest at and ap.>undthe leading t:d$e,a:id only ia crindi electrode area near 'the luding cdg: Ipanici,latcs in c<llie,:ting the b d k of t.he ret&rningcurrent I t:;teed c'f trying tqi:liniinate the leading edge Bifect;xecariIcn!tlientht leading e&i: and shortep its uiidih in the v. directioi, tci rediice the i : I I'UI ; L ; ~w ~ a i : cii:tI ,de :lebiii,ig edge effect. We raiodeled the ring elerr:ode uith a 21 < ! II, .F a x i r e * tend-location cifi-nidehand encircling the 1'3.cni-radiuis,cyliiisier at 'ayer 1 , 'retiui:.ing in a 1as.7 crn' cobtact area arid a o;!.& cm leading ,e& The maximum temperature rise after 1 -.in of O ?-ARF i,! ,)i:illi in .,a.,skeyed jcjricnt was only 1.14"C. men we modtled tie ,hay active ,!,: i iqer. .elt:st:ode in level 3 instead of the eiitirc leiiel J ,t k m simum ~ ! , ! ~1 !$,,ewi l l,,!> I,, I / 13. la , " , : , , elec. tqiilerature r i w o f the! ririg ekctrode at I;iye~13 was 137°C. ' I , 'imi :xn jeratii e ['se. for tar- I , i.!~rhc.iiiispc!rsl!c <b:ctmd.es. , ! '(i11I :!ii:wic i;!,e, , i f :he cbm, I '01 e ' , Y hile 1 he .rltiare eleci I i I ¡!;e H:I NCVCI thdJference I ' I:, :(!:I tlian 1,ü iei.iirit. Wlley , I I: I I c i > d i :'L Iiic t i i, iiivitled I , :, , : I i ~ :' I !,ti[ I t e t i : ¡I(:[ y ' < i t , , e an1 ri: Lit )I values i i i , : i i ' i i i ~ . 1.h: ,e er. they ! , : 1 , I S I K I I ! ' ~' I, l i i itrly far , ' 11 ! ) i i i i i ctry; :h; I! ,,cur(ent I L'c !,'s i t t h t i i 11: ' J iie.iiiiiii- I ,I I 'iI , , iii~:~:t:dto:the Tb,:r.:fore, we conclude that lby leiigthewig the &ad.ng edge dktmce in desigbing the <Iispeisive electr(i.de, r'tiichu1 nnntely letids to a ringelectrode, we should he able to 1e:rdase fhetemp$i;iiure rises sipificantly , and consequently. redlice the risk olpcssible burns. Tmle It show6 the maximum tt:mperature rises of square, ov;il. and figure-~ight-slhap,:dtlectrcideswitha: 6 cmr vectrode ; a h after 1rnin with the rlectrosur?icalunit c 11, 2 min off,and 1.rwn on again.,in sequence. The small S ~ U Í I : elpctr.xle had "t8e highest teniperature rises. while IIII: .ii."ie..tigh..shaped ekcrwde had tHe lowest temperature ris,i:i. 'Wtien we applied a0.7-ARF current for I iriin to thr s q u w rlirlicrrive e cctrode r r.he first time, thte niaxiiiium temp<:i:iir;iewas :9.6SoC. miparing Tablus I and I i , the singk mw;r iiinix~rt;~t fxtar for the 'emperaturn rise in the dispersive elecIriJ,.li: was .he elect w h ' s area. which is ittie traditional puiiir 01' view. lquition (1),,Iiowi that the power dem<.ityi r pro~ioiricii;iIto t h J squue < J I !,liecurrent density Equation 1 9 )s h i w , !.:it the iurnpcritu:.: . t u n g is linc.>rl> rel:itr.J t o i t i i p(wicr d::i,;ii) i i i w e v e r . . . <! Fguia . i g M - W l 6ü2.C L.931: I*Et.Cd. ''- I " - in Table 11,we reduced the electrode's area by a factor o f 3.61 from 130 cm' to 36 Em2. The maximumtemperaturerise ratio is 3.23 (8.65/2.68) instead of the expected ratio of 13.03 (3.612). This discrepancy exists because human tissue conducts heat quickly t o the immediately surrounding area, and there are effects of convection, radiation, blood circulation, and others. When we applied this current again after allowing 2 min of cooling, the maximum temperature was 4236°C. This clearly indicates that factors in evaluating this dispersive electrode must include time or history of current application, and the ability for the dispersive electrode to dissipate heat quickly. The only standard existing to guide in designing the dispersive electrode is the suggestion made by the National Fire Protection Association that 1cml of electrode area is required for each 1.5 W of applied RF power [24]. In this guideline, both the actual temperature rise under the dispersive electrode and the duration of the electroiurgical unit's activation are neglected. Our full-size electrodes have 0.81 W/cm2, which is well below the suggested maximum power density of 15 W/cm2, and mallsize electrodes have 2.92 W/cm2. However, i f we use the full-size electrode and turn on the electrosurgical unit for more than IO min, the maximum temperature can be dangerously high, even though the full-size electrode satisfies the power density requirement. On the other hand, for less than 30 s of RF power application, the small-size electrode does not pose any hazard even with its unsatisfactory power density. A more relevant standard might include the following factors. I ) The maximum temperature under the dispersive electrode applied on a fixed location o f a surrogate medium in a controlled environment, after applying constant RF current for constant time through a fixed active electrode, should not exceed a prespecified maximum regardless of the electrode's shape,size,and whether it is gelled or dry. 2) After another constant time of cooling o f f , the maximum temperature should be lower than another prespecified tempeiature. 3) After applying RF power again for yet another constant time, the maximum temperature should be lower than the third prespecified temperature. Requirements 2) and 3)could be combined into one standard. For pediatric dispersive electrodes, a similar set of standards could be written due to the smaller amount of RF current and power used in pediatric operations. Our experimental results have been based on using a dry dispersive electrode which has only a thin layer o f conductive and adhesive polymer. However, there is no major difference in temperature characteristics between dry and gelled electrodes, so we can apply the above analyses also t o gelled dis- R.IoIoIM Fwior Fig, The number of . range and the rclpxation factor usad in with bounduy conditions. Initial guess except those with the Dirichiet bounduy voltage values at the active and dispersive c o v,respectively. x indicates R I O ~ rangc O error range of 0.01 V,and q u a r e indicates c persive electrodes. One difference is that the skin te drops from 1t o 2°C when we apply the gelled electro skin because the gel in the electrode has cooled to r perature. After the gel and skin temperatures have w due to the applied power dissipation, the rate of coo somewhat lower than that of the dry electrode because gel's added heat capacity to the electrode. For solving Laplace's equation, Fig. 14 shows the r number of iterations as functions of the error range a relaxation factor used. We start all node voltage values those with the Dirichlet boundary condition with the guess of 50 V. If we use the underrelaxation techni this Gauss-Seidel iterative method,the rate of converge down, whereas the overrelaxation technique speeds u of convergence. The purpose of overrelaxation is to ac convergence, rather than to promote convergence in an wise divergent iteration scheme. The use of too large an relaxation factfr b e a t e r than 1.9) causes divergence. minimum numbers of necessary iterations are 35, 55, when the relaxation factor is 1.8 for the error ranges O. and OaOl V,respectively. We used the error range of 0.001 throughout our simulation to achieve high accuracy in the tion. With an error range of 0.0001 V. we could not ac any completely converged solution within 500 iterations R gardleu of the relaxation-(actor value. The ratio between t required number of iterations without the relaxation techniq employed (relaxation factor of 1.O), and 11131 with an o p t i d reiaxation factor, was 6 3 when the error range was 0.001 v. Therefore, findinga best relaxation factor is iiiiportant for uivinl computer time in any iterative problem solving. Also,thenunl. ber of iterations is a function of the elcctrode 1ocaiion.shap. area, and initial guess, but in a less dramatic way. There are some limitations in our iiiodeI3nd ntodelinp tech. niques that can be improved in future rcx3rch. The effccl @f blood circulation is not considered in wlvinp the heat transftr equation (9) because blood carries auay little iif thc heat pew rated during the I-min test. 1nteriaceshctwcr.n the skinandil' layer and the muscle layer and betweir the iiiuscle layer 2nd the femur are not smooth. Therefore, their shapes are not r4urate compared t o the cross sectional picture of the thigh 1151. ~ c t i L T: E W I ' ~ l ~ . . ~ , T U' P, II/ ' ! I~ i l l IN .\ROLIN<> 1.1- : ,,)r~iiiatc s!stcii. ' l i r o ~ g I ,'.:,udirjtc tcinsion id of uún3 I :IC ( 3rteij: KIII: . rciiiilt: s);tciri F 16 problem '111,: ;tiarbcs (11 o v i l atid fipis.e.eig1 &a used i n Fip. 6,8,a m ! :ir( iiilt p ~ r edy , ~ ~ l ~ t r o d e si odthe i i ~ iriite vkiiient ii:itureo :htiique. 1lic:e 3i c nosliiir~:~c~:rricrriiialirirnc.r 31iJ ti~ure.r.i~:tic-alr.ip~~d rlwt :ode:i. 'lliereft ~ q r r a t i u edistribu:.ions e:ipr.,:hilly those of 1115. \ ~ i c c 9, have siqniiLii 11 aitiiac: diie to tile p:eserict o: $ ! i ~ r pcr. in small arca:;. I f we roriotetl tlihi error in r i)i:d trodes, the iwxiiiiuin iei7ipc"atiire rises for tl cs: d:;;i~n;dzi mirized in TaSI: I1 woiilil h.iv: been lower. \Ve . < ! i i < L ) r t . e this problein tNy criip!oying triangular el4m 111, OII til-:. aceand usingmxe c1eni~:ntjirittieniodel. q o 1x1:iiriexic d e r inwlving dimensuns of the model, resis i v I I , w (ir.. at L D L c I I , . ' ' ut layeis, and thi,ir theirnd chiractrristics copld Ik.id :c :it1 lanation of wh). individid .differences in t h l tmcer:i[urc ributions around the dislmsin: electrodesexht, !io.': signil.. mt it is. and how to predict it -. Phpdmi T.:din;)u~?s Bu,lc,gi'dReseurch:ck~Vol. 6,W. L. N a m k , 19 3. 121 J. A. J. SioIwi!L :mi1 I. I ) ~11 dy, "Temperature rcwlatiin in mai-.A thiore.jc.it SIL:^) ." t' u g m Archir., vol. 291. pp. 129162, 1966. ; ,I. C o b and Y:Houd~~,"Er~iprimentdderemilialion of cwífii(11 Ed. Newiork:Acad:mi,. CIIKLIISIONS i k We constructed a three-diniensiondc y l i d r ca' cjrirpiter el of the thigh ibiised i.mthe finite element n etliti.1 to si)Iva the current density (clisiribution and tern r a ' w ~prc,fili: mund diapersive ele,:trod.es, Our model is versa1 le .iilri [Iruiblir M.Woods, "Thmry.meaiunthat we can easi..y simiilate the sizeof the cy,inii:r, a n J the , shapes. and locations of different active p i c!is?CriiVi: rodci. In spiti: of it!, Iiniitations,it isa usefiil !s,,>iY i >re. k t i g current den:;it:ies and temperature rises arciiir 1: 61 Y. Kim. W. I. Tiripkins,i i i d li G. Webrter, "Athrce-dhnensbd trades. We coinpared tkie results from our F~I.I:J~IOII; ti:# rimentd resuiis not oriiy for the rnaximuiii !cni)JcrJ urtl but also for tooling. characteristics with rJrp:¿: :o tinic. sirnulitions shuwed tlia!. tho current densityldibt riktiticn i!r uniform transversely. It is dso nonuniform Jorgircdiii;iliy, Fronriers Cornput. Med., vol. 1, lhich is called the leading tdgs effect. Electrobe scimetiy :!I elactor in determining ithe maxiniurn temp rature ris: i r i shaped elec:tro'de. The s q w e ele .tr(ide Ius the est temperiiuie rise, whila oval and figuh.-i~~ylit-slibpe<l .... *, have sinilar temi:ierature rises. The i o c h m of tho I ! I D. O. Coomy. Iliornedicil Cbgineering Rincipleu. New I'ork Marcsl I)ekker, 1976. ive elec~rod: is not inil?ortant as long iis !I 15 pi;tcetl i:! J.@ A. ]Pcarcs, proposcrl inelhod for quantitative pdorniance far away from the active electrode aid riot close to evaluation of eldc:rosuruic.il düpcrsive electrcdes.".Med.Inshn<nwil.. vol~13.pp.52- 4 1979 the extri:mitie!i. 'The unportant facto/sin evliuating [::!DI H.N. N o r t i i n , I b i ; d ~ ~ ! k ~ , T * n r d u c s r ,EkcIrodcMeomrlmg ~ ive electiodeart: the electrode size, tlieiclcr tr<wrgii:al Synemr. I:ngl&nod C1if.s. NI: PienticeHall. 1969. I activation time, at:d the electrode's abil$y tv t l i s s i : > m The ,%fe llse of Hipti-Frequ+cy Equipment in Hospital., wl. 76C, National Fir: Protection Arsuciation. Boston, MA. 1971. und it. Wi:prop.iscsd fwtors that mightlbe :nc!iiúcd i n %" k 1 It1 k9, e t. .. . . "4 [::!hi rd for evaliuiing tiis,per:iiveelectrodes. )ie a I ; c qu:!nti. y examined .I disparsive i:l<:ctrode with uliiftorin current and a ring elec~ri:,dowith a long leadin4rcig.e. I f 1,lt:se es were rn,ide aviiihble commercially. !hey !;liould re. ower teiiip:raturt: ri,ses,and thus reduct$tli,: kizarii of t e burns iiiidi!r the ~.lisperr,ive electrode. W a:Imdiuwsed cal aspects i'fouriii«~drl:indtheeffrctof he ~iver.reI~~:ci' ' ': hnique in rubstant idly ri:ducingoveraIl cdinl.Mmgtiine. Yonlpnin Kim ( S ' 7 9 4 ' 8 2 ) was bora in <!h4u. Korea, in t%3. He receival t b B.S. degnc In electronics acgincerins from Seoul Nitmnal University. S i u d . Korea. in 1975. and the MS.and Ph.11. d8:greqs in electrid and computer e@ nrcriny fruq tho University of Wisconsin. Madiw n . ~n IY7Yiand 1982. respoc1ivi:ly. Sinc: IYal he has been mAwsiin1 Profes%>r in it!< llq~.~r!men!o f Elcctricd Engllieering 11 ihc l,u\,:nii> <if U.~diinei..n. ScJiik. and >cr.hs* Lh.: t < ~ p ~ . ~ .<i i>mi - t i i ~ . rw.hiteiturC. p . d i e l cumputcr~ and applicatmnr. i u i n p ~ r ~w íh * )-!cm dcs!pn. d d . \anted (16- and 32-bit) minocomputer system d c r p . and i m r p rTocrvinp computer syrtcrns. He has drwldprd nim, ncu wniorand grrd. uate level computer engineering c o u r ~ ai t the l!nivn*ity of Washington. His research intercrts include wmputcriied impcdmcc h a g i n g , micro- computer-bas& medical instrumentation, human body modelin@ and simulation, image and signal proccssbg. and advanced computcr architecture. He is a ninuibuting author to the textbook Design ofMiCr0. mmputer-Emed Medimi Insrrurnmrofbn W.J. Tompkins and J. G . Webster, Edr.. Englewocd C W s , NJ: Rcntice-HaU, 1981). and other books in press. In 1981 he was1 finalist in the student paper wmptitionr at both the SCAMC and ACEMB conferences. Dr. Kim is a member of the IEEE Engineering in Medicinc and Biology and Computer Sacktier. the Awciation for Computing Machinery, and Tau Beta Pi. He ia a Faculty Advisor for the Washington Alpha Chapter of the Tau Beta Pi Association. rc""". .. . John C. Webuer (M'S9SM'69J r e d v e d the B S E . degree from CurncU University. Ithaw. r m N Y , i n 1953.andthcMS.E.E.rndPh.D.dcgrcer from the University of Rochester, Rochester, NY.in 1965 and 1967.rcspectively. He is a Professor of Electrical and Computer Engineering. at the University of Wisconsin, Madison. in the field of medical inrtrumenlation, he tenches undergraduate. graduate, and short courses. and does research on electrodes, biopotcntial amvWieis, impedance measurements, and tactile vieon. He iscoauthor. wilh B. Jacobson. of Medicine and Clmionl En&ecnnf (Englewood C W s , NI: Rentice-Hall, 1977). He is the Editor of M e d i a l Instrumentation: Appliwtion and DeJign (Boston. MA: Houahton Mifilin. 1978). He is co-editor. with A. M. Cook, if Cliniml Éngineering: .findpies and h c t i c e s (Englewood W f s , NI: Rentice-Hall, 1979);wilh W. I.Tomplunr, of Design ofMicrocumputer-Based Medical Insmrrnrntarion (Englewaod C W s . NJ: Ren<-... ' ., a I- .[.. t, i r I- s , i ,-, , ' I. 1, :rmc ¡Oi ~ A~iiiii:c:tioris of NMR Irnagi!:iy in Hyperthermia: At1 E\!c?Ii_iationof the Potential for Localized ,. . 1 issue Heatinig and Noninvasive , i Tern peratu re Mon¡to ring . . -. h,.I I I. ', . z.i 1 ' , /I /I! Df:NNíS L . t ' 4 R K I R 1 ' , . < “__-I_ -If h l l H A 5 S > A t l I < ) N S < ’ ~ 161 rate o f teniperature increase of about O.OOl°C!s fainiosi 4°C per hour) would result. This heating process is equivalent to microwave techniques and is not localized by gradients in the static magnetic field such as are used for imaging. For imaging purposes. the R F field is only on a small fraction o f the tinie and the resulting tissue heating should in general be negligible. :r’ 1 \ 111. NONINVASIVE TEMPERATURE MONITORING The potential for noninvasive temperature monitoring arises because the relaxation rates, longitudinal ( T I ) and transverse (Tl) are both functions o f temperature. The problem o f using the relaxation rates to measure temperature is complicated not only by the fact that tissue water exists in multiple compartments between which the relaxation rates differ substantially. but also by the fact that the rate o f repetitive measurements is limited by the relaxation rates themselves. There is therefore a tradeoff between temperature sensitivity, spatial resolution, and temporal resolution. \ ‘ A. Primmy Tempemhrre Dependence -- The temperature dependence o f the NMR relaxation rates was predicted by Bloembergen et al. [I31 and demonstrated experimentally by them and others [14]. Detailed derivations of the temperature dependence can be found in many text books [ 9 ] , but for completeness a brief derivation is given in and Appendix B. The net result is that the longitudinal (TI) transverse ( T z ) relaxation rates can be written: - 1/Ti = 72HzTo/(1 + w87:) l/T, = -rZ$[r0 + so/(i + wxs:)] (3) (4) where 7 is the gyromagnetic ratio, H is the local magnetic field due to local magnetic moments and which therefore changes with thermal molecular motions, so is a molecular position correlation time, and wo is the iarmor frequency. The correlation time so is found to approximately follow the relationship [13], [I41 ro = constant X d T 2 KIT (5) where K is roughly constant as the viscosity q o f water changes very slightly as a function o f temperature. A plot o f predicted relaxation times TI and T2 versus correlation time is given in Fig. 1. From tissue TI measurements made at two frequencies (24 MHz and 2.5 MHz) by iing eral.. it is possible to estimate the value of K to be in the range of 2 X IO-” s-K [15]. This is sufficiently small that in the temperature region where water is liquid (O-100°C) and at frequencies used in NMR imaging (10-60 MHz), the quantity wore is found to be much less than 1. Thus, for pure water the relaxations times TI and Tl are about equal and both arc approximately linearly related to the temperature. In tissue, due to various factors, Tlis found to be about a factor of 1 0 shorter than TI [16]. Fig. 1. Plot of expected reiaxation times v c r ~ u sconehtion tinit,.: i s generally assumed that temperature is inversely rested to lation time. The minimum in TIoccurs when v u = I . tion in the magnetization. If the relaxation process is exponential, attempts to characterize it with a constant will be inaccurate and will depend upon and timing o f measurement. The simplistic model of relaxation given in the section becomes very complicated when considering o f protons in tissue. The “inhomogeneity” d microstructure results in a large variation in water pm relaxation rates. There is empirical evidence that wate tissue resides in either bound states (hydration of large m cules) or free states [IS], [17]. The relaxation rates for states are found ¡o be much faster than those for wit free state. bhen multiple compartments (states) exist an exchange between states occurs, the observed is the sum o f the magnetization in the various each compartment decaying with its own characteristic d time [IS]: m) 2Piie-”’j n =lor ir! is I where P,j is the fraction o f the original magnetization comp. nent Io, in the j t h compartment. A typical curve for IQ compartments is shown in Fig. 2(a). When exchange is pc mittcd between compartments, the separate decay ratis h come less obvious. in the limit where exchange is very rapl. (i.e., much faster than the rate o f relaxation) the relaxatiiv becomes exponential with a single relaxation rate given by B. Nonexponential Rebarion The potential for relating relaxation time to temperature depends upon the existence o f consistent, exponential, relaxa- -- Lo-,: 1lTaw = 2PijlTj. n i- I i where I, is tlie equilibrium niagnetiza1ii)n uliicli is determined by the applied static field. u is the time betueen tite 90' pulse and the 180" pulse, and b is the time beiweeii successive 90" pulses. The times u and b can be varied independently. Hliile holding b constarit and measuring I(t) for two values of a (a = 01. u2j, one obtains for T2 T2 = (ai -uZ)/ln (12/Ii). (9) Assuming independence for It and I2 and defining K = .'(Ij/G and 3! = (u1 - u2)/Tl the relative variance in T2 can be obtained as o2(T2)/T:= Ke2"/r2(e2@ + 1)/O2. (10) The function of /j is minimized when 9, I1 (Le,, when the time between measurements is about equal to T 2 )having then a value o f about 9 . The exponential in u1 is minimized when 01 is zero, becoming about I when 01I! T 2 . I f it is assumed that the relative standard deviation in the maximum signal is about 1 percent, then K I!0.0001. Using these approximations, the relative uncertainty in T, can be expressed: u ( T ~ , ) / TIO.08. ~ (1 1) In a simidar manner, two measurements of I(2) obtained for different values o f b(b = bl , h2) while holding a constant allow Ti t o be computed. The expressions are complicated for arbitrary b l , b2 but can in principle be solved. If a simple solution is assumed the relative variance in TI can be computed as Although the expression in j3 (which is here defmed as j3 = (b2 - b l ) / T l ) is complicated, i t has a minimum of about O when fl I! 1.5. Using again K I0.0001, the relative standard enor in Ti is given by o(TIJ/TiI0.06. (13) D.Temperature Sensitiviry The precision with which temperature may be measured using NMR depends upon the precision of individual relaxation time measurements, on the number of such measurements which can be made and averaged together, and on the sensitivity (proportionality) between Ti and temperature for the tissue studied. In a nonimaging study of relaxation time ( T I ) versus temperature, iewa and Majewaka demonstrated a sensitivity of about 0.8 percent per "C for spleen, heart, lung and muscle tissues 1211. in the imaging experiments performed by the author, a sensitivity for blood o f about 1.4 percent per "C was obtained for T I 161. Thus, in order to measure tissue temperature changes t o within lec, it is necessary to measure T, to within 1 percent. An example of potential temperature precision in imaging is given in the two compartment blood study of Fig. 3. The Fig. 3. (a) An example of cross-sectional Ti temperahm difference of about 1S'C. (b) certainty obtained from an average of five bars represent one standard deviation for and conespond to a temperature uncertain1 image is a T~ cross section of two approxinlateiy cy blood samples, the brighter one maintained a1 ?OeC and darker maintained at 2°C. The sample cross sections approximately 1 cm2 . The tempeiature precision camp from an average of five such scans was ipproxiinately It was very evident in this study that improved prcc results when multiple scans are averaged together. Assumir: the measurements are independent and that the noise bi zero mean, the precision is improved hy tlie square 10: of the number of measuremenis included in Uie average. If it does prove essential to average multiple measure together, serious timing constraints result when us ' , <111': 8 YLI 4 I.$! ,. , .' '1,115. &retit 1 18 g"'ie:it, , I , : 8'' , , Jture iiicdsurmen:, a d .yT i t d l . I'liis. i t TI i r less thin I s. as appears c;.se i i ib i t ) l 6 ~ ~ ~tiuiies. i,A JS many .is 60 s e p t a t e :.Lwretticncs I trcni 'u tiicii TI is coriiputed:l could ed in onc ii,iiiiiic, :;id;iing precisicn in tenipara. other facti,:s uIi.\:ha r e i t thc precisian of measure- icli is b1:iiig ,:c.isured The signal will therefore vary c r i ~o' .he :iiiciir d::iieniii.in of die volume being ,\11'1 \ D I X .!\ ~:-~oio !mains less than I , the signal can also be prupor:itonit1 t o the squire of the applied static &Id, H,, itiie induced signal i s proportional to both etic moiient and the lreqiiency, both of which are na1 to tlic .ipplicd ficid). Athough 7 , is found i o frequcricy in accordance with (3), is s m l l [ 151 ( w o í o is much less than 1) and ttle i!flect on i:he sig~al-to-noise ratio. Whereas experirnenr!i were performed at 0.35 Tesla, curng has heeri successfully performed d a . an increase in a factor of over 4, corresponding tbarl an order o f magnitude increase in the signai.10- ai omiriuus observation concerning temperature he data o f Lewa and Majewska [21]. on tissue TI relaxation times versus temperand an irreversible decrease in TI occurring c. I t wuuld thus a p p e ~ rthat a t the point where eded, their: is a coniplete lass in e catise of the d?cre:isa appears t o be a great fU,ridanien,tally related to the hyperthermia Pouitile that an abrupt change in TI at just over be a very precise indicator ofphysiological ' Further re,ieirch i:i clearly justified. The rate o:' heat abswpti ' r i:i a iti:,.,n(rue :o UMR le,< nant absorptiuii depeiiili 11: .ti i w se:iara:e ::itej of inn:^^ actions: the rate ;it wlii:l~ ~ ! I : I<€ field úter;icth with i.hs local magnetic m«meiiti. L I I . ~ 'he 121- at wiiich the lox! magnetic moments trarisf:i 1' erriial i:nti-gy tsi tli? siirrouriding environment. In the pro ,e:w< ( c t a lar:c in~piieiicfield Jf, the degenerate energy lei .i~;ad,ihie to prm>toriso f spin I / ? are split into two levels 9 did by l i =l!y€I,,.Thefluctu~ ating local magnetic field. ,Iiic :c the r a n h thermal ~ motions of neighboring nuclei dila) irieriict \\irh the protori magnetic moments and cause the-nial quilihritlm, riccording to the B o l t m a n distribution, t , j 3:: whieved. If' no is defined as the equilibrium populatioii ,differi:ni:e between the two states and n is the population d i l f e r x c c ivliich exists a i some instant in t h e , the return to equilihr,iim in be expressed [9] : dnfdt = (no.-")/TI. (AI) For thermal interdctions, i f i !,iti:ir.s ~ which tend io cstablisheil thermal equilibriuni occur sr: xpidly ( o r rnori: often) than the reverse transitions. The addition of energy t i ) tlii: !$;?in !;yriem is .iccomplisheil by the use of an RF ma::ni:i.c fiiid. o~rtliogunalto the static field. Neglecting thermal k1.x r:ciiloris. in the p:esence i1f the RF field, stimulated enii 111 ;uid ;ibsorprio;i o,:cur with equal probability. W 191: 1111 ltn"dt = itie ~-' t i t i rdt: (!,e :.,..,, e:' (A') Wtr. ,,! .rAn\ltiL,r i,; 11: .I :..< ! ,111' :' ',: ,'I ,:I.: ir df -= u .: !ields for 11 n = n o / (I + ?hT,1. (A31 The net rate oí energy absorption is * d€/dl = fiw Wn = nofiwW/(1 + 2WTl). 644) Because W is proportional to Hi (the square of the RF field) 191,the rate of energy transfer is increased by increasing the RF field strength. Unfortunately, as W increases, the quantity W/(l + 2 W 7 , ) approaches the limiting value l / 2 T i . BecauseliyHo is much smaller than kT,the Boltzmanndistribu. tion reduces to no = h%7Ho/2kT. (As) The rate o f energy transfer becomes (A61 dE/dt = N y 2 h 2 H i / 4 k l T T , . For the case of protons in water, N = 0.66 X protons/ c m 3 , y = 2 . 6 7 5 2 X 108s-1-Tesla-i,6=1.0546X 1 0 - 3 4 J * s , k = 1.38 X J/K, and the temperature is about 3 1 0 K . For protons in tissue, the energy transfer rate is thus dE/dt 2 3 X 10-9H?,/Ti l/s. APPENDLXB (A71 (U*)--Io) where the longitudinal relaxation time is then given by 1iTi = y ' I k x A w o ) + ky,(woIl. Similarly, the x component of the niagnctization acccording to dUx)ldr=1í(1)XHo)x -y2[kyy(wo)+ kzz(O)]V,) with ]IT2 = y21ky,(wo) + kzz(0)l. It is generally assumed that the thermal motions show short range correlation such that Hkr)H,fr T + T ) =H ~ e - l r l / r o where the bars imply ensemble average, the subscript sents one o f the components x,y, or z, and TO is the tion time of the motions. The power spectral density. obtained as the Fourier transform of the correlation func is therefore given by Bloembergen demonstrated that, for a system of molecules of identical magnetic moments, the relaxation of the system k,Xw) = H f r o / ( l + w2r;). to thermal equilibrium is accomplished through the random Brownian motions of the molecules [13]. If, for example, It is also generally assumed that the various coniponcnk the system of molecules is held rigidly, with only motions the fieldHi are equal. The relaxation rates can then be writ (rotations) of the magnetic moments of the nuclei are allowed, the only interactions between the nuclei which can occur are 1/T1 = y2H%o/(1 4- W?,7;) those which do not change the total energy of the system 1/T2 =r2H2[ro TO/(^ + U?,.?,)]. (Le., those which do not change U,).the average z component of the magnetization). When motions of the molecules ACKNOWLEDGMENT are allowed, transitions can occur which transfer energy In addition to others previously acknowledged, between the system of magnetic moments and the molecular motions and which therefore lead to thermal relaxation o f suggestions have been received from C. Durney, D. the z component of the magnetization. B y taking ensemble and D. Christensen of the University of Utah. averages o f the possible molecular motions, the power spectral and k,,(w) of cordensity Components k,,(w), &,,,,(u), REFERENCES responding components of the fluctuating magnetic field at [I]E. M. Purcell. H. C . Tomy. and R. V. Pound. "R~SOMKI b a typical nucleus can be obtained. It is easy to show that sorption by nuclear magnetic moments in I solid." Phys. Rrv.. *D 69. p. 37. 1946. only the x and y components have an effect on U,),the y 121 F. Bloch. "Nuclear inducrion." Ph,vs.Rev.. WI.70. pp. 4MU'; and z components affect <I,),and the x and z components 1946 ._ affect U,). Furthermore, only components o f the power 131 E. L. Hahn. "Spin echoes." P h k Raw. w .UO. nu. 4 . F 58CL594, 1950. spectrum which represent a local magnetic field which is 141 P. Mansfield and P. G . Monis. NMR I m q i n p tn BirimrdiiW stationary with respect to the precessing moments will have New York: Academic. 1982. any nonnegligible long range effects. Because the expecta151 L. Crooks. L. Ksuimin. md A . Marpulir. NMR lrnupinp in YW tion values o f the magnetic moment components form a cinc. New York: IgakuJhoin. IVn1. I61 D. L. Parker, V. Smith, P. Sheldon. L. E Criwb. iind L. F u S i vector which precesses around the static field at the iarmor "Temperature dirinbutian measuxmcnir in iuo-dinicowonil hM' frequency. wo = yHo, the components which are stationary imaping."Mcd. Phw.. vol. IO. no. 3. pp. X I - X S . IY83. with respect to the precession are k,,(wo), k,,,(wo), and 171 K . S. h c r and R. Damadiui. "NMR in cancer: IX.T k mrt - I 3 .... .... J. O 'I 1 < !, I. L L ....... ......... . . . . . . . . . . ..... ~ ..... --_.. ....--..... -<.,.,................ ................ -,,, ,_" b 91I I ru h (a) . (C) (b) Tip. 1. Three arrangements of cunent Imps and the conerpondinp d$ rcctions of magnetic Yield lines arc shown (a) Single-turn c o i l (b)Coaxial pair ofcoüs. (c) Concentric c o t - assigned values of complex admittance to cells of tissue, as represented on computed-tomographic scans of human cross sections, to obtain a three-dimensional model of SAR. The essential features of the SAR distribution in tissue produced by a single-turn coil are that the SAR rises from values of zero along the coil axis to maximum values at distances from the axis similar t o the coil radius. The maximum SAR in any plane perpendicular to the axis diminishes with increasing depth into tissue (or distance away from the plane of the coil), within a region o f fixed complex dielectric permittivity 121, [3]. The improvement in SAR at a given depth that results from using a coaxial paU of coils can be estimated from Fig. 2 for a pair having a radius of 10 cm and a separation of 34 cm. The ratio of maximum SAR on the skin surface t o maximum SAR at the body midplane for varying coil radius a , coil separation of 34 cm, and body diameter of 30 cm is obtained approximately from Fig. 3 by multiplying the values on the ordinate by the ratio of electrical conductivity for superficial tissues by the conductivity for viscera. The coil radius required for maximum midplane SAR of more than 25 percent o f maximum superficial SAR is > 10 cm. Standard formulas were used for the calculation of the magnetic fields in this example 1171, and the approximation results from using SAR a$IF& electrical conductivity, and by ignoring effects of finite load size upon SAR, as will be discussed next. When the load has finite extent in the plane perpendicular to the coil axis and also is noncylindrical in this plane, the SAR distribution has the general features described above, but with possibly marked variation in SAR at a given radius from the coil axis resulting - from electric fields associated with charge displacements onto the boundaries of the load, as illustrated in Fig. 4. Numerical techniques are essential for elucidating the SAR distributions in the case of single or paired coils with finite, noncylindrical loads, in order for appropriate boundary conditions to be satisfied. The deviations in SAR from the toroidal distribution predicted for semiinfinite loads. increase as the coil diameter becomes similar to the minimum load dimension in a plane perpendicular to the coil axis. This conclusion is based upon a series of phantom heating experiments w e have done at the University of Arizona. The highly nonunifom SAR produced by magnetic induc~ ~~~ wh . 4 . ~ ~ iwuh * w .torn R.U --- 'Dm U .. .I I W 6 z O. 2 e I z kml -- -- ----_ IZ u 16 Fig. 2. The squared value of axial magnetic fieid, in arbitrary I evaluated at a mdius of 10 m tor a coil pair with radius of 1 and reparation of 34 cm ( s o u h e ) is shown versus the i x i tan= z from the pkne of one COL Similarly the results for I# coil of 10 cm radius are shown (dotted Une). Fw. 5. Un6a inten nnu The c ' I ~ Fig. 3. u&l 6cld *,, wlun(cv~l a1 a ndiusa of a coil pait of radiur a separated by 34 cm) u# (skin a<rface) + H2 (body niaplane) I V ~ I S Uhlul . bled as ing the ratios of @ by resp&ive tissue elccViwl conducti an utimstc of the mrio oT SAR nlucs uiñaee to pknc.A Foilmdiu~of>10 cm i r r q u u o d for sdnnagmusratl tion, particularly in the c a s o f the pancake coil or pairec arrangements, has led t o the suggestion by von Ard 1181 that the SAR may be time averaged to mure un? values by scanning coils over the body region of intc Other simple phantom experiments at die Univeriit! Arizona lead us to be skeptical that SAR disiribuiions ca dteend. scannin, from di Iir dab ofthc i c i iir iiurnericd so:utions of ikic lii.)b.ear e<iii.Ltibn (hce the thy Strohhsiin and Roemer i n :!lis isme). I r , I>,LI:~s~iliii:ic;ri>, niodels niiist be choien h r iri!r~tutn<iral 5k)<><! flow rates 2 n d distrih.iiii>ns, and 11c>n1i.i11:ssiic blo,id nou rates !nus: be par;iinetii-!red as well [241. 1251. The temperatriie distribiitioris iin I I O I P ; ; ~ti.,sui ' obtained w t t i a Iielicd p:incakc cod were :d:ulatei hy lirrid et ai. 1:31 u\irip ail aridytical solutiixi tiir SAK logediet Uitli a :iiiii:e-dirfererice iiiiirie:iciil metliiid ,of solving i i 6 bioheal :quaAm. These .:iuthors studied 111: cflect 01' coü tile. coil>kin >c.paratiun, !at tliickncss, mid hicocilirig ~orit~itiiins iipoii the tempcratiite distribution. Itripioiie<i I citing at ieprli relative 1:) superficial tissiics rwdtud fro,< a larger .!itxi d .dwri I .L :, !.\is;.t 11. .id reliably by means o.f pattern resulting the influence of 1 Ill,,,:,: '.# e in SAR distri. s less intuitively SAR in a given 'Ik.; [I t. >: I , , I!IC iiiagnetic field intensity iurfacc is >92 percent gnetic skin depth ~ i i: dl l i u s , and the temperature distrihuticic caicdlated f o r .ilti$c!e foUowed the toroidal SAK pdtterii chisely. In the ' a t la!er, howeier, steady-state ierriperaí~ire diskibutions .i:flwicd the effect o f heat transfer procerser and #:onformed .i:ss W e i i i o the S A R h a n did the ieriip,eratiire d6tr;bution in 11111scic Excessive temperature rise i n the in! layer resulted irom rclatively h a h SAR values tiigether wit11 Iciwei. perfusion ia1e.i rlian in the deeper muscle layen, a pn;,l>lenithat was menruated with increasing fat thickness. <:oo!inp o? the skin w i t h cliiued water at 10°C, however, cu iid dEplace the maxkniim temperature 1.5 cm deeper that, the r';;it-murle iitertace. assuming ii i cm thick fiit Iayei. The normal tissue temperature di..:ribui,ionii obtained .*.it11 ,,iitde pancake c<irlssuggest that elíecti;r iunlcr heating :(iuldt e obtained ori,.y for tumor; cc,ritinec r,o a few centi. ':ietci> dcplli from t h e skin, and thar. !,k:in 8.u,;~lin{: ,drerr the ;l:wr;.ttue distribilti~>nsignificanti\ cmrily iri tlhe m'ict íiiperI' \i :. ,. , ' ,.c f r o m die axis than tumor niudri (IOU perfurlon in cmlral zune. high perfusion in outer zone) with scanning of the coil over the tumor bearing tissue. With such a model. intratumoral temperatures 242°C could be achieved in a 2 cm radius X 2 cm len?th cylindrical tumor extending to 3 cm below the skin surface. The reports of Hand and colleagues are valuable for defining conditions under which this magnetic induction method can produce therapeutic temperature elevations (>42'C) in tumors, and for revealing the rather limited application of the small radius pancake coil method to treatment of small superficial tumors. Similar bioheat analysis for tumor and tissue temperatures with a paired coil arrangement have not been reported, and would be markedly more difficult to perform accurately bec a w of the complex SAR distributions associated with this arrangement, the fmite load size effects, and the greater variety of blood perfusion rates that would probably be present in large tissue volumes. Modeling o f temperature distributions obtained by magnetic induction with concentric coils has been reported by Strohbehn 1281, Brezovich ez of.1201, Halac et ni. 129) ,and by Paulsen er al. 1301. These models all include tumors of varying size, blood perfusion, and depth from the skin surface, and differ somewhat in the method of calculating SAR and solving the bioheat equation. The aim of such modeling, as indicated previously, is to calculate intratumorai temperatures likely to be achieved for conditions simulating clinical practice in which maximum temperatures in normal tissues are limited to 42-44OC, depending upon tissue type. Reasonable values of conductive or convective heat transfer across the skin surface may also be included to model the clinical use of forced air or chilled water cooling. Only the study by Paulsen et al. has included numerical methods of calculating electric fields in tissues with numerical bioheat equation solutions. This,in principie, allows the effect of areas of excessive heating to be included in the analysis. Excessive heating can result from the presence of fat, bone, and air volumes in the superficial tissue that ])can deviate eddy current flow and produce h& current densities in surrounding high water content tissues (analogously to a parallel electrical circuit) and 2) can result in predominant eddy current flow perpendicular to tinue interfaces and excessive heating in low water content tissue (analogously to a wries electrical circuit). On the other hand, the fact that induced electric fEldr are, on average, tangent to the major annular tissue interfaces in the body is an advantage o f the electric field configuration produced by magnetic induction, as Elliott ef al. have observed 171. The conclusions of the referenced papers on bioheat transfer modeling are similar and consistent and can be summarized as follows. I) Magnetic induction heating with a concentric coil produces the maximum SAR and maximum normal tissue temperature elevation in the outermost 5-6 cm of tissue. With blood perfusion values typical of resting muscle (2.7 m l i l 0 0 r m i n ) , homogeneous perfusion, and a cylindrical patient with radius of 15 cm, Strohbehn [28] found that .a IKU-ZUIIC' x.Iieii rlie maxmium . I (arteri,, blood temperature 37OC) a t a dcplh of 1.5 cm. the b,,dil center temperature was 38.6"C in stead! state. t Maximum temperatures in necrotic tunam can cxcC ec 42°C for sufficiently large tumors (eg.. 4.5 cni radius) evg at the center o f the patient. although the time required to' reach temperatures X 2 - C by thermal conduction can &,' quire long periods of time exceeding 60 min. The edge nonperfused tumor in Strohbehn's model would not re*' temperatures >42"C. 2) Portions of spherical, uniformly perfused tumors pir. rounded by lung in the model of Brezovich el of. 120) reach >42"C for tumor radii >5 cm and for values of S& that produce temperatures near 42'C in subcutaneous fat and chest wall muscles. lntratumoral temperatures are predktM to be nonuniform and minimum temperatures >42OC at ch< tumor-lung interface are unlikely, especially at the poj,, regions of the tumor. The maximum temperature in turno,, <5 cm radius may not exceed 42°C. Cooling o f the sum. ficial tissues is important for elevating applied power levy t o maximum values. 3) The model o f Halac et al. 1291 considered tumon al uniform or annular patterns of blood flow surrounded viscera, muscle, or fat, as would b e the case for pelvic and abdominal tumors. Solutions were obtained for three valua of the tumor blood perfusion rate. the two perfusion pattern; three tumor positions, three tumor sizes. and three no tissue blood perfusion rates. Particular solutions were idenql fied where all intratumoral temperatures could be elevatedi to >42" without exceeding 44'12 in muscle and fat or 42.4 in a significant volume of viscera. The principal fmdings w q that proper. tumor heating was achieved only when most d the tumor was within the superficial muscle tissue, this in tun limited tumor size to a diameter of 2 un. No proper i d heating was found for any tumors that had a margin extend' to the center of the body. Only 11 percent of al1 cases which the tumor was contained within the visceral annul4 (IO cm radius) were properly heated. In a majority of cas% applied power levels were limited by excessive temperatura rise in superficial muscle and fat annuli. Similarly to the c o b clusions o f Brezovich et al., these authors concluded that marked temperature elevation of necrotic tumor cores i i possible, but portions of the tumor periphery are usually below 42OC. The study of Paulsen er aL (301,including tumor models in both lung and viscera, corroborates these conclusions. issue ieriipcrxiure nd<i 45°C 9 1 LABORATORY INVESTIGATIONS Magnetic induction methods have been studied in phanrmi [19],1271, [31] and in large animals (31]-(33], and such studies are an important aspect of the physical cliaracteriri, lion of any hyperthermia technique. Nonperfused phantom studies are useful for revealing SAR patterns. as Cuy ha~ demonstrated in analysis of microwave applicators 1341. The principle involved is that of construct in^ electrically accur~te phantoms modeling tissue properties so that the teniperaturc rise produced during a brief heating interval is proportiona! to SAR. Temperature distributions after heating c m be oh served accurately with split phantums and therniogrnphk .. 96 t i I I I H - \ Y S A < T I O \ ~ O \ I~IO:II.IKA~. t i ~ e r n ~ m i c i r in y order to quantitate the ctricac) of h!per. i l i c n i i i a therapy and to assure quality. This prognostic inipuriance of niininiuni temperature. i f also true for human tuni~irs. justiíies the need for assessing ability of Various hyperthermia devices to achieve minimuni temperatures of therapeutic vplue (>42’C) in theoretical modeling studies. In the work of Baker eral. [46], 1 1 8 patients were treated with a concentric coil. Maximum tumor temperatures 2 4 3 ’ were observed iii 21 o f 99 patients. Minimum temperalure data were nut reported. The experience of Twoomey and Frey 1441 in 19 patients with a concentric coil revealed that the temperature o f at least one intratumoral site exceeded 42OC in about 1/3 of the patients. with a trend of lower temperatures with increasing depth and decreasing tumor s u e . Corry, Meoz, and collaborators [36], [37], [50] have clinical experience with use of single or paired coils in superficial. intrathoracic. and visceral sites. In 16 patients with tumor diameters >5 cm, 33 o f 50 superficial tumors had intratumoral temperature? a42OC, and m 1 1 of 26 deep tumors, temperalures were >42’C. In nine patients with intrathoracic tumors, average temperatures were X 2 O C in 30 percent o f hyperthermia sessions. Thermometry in this latter series could be done at few sites because of the limitations associated with intraoperative thermocouple placement. Use of a single pancake coil for treatment of superficial lesions has also been reported by Kim erni. 1431 Thermometric analysis o f this series was described by Antich qr u/. 1511. These authors investigated the possibility of correlating temperatures with S A R in both tumor and normal tissue sites. For given S A R , intratumoral temperatures were higher than in normal tissue in 213 of. the cases. The correlation o f S A R and temperature was higher in the case of normal tissue than in that of tumors. Their conclusion was that blood flow rates in tumor are frequently lower than in normal tissue, in part because o f thermoregulatory vasodilation in normal tissue. Variation in values of average tumor blood flow rates relative t o normal tissue weaken the correlation between S A R and average blood flow in the former case, but close correlation could still remain for minimum tumor temperature and SAR. i ~ ~ , ~ ~ i ~ ~ , i ~ i ~ ~ , . \~~ . ~J iA..&)<yIp Y. n ~ ~ ,!:~ i : ~ i . v u ‘ii’OLI.SON:’ Small p m i a k e coils are an eflcr.iivc nican, r d lieak small tumors with dimeiisions <4 cni i n ihr musi supcflrk several centimeters of body tissue. Largr dimieiei D ~ J ~ , paired coils niay produce higher S A R at given depths th% concentric coils. These coils produce a toroidal S A R discrib, lion that is complementary t o ihal produced by ConcrnN coils. The sites, depths. and tumor sizes appropriately trepb wiih paired coils reniain to be defined. r ACKNOWLEDGMENT S. McFarland typed themanuseripi.K.Crochowskipre illustrations, and J. Conrad and A. Fletcher assisted laboratory and clinical studies. REFERENCES H. P. 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Ncu Yurt: McCnv- Theoretical studies of S A R and temperature distributions obtained with various magnetic induction methods of achieving hyperthermia have been reviewed. Sophisticated models have resulted that are also being applied to the study o f other heating modalities. A considerabk amount of human clinical experience has confvmed the model predictions and this supports the concept o f extending’ the application of numerical models t o clinical treatment planning and thermal dosimetry, as i s described elsewhere in this issue. The most appropriate applications of magnetic mduction methods appear to be in treatment o f tumors c o n f n e d t o the outermost 6-7 cm of tissue in subdkphragmatic sites with concentric coils. Limitations o f induction methods for treat- I 181 nient of intrathoracic tumors are less well defined clinically. Substantial volumes o f such tumors may be elevated t o >42‘C only in the case of tumors with diameters >IO cm. ~ ~~ Hill. 1941. p. 263. M. 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