pdf page1-38 - Beckman Laser Institute

pdf page1-38 - Beckman Laser Institute

Computational Biophotonics Workshop: August 2016
Diffuse Optical Spectroscopy and
Imaging
BLI
Bruce J. Tromberg
Laser Microbeam and Medical Program (LAMMP)
Beckman Laser Institute and Medical Clinic
Departments of Biomedical Engineering and Surgery
University of California, Irvine
http://www.bli.uci.edu
Disclosure
Co-founder:
Industry Collaboration:
Medical Imaging
Mainstream Modalities
MR, X-ray, Nuclear, US(Optical)
Where Does Biophotonics Fit In?
Diagnostics
Therapeutics
Imaging/spectroscopy
Medical Lasers
>$60B/yr
Vioptix Odissey
Heidelberg Engineering
Spectralis
Masimo Pronto
St. Jude C7-XR
Medtronic-Covidien Invos
Syneron-Candela, Lumenis,
Alma, Cutera, Cynosure,
Fotona, Lutronic, etc
Perimed Periscan
NOVADAQ Pinpoint
Pentax Endoscope
AMO Intralase FS
Where Does Biophotonics Fit In?
Diagnostics
Therapeutics
Imaging/spectroscopy
Medical Lasers
>$60B/yr
Vioptix Odissey
Odisse
ey
Heidelberg Engineering
Spectralis
Masimo Pronto
St. Jude C7-XR
XR
Me
edtronic-Covidien Invos
Medtronic-Covidien
Syneron-Candela, Lumenis,
Alma, Cutera, Cynosure,
Fotona, Lutronic, etc
Perimed Periscan
NOVADAQ Pinpoint
Pentax Endoscope
AMO Intralase FS
Diffuse Optics
• Multi-Spectral (NIR)
• Structured Light: Space and Time
• Optical Pathlength Control
Multiple Light Scattering
850 nm NIR LEDs
O'Sullivan TD, et al. J Biomed Opt.
17(7):071311 (2012).
Tissue Optics Quantitative Challenge
Measuring Optical Pathlength
Molecular Absorption Loss
A = bC; b = 1cm
Fixed pathlength
Absorption + Scattering Loss
A = bC; b = ??
Unknown pathlength
Why Measure Optical Pathlength?
Physics
1) Separate Absorption from Scattering
2) Localize Information in 3D (Tomography)
Physiology
• Determine Perfusion and Metabolism at depth (Oxy/Deoxy Hb)
• Determine concentration of other NIR absorbers/fluors (e.g. Water,
Lipid, exogenous dyes/particles)
• Correct fluorescence for tissue optical property distortions
Controlling Pathlength
Three Ways to Control Pathlength
1) Wavelength:
labs ~ lscat
blue
labs >> lscat
green
Scatter
Dominated
red
Controlling Pathlength
Three Ways to Control Pathlength
1) Wavelength:
Sensitive to small
absorption changes
blue
100% StO2
green
50% StO2
red
400
labs ~ lscat
LID labs >> lscat
EE
Controlling Pathlength
Three Ways to Control Pathlength
l
l
2) Space: abs ~ 10 cm; scat ~ 20-40 μm;
D-1
Reflectance vs D
D-2
μa = 0.01 mm-1
μs’ = 0.1 mm-1
Scatter dominated
Scatter + Absorption
10
2
mm
20
400
labs ~ lscat
f = 0 mm-1
LID labs >> lscat
f = 0 mm-1
EG
400
labs ~ lscat
f = 0 mm-1
LID labs >> lscat
f = 0.2 mm-1
EH
Controlling Pathlength
Three Ways to Control Pathlength
3) Time: abs ~ 0.5 ns, scat ~ 0.20 ps
Intensity vs. Time (2 cm s-d)
T-2
Laser
pulse
Absorption
dominated
Scatter
dominated
0.2
ns
0.6
1.0
T-1
2 cm s-d
Measuring Optical Path Length
#')1-
! -
"
(1-)1-
#')1-
(1-)1-
4
! Measuring Optical Path Length
#')1-
$#* -
! (1-)1-
#')1-
(1-)1-
4
-
! FT(t)
FT-1()
FT(t)
! "
#')1-
-
(1-)1-
#')1-
(1-)1-
4
FT-1()
$#* -
! Measuring Optical Path Length
#')1-
(1-)1-
#')1-
(1-)1-
4
-
! FT(t)
FT-1(()
F
FT(t)
FT
! "
#')1-
$#* -
! (1-)1-
-
~10 cm depth, ~ cm resolution
Tromberg, et al., Appl Opt., (1993)
#')1-
(1-)1-
4
FT-1()
$#* -
! ~1 cm in depth, ~mm resolution
Cuccia et. al., Opt Lett, (2005)
Temporal Frequency Domain Photon Migration (FDPM)
source
( r , )
detector (re#ection)
scattering
tissue
intensity
detected light
A(r , )
source light
time
2#3:<1%%#2'-%;;#(&;)-;EK@KA9@FDEFA;
Controlling Pathlength
In Scatter-Dominated Region: Diffusion Equation
Light Tissue Distribution
Light source
n (r , t )
D(r ) (r , t ) + a (r , t ) = S (r , t )
c t
Fluence rate:
Space, time
Build up:
Light Scattering
D = 1 /[3( a + s ' )]
1/labs
1/ltr
Loss: Light
Absorption (f/)
Photon Diffusion Coefficient
T. O’Sullivan et al., JBO, 2012
Diffusion equation (time dependent)
frequency domain scalar photon density wave
modulated fluence rate (t , r ) = DC (r ) + AC (r ) exp(it )
In"nite medium:
S AC
S AC
AC (t , r ) =
exp(kr + it ) =
exp(k real r ) exp(i[t kimg r ]) =
4Dr
4Dr
a i
k =
+
D cD
2
damped wave
Boundary Conditions: Haskell, Tromberg et al, JOSA-A (1994)
1/l
c
a= 200 MHz
Modulation Frequency
(Mhz)
Photon density wave
1200
1000
800
600
400
200
0
kimag
a = 0.006 mm-1
s’ = 1 mm-1
n=1.4
kreal
0
0.02
0.05
0.04
0.1
0.06
0.15 0.08
0.2
0.1
0.25
k (1/mm)
AC = 1/k
real
{
DC = 1/
eff =
(D/!a)1/2 = 7.4 mm
<< c
a Vp = 2(D/c
a )1/2 16 mm/ns
phase velocity Vp = /kimg = >> c
V = (2Dc)1/2
a
p
(independent of )
(dependent on : dispersion)
photon density wavelength = 2/kimg 10 cm @ 200 MHz
(if no scattering, in air 9 m @ 200 MHz )
,1+&)%#-1>",#--((%(#!"-+',)(+-
-4
x 10
Data
Model Fit
5
4
3
2
1
0
250
Phase (deg.)
Amplitude (a.u.)
300
Data
Model Fit
200
150
100
50
200
400
600
800
Frequency (MHz)
1000
0
200
400
600
800
Frequency (MHz)
%!,,&
1000
FDPM
0.9
0.8
0.7
0.6
700
800
900
Wavelength(nm)
1000
0.02
FDPM
-1
1
Absorption Coefficient (mm )
-1
Reduced Scattering Coeff. (mm )
,',&
0.015
0.01
0.005
0
700
800
900
Wavelength(nm)
1000
FDPM
Power Law Fit
0.9
0.8
0.7
0.6
700
800
900
Wavelength(nm)
1000
0.02
FDPM
-1
1
Absorption Coefficient (mm )
-1
Reduced Scattering Coeff. (mm )
(3+3#-(+,&)"*
0.015
0.01
0.005
0
700
800
900
Wavelength(nm)
1000
#"(+5:,&)"*+"(
2#%*1-%9))%)-GM@GHA9@FDDDA
-')-+1&(++-(+,&)"*
0.9
0.8
0.7
0.6
700
1
FDPM
Power Law Fit
0.8
0.6
0.4
0.2
800
900
Wavelength(nm)
0
700
1000
0.02
FDPM
-1
1.2
Absorption Coefficient (mm )
1
Reflectance (a.u.)
-1
Reduced Scattering Coeff. (mm )
0.015
0.01
0.005
0
800
900
Wavelength(nm)
700
800
900
Wavelength(nm)
1000
1000
2#%*1-%9))%)-GM@GHA9@FDDDA
FDPM
Power Law Fit
0.9
0.8
0.7
0.6
700
800
900
Wavelength(nm)
1000
0.02
FDPM
SSFDPM
-1
1
Absorption Coefficient (mm )
-1
Reduced Scattering Coeff. (mm )
+(',(+).(')-+1&
0.015
0.01
0.005
0
700
800
900
Wavelength(nm)
1000
2#%*1-%9))%)-GM@GHA9@FDDDA
+('"+(&()"(+#-
-1
-1
Absorption (mm mM )
H 2O
0.8
HHb
0.6
BULK LIPID
0.4
0.2
0.0
0.02
-1
1.0
Absorption Coefficient (mm )
Tissue NIR absorbers
O2Hb
650 700 750 800 850 900 950 1000
Wavelength(nm)
$4$&+
I0 log = c L
I 0.015
FDPM
SSFDPM
Chromophore Fit
0.01
0.005
0
700
800
900
Wavelength(nm)
Oxyhemoglobin = 12.7 μM
Deoxyhemoglobin = 4.1 μM
Water = 21.5%
Lipid = 79.6%
1000
9;@@=
9;@@;
9<::?
9<::;
1 !+2
#1,).%)-+(,()#
&!#'!@
A
#1,).%)-+(,()#
&!#'!@
A
#1,).%)-+(,()#
&!#'!@
A
Oxygen
Metabolism
Oxygen demand
Mitochondria
2<30 mmHg
Cell
10-30 mmHg
Oxygen Supply
Cell-vascular
coupling
Tissue
17 < 47
mmHg
Venule
35
mmHg
Arteriole
90 mmHg
Predicting Clinical Outcome
Covidien INVOS
Optical endpoint: Pre-Surgical StO2 = HbO2/Hbtot
Clinical endpoint: 30 day and 1 yr survival
n = 1200, Cardiac Bypass Surgery
Total Population
High Risk Group
M. Herringlake, et al., Anesthesiology, 114, 58 (2011)
34
Predicting Clinical Outcome
Covidien INVOS
Optical endpoint: Pre-Surgical StO2 = HbO2/Hbtot
Clinical endpoint: 30 day and 1 yr survival
50% StO2 = ~25% greater chance of death at 1 year
50% StO2 = 45% SURVIVAL at 1 year (high risk group)
Total Population
High Risk Group
M. Herringlake, et al., Anesthesiology, 114, 58 (2011)
35
Cerebral hemodynamics during anesthesia
Phenylephrine
Lingzhong Meng
L. Meng, et al. Brit J.
Anes, 107, 209 (2011)
ISS Oxiplex
(Frequency Domain)
Ephedrine
Cerebral hemodynamics during anesthesia
Phenylephrine
Lingzhong Meng
L. Meng, et al. Brit J.
Anes, 107, 209 (2011)
ISS Oxiplex
(Frequency Domain)
<65% ~3-4 minutes/bolus
Ephedrine
Cerebral hemodynamics during anesthesia
Phenylephrine
Lingzhong Meng
L. Meng, et al. Brit J.
Anes, 107, 209 (2011)
<65% ~3-4 minutes/bolus
ISS Oxiplex
(Frequency Domain)
Cardiac Output Drop
Ephedrine