Is this condition - ETD Index Page
Transcription
Is this condition - ETD Index Page
A CBCT ANALYSIS OF CLASS I AND II ORTHODONTIC CASES: A CORRELATIVE STUDY OF AIRWAY MORPHOLOGY AND FACIAL FORM A Thesis Presented for The Graduate Studies Council The University of Tennessee Health Science Center In Partial Fulfillment Of the Requirements for the Degree Master of Dental Science From The University of Tennessee By Kyle David Fagala, D.D.S. May 2013 Copyright © 2013 by Kyle David Fagala. All rights reserved. ii ACKNOWLEDGEMENTS I would like to thank Dr. Edward Harris for his expertise, guidance and inspiration. Under his direction, I gained an enthusiasm for the research process and valuable experience that I will apply throughout my career. I would also like to thank Dr. Dan Merwin and Dr. Bill Parris for serving on my thesis committee. Their thoughtful insight and support were invaluable throughout this process. I would also like to thank Dr. Ken Dillehay, Dr. Dan Merwin, and Dr. Preston Miller for allowing me access to their CBCT images. I would also like to thank my parents Bill and Mary Jane and brother Phil for teaching me hard work and instilling in me a thirst for knowledge. Lastly, and most of all, I would like to thank my beautiful wife Anna and son Charlie for all their support during this 3-year process. iii ABSTRACT Introduction: Morphology of the pharynx affects the volume of airflow and facial growth patterns, the risk of sleep apnea, and swallowing patterns. Since the pharynx is housed in the facial structures, there may well be an association between the two. Evidence to date implies that the type and severity of Class II malocclusion affects the size and shape of the pharynx. Various researchers have classified Class II malocclusions into groups based on size and positioning of the maxilla and mandible, and these groups may exhibit different pharyngeal characteristics. Purpose: This study compares the pharyngeal sizes of Class II, division 1 orthodontic patients with those of Class I patients. This study also mimics Class II malocclusion groups to see whether different Class II types stand out as having distinct pharyngeal dimensions. Methods: This retrospective, cross-sectional study of 131 routine orthodontic patients (71 Class II, 60 Class I; aged 9 to 13) quantified volume and midsagittal area of the pharynx, defined as (A) the nasopharynx (dorsal and cranial to the posterior nasal spine), and (B) the oropharynx (the airway between PNS and the epiglottis), plus (C) the combined dimensions of these two regions. CBCTs were analyzed using Dolphin3D©. ANCOVA and general linear models were used to test for sex, age, and skeletal class changes. Additionally, Class II patients were separated into groups using cluster analysis based on the following criteria: (1) 11 pharyngeal variables, (2) 15 cephalometric variables, and (3) 4 Class II variables. Results: Airway size and volume increase significantly within each sex with increased age, but growth is significantly faster in boys. There is no statistically significant difference in the size of the oropharynx between Class I and Class II patients. By the time the 71 Class II patients were separated into groups using cluster analysis, the group sample sizes were too small to find any clinically relevant differences in airway size. The minimum oropharyngeal constriction occurs inferior to the soft palate in 76% of Class II patients and in 68% of Class I patients. Conclusions: With due caution for the crosssectional nature of the study, these results show that pharyngeal growth occurs at a linear pace during the key orthodontic ages. Rather than being tubular, the pharynx is broader mediolaterally, which cephalometric studies cannot capture. Generally speaking, there is no difference in size of airway between Class I and Class II patients. iv TABLE OF CONTENTS CHAPTER 1. INTRODUCTION .....................................................................................1 CHAPTER 2. REVIEW OF THE LITERATURE .........................................................3 The Airway and Pharynx .................................................................................................3 Anatomy of the Pharynx ..............................................................................................3 Soft Tissues of the Nasal Cavity and Pharynx .............................................................3 Three-dimensional Analysis of the Pharynx ................................................................5 Effect of Mandibular Position on the Pharynx ............................................................6 Airway Obstruction..........................................................................................................7 Nasal Obstruction.........................................................................................................7 Effect of an Obstructed Airway on Respiration ...........................................................9 Classification of Airway Obstruction ........................................................................10 Growth and Development ..............................................................................................10 Growth of the Face.....................................................................................................10 Growth of the Pharynx ...............................................................................................11 Relationship Between Muscle and Bone Development .............................................12 Class II Malocclusions ...................................................................................................13 History of the Class II Malocclusion .........................................................................13 Classification of Class II Malocclusions....................................................................13 Imaging ..........................................................................................................................16 Cephalometrics ..........................................................................................................16 Cephalometric Airway Analysis ................................................................................16 Cone-beam Computed Tomography ..........................................................................17 CBCT Airway Analysis .............................................................................................17 Disadvantages of CBCT ............................................................................................19 Technological Aspects of CBCT ...............................................................................19 CHAPTER 3. MATERIALS AND METHODS............................................................21 Sample Description ........................................................................................................21 Pharyngeal Analysis ......................................................................................................21 Volumetric Analysis ......................................................................................................21 Cephalometric Analysis .................................................................................................23 Class II Analysis ............................................................................................................29 Error Calculation............................................................................................................29 Statistical Design ...........................................................................................................32 CHAPTER 4. RESULTS .................................................................................................34 Geographical Cephalometric Differences ......................................................................34 Intraobserver Repeatability ............................................................................................34 ANCOVA ......................................................................................................................41 Summary and Interpretation of ANCOVA Results .......................................................45 Cluster Analysis .............................................................................................................55 v CHAPTER 5. DISCUSSION ..........................................................................................87 CHAPTER 6. SUMMARY AND CONCLUSIONS......................................................96 LIST OF REFERENCES ................................................................................................97 APPENDIX A. RESULTS OF ANCOVA TESTS FOR DIFFERENCES BETWEEN GEOGRAPHICAL SITES (KANSAS VERSUS TENNESSEE) WHILE CONTROLLING FOR THE PATIENT’S AGE, SEX, AND CLASS OF MALOCCLUSION ........................................................................................................107 APPENDIX B. BIVARIATE PLOTS (REGRESSION OF Y ON X) FOR THE REPEATED MEASUREMENT SESSIONS...............................................................152 VITA................................................................................................................................196 vi LIST OF TABLES Table 3-1. Cephalometric landmarks .............................................................................26 Table 3-2. Linear (millimetric) dimensions and angles measured on the lateral cephalograms................................................................................................28 Table 3-3. A list of the variables measured from the lateral cephalometric images in the present study...........................................................................................30 Table 4-1. Descriptive statistics of intraobserver repeatability, showing the difference of each variable and a t-test evaluating whether the mean differed statistically from zero .....................................................................39 Table 4-2. Results of one-way ANOVAs testing for differences in mean sizes among the 8 clusters developed using 4 maxillo-mandibular discrepancies ................................................................................................79 Table 4-3. Descriptive statistics for SNA among the 8 groupings generated by cluster analysis .............................................................................................79 Table 4-4. Descriptive statistics for SNB among the 8 groupings generated by cluster analysis .............................................................................................80 Table 4-5. Descriptive statistics for ANB among the 8 groupings generated by cluster analysis .............................................................................................80 Table 4-6. Descriptive statistics for Wits among the 8 groupings generated by cluster analysis .............................................................................................81 Table 5-1. Results of two-way ANOVA tests for Total Airway Volume factored by Angle Class and sex .....................................................................................91 vii LIST OF FIGURES Figure 2-1. Diagrammatic representation of the pharyngeal sections: nasopharynx (blue), oropharynx (orange), laryngopharynx (green), and trachea (pink) ............................................................................................................4 Figure 3-1. Bar charts of age distributions (sexes pooled) by geographical site ..........22 Figure 3-2. Sketch of lateral view of skull with skeletal and soft tissue landmarks identified and the airway segments delineated and labeled .......................24 Figure 3-3. Two-dimensional rendering of the pharyngeal airway ..............................25 Figure 3-4. Example of a box plot ................................................................................33 Figure 4-1. Box plots of the age distribution of the sample, partitioned be sex and geographical site (either Kansas or Tennessee) .........................................35 Figure 4-2. Histograms of the age distributions (sexes pooled) by geographical site (Kansas, Tennessee)...................................................................................36 Figure 4-3. Pie charts of the proportions of Class II patients by geographical source .........................................................................................................36 Figure 4-4. A metaphor of a “bull’s eye” characterizes the concepts of precision and accuracy...............................................................................................37 Figure 4-5. Bland-Altman plot for the cephalometric angle ANB ...............................42 Figure 4-6. Bland-Altman plot for the cephalometric distance B to NasionPerpendicular .............................................................................................43 Figure 4-7. Form of the ANCOVA model used to test for group differences for (45) cephalometric variables ......................................................................44 Figure 4-8. Bivariate plot between chronological age (in years, X axis) and volume of the nasopharynx (in cubic millimeters, Y axis), partitioned by Angle’s Class ........................................................................................46 Figure 4-9. Bivariate plot between chronological age (years) and pharyngeal volume (cubic millimeters), labeled Total Airway Volume ......................47 Figure 4-10. Bivariate plot between chronological age and the two-dimensional measure of Total Airway Area (mm2) .......................................................48 Figure 4-11. Bivariate plot between chronological age and volume of the inferior oropharynx .................................................................................................49 viii Figure 4-12. Bivariate plot between chronological age (years) and volume of the total airway (mm3) .....................................................................................51 Figure 4-13. Box plots showing the difference in distributions between the two Angle Classes .............................................................................................52 Figure 4-14. Bivariate graphs showing the difference in distributions between Angle Class I and Class II samples (sexes pooled) for the cephalometric angle SNA ..........................................................................53 Figure 4-15. Twin bivariate plots showing the association between chronological age (X axis, in years) and size of the angle SNB (degrees; Y axis) ..........54 Figure 4-16. Box plots showing the difference in distributions by Angle Class ............56 Figure 4-17. Box plots of the distributions of Wits values (mm) by Angle Class .........57 Figure 4-18. Box plots of the distributions of IMPA by geographical site and Angle Class measured at the start of treatment ....................................................58 Figure 4-19. A depiction of cluster analysis applied to Fisher’s three species of iris data (150 specimens; 4 variables) ..............................................................60 Figure 4-20. The “scree plot” associated with the following dendrogram (cluster analysis) .....................................................................................................60 Figure 4-21. Dendrogram of the 71 Class II cases analyzed from CBCTs ....................62 Figure 4-22. Results of cluster analysis using the 11 pharyngeal dimensions ...............63 Figure 4-23. Results of cluster analysis using the 11 pharyngeal dimensions, specifically for the airway 1 area (mm2) ....................................................64 Figure 4-24. Results of cluster analysis using the 11 pharyngeal dimensions, specifically for the airway 1+2 volume (mm3) ..........................................65 Figure 4-25. Results of cluster analysis using the 11 pharyngeal dimensions, specifically for the airway 1+2 area (mm2)................................................66 Figure 4-26. Results of cluster analysis using the 11 pharyngeal dimensions, specifically for the airway 2 volume (mm3) ..............................................67 Figure 4-27. Results of cluster analysis using the 11 pharyngeal dimensions, specifically for the airway 2 area (mm2) ....................................................68 Figure 4-28. Results of cluster analysis using the 11 pharyngeal dimensions, specifically for the airway 1+2+3 volume (mm3) ......................................69 ix Figure 4-29. Results of cluster analysis using the 11 pharyngeal dimensions, specifically for the airway 2 area (mm2) ....................................................70 Figure 4-30. Results of cluster analysis using the 11 pharyngeal dimensions, specifically for the airway 1+2+3 volume (mm3) ......................................71 Figure 4-31. Results of cluster analysis using the 11 pharyngeal dimensions, specifically for the airway 3 area (mm2) ....................................................72 Figure 4-32. Results of cluster analysis using the 11 pharyngeal dimensions, specifically for the total airway (mm3) ......................................................73 Figure 4-33. The scree plot for the cluster analysis based on 19 skeletal dimensions ...75 Figure 4-34. Cluster analysis (dendrogram) of the 71 Class II cases based on 19 skeletal dimensions ....................................................................................76 Figure 4-35. The scree plot resulting from clustering of four cephalometric dimensions (SNA, SNB, ANB, and AOBO) .............................................77 Figure 4-36. The dendrogram produced by four cephalometric variables (SNA, SNB, ANB, and Wits)................................................................................78 Figure 4-37. Box plots of the arrangement of the angle SNA among the 8 clusters ......83 Figure 4-38. Box plots of the arrangement of the angle SNB among the 8 clusters ......84 Figure 4-39. Box plots of the arrangement of the angle ANB among the 8 clusters......85 Figure 4-40. Box plots of the arrangement of the Wits measurement among the 8 clusters .......................................................................................................86 Figure 5-1. Bivariate plots by Angle Class and sex for Total Airway Volume (mm3) .........................................................................................................91 Figure 5-2. Bivariate plot between the patient’s age at the start of treatment and Total Airway Volume for the complete sample (n = 131) .........................92 Figure 5-3. A stacked chart of the average sizes of the 11 measures of pharyngeal size analyzed in the present study. .............................................................94 x CHAPTER 1. INTRODUCTION Morphology of the pharynx affects the volume of airflow and facial growth patterns, the risk of sleep apnea, and swallowing patterns. Since the pharynx is housed within the facial structures, there may well be an association between the two. Preliminary works by Kim et al. (2010) and Grauer et al. (2009) suggest a link between craniofacial dimensions and pharyngeal shape. However, sample sizes have been small. This project will pursue these statistical dependencies (between facial form and pharyngeal morphology) on a broader scale with a group of 131 American white adolescents. The purpose was to compare the pharyngeal shapes and sizes of Class II, division 1 orthodontic patients with those of normal Class I patients. The original expectation was that Class I subjects would have larger airways than Class II subjects. Chronic nasal airway obstruction is regarded as one of the prime etiological factors in malocclusion and disharmonies of the craniofacial skeleton (McNamara 1979). Disproportionate growth tendencies may result from altered neuromuscular activity and function of the enveloping craniofacial muscles and soft tissues (Miller and Vargervik 1979, 1980, 1982). Alterations are brought about by the physiologic demand for adequate ventilation when airflow through the nasal cavity is obstructed. The result is a recruitment of muscles, whose primary functions are mastication and maintenance of posture, to aid the primary muscles of respiration in maintaining required gaseous exchange. The muscles of mastication complement the volume of nasal airflow through a variety of compensatory lip, tongue, and jaw movements and posture. It is by means of this altered muscle function that skeletal growth may be affected (McNamara 1979). The three dimensions of height (craniocaudal), width (mediolateral), and depth (anteroposterior) determine the size and shape of the pharynx. Studies by Brodie (1941) and King (1952) found that the total depth of the nasopharynx is established in infancy, with little change thereafter. Linder-Aronson and Woodside (1979) reported that sagittal depth of the nasopharynx increases in small increments up to 16 years of age for females and 20 years of age for males. Johnston and Richardson (1999) found that the bony periphery of the nasopharynx remains stable during adulthood but soft tissue changes cause an increase in sagittal depth of the nasopharynx and a reduction in sagittal depth of the oropharynx posterior to the soft palate. Streight (2011) found that growth of the pharynx did not decline during childhood, but was linear throughout the child-to-adult age interval. Class II malocclusions are some of the most common facial disharmonies encountered in orthodontics. Edward H. Angle defined the Class II malocclusion as an occlusal relationship wherein the lower molar is positioned distally relative to the upper molar (Proffit 2007). However, the Class II malocclusion is more complicated than this dental definition suggests. A Class II malocclusion can be a dental problem, a skeletal problem, or some combination of the two (Graber 2005). 1 Evidence to date implies that the type and severity of Class II malocclusion affects the size of the pharynx. For the purposes of this study, we measured various cephalometric predictors of the Class II malocclusion and then tested for relationships to linear, area, and volumetric pharyngeal dimensions. Various researchers (Elsasser and Wylie 1943, Renfroe 1948, Riedel 1952, Henry 1957, Hunter 1967, Hirschfeld 1975, Moyers 1980, McNamara 1981, Whitney 1984, and Rabosi 1985) have classified Class II malocclusions into groups, but there is disagreement regarding the relative components of a Class II malocclusion. Most authors agree that mandibular skeletal retrusion due to size deficiency or posterior positioning is an important component with an often-occurring maxillary dental protrusion. The studies also tend to agree that the mandibular incisors are usually in a normal position relative to the skeletal base and, thus, not an etiologic factor in the malocclusion. The position of the maxillary skeletal structure relative to the cranial base is the finding most often disagreed upon. Some of the varying reports of maxillary protrusion, retrusion, or neutral positioning, can be attributed to differences in the samples or methods of analysis. However, it is readily apparent there is a wide range of maxillary positioning in this malocclusion. The present study mimicked the Class II malocclusion groups of these authors by using cluster analysis to see whether different Class II types within the continuum stand out as having distinct pharyngeal dimensions. Pharyngeal measurements were made using Cone-beam CT imaging. Availability of CBCT systems in dentistry now makes evaluation of the pharyngeal structures practical. 2 CHAPTER 2. REVIEW OF THE LITERATURE The Airway and Pharynx Anatomy of the Pharynx The pharynx is the muscular tube that is located immediately dorsal to the oral and nasal cavities, and superior to the esophagus, larynx, and trachea (Netter 2006). The pharynx is divided into three components: the nasopharynx, laryngopharynx, and oropharynx (Figure 2-1). The nasopharynx, also known as the epipharynx, is the region of the pharynx inferior to the nasal cavity that extends from the soft palate to the nasal passages. The nasopharynx serves as the portal into the oropharynx (Drake et al. 2005) and permits air to pass from the nasal cavity in and out of the lungs. Bergland (1963) described the skeletal boundaries of the nasopharynx as follows: The anterior part is formed laterally by the medial plates of the pterygoid processes and medially by the dorsal border of the vomer. The posterior part is formed by the pharyngeal surface of the body of the sphenoid and the basilar part of the occipital bone. The skeletal elements forming the caudal portion are the posterior border of the horizontal part of the palatine bones anteriorly and the anterior margin of basilar occipital bone posteriorly. Bergland (1963) described the bony nasopharynx as having the geometrical shape of a gable when viewed from the midsagittal plane. A line from posterior nasal spine to Hormion demarcates the anterior part of the nasopharynx (Hormion is the dorsocaudal point of contact of the vomer with the sphenoid bone). A line from Hormion to Basion can delineate the posterior part. The roof is formed by the inferior aspect of the clivus composed of the midline portions of the sphenoid and occipital bones. The oropharynx lies dorsal of the oral cavity, superior to the laryngopharynx and inferior to the nasopharynx, extending from the soft palate to the epiglottis (Netter 2006). Airway constriction in the oropharyngeal region is often associated with breathing problems (Ozbek et al. 1998; Singh et al. 2007; Mah et al. 2011). The laryngopharynx, also known as the hypopharynx, is the region of the pharynx below the cranial edge of the epiglottis, opening into the larynx and esophagus at the level of the hyoid bone (Netter 2006). Soft Tissues of the Nasal Cavity and Pharynx The mucous membrane that lines the nasal cavity also covers the surface of the cartilages and bones of the nasal tract and paranasal sinuses. Because this mucosa is easily irritated and inflamed, even a slight disturbance can cause thickening inflammation of the membrane. The level of inflammation of the nasal mucous membrane frequently dictates breathing cycles throughout the day. The nasal turbinates are bony shelves lining 3 Figure 2-1. Diagrammatic representation of the pharyngeal sections: nasopharynx (blue), oropharynx (orange), laryngopharynx (green), and trachea (pink) PNS is the abbreviation for posterior nasal spine. C2, C3, and C4 are cervical vertebral outlines. Diagram provided by Dr. Edward Harris on March 11, 2011. 4 the lateral wall of the nasal cavity and are involved in breathing, immunology, and olfaction. There are three turbinates in each cavity: the superior, middle, and inferior turbinates (Netter 2006). They are lined with pseudostratified columnar, ciliated respiratory epithelium. Turbinate size varies greatly among individuals and can be a primary site for respiratory obstruction (Standring et al. 2005). The nasal portion of the nasopharynx is similar to the mucosa of the nasal cavity (Standring et al. 2005). It possesses a highly vascular mucosa that contains an abundance of lymphoid tissue. The posterior part of the nasopharynx resembles the mucosa of the oropharynx in that it is comprised of stratified squamous epithelium. The nasopharynx begins at the level of the superior constrictor muscle and ends at the level of the soft palate. It communicates with the nasal cavity via the choanae and with the middle ear cavities via the Eustachian tubes. The bony elements in the walls of the nasopharynx make it rigid, while the oropharynx is contractile because of the surrounding musculature. The muscular wall of the oropharynx consists of the middle and inferior constrictor muscles. Three-dimensional Analysis of the Pharynx Kim et al. (2010) studied the three-dimensional airway volume and crosssectional areas of 27 children with a mean age of 11 years. Subjects were sorted into two groups based on their ANB angle. Statistically significant differences were found between several cephalometric measurements, including height of the posterior nasal plane, Pogonion to Nasion-perpendicular distance, ANB angle, mandibular body length, and facial convexity. Of note, total airway volume was significantly smaller in the Class II subjects. However, when the total airway was sectioned into 4 subregions, no significant difference was found between the two groups, though this is likely a type II statistical problem due to small sample sizes. Grauer et al. (2009) studied the CBCT records of 62 nongrowing subjects (aged 17-46 years) to evaluate pharyngeal airway volume and shape. Class II subjects had significantly smaller inferior airways, as measured from PNS to C3, than Class I subjects. Class II patients also exhibited forward inclination of the airway and a greater frequency of tongue indentations. Size of the face and sex were positively correlated with airway volume. No significant relationship was found between vertical skeletal components and airway volume. In contrast, Alves et al. (2008) found that the majority of airway measurements were not affected by malocclusion type, with volume and area measurements that were statistically equivalent between Class II and Class III groups. Findings did indicate increased airway volume and area for males when compared to females. However, the results should be considered with caution due to small sample sizes of 30 adults per skeletal class. Ogawa et al. (2007) found that patients with obstructive sleep apnea had higher body mass index, lower total volume of the airway, smaller anteroposterior dimensions of the minimum cross sectional area. Moreover, the minimal cross sectional area was 5 positioned below the occlusal plane in 70% of the cases, and the shape of the airway was most often concave (exhibiting a dished appearance in the sagittal dimension) or elliptical (when viewed axially, the airway is wider mediolaterally than anteroposteriorly). Shigeta et al. (2008) analyzed the CT images of 19 males and 19 females of a comparable Body Mass Index. The patients’ total and lower oropharynx lengths and volumes were statistically different in males and females. Males were consistently larger than females even when controlling for height. In men, the upper oropharynx soft tissue volume decreased with age while the lower oropharynx soft tissue volume increased. Age was a significant predictor of oropharynx length. Streight (2011) analyzed the CBCT images of 263 routine dental patients to develop normative standards of pharyngeal dimensions by sex and age. Sexual dimorphism (M > F) develops in childhood because of faster growth in boys, especially for craniocaudal heights, but the percent dimorphism typically becomes fully developed in adulthood (> 20 years). Pharyngeal volume, midsagittal area, and craniocaudal height are significantly larger in men. Sexual dimorphism was greater for craniocaudal than anteroposterior or mediolateral dimensions. Some variables (upper airway volume, some cranial pharyngeal areas, Sella-Hyoid distance) continued to increase during adulthood in men, but not women. No variable became significantly smaller with age, either in childhood or adulthood. Effect of Mandibular Position on the Pharynx Certain conditions have been associated with constriction of the oropharynx, including a retruded mandibular position and Pierre Robin Sequence. A retruded mandibular position may be associated with airway constriction by means of the lingual musculature and its attachment to the hyoid bone (Tsai et al. 2009). A retrusive mandibular position can cause excessive vertical facial growth, due to a downward, backward positioning of the mandible (Kiliaridis et al. 1989; Mew 2004). As the mandible moves downward and backward, there is an increase in lower facial height and the gonial angle becomes more obtuse (Tsai et al. 2009). When these increases are combined with the lingual muscular attachment to the hyoid bone, the result is a hyoid bone that is positioned both more dorsally and inferiorly. An inferior displacement of the hyoid bone and increased lower facial height are predisposing factors for upper airway obstruction (Lowe et al. 1986). Park et al. (2010) studied the pharyngeal airways of 12 subjects who underwent mandibular setback surgery. Lateral cephalograms and CT images taken before surgery and 6 months after surgery were used to make linear and volumetric assessments. The linear analysis showed posterior dorsal movement of the soft palate, tongue, and hyoid bone following surgery. The oropharyngeal volume decreased following surgery, but the changes were not significant. The volume of the nasopharynx, however, remained relatively constant, which suggests that deformation occurs to preserve the airway capacity in the changed environment following mandibular setback surgery. 6 Pierre Robin Sequence (PRS) is a clinical entity consisting of congenital micrognathia, cleft of the secondary palate, with glossoptosis, and upper airway obstruction (Figueroa et al. 1991). Figueroa and associates compared the lateral cephalograms of 17 infants with PRS to groups of 26 normal infants and 26 infants with isolated cleft palate. While the groups were distinct throughout the two-year period of study, differences were greater at the earliest age. Initially, the PRS infant had a shorter tongue and mandibular length, narrower airway, smaller tongue area, and exhibited a hyoid position that was posterior and inferior when compared to normal infants. PRS infants did experience “partial mandibular catch-up growth” leading to improved airway dimensions and concurrent resolution of respiratory distress. The increased growth rate, however, did not allow PRS infants to recover to values equal to normal. Airway Obstruction The relationship between upper airway obstruction, muscular adaptation, and skeletal modification has been studied in animals by Harvold and Miller (1979). They were able to demonstrate in monkeys quantifiable, electromyographic change in function of some respiratory and craniofacial muscles in response to nasal obstruction. Furthermore, Harvold (1979) documented morphological changes in these same monkeys with altered EMG muscle patterns. The most notable were 1) an increase in facial height 2) an increase in maxillary height 3) an opening of gonial angle, and 4) increased incidence of malocclusion. The morphologic changes shown in this animal model were thought to be redirected growth and remodeling. Changes would only be expected in bone morphology when muscle function is altered over an extended period of time and is of sufficient magnitude. Nasal Obstruction The effects of compromised nasal respiration on orofacial growth have concerned investigators for more than a century. Tomes reported in 1872 that children with large adenoids usually displayed V-shaped dental arches. Ziem, in 1879, placed a piece of cotton unilaterally into an animal's nostril and studied the consequent asymmetric development of the face. Angle, in 1907, stated that, "This form of malocclusion (Class II, division 1) is always accompanied and, at least in its early stages, aggravated, if indeed not caused by mouth breathing due to some form of nasal obstruction” (Angle 1907). With the advent of the cephalometric roentgenograph, it became easier to identify aberrant facial growth patterns. Early studies by Brodie (1941) and King (1952) focused attention on the changes in both the size and shape of the bony nasopharynx of growing children. When the craniofacial growth patterns of chronic mouth breathers were found to exhibit significant differences from established norms, considerable efforts were made to identify causative agents. 7 Harvold (1979, 1981) and Miller and Vargervik (1978, 1979, 1980, 1982, 1984) induced nasal obstruction in otherwise normal laboratory animals. They found changes in craniofacial morphology with adaptations of the neuromuscular system in all experimental animals. In 1979, Miller concluded that experimentally induced nasal obstruction in monkeys modifies normal sensory feedback, which reflexively induces changes in neuromuscular function of craniofacial muscles. He further stated that neuromuscular changes involve the alteration of the discharge of specific facial muscles in one of two modes: (1) introducing a periodicity in a discharge correlated with respiratory muscles, i.e., "rhythmicity", and/or (2) sustained tonic discharge. These clinical and experimental findings strongly suggest that there is a cause-and-effect relationship between nasal airway impairment and craniofacial morphology. It is noteworthy that airway obstruction due to adenoid hypertrophy has received far more attention than any other form of nasopharyngeal restriction (Levy 1967, Quinn 1978, Bluestone 1979, Bushey 1979). Other modes of obstruction such as allergic rhinitis can lead to altered nasal function resulting in malocclusion. Allergic responses increase nasal airway resistance, and Hunter (1971) among others, has suggested that the severity of the malocclusion is proportional to this increase in nasal airway resistance (Gwyne-Even 1958, Klechak 1972, Harvold 1979). Other causes of nasopharyngeal airway obstruction may include enlarged tonsils, nasal polyps, a deviated nasal septum, a small nasal cavity, bony nasal atresia, foreign body obstruction, and combinations of the above (Ricketts 1954, 1968). Linder-Aronson (1960, 1979) has offered a more specific description of the effects due to a compromised nasal airway. In addition to the cranioskeletal aberrations, such as a Class II skeletal relationship, proclined upper incisors, a narrow V-shaped upper jaw with a high palatal vault, and increased anterior facial height, he has focused attention on the enveloping soft tissues. Included here are characteristics such as open mouth posture, the nose appearing flattened, nostrils that are small and poorly developed, a short upper lip, a voluminous and everted lower lip and a vacant facial expression resulting from a hanging posture of the lower jaw. To further aid in the diagnosis of the cranioskeletal malformations, LinderAronson and Ricketts (1979) described systemic manifestations dependent on altered nasal airway function. Their findings include restless sleep, poor appetite with consequent undernourishment, complaints of being tired, hyperkinetic when not resting, and poor school performance. During the years of normal development, 60% of adult craniofacial size is reached by age four, and by age 12 it has reached 90% (Meredith 1953). These percentages emphasize the need for early interceptive guidance in order to accomplish successful orthodontic treatment of the growth-linked vertical and anteroposterior discrepancies. According to Rubin (1979, 1980), even more important than interception is the possibility of prevention of cranial dysmorphogenesis by identifying and removing adverse 8 influences on normal facial growth. Treatment, focused on prevention or early interception, would serve to lessen the severity of a developing malocclusion. Effect of an Obstructed Airway on Respiration In the following discussion the possible sequelae of craniofacial dysmorphogenesis is reviewed as occurring by way of four basic events: 1) upper airway obstruction; 2) deviation from normal physiological respiration as a result of hypoventilation; 3) recruitment of secondary respiratory muscles because of increased inspiratory demand resulting in skeletal muscle adaptation; and 4) altered craniofacial bone growth in response to altered muscle function. The body protects its tissues by responding rapidly to changes in oxygen and carbon dioxide concentrations in the blood. Obstruction of the upper airway increases resistance and decreases the airflow and oxygen volume reaching the lungs. Simultaneously, airflow is impeded during expiration so that carbon dioxide is not expelled to the normal extent (shallow respiration). Therefore, obstruction of the nasal cavity can lead to transient hypoxia and hypercapnia, and these states stimulate neural receptors, which modulate the respiratory system. When nasopharyngeal airflow is insufficient, the oral port becomes the established and predominant route. This alteration not only causes an increased workload by the primary muscles of respiration, it may also recruit the facial, suprahyoid, and masticatory muscles as accessory muscles of respiration (Miller 1979, 1980). Both the rate of onset of the nasal inadequacy and its magnitude are significant factors to be considered in the adaptive response. This adaptation leading to mouth breathing may occur as an alteration in the structure or function of a person for survival in an altered environment (Leoke 1964). This may require that the person continually adapt to better meet environmental requirements, or it may maintain equilibrium in spite of changing environmental conditions. Both types of adaptation may be significant in the response of the muscles of mastication to compromised nasal respiration. Since respiration can be thought of as an involuntary act under neural control, an alteration in its function elicits a feedback mechanism from the central nervous system resulting in altered muscle function to maintain homeostasis (Faulkner 1978). Therefore, muscles (whether primary respiratory muscles or recruited accessory muscles of the orofacial complex) provide the link between altered respiratory function and craniofacial form. Enlarged tonsils and/or adenoids are the primary source of upper airway obstruction in young patients (Rowe 1982). The severity and potential detrimental effects of this obstruction remain in question. In the present study, patients with adenotonsillar hypertrophy were eliminated in an attempt to focus on airway morphology associated with malocclusion. 9 Classification of Airway Obstruction Bluestone (1979) devised a classification scheme, which correlates the degree of obstruction with known cardiorespiratory complications and potential sequelae. He characterizes mild obstruction by mouth breathing, stertor (snoring), and speech distortion. Either enlarged adenoids and/or tonsils may distort speech; obstructive adenoids give a hyponasal sound quality, while large tonsils produce a muffled quality to speech. Moderate obstruction would include some disturbance of sleep and possibly hypersomnolence. Severe obstruction is not only marked by a more pronounced degree of these signs and symptoms, but also causes sleep apnea. Bluestone lists the three most serious complications of upper airway obstruction as follows: 1) obstructive sleep apnea, 2) alveolar hypoventilation, and 3) cor pulmonale. Associated potential problems are difficulties in speech and olfaction, maldevelopment of the nose and perinasal sinuses, maldevelopment of the middle ear, impaired cognition and language development, diminished school performance and psychosocial development. These are in addition the sequelae of craniofacial malformations. Of interest, Bluestone considered that dysmorphogenesis of cranial structures occurs with moderate or even mild airway obstruction. Growth and Development Growth of the Face The relationship between facial and general body growth has been the subject of many investigations, and the period of rapid growth known as the pubertal growth spurt has been of particular interest. Since the first description by Montbeillard in 1759 of the pubertal growth spurt (Scammon 1927), its influences on the facial structures have been studied in depth and reported throughout the literature. The numerous methods used to evaluate body growth during this period include the measurement of height and weight, determining skeletal age from radiographic assessment of ossification centers, onset of menarche, and the development of other secondary sexual characteristics. In a longitudinal study relating the craniofacial skeleton to body height, Bambha determined that a circumpubertal growth spurt of the face occurs just after the corresponding spurt in body height (Bambha 1961). While the facial dimensions followed the general curve of growth in stature, the onset and peak of the growth spurt displayed large interindividual variability. Females had smaller absolute measurements, a slower rate of growth, and matured two to three years earlier than males. 10 Growth of the Pharynx Until the recent advent of CBCT technology, status of the pharynx was limited to anteroposterior dimensions evaluated from lateral cephalograms. Brodie (1941) and King (1949) argued that the anteroposterior dimension, as measured from posterior nasal spine (PNS) to the anterior arch of the first cervical vertebrae (the atlas), does not change much after the end of the second year of life. Although dimensional growth occurs during development, Brodie (1941) and King (1952) proposed that the ratios formed in the anteroposterior dimension remained constant throughout life. Brodie (1941) looked at sets of 14 serial cephalograms from the Broadbent-Bolton growth study for 21 children, all boys, from the age of 3 months to 8 years of life. From a number of cephalometric points, Brodie derived lines and angles that divided the head into several parts. One part was termed the brain case, another the nasal area, followed by the upper dental region, and the mandible. By observing the various regions, Brodie was able to qualitatively assess growth. In reference to growth of the cranium, Brodie remarked, “The most striking impressions gained from it are the regularity and steadiness of the process and the fact that the morphologic pattern, once attained, does not change.” Concurrently, if a child was markedly dolichocephalic at the start of growth, he remained that way throughout growth. Thus, the proportionality of growth remained constant. King (1949) studied the serial cephalometric radiographs of 24 boys and 26 girls that had been taken at three months of age, six months, one year, and then annually to six years, and biennially from 6 to 16 years. Films were traced and superimposed along the Sella-Nasion plane with registration at Sella. From the age of three months to 16 years the anteroposterior growth between the atlas and the posterior nasal spine averaged 3.8 mm in boys and 2.6 mm in girls. Most of this growth occurred in the first year of life. More inferiorly, in the oropharynx, the distance between the cervical vertebrae and the hyoid bone was relatively constant until puberty when the hyoid bone moved slightly forward. This suggests that the anteroposterior dimensions of the pharynx are established in early infancy. In contrast to the small increases in its anteroposterior dimensions, the superoinferior growth of the pharynx was much greater. Growth in height of the pharynx was also continuous, with a slight prepubertal spurt in girls and a slight postpubertal spurt in boys. These studies demonstrate that, surprisingly, little growth occurs in the anteroposterior dimension of the nasopharynx, when viewed laterally. Linder-Aronson and Woodside (1979) analyzed 140 boys and 120 girls from the Burlington Growth Center (Toronto, Canada) to cephalometrically evaluate growth in the anteroposterior depth of the nasopharynx. They concluded that the sagittal depth of the bony nasopharynx increased in small but steady increments up to 16 years of age in females and up to 20 years in males. In this sample, the velocity of increases in sagittal depth for males peaked between the ages of 12 and 14 years. The peak velocity for females was between the ages of 9 and 12. They found considerable variability in the amount of increase and in the timing of the peak velocity. They also concluded that the sagittal increase was unrelated to other cephalometric dimensions of the facial complex. 11 Therefore, both environmental and physiological factors might play a role in size of the airway. While the anteroposterior growth of the pharyngeal depth is minor, the greater increase in size of the pharynx occurs in the vertical dimension. Ricketts (1954) documented a positive association between cranial base morphology and nasopharyngeal depth. The more obtuse the angle of the cranial base (Se-Na-Ba), the greater the depth of the nasopharynx. Growth of the palate occurs in a downward path, and there is little forward change in the posterior region (Enlow 1965). The growth of the palate as well as growth of the spheno-occipital synchondrosis occurs in principally a caudal direction. Tourné (1991) stated that growth of the palate and the spheno-occipital synchondrosis cause the bony nasopharyngeal height to increase by about 38%. As a consequence, the superoinferior dimension contributes most to the increase in nasopharyngeal capacity. Few studies have analyzed changes in the pharynx during adulthood. Johnston and Richardson (1999) performed a cephalometric study of 16 adults. The adults began the study with a mean age of 20.2 years and had a cephalometric film repeated 32 years later. They measured changes in pharyngeal skeletal size, pharyngeal soft tissue thickness, pharyngeal airway depth, and soft palate dimensions. The results showed nasopharyngeal skeletal dimensions were unchanged over the 32-year interval, while the anteroposterior depth of the nasopharyngeal lumen increased as a result of a reduction in thickness of the posterior nasopharyngeal wall. The oropharynx showed a decrease in depth of the airway due to the soft palate becoming thicker and longer. The actual size of the airway and its relative obstruction depend on the growth of the soft tissues of the pharynx, which the literature shows to be variable. Relationship Between Muscle and Bone Development The pharynx is made up of both bone and muscle, and its anatomical shape and position are partly influenced by the positions of the mandible and tongue. Wolff’s law suggests that there is an interplay between muscle function and bone development (Enlow 1968). Functioning muscles exert significant morphogenic effects on skeletal tissues to which they are attached (Moss 1975). Harvold (1979) demonstrated that, when bone grafts are implanted under the temporalis muscle, bone formation is stimulated at that site when associated with a regimen of vigorous muscle activity. However, the same muscular activity results in bone resorption and remodeling at sites distant to this muscle force. Decrease in size and alteration in the shape of the coronoid process also has been shown to be directly related to the amount and position of the functioning temporalis muscle fibers remaining after experimental partial myectomy (Moss, 1970). An increase in muscle function, as in human masseteric hypertrophy, produced a corresponding localized increase in bone size (Bloem 1971). This responsiveness of bone to changes in muscle function occurs both in the growing animal and in the adult (Moss 1969, 1975). 12 Class II Malocclusions History of the Class II Malocclusion Edward H. Angle designated the Class II malocclusion as a molar relationship where the buccal groove of the mandibular molar is distally positioned when in occlusion with the mesiobuccal cusp of the upper molar (maximum intercuspation). The Class II malocclusion can be further divided based on variations in the inclination of the maxillary anterior teeth. A Class II, division 1 malocclusion, for example, features maxillary anterior teeth that are proclined with a large overjet. A Class II, division 2 malocclusion, instead, has maxillary anterior teeth that are retroclined with a deep overbite (Riolo and Avery 2003). While this system provides a means of describing the anteroposterior relationship of the maxillary and mandibular dentition, it does not recognize vertical or transverse relationships, which directly affect the anteroposterior dimension, nor does it differentiate between skeletal and dental causes of the Class II malocclusion. The system is merely a means of describing dental relationships between the two arches. As the deficiencies in this system have been well documented (Van Loon 1915, Hellman 1921, Hixon 1958), the need exists for a more complete and discriminating system for classifying malocclusions of this type. Classification of Class II Malocclusions The Class II malocclusion is not a single morphological entity but, instead, results from combinations of skeletal and dentoalveolar components (Graber 2005). For over 65 years, investigators have examined Class II series to determine the nature and occurrence of factors contributing to the malocclusion. Elsasser and Wylie (1943) noted in a sample of Class II individuals that maxillary protrusion occurred in males while the maxilla was in a relatively neutral position in females. They found no difference in maxillary molar positioning when compared to a Class I group. They also found the mandibular length to be within normal limits for males while it was less than normal in Class II females. Renfroe (1948) in a study of the facial patterns in Class II malocclusions found that the average maxilla was in a retrusive position in both sexes with maxillary incisor protrusion and a molar retrusion relative to a Class I sample. He noted, as did Henry (1957), that while some Class II individuals have a deficiency in mandibular size, other individuals had well formed mandibles of normal size that were in a retruded position due to the posterior position of the glenoid fossa. He concluded that the mandibles of Class II individuals were retrognathic relative to other craniofacial structures. Riedel (1952) in an investigation of Class II individuals determined that the maxillary skeletal base was positioned normally in both sexes but with protrusion of 13 incisors. He also noted that the mandible was in a retrusive position when compared to averages for Class I individuals. Henry (1957) studied the lateral cephalograms and dental plaster casts of 103 patients with Class II, division 1 malocclusions. The majority of the malocclusions were due to posteriorly positioned and slightly underdeveloped mandibles. He suggested that the cases could be classified into four discernible groups: (1) maxillary alveolar protrusion; (2) maxillary basal protrusion; (3) a condition Henry describes as “micromandible” and (4) mandibular retrusion. He also detected an increased mandibular plane angle compared to his Class I norms, suggesting an increase in lower facial height. In assessing a Class II sample, Hunter (1967) found the maxilla to be in a relatively neutral position but with incisor protrusion. The mandibular incisors were retruded while the mandibular skeletal position was retrognathic. He also determined that there was a slight increase in anterior facial height. Hirschfeld and coworkers (1975) studied a sample of children to develop categories of facial skeletal types. Of the five groups assessed, three appeared to be subgroups of Angle's Class II molar relationship. Moyers et al. (1980) studied 697 lateral cephalograms of North American white children with Angle Class II malocclusions. They found that, on average, Class II patients have smaller faces than Class I or Class III patients. The researchers used methods of numerical taxonomy to construct six subgroups of Class II patients (Types A, B, C, D, E, and F) distinguished by horizontal variables. Of those six Moyers and coworkers identified four subgroups (Types B, C, D, and E) that they labeled as syndromic types with distinctive skeletal and dental features. Those four groups were: (B) mid-face prognathism; (C) maxillary retrognathism plus dental protraction and mandibular retrognathism plus dental procumbency; (D) mandibular retrognathism and maxillary retrognathism plus maxillary dental protraction; and (E) maxillary prognathism and dental protraction plus dental procumbency. They also detected an increased mandibular plane angle when compared to Class I norms, suggesting an increase in lower facial height. McNamara (1981) reviewed lateral cephalograms of 277 Class II children with an average age of 9 years. Measures of the craniofacial structures were divided into five principal components of the Class II malocclusion: (1) maxillary skeletal position; (2) maxillary dental position; (3) mandibular dental position; (4) mandibular skeletal position; and (5) vertical development. The average SNA angle was 80.4° and most cases featured a retruded maxilla relative to established norms. Upper incisors tended to exhibit protrusion when cephalometric measurements were related to the mandible, but when measurements were related to the maxilla itself, the incisors appeared normal. Lower incisors were aligned in a normal relationship to the mandibular plane angle in more than 60% of the Class II patients. Mandibular skeletal retrusion was the most common single characteristic of the Class II sample, while almost half of the subjects 14 exhibited excessive vertical development, especially of the lower face. Additionally, more than 40% had a mandibular plane angle of 28° or greater, further indicating an increased vertical growth component. Utilizing a counterpart analysis to analyze an untreated longitudinal Class II sample population, Whitney (1984) recognized eight groups within this type of malocclusion. The groups displayed a broad array of skeletal variations and severities of protrusiveness and retrusiveness of the skeletal base. Overall, there was a distinct composite mandibular retrusive effect. Whitney also found that the male Class II malocclusion might exhibit any of several morphological patterns. There was a tendency for maxillary protrusion with a maxillary bony arch that was consistently longer than the mandibular corpus. The differential between the two arches increased with age, resulting in a progressive worsening of the Class II relationship. In a limited follow-up study using the same sample, Behrents (1985) found that, while growth continues into adulthood, existing maxillomandibular relationships would be maintained in a fairly uniform manner with only small variations. A morphological system of classifying Class II malocclusions has been proposed by Rakosi (1985), which identifies the area at fault. Rakosi has also offered a more involved cephalometric system of classification to describe five basic groups of Class II malocclusions. These include: 1. Class II malocclusion based on a Class II sagittal relationship without a skeletal component. The ANB angle is usually normal but both SNA and SNB may be slightly retrusive. The upper incisors are likely to be tipped labially while the lower incisors may be tipped either lingually or labially. 2. A functionally created Class II malocclusion in which the skeletal base is normal. The skeletal base is the supporting osseous structure for the alveolar process. The mandible is forced into a retrusive position upon closure due to the influence of tooth guidance. A deep anterior overbite and infraocclusion of the buccal segments are often seen in this condition. 3. Class II malocclusions due to fault in the maxilla. These may be the result of protrusion of the skeletal base, dento-alveolar, or dental components. In cases of maxillary protrusion, anterior tipping of the palatal plane downward may compensate for this discrepancy. 4. Class II malocclusions with the fault in the mandible. The retrognathic mandible may be small in size or it may be normal in size with a posterior positioning and an accompanying increase in lower facial height. 5. Class II malocclusions that are some combination of the above four conditions. 15 Imaging Cephalometrics Radiographic cephalometry represents one of the most significant technological advancements in orthodontic diagnosis and treatment planning. For the past 75 years (Lamichane et al. 2009), cephalometric imaging has been the gold standard for assessing relationships among all areas in the craniofacial complex (Berco et al. 2009). However, two-dimensional cephalometry has disadvantages that are well described in the literature. Some of the disadvantages are horizontal and vertical displacement of anatomical structures, imperfect superimposition of right and left sides, image distortion due to improper patient positioning, inaccurate landmark location or identification, and inconsistent calibration of source-to-film distances (Lamichane et al. 2009). Despite these disadvantages, radiographic cephalometry remains the mainstay in orthodontic diagnosis because it evaluates the spatial evaluation of both skeletal and dental structures with high resolution (Mah and Hatcher 2005). Cephalometric Airway Analysis Two-dimensional lateral cephalometry has traditionally represented the gold standard in the analysis of airway dimensions (Malkoc et al. 2005). Although useful for analyzing airway size in the sagittal plane, three-dimensional anatomical measurements are not imaged (Abramson et al. 2009). Research has revealed many limitations of twodimensional radiographs (Lowe et al. 1986; Finkelstein et al. 2001), particularly problems with the transverse dimension (Hanggi et al. 2008). Previous studies that used two-dimensional cephalometric analyses to determine airway dimensions were obliged to draw major conclusions from the narrowest points in the airway. Simply measuring the narrowest constriction of a two-dimensional image cannot fully quantify the spatial relationships between the two structures (Lowe et al. 1986). Lateral cephalograms are derived from a method called perspective projection. The result is an image that is magnified, dependent on the distance from the structure to the film. Because of this, it is difficult to determine whether a double structure (such as the lower border of the mandible) is the cause of a true skeletal asymmetry or merely a radiographic artifact. “With CBCT, this projectional magnification is computationally corrected during primary reconstruction, creating an orthogonal image (Mah et al. 2011).” This allows a CBCT derived lateral cephalogram to be calibrated to a true 1:1 representation of the anatomical structures in question. Furthermore, with CBCTs, it is possible to correct errors in head position, plus visualization presets allow for enhanced visualization of both soft and hard tissues (Mah et al. 2011). 16 Cone-beam Computed Tomography Cone-beam computed tomography (CBCT) records maxillofacial structures in three dimensions, allowing for a volumetric analysis of the oropharyngeal airway. CBCT is becoming more commonplace in clinical practice. It provides images comparable to magnetic resonance imaging (MRI) and computed tomography (CT), but is quicker and cheaper than either. CBCT differs from medical CT in many ways, including the type of imaging source detector complex and method of data acquisition. According to Mah and Hatcher (2004), the x-ray source for CT is a high-output rotating anode generator. CBCT, on the other hand, uses a low-energy fixed anode, similar to ones used in dental panoramic machines. CT incorporates a fan-shaped x-ray beam and data are recorded on solid-state image detectors that are arranged 360° around the patient. Conversely, CBCT uses a less highly collimated cone-shaped x-ray beam with a specialized image intensifier. The radiographic image is then captured on a solid-state sensor or an amorphous silicon plate (Mah and Hatcher 2004). The consequence of reduced collimation is increased noise and image degradation due to secondary radiation, resulting in images of lowered gray-scale resolution (Baumrind 2011). Medical CT and CBCT also differ in mode of image capture. Medical CT images use a series of axial plane slices to image patients. CBCT is similar to panoramic radiography and only uses one rotation around the patient, collecting the complete maxillofacial volume or a small area of interest (Mah and Hatcher 2004). In addition, CBCT does not require patients to be supine. Patients can be seated in a natural, upright position, which is important when imaging physiological hard and soft tissue relationships. CBCT is also the preferred method for airway volume measurement, due to its relatively low cost, ease of access, availability to dentists, and lower effective absorbed dose when compared to CT (Ogawa et al. 2007). CBCT Airway Analysis Osorio et al. (2008) described CBCT as “X-rays to the head and neck, providing both two-dimensional and three-dimensional images. The radiograph source is a lowenergy fixed anode tube similar to those used in a dental panoramic machine.” Conebeam images can be used to analyze skeletal cephalometric measurements, soft tissue structures like the tongue and soft palate, and airway shape and airway caliber. In addition, three-dimensional reconstructions and volumetric analysis can be performed (Osorio et al. 2008). The present study uses Dolphin3D® (Dolphin Imaging and Management Solutions, Chatsworth, CA) to analyze CBCT images. Shi, Scarfe and Farman (2006) developed an automatic algorithm that performed segmentation of the airway and compared it to the more tedious manual segmentation methods. This automatic algorithm estimated upper airway volume, the minimum distance from the posterior pharyngeal wall to the caudal region of the soft palate, and the minimum distance from the lower 17 posterior pharyngeal wall to the base of the tongue. The authors were able to automatically and reproducibly find: 1. Total airway volume (TAV): the volume of the upper airway bounded superiorly by a horizontal plane at the level of the most posterior extent of the palate and inferiorly by the maximum extent of the scan. 2. Smallest transaxial-sectional area (TSCA): the smallest cross-sectional area on the axial images. 3. Largest sagittal view airway area (LCSA): the largest cross-sectional area on the orthogonal sagittal images. 4. The smallest cross-area and the anteroposterior distance of the retropalatal space. 5. The smallest cross-area and the anteroposterior distance of the retroglossal space. The authors found strong positive correlations between the manually segmented and automatic measurements. This is important because automating the process allows for an easy and accurate assessment of the airway every time the patient is scanned. Aboudara et al. (2009) compared airway space in conventional lateral head films and the three-dimensional reconstruction from CBCT. They studied 35 consecutive adolescents (mean age of 14 years) who presented at a dental imaging center for either orthodontic, temporomandibular, or possible pathology evaluation. Both a lateral cephalogram and a three-dimensional scan were performed on each subject. One limitation of this study was that the three-dimensional scans were taken in a supine position, whereas the lateral head films were taken in an upright position. The supine position can confound the airway measurements due to the effect of gravity on the soft tissue of the oropharynx. The following landmarks were used for the lateral cephalometric analysis and the three-dimensional scans: 1. The axial plane passing through PNS. 2. The plane perpendicular from PNS extending to the superior aspect of the pterygomaxillary fissure. 3. The soft tissue contour of the posterior pharyngeal wall extending from the superior aspect of the pterygomaxillary fissure inferiorly to the axial reconstruction plane. The following four measurements of the nasopharyngeal airway space were made: 1. 2. 3. 4. Subjective airway classification (1-5) from the lateral cephalogram. Airway area of the region of interest from the lateral cephalogram. Airway volume over the same region of interest from the CBCT scan. Volume of the soft and hard tissue components of the inferior turbinates that protruded into the nasopharyngeal potential space. 18 The authors found that there was a significant positive association between nasopharyngeal airway size on the lateral head film and its true volumetric size from a CBCT scan. Accurate determination of the airway volume from the lateral head film is difficult because of great variability in the three-dimensional airway. The authors also found on the three-dimensional scan that the inferior turbinates often protruded into the airway space and caused restrictions. This is not visible on a traditional cephalometric film. Disadvantages of CBCT While CBCT offers several advantages to planar cephalometry, there are also a few disadvantages. Perhaps the most important of these concerns is radiation dose. Although definitive data are not yet available, it is apparent that the radiation dose of a CBCT scan (~40 to 135 microsieverts [uSv]), is greater than that typically administered by a single lateral cephalogram plus a panoramic image (~8 to 18 microsieverts [uSv]). A further inherent consequence of using cone-beam rather than fan beam geometry is a reduction in collimation and an increase in noise artifacts, making it much more difficult to discern differences in soft tissue density in cone-beam images. However, as voxel size gets smaller (and thus more accurate) with improved technology, this disadvantage will lessen. Another issue concerns the risk and responsibility for diagnosing pathology present on CBCT scans (information that orthodontists are not trained to interpret). Although not legally mandated, referral to a qualified radiologist for full reading of all CBCT scans is advised (Scholz 2011). In the present study, no new CBCT images were taken, but rather existing CBCT images were used. Thus, the issues of radiation exposure and pathology diagnosis were not a direct concern. Technological Aspects of CBCT Next Generation iCAT® CBCT machines were used to take all scans for the present study. The iCAT® “relies on an advanced amorphous silicon flat panel image sensor, instead of image intensifier technology employed by competitive units, to reduce the overall size of the unit and deliver a higher image quality and resolution” (Cifelli 2004). Flat panel detectors result in cylindrical-shaped volumes instead of the sphericalshaped volumes produced by image intensifiers. Detectors come in different sizes, but should be large enough to capture the clinician’s region of interest (ROI) (Molen 2011). The resolution of the reconstructed scan is influenced by several variables. Resolution or spatial resolution is the minimum distance between two distinguishable objects. Resolution is often associated with voxel size, but they are not synonymous. “The voxel size represents the dimensions of the volume element into which a volume is being subdivided and is usually measured in millimeters or microns. Each voxel is assigned a value representing the density of the object contained within its boundaries as determined by the attenuation of the photons passing through it (Molen 2011).” A smaller voxel size does not necessarily indicate a higher resolution, due to the effects of 19 scatter radiation, volume averaging, and artifacts. Because of this, it is inappropriate to compare CBCT systems on voxel size alone. The gray scale bit depth of a CBCT system is also important to image quality. CBCT systems range between 12 and 16-bit gray scale. The human eye can only detect up to 10-bit gray scale, and while most computer monitors are only available in 8- or 10bit gray scale, a higher gray scale does lead to a cleaner or more defined volume (Molen 2011). 20 CHAPTER 3. MATERIALS AND METHODS Sample Description Subjects in the present study were collected from two private orthodontic practices (Jackson, TN, and Wichita, KS). One cone-beam computed tomography image per person had been taken for various dental or orthodontic concerns unrelated to this retrospective project. The pretreatment orthodontic CBCT files were used from the orthodontic patients. The private practice CBCT scans were made on a Next Generation iCAT® (Imaging Sciences, Hatfield, PA) with a grayscale resolution of 14 bits and voxel size of 0.4 mm. A total of 131 serially selected subjects (65 males; 66 females) were analyzed in this study. 71 Class II and 60 Class I patients were selected with an age range of 9 to 13 years at the start of treatment. We limited the study to Class II, division 1 malocclusions by selecting subjects with a positive overjet of at least 3.5 mm. Subjects were phenotypically normal; no clefts or syndromes were included (Figure 3-1). Analysis of covariance (ANCOVA) was used to simultaneously test for sex and age differences (the covariates) so males and females could be analyzed in tandem while controlling for sexual dimorphism. With cross-sectional data, age trends are somewhat speculative because there is no information on how the individuals actually grew. Pharyngeal Analysis The pharynx was imaged from CBCT images (n = 131) of the head. The skulls were oriented in Frankfort Horizontal, with care taken to make measurements in the midsagittal plane. Dolphin 3D® (Dolphin Imaging and Management Solutions, Chatsworth, CA) was used to collect dimensional data. Version 11.5 was used, which employs an “airway” module. Images were imported as DICOM (Digital Imaging and Communications in Medicine) files into Dolphin 3D®, which is an orthodontic imaging and analysis software program. The DICOM files were used to create a lateral cephalometric view from within Dolphin. Measurements were made using a custom analysis wihin the Dolphin program. Volumetric Analysis The airway is easily distinguished from the surrounding tissues because of the large difference in x-ray attenuation between air in the pharynx and the high water content of the surrounding tissues (Hans 2011). The pharynx was partitioned into three 21 Figure 3-1. Bar charts of age distributions (sexes pooled) by geographical site Mean age of Tennessee sample (n=65) was 11.97 years (sd = 1.38); mean age of the Kansas sample (n=66) was 11.97 years (sd = 1.37). 22 regions (from superior to inferior): nasopharynx, oropharynx, and laryngopharynx (Drake et al. 2005). Due to the limited view of the laryngopharynx on the majority of the CBCT images, we did not measure the laryngopharynx. The nasopharyngeal airway was measured by constructing a triangular area of interest (Park et al. 2010) (Figure 3-2) using these three planes: 1. Pt Plane: The plane passing through Pt (Pterygomaxillary fissure) and PNS. 2. PNS Plane: A horizontal line parallel to Frankfort Horizontal passing through Posterior Nasal Spine (PNS). 3. Pharyngeal Tonsil Plane: Soft tissue wall of the posterior nasopharynx. Three horizontal planes were used to construct a region of interest to surround the oropharynx and to divide the oropharyngeal airway into superior and inferior oropharyngeal regions. 1. PNS Plane: The horizontal line parallel to Frankfort Horizontal passing through Posterior Nasal Spine (PNS). 2. Soft Palate Plane: The horizontal line parallel to Frankfort Horizontal passing through U point, which is the most inferior point on the soft palate at the uvular tip (Mazaheri 1994). 3. Epiglottis Plane: The horizontal line parallel with Frankfort Horizontal passing through Et, the most superior point (tip) of the epiglottis. Once the airway was defined, the “sensitivity” slider tool in Dolphin, which allows the software to detect differences in grayscale resolution, was adjusted to best recognize the airway (sensitivity value of 45). The Dolphin 3D® module calculated the volume and the minimum cross-sectional area using segmentation and Dolphin’s computer algorithm. This segmentation method has been shown to be superior to the manual slicing and manual tracing method (Yushkevich et al. 2006). The level of most constriction (minimum cross-sectional area) was recorded as well (Figure 3-3). Cephalometric Analysis Lateral and anteroposterior cephalograms were constructed from the CBCT scans with no magnification. Linear skeletal measurements of the size of the pharyngeal skeletal encasement were obtained. A custom analysis was created in Dolphin version 11.5 and used to make all measurements. The following list (in alphabetical order) provides descriptions all landmarks used in this study. All minima and maxima assume the head is oriented in norma lateralis (Table 3-1). The following linear distances and angles were calculated for each constructed, non-magnified lateral cephalogram. This list (in alphabetical order) provides definitions of all measurements used in this study (Table 3-2). 23 Figure 3-2. Sketch of lateral view of skull with skeletal and soft tissue landmarks identified and the airway segments delineated and labeled The C3 Plane was removed for this study due to inconsistent field of visisbilty on selected CBCT images. Thus, the laryngopharyngeal airway was not measured. Diagram provided by Dr. Edward Harris on March 11, 2011. 24 Figure 3-3. Two-dimensional rendering of the pharyngeal airway Dolphin calculated the level of most constriction, airway volume, and airway area. Diagram provided by Dr. Edward Harris on March 11, 2011. 25 Table 3-1. Cephalometric landmarks Landmark A Aa ANS B Cd Et FH FOP Go Gn H Ii Is L6 M Me Na Or Pg Phw PNS Po Definition A Point (Subspinale): the most posterior point on the exterior ventral curve of the maxilla between the anterior nasal spine and Supradentale. Anterior arch of the atlas: the most anterior point of the atlas vertebrae. Anterior nasal spine: the spinous process of the maxilla forming the most anterior projection of the floor of the nasal cavity. B Point (Supramentale): the most posterior point on the bony curvature of the mandible between Infradentale and Pogonion. Condylion: the most superior-posterior point on the curvature of the capitulum of the condyle. Tip of epiglottis: the most superior point of the epiglottis. Frankfort horizontal: a horizontal plane drawn from porion to orbitale, with patient in natural head position. Functional Occlusal Plane: a line drawn between the cusp tips of the permanent first molars and the most mesial premolars (or deciduous molars in mixed dentition). Gonion: the most posterior-inferior point on the gonial angle of the mandible. Gnathion (anatomic): the most anterior-inferior point of the mandibular symphysis. H Point: the most anterior and superior point on the hyoid bone body. Incision Inferius: the incisal tip of the most anterior mandibular central incisor. Incision Superius: the incisal tip of the most anterior maxillary central incisor. L6 mesial: the most mesial point on the lower first molar. M Point: the most posterior point of the mandibular symphysis. Menton: the most inferior point on the mandibular symphysis. Nasion: the junction of the frontal nasal suture at the most posterior point on the curvature at the bridge of the nose. Orbitale: the most inferior point on the lower margin of the bony orbit. Pogonion: the most anterior point on the anterior contour of the bony chin below B point and above Gnathion. Posterior pharyngeal wall: point on the pharyngeal wall at the level of the Psp (Posterior soft palate). Posterior Nasal Spine: the spinous process formed by the most posterior projection of the juncture of the palatine bones in the midline of the roof of the oral cavity. Porion: the midpoint on the superior aspect of the rim of the external auditory meatus. 26 Table 3-1. (Continued) Landmark Definition Psp Pt Posterior soft palate: the most superior-posterior point of the soft palate. Pterygomaxillary fissure: the most superior-posterior point on the average of the right and left outlines of the pterygomaxillary fissure. Se Sella turcica: the center of the hypophyseal fossa, determined by visual inspection. Se Sella-Vertical: the imaginary line passing through Sella, perpendicular to Frankfort Horizontal plane. U6 U6 mesial: the most mesial point on the upper first molar. Table developed in consultation with department colleague Dr. James K. Killehay and reproduced with his permission. 27 Table 3-2. Linear (millimetric) dimensions and angles measured on the lateral cephalograms Dimension AFH ANB AO-BO Co-A Co-Gn FMA H to FH Na-Me Na -A Na -B Na -Pg Psp-Phw Se-Go Se-Me Se-Na Se -A Se -B Se -M Se -Po SNA Description Anterior Facial Height: the linear distance from Nasion to Menton. the inferior angle formed at the junction of the Nasion-A Point line and the Nasion-B Point line. Wits Appraisal: the linear distance between two points along Downs’ occlusal plane obtained from the intersection of a perpendicular line from point A and from point B to the occlusal plane. The linear distance from Condylion to A Point. The linear distance from Condylion to Gnathion. The anterior inferior-angle formed at the junction of the Frankfort Horizontal plane and the mandibular plane. The linear distance from H point to FH, perpendicular to FH. The linear distance between Nasion and Menton. The linear distance from point A to Nasion when projected perpendicular to the Frankfort Horizontal plane. The linear distance from point B to Nasion when projected perpendicular to the Frankfort Horizontal plane. The linear distance from Pogonion to Nasion when projected perpendicular to the Frankfort Horizontal plane. Superior Airway Space: the linear distance from Psp to a point directly posterior to Psp on the posterior pharyngeal wall, parallel to FH. The linear distance from Sella to Gonion. The linear distance from Sella to Menton. The linear distance from Sella to Nasion. The linear distance from Sella to A point when projected perpendicular to the Frankfort Horizonal plane. The linear distance from Sella to B point when projected perpendicular to the Frankfort Horizonal plane. The linear distance from Sella to M Point when projected perpendicular to the Frankfort Horizonal plane. The linear distance from Sella to Porion when projected perpendicular to the Frankfort Horizonal plane. The posterior inferior angle formed at the junction of the Sella-Nasion plane and the Nasion-A Point plane. SNB The posterior inferior angle formed at the junction of the Sella-Nasion plane and the Nasion-B Point plane. Y Axis The angle formed by the intersection of a line from Se-Gn with the FH plane. Table developed in consultation with department colleague Dr. James K. Killehay and reproduced with his permission. 28 Each cephalometric measurement defined above was categorized into skeletal and dental measurements along with the individual purpose for each measurement in the cephalometric analysis (Table 3-3). Class II Analysis Several methods have been used to distinguish Class I from II malocclusions, but it seems that the principal cephalometric measurement most pertinent to the present analysis is the angle ANB. ANB is an imperfect measurement, and its shortcoming depends primarily on angulation of the Sella-Nasion plane that is variable (Jacobson and Jacobson 2006). However, its usage is perhaps the most widespread and well understood by the orthodontic community. We compared the Sella-Nasion line to Frankfort Horizontal plane and eliminated cases with too large a discrepancy. In order to achieve proportional sample sizes throughout the range of conditions, the total 131 subjects were divided into two groups based on ANB classification. Subjects with an ANB between 3° and -1.5° were classified as Class I. Subjects with an ANB of 3.5° or greater were labeled as Class II. These allowed us to compare severity of Class II malocclusion with the pharyngeal values. In addition, several Class II cephalometric predictors were used to determine skeletal classification, relative position of the maxilla and mandible, and anteroposterior length of maxilla and mandible. These Class II predictors were then compared to the range of pharyngeal outcome variables, and associations between the two were evaluated statistically. Lastly, we mimicked the Class II malocclusion groups of Moyers, McNamara, and Henry by using cluster analysis to see whether different Class II types within the continuum stand out as having distinct pharyngeal dimensions. It is unlikely that dental characteristics have any effect on pharyngeal dimensions, so we focused on the maxillary and mandibular skeletal discrepancies evaluated against pharyngeal shape. Error Calculation A total of 28 CBCT scans were randomly selected and their cephalometric variables, as well as airway dimensions were re-measured two weeks after the initial measurements by the same investigator. The results of the original and re-measured groups were compared, and a repeatability index was calculated (Dahlberg 1940), and error was found to be statistically insignificant. The remaining subjects were then analyzed according to the established protocol. 29 Table 3-3. A list of the variables measured from the lateral cephalometric images in the present study Dimension Variable Cranial Base Se-Na Anterior Cranial Base Length (mm) Midface Co-A Horizontal length of the midface (mm) Facial Height Na-Me PFH/AFH Se-Go Total Anterior Facial Height (mm) Ratio of posterior facial height to anterior facial height Posterior Facial Height (mm) Maxillary Position Na Perp-A SNA Se -A A-P positional change in the maxilla (mm) Positional change in the maxilla relative to anterior cranial base (°) A-P positional change in the maxilla (mm) Mandibular Size and Position Co-Go Co-Gn Go-Me Na Perp-B Na Perp-Pg SNB Se -B Se -M Y Axis Vertical Mandibular Ramus Length (mm) Mandibular Length (mm) Mandibular Body Length (mm) A-P positional change in the mandible (mm) Protrusive growth of the chin (mm) Positional change in the mandible relative to anterior cranial base (°) A-P positional change in the madible (mm) A-P positional change in the madible (mm) Rotation of the mandible (°) Maxillomandibular Relationships ANB AO-BO FMA Na A-Pg A-P relationship of the maxilla-mandible (°) A-P relationship of the maxilla-mandible (mm) Maxillomandibular divergence (°) Facial convexity (°) 30 Table 3-3. (Continued) Dimension Variable Dental Relationships FMIA Inclination of lower incisors relative to the Frankfort line. The distal angle is measured. (°) IMPA Inclination of lower incisors relative to the mandibular plane (°) Overbite Vertical overlap of the upper and lower central incisors (mm) Overjet Horizontal overlap of the upper and lower central incisors (mm) U1-L1 Angular relationship between the maxillary and mandibular central incisors (°) U1-NA Angulation of the maxillary central incisor to the maxilla (°) U1-NA mm Position of the maxillary central incisor to the maxilla (mm) L1-NB Angulation of the mandibular central incisor to the mandible (°) L1-NB mm Position of the mandibular central incisor to the mandible (mm) Table developed in consultation with department colleague Dr. James K. Killehay and reproduced with his permission. 31 Statistical Design Measurements were exported from Dolphin 3D® into a spreadsheet in Microsoft® Excel 2010 (Microsoft Corporation, Redmond, WA). The spreadsheet was used to combine patient information including demographic information (patient’s age, sex, occlusion classification, and skeletal classification). The measurements were then transferred to the statistical package JMP® Pro 10.0 (SAS Institute Inc., Cary, NC). Analysis of covariance (ANCOVA) was used to simultaneously test for differences between malocclusions while controlling for age and sex differences (the two covariates). Some size changes tended to be curvilinear with age (faster growth in children than adolescents), and curvilinear (polynomial) models were used to more accurately model the curves (Appendix A). Exploratory data analysis (Tukey 1977) was performed, searching for outliers; those due to technical errors were corrected. Conventional descriptive statistics (e.g., Sokal and Rohlf 1995) were calculated; these (and their abbreviations) were sample size (n, taken as counts of individuals, not sides), the arithmetic mean ( x ), the standard deviation (sd), and the standard error of the mean (sem). The conventional alpha level of 0.05 was used throughout, and all of the tests were two-tail. No correction was made for multiple comparisons. Salient results of the analysis were graphed using Delta Graph® 6.5 for Windows (Red Rock Software, Inc., Salt Lake City, Utah) or the graphics subroutines within JMP® Pro 10.0. Box plots were produced to explore the data and to screen for outliers. A box plot is a graphic technique in the family of descriptive statistics. It is a graphical display of the sample distribution that resembles a box with two lines or “whiskers” coming out the ends (Figure 3-4). The box can be drawn horizontally or vertically. The five vertical lines in each box plot denote 10, 25, 50, 75, and 90th percentiles. The ends of the box fall at the upper and the lower quartiles of the distribution, QU and QL, so the middle 50% of the cases (the median) falls within the QU-to-QL range of scores. Sample variability is shown by the height of the box. The line in the middle of the box represents the median of the distribution. The median is an estimate of the central tendency, and placement of the median suggests whether the data are skewed. If the median is closer to the upper quartile, the data are negatively skewed; if the median is closer to the lower quartile, they are positively skewed. Individual data points above and below the 10th and 90th percentile are denoted by symbols. Data points that fall outside the 10% and 90% are called outliers (Norman and Streiner 1994). 32 Figure 3-4. Example of a box plot The centiles of the sample distribution are labeled to the right. “Jittered” points are offset to the left and right of the midline simply in order to make the distribution more apparent (otherwise points might be superimposed and not visible). Diagram provided by Dr. Edward Harris on March 11, 2011. 33 CHAPTER 4. RESULTS Geographical Cephalometric Differences The CBCTs of the sample of 60 Class I patients and 71 Class II patients were obtained from two private orthodontic practices, one in Wichita, Kansas, and the other in Jackson, Tennessee. This provided a total sample of 131 adolescent American white patients. It was of interest whether these two samples differed geographically in their pharyngeal and/or cephalometric values. The starting point was a comparison of the chronological ages at the start of treatment (Figure 4-1), where the distributions were largely overlapping. As shown in Figure 4-2, the majority of cases were in the range of 10 to 14 years. Slightly different ratios of Class I and II patients were chosen from the Kansas and Tennessee offices but the difference was not significant (Figure 4-3). Intraobserver Repeatability Repeated measurements taken on the same article are never exactly the same. Dissimilarities are due to a combination of operator differences in selection of landmarks, differences in how operators define a variable, and also the level of precision or number of signficiant digits documented (Houston 1983; Houston et al. 1986). Repeatibility can also differ due to inconsistencies in the measuring instrument. Measuring instruments all contain a certain number of digits that are only so accurate and can measure only so precisely. Calipers and computers do not always provide consistent measurements or work equally well in all planes of space. There are two sources of instrument error, namely systematic error and random error. Systematic error occurs due to an issue with the instrument itself. Random error occurs when the measurement is restricted to fixed increments. For example, evaluations from a computer monitor that has distorted images or a screen with incorrect resolution will give false readings. Or, in the example of bent calipers, measurements can be larger or smaller than they should be (Harris and Smith 2009). Intraobserver reliability, also known as Technical Error of Measurement or TEM, is a useful measurement since it points out the inherent imprecision in a system. The goal of systematic methods in a research project is to attain repeated measurements that are both precise and accurate. Precision (also known as reproducibility and repeatability) is a calculation of how close together measurements of the same object are. Vierira and Corrente (2011, p 488) declared: “By definition, repeatability is the closeness of agreement between successive readings obtained by the same method on the same material and under the same condition (same operator, same apparatus, same setting and same time)”. On the contrary, accuracy is how closely the measured values approximate the exact value. We have used the classic target comparison (Figure 4-4) to show that measurements can be accurate but not precise, and vice versa. The objective is to produce 34 Figure 4-1. Box plots of the age distribution of the sample, partitioned be sex and geographical site (either Kansas or Tennessee) Visually, there is considerable over-lap of the four distributions. Statistically, by chisquare test (1 degree of freedom) X2 was 1.28 with an associated P-value of 0.2574, so the distribution of Class by Site did not differ statistically. 35 Figure 4-2. Histograms of the age distributions (sexes pooled) by geographical site (Kansas, Tennessee) The majority of ages were from 10 to 14 years at the start of treatment. Figure 4-3. source Pie charts of the proportions of Class II patients by geographical Somewhat more Class I cases (shown in blue) were chosen from the Kansas office (55%, 39/56), while somewhat more Class II patients (shown in red) were used from the Tennessee office (55%, 33/65). But, by a chi-square goodness-of-fit test (1 degree of freedom), there was no statistically significant difference in the ratios of Class II patients (P = 0.2574). 36 Figure 4-4. A metaphor of a “bull’s eye” characterizes the concepts of precision and accuracy (A) The mean of the measurements is close to the center of the bull’s eye, which is the true value. These measurements have low repeatability, however, because of their scatter and individual departures from the true value. (B) The measurements are close together (good precision), but all are approximately equally biased from the true value. For example, calipers might be out of kilter, so all measurements are exaggerated by, say, 0.1 mm. (C) Here the measurements are all close to the measurement (high accuracy) and close to one another (high precision). Adapted with permission. Harris EF, Smith RN. Accounting for measurement error: A critical but often overlooked process. Arch Oral Biol 2009; 54, Supplement 1:107-17. 37 measurements that are both precise and accurate, with as small a TEM as possible. Ideally, the TEM is much smaller than the differences between the groups being compared. A small TEM guarantees that observed differences between groups are not unfairly influenced by technical measurement errors. Introducing the concept of TEM makes it impossible to ever determine the true value of a quantity, but with a large sample size, measurements draw closer and closer to the true size (Winer et al. 1990). We next analyzed a set of replicate measurements. From the original set of 131 cases, 28 were remeasured two weeks later while blinded to the subject’s original readings. All variables were remeasured, so there was a sample size of 28 replicated pairs of numbers per variable. Systematic Error: It is possible that the operator’s definition of landmark location has changed during the time between measurements, thus making the second set of measurements systematically different from the first. Matched (paired) t-tests were used to test for this (two-tail tests). Random Error: The Dahlberg statistic (Dahlberg 1940) was calculated for each variable as: where X1i and X2i are the two measurements for subject i and n is the number of replicated (pairs of) subjects (Dahlberg 1940; Knapp 1992). The differences are then squared to make them all positive. Despite certain claims, this value does not represent the mean difference of the measurement error. It is rather the standard error of the measurement difference (Altman and Bland 1983; Bland and Altman 1996, 1999, 2003). The Dahlberg statistic is a reliable value, but there is certainly value to be found in the arguments of Vierira and Corrente (2011). They submit that the Dahlberg statistic only works when readings are (1) identically distributed random variables, (2) independent, and (3) the average of the differences between readings average to zero. Bland-Altman plots were first created for the statistically significant variables. These are provided in Appendix B. Repeated-measures descriptive statistics were then computed. Particular concentration was placed on differentitating between sessions (session 1 minus session 2), and testing whether this difference differed significantly from zero. An average variation of zero would imply a lack of systematic bias between measurement sessions. A regression slope that was significant indicated that the difference between repeats was associated with trait size, either by an increase of differences with trait size (positively) or by a decrease in repeat differences with trait size (negatively). Table 4-1 lists the results of the intraobserver data in a different fashion. Using the differences between the repeats (X1j - X2j), it was tested whether this mean differed 38 Table 4-1. Descriptive statistics of intraobserver repeatability, showing the difference of each variable and a t-test evaluating whether the mean differed statistically from zero Variable AFH Airway 1 Area (Nasopharyngeal) Airway 1 Volume (Nasopharyngeal) Airway 1+2 Area Airway 1+2 Volume Airway 1+2+3 Area Airway 1+2+3 Volume Airway 2 Area (Superior) Airway 2 Volume (Superior) Airway 3 Area (Inferior) Airway 3 Volume (Inferior) A-Nasion-Perpendicular ANB B-Nasion-Perpendicular Conylion-A Conylion-Gnathion Facial Convexity FMA FMIA Gonion-Menton IMPA Interincisal Angle L1-NB (°) L1-NB (mm) Mesial Molar Relation Minimum Constriction Overbite Overjet PFH Pogonion NasionPerpendicular Sella-Vertical-A Sella-Vertical-B Mean Difference SD of Difference t-Test P Value 0.286 -11.389 1.731 40.486 0.87 -1.49 0.3901 0.1482 17.161 551.191 0.16 0.8704 -2.425 -27.357 -7.582 -482.678 4.289 -44.518 83.603 2374.897 45.858 2125.719 60.098 1980.105 -0.15 -0.06 -0.87 -1.18 0.37 -0.12 0.8792 0.9518 0.3893 0.2487 0.7138 0.9062 -5.157 -360.729 79.210 1286.853 -0.34 -1.48 0.7331 0.1496 -0.321 -0.189 0.271 0.350 0.532 -0.336 0.004 -0.454 0.414 0.446 -0.564 0.275 -0.032 0.100 -0.050 0.054 -0.132 -0.154 -0.404 1.210 0.336 0.487 1.532 1.811 0.698 2.151 2.802 2.428 4.132 5.172 2.571 0.573 0.456 21.965 0.801 0.286 3.250 2.203 -1.41 -2.98 2.95 1.21 1.55 -2.54 0.01 -0.86 0.90 0.57 -0.58 0.57 -0.30 1.16 -0.01 0.35 -2.45 -0.25 -0.97 0.1713 0.0060 0.0065 0.2370 0.1317 0.0170 0.9931 0.3993 0.3746 0.5722 0.5685 0.5760 0.7688 0.2563 0.9905 0.7262 0.0211 0.8045 0.3410 0.932 0.986 3.022 3.448 1.63 1.51 0.1143 0.1420 39 Table 4-1. (Continued) Variable Mean Difference SD of Difference t-Test Sella-Vertical-M Sella-Vertical-Pogonion SNA SNB Superior Airway Space Total Airway U1-NA (°) U1-NA (mm) U1-Sella-Nasion Wits Discrepancy Y-Axis 0.796 -0.271 -0.425 -0.257 0.129 -388.086 0.486 0.011 0.046 -0.096 -0.321 3.599 2.822 0.965 1.081 0.422 2145.194 2.925 0.951 3.310 0.498 2.121 1.15 -0.51 -2.33 -1.26 1.61 -0.96 0.88 0.06 0.07 -1.03 -0.80 40 P Value 0.2607 0.6149 0.0275 0.2189 0.1189 0.3469 0.3873 0.9529 0.9414 0.3144 0.4297 significantly from zero (a two-tail one-sample t-test). Just two of the variables differed significantly between measurement sessions, ANB and B Point to Nasion-Perpendicular. This first variable (ANB) is shown in Figure 4-5. The mean difference was -0.189 degrees with a standard deviation of 0.336 (n = 28). The second measurement session of ANB measurements tended to be larger than those made the first time (Figure 4-5) with a mean difference of -0.189 degrees. The second significant variable was B to Nasion-Perpendicular. Here, the mean difference was significantly positive (0.271 mm), meaning that the first measurements tended to be larger than the second (Figure 4-6). In both instances, however, we placed no clinical importance on these very small differences. ANCOVA Our next focus of interest was to simultaneously test for differences among patient’s sex, Angle’s classification (Class I versus Class II), and patient’s age (specifically, the chronological age at the start of orthodontic treatment). A series of univariate ANCOVA analyses also were used to test for geographical differences (Figure 4-7). It was valuable from experience to include four factors in the model, (1) geographical location (Kansas or Tennessee), (2) patient sex, (3) patient’s Class of malocclusion (Class I versus II), and (4) patient age at the pretreatment records. The first three factors are fixed effects, while age is a continuous covariate (Figure 4-7). The full model (i.e., all interactions) was calculated using the JMP Pro 10.0 software, and the results are listed in Appendix A. There were 45 variables studied, and nine of these attained significant differences between the two geographical sites. Because of the numerous tests in these ANCOVAs, we discuss just those significant at an alpha of 0.01 or better. The remainder of this section describes these statistically significant differences. The reasoning here for the model design was straightforward: Sex was included in the linear, ANCOVA model to account for the common perception (e.g., Ursi et al. 1993) that boys are larger girls. Particularly after the onset of puberty, sexual dimorphism is a common finding in the body as a whole (e.g., Wells 2012) as well as the craniofacial complexes (Riolo et al. 1974). Angle’s classification (Class I versus Class II) was the dependent variable, so insofar as we were able to correctly classify the patients’ malocclusion, there may well be a statistical difference between classes (supposing that cephalometric dimensions are associated with Angle’ classification). Thirdly, age (chronological age at the start of treatment) was aimed at accounting for the obvious relationship that chronologically older subadults are larger than younger subjects—children grow larger with age (Riolo et al. 1974). 41 Figure 4-5. Bland-Altman plot for the cephalometric angle ANB The mean difference is a bit above the mean, showing that the first session of measurements exceeded the second, resulting in a systematic difference. 42 Figure 4-6. Bland-Altman plot for the cephalometric distance B to NasionPerpendicular For this variable, the mean was a bit below zero, showing that the second measurement session produced larger values than the first. 43 Figure 4-7. Form of the ANCOVA model used to test for group differences for (45) cephalometric variables 44 Importantly, these three factors were examined simultaneously (in the same model) so the correct source of the variation could be identified rather than being confounded (e.g., Winer et al. 1991; Sokal and Rohlf 1995). For example, a traditional approach (when calculations were done by hand) would have been to compute a series of one-way ANOVAs, say testing for class differences, then another series testing for sex differences, and so on. Unless class and sex are perfectly independent of one another, it is possible to confound sex differences with class differences and class differences with sex differences—which would complicate and distort interpretations of the statistical results. Evaluating the effects simultaneously avoids this pitfall (e.g., Woolf 1968). Sex and Angle’s class are fixed, model I effects; and age is a continuously-distributed covariate (Winer et al. 1991. Univariate ANCOVA calculations were performed using JMP Pro 10.0 (SAS Institute Inc, Cary, NC), and the resulting tables are listed in Appendix A. The full model was calculated (Winer et al. 1991), so there were three main effects (Sex, Class, Age), three first-order interactions (Sex-x-Class, Sex-x-Age, and Class-x-Age), and one second-order interaction (Sex-x-Class-x-Age). In the JMP design, there is one degree of freedom associated with each of these seven effects. Summary and Interpretation of ANCOVA Results Volume of the nasopharynx disclosed both a significant class and age effect (Figure 4-8). The two classes both showed an increase in airway 1 volume with age, but at significantly different rates. This measure of the rate of increase in the Class II sample is significantly steeper (faster) than in the Class I sample. The data also suggested that the tempos of airway growth differed between classes: In this age interval, size in the Class I cases grow appreciably but not so in the Class II cases, though the two groups are similar in size around the end of childhood. The next noteworthy difference (P < 0.01) was the positive association between chronological age and the airway volume labeled “Total Airway Volume”. There was no significant class or sex effect for the variable (Figure 4-9). The best-fit regression line fit to these data (n = 131 patients) is Volume = 825.5 + 1,382(Age), where, of course, volume (the dependent variable) was “Total Airway Volume” measured in cubic millimeters and chronological age was in years (r2 = 11%). This suggested that, within this age interval, this volume increases almost 1,400 mm3 each year, and the ANCOVA model suggests that it is of no consequence whether the cases were boys or girls or whether they had Class I or II malocclusions. This same theme extends to one of the comprehensive measures of pharyngeal size used here, namely Airway 1+2+3, or “Total Airway Area” (Figure 4-10). The bestfit regression line to these data is Area = -1962 + 481.4(Age). Several curvilinear regression models were assessed, but this straight line model had the greatest explained variation. In keeping with this theme of growth of airway growth with age, Volume of the Inferior Oropharynx is also noteworthy (P < 0.01). Here (Figure 4-11), the linear 45 Figure 4-8. Bivariate plot between chronological age (in years, X axis) and volume of the nasopharynx (in cubic millimeters, Y axis), partitioned by Angle’s Class The blue crosses are Class I cases; the red squares are Class II cases. The lines are the least-squares regression lines fit by Angle Class. 46 Figure 4-9. Bivariate plot between chronological age (years) and pharyngeal volume (cubic millimeters), labeled Total Airway Volume There was a statistically significant, positive association between these two variables (P = 0.0004). 47 Figure 4-10. Bivariate plot between chronological age and the two-dimensional measure of Total Airway Area (mm2) Patient’s class of malocclusion and sex played no significant part in this ANCOVA model. 48 Figure 4-11. Bivariate plot between chronological age and volume of the inferior oropharynx This positive association is highly significant in the ANCOVA model (P = 0.0023). The line in the graph is the sample’s least-squares regression line. 49 regression accounted for about 8% of the variance (r2 = 0.08122), and the regression equation was Volume = -1962 + 0.048(Age). Age, of course, is measured in years and refers to the patient’s age when the pretreatment records were taken. The suggestion was, then, that all measured segments of the oropharynx increased with age (they “grew”) and there was no sign in these cross-sectional data of any plateauing (slowing) of the rate of increase. Growth is expected to stop by the onset of adulthood (by definition), but the denouement seems to come in the later teenage years, not in the age interval examined here (which was roughly 8 to 15 years). Moreover, as noted, growth appeared to be linear in the observed age interval. Curvilinear regression lines did not significantly improve the explained variance. Total Airway Volume (mm3) was the final, summary measure of pharyngeal size examined here. Comparable to its constituent parts, Total Airway Volume exhibited a significant, positive association with age (Figure 4-12). The best-fit line was Volume = 825.5 + 1,382(Age), which accounts for 10.6% of the variance in the ANCOVA model (r2) and this association was highly significant statistically (P = 0.0004). The regression line suggested that three-dimensional volume increased about 1,400 mm3 per year in this age interval, with no difference among patients of different sexes or malocclusions. The subsequent analyses of associations in this section involved cephalometric variables rather than measures of airway size, and the clinically noteworthy associations (P < 0.01) were less common. The difference by Angle Class and degree of facial convexity (Na A-Pg) was significantly smaller in the Class I sample (P < 0.0001). This high level of significance is not surprising (Figure 4-13), though, because facial retrognathism was one of the dependent variables used for case selection. What we have, then, is a vindication of the author’s ability to identify Class I from Class II skeletal relationships. Similarly, another variable associated with classification of malocclusion is the angle SNA, which was also significantly different between Classes (Figure 4-14). This double-paned graph seems to be most informative for showing the results, in that the Class I and II patients grew differently with age. There was a significant increase in SNA angle with age in the Class I sample, which reflected normal anterposterior jaw growth (e.g., Riolo et al. 1974), whereas the average SNA angle did not change with age (in roughly the 10 to 15 age interval) in the Class II sample. Similar results were encountered for the SNB angle, which is a measure of mandibular prominence (Figure 4-15). The slopes of SNB were distinctive by Angle Class. In the Class I sample, SNB increased with age, but the slope was effectively level (no change) in the Class II sample. Given the predictable differences in the angles SNA (increasing with age in Class I cases) and SNB (increasing with age in Class I cases), the difference between these maxillary and mandibular angles (angle ANB) is also predictable. Again, though, the 50 Figure 4-12. Bivariate plot between chronological age (years) and volume of the total airway (mm3) The increase in size with age is positive and statistically significant. The least-squares, best-fit line is Volume = -825.5 + 1,382(Age), which accounts for 10.6% of the variance in the ANCOVA model (r2, P = 0.0004). Note: Total Airway Volume is the summation of airway parts 1, 2, and 3. So, while the variable is the same, the interpretation is slighty different. 51 Figure 4-13. Box plots showing the difference in distributions between the two Angle Classes The horizontal gray line across the plot is the grand mean. Patient’s age and sex did not significantly influence the analysis. 52 Figure 4-14. Bivariate graphs showing the difference in distributions between Angle Class I and Class II samples (sexes pooled) for the cephalometric angle SNA The mean angle was significantly larger in the Class II series, which reflected their greater maxillary protrusion. Notably, the angular increase in SNA with age was significant in the Class I sample, but not in the Class II sample. The blue bands around the regression lines are the 95% confidence limits. 53 Figure 4-15. Twin bivariate plots showing the association between chronological age (X axis, in years) and size of the angle SNB (degrees; Y axis) The blue bands around the regression lines are the 95% confidence limits. 54 difference in ANB reflects selection on the dependent variable. That is, orthodontists anticipate that ANB will differ between Class I and II cases; indeed, B was used as one of the key criteria for defining which cases exhibited a Class II skeletal relationship, so finding a high statistical difference largely just confirms the author’s consistency in sample selection (Figure 4-16). The same is true for the Wits appraisal (AO-BO discrepancy) that showed a highly significant difference (P < 0.0001) between Classes (Figure 4-17). The next statistically significant variable was IMPA, which measures torque of the mandibular incisor. Here, too, was one of the few significant differences between geographical sites. Measurements were at the start of treatment, so these site differences are thought to reflect geographical differences in the nature of the malocclusions, not treatment preferences (Figure 4-18). Cluster Analysis One of our interests in this study was to see how the present sample of 71 Class II cases mimics earlier researcher’s efforts at partitioning the sample into groups of subjects sharing similar craniofacial morphologies. That is, the Class II, division 1 malocclusion is defined most simply as distoclusion of the permanent first molars viewed anteroposteriorly (Angle 1907). But, as every orthodontist knows well, a Class II relationship can be configured from several different conditions, such as a recessive mandible or a prognathic maxilla or many combinations thereof, including both dental, skeletal, or skeletodental conditions (Elsasser and Wylie 1943; Renfroe 1948; Riedel 1952; Henry 1957; Hunter 1967; Moyers et al. 1980; McNamara 1981). The solution to the question of “how many groups” are intermingled in a sample is not commonly dealt with in orthodontics but the answer certainly has been addressed in other areas. In other disciplines, such as paleontology and numerical taxonomy, several approaches to this question are fairly common. The major steps to the question are: 1. Compute some measure on phenetic (phenotypic) “distance,” either a distance of similarity or of dissimilarity. This converts a visual problem of similarities among subjects into a quantified arithmetic problem, 2. Use a computer algorithm and a set of assumptions to build a “tree” or hierarchy, where geometrically similar cases are connected by short lines and, progressively, less similar cases are connected by longer lines, and 3. Use a test to determine how many clusters are present gauged against some statistical criterion. This statistical problem is termed cluster analysis (e.g., Gower 1967; Blackith and Reyment 1971; Sneath and Sokal 1973), and the procedure just outlined is far more complex, containing many more statistical and epistemological choices than just outlined. Fortunately, the JMP statistical package, as with other large packages (e.g., SAS, SPSS, 55 Figure 4-16. Box plots showing the difference in distributions by Angle Class The mean is around zero for the Class I sample (left panel), but averages about 6 in the Class II group (right panel). Patient’s age did not affect the ANB angle. There was no statistical difference within Class between sites. 56 Figure 4-17. Box plots of the distributions of Wits values (mm) by Angle Class Since the Wits value was a dependent variable for skeletal Class II selection, there should indeed be little overlap between the Classes. 57 Figure 4-18. Box plots of the distributions of IMPA by geographical site and Angle Class measured at the start of treatment IMPA was significantly lower (more upright) in the patients from Kansas compared to Tennessee. Within each site, IMPA was larger (the incisors were more proclined) in the Class II patients. 58 ClustanGraphics) contains a package of cluster analysis programs with numerous options, and that is the platform used for the results described here. For example, it is fundamental to decide how the clusters are put together. Should the most similar cases be put together first (agglomerative techniques), so the “tree” successively builds up by progressively adding more dissimilar subjects, or should the most dissimilar groups be found first, so the “tree” begins with dissimilar branches and successively adds phenotypically less-distant subjects. Cluster analysis probably can be traced back to the eminent statistician and geneticist, Sir Ronald A. Fisher (1936), though his emphasis was quite different. Fisher was interested in a different problem: if you have a number of measurements from samples of specimens from multiple groups, how can you maximally discriminate among them? Discriminant functions analysis (Fisher 1936) and cluster analysis are actually two sides of a coin; the groups are known ahead of time in discriminant functions, while cluster analysis asks how many groups exist. Both are multivariable statistical techniques. Fisher’s specific example was to use four measurements on 50 specimens each from three iris species. The object was to use the four measurements simultaneously (multivariately) to distinguish between the three species. Applying cluster analysis to these iris data produced the display in Figure 4-19. The present sample size of 71 Class II cases examined here probably does not fully encapsulate the breadth and variety of cases accessed by other researchers, for example the 497 cases studied by Moyers et al. (1980). Also, the results of cluster analysis are specific to the variables examined. Prior studies have used lateral cephalometric variables; the present study used CBCT files, with emphasis on pharyngeal size. To give an example of agglomerative cluster analysis using Ward’s method (Ward 1963), our assessment was based on the 11 pharyngeal variables: 1. Airway 1 Volume (Nasopharyngeal) 2. Airway 1 Area (Nasopharyngeal) 3. Airway 1+2 Volume 4. Airway 1+2 Area 5. Airway 2 Volume (Superior) 6. Airway 2 Area (Superior) 7. Airway 1+2+3 Volume 8. Airway 1+2+3 Area 9. Airway 3 Volume (Inferior) 10. Airway 3 Area (Inferior) 11. Total Airway The “scree plot” of the cluster analysis (e.g., Gorsuch 1983) was used to determine the number of clusters produced by the analysis (Figure 4-20). So long as the slope of the scree plot remains relatively flat, the groups are similar. It is at the inflection point (where the rate of slope rises) that the informational content rises, and the 59 Figure 4-19. A depiction of cluster analysis applied to Fisher’s three species of iris data (150 specimens; 4 variables) Cluster analysis was used to array the specimens but they are arrayed here along the canonical axes. The first two canonical variates (X and Y axes) are labeled “Can1” and “Can2.” Figure 4-20. The “scree plot” associated with the following dendrogram (cluster analysis) The scree plot begins to rise very slowly from left to right as cases are successively grouped together; the important point, visually, is where the slope of the plot changes inflection and begins to rise more rapidly. This analysis, based on 11 pharyngeal variables suggests that there are four distinctive clusters of Class II cases among the 71 subjects in the study. 60 investigator concludes that subsequent “branches” of the tree (dendrogram) are different from one another. This particular analysis suggested there were four distinctive groupings of the 71 Class II cases, based on the 11 pharyngeal dimensions. The question, of course, is which of the eleven dimensions are important in distinguishing the clusters of cases and how. In other words, how can these four clusters be characterized based on these variables? We labeled the clusters, from top to bottom in the figure, A, B, C, and D. Our assessment of the cluster derived from the 11 pharyngeal measures was a set of five clusters (shown to the left of the vertical red line in Figure 4-21). This number (5 clusters) coincides with the deflection point of the scree plot. One-way factorial ANOVA was then used to assess how the univariate dimensions contributed to the clustering. Tukey’s HSD (“honestly significant difference”) post hoc test was used to test the assortment among groups (see, e.g., Mosteller and Tukey1977 for description of the HSD test). It turns out that all 11 exhibited statistically significant differences among the clusters. Just for this first cluster result, the individual variables are detailed in a set of bar charts, that is, the 11 pharyngeal dimensions. The following graphs (Figures 4-22 through 4-32) detail these differences. The cluster analysis based on the 11 pharyngeal dimensions suggested four “kinds” of Class II cases among the 71 subjects analyzed here (Figures 4-22 through 4-32). These were assorted on the basis of pharyngeal size. The most common cluster consisted of the majority of cases (n = 48) with a midrange of airway sizes. Cluster 2 (n = 2) had the smallest airways, while cluster 5 had the largest. Clusters 3 and 4 had the largest dimensions aside from the one, very large individual in cluster 5. The bar charts show that the orderings of the groups are similar across variables, though, of course, the units of the dimensions differ. The next effort was based on an analysis based on 19 skeletal dimensions (omitting the several tooth-based dimensions often considered in orthodontic diagnosis). The 19 variables (all assessed at pretreatment) were: 1. Y-Axis 2. Facial convexity 3. SNA angle 4. SNB angle 5. ANB angle 6. Wits appraisal 7. FMA 8. Condylion-A distance 9. Condylion-Gnathion 10. A-Nasion-perpendicular 11. Pogonion-Nasion-perpendicular 61 Figure 4-21. Dendrogram of the 71 Class II cases analyzed from CBCTs Analysis was based on 11 pharyngeal dimensions (sexes pooled). The shorter the horizontal branches, the closer the phenotypic similarities connecting the cases. Analysis suggests five groups (identified by the vertical red line). The case numbers of the subjects and the icons (left of diagram) simply are the order of case entries and the cluster, but they do permit analysis of the grouping characteristics. The subjects are uniformly arrayed vertically, so the vertical closeness of the subjects is immaterial; indeed a node of a cluster can be rotated without affecting the analysis. The JMP program color-codes the subjects within the smaller units to aide in visualization. 62 Figure 4-22. Results of cluster analysis using the 11 pharyngeal dimensions The mean (+ 1 sd) of the size of each cluster is graphed, specifically for the airway 1 volume (mm3). Cluster 1 contained the most cases (n = 48), cluster 2 was n = 2, cluster 3 was 15, cluster 4 was 5, and cluster 5 contained just 1 case (thus, no standard deviation). 63 Figure 4-23. Results of cluster analysis using the 11 pharyngeal dimensions, specifically for the airway 1 area (mm2) The mean (+ 1 sd) of the size of each cluster is graphed. Cluster 1 contained the most cases (n = 48), cluster 2 was n = 2, cluster 3 was 15, cluster 4 was 5, and cluster 5 contained just 1 case (thus, no standard deviation). 64 Figure 4-24. Results of cluster analysis using the 11 pharyngeal dimensions, specifically for the airway 1+2 volume (mm3) The mean (+ 1 sd) of the size of each cluster is graphed. Cluster 1 contained the most cases (n = 48), cluster 2 was n = 2, cluster 3 was 15, cluster 4 was 5, and cluster 5 contained just 1 case (thus, no standard deviation). 65 Figure 4-25. Results of cluster analysis using the 11 pharyngeal dimensions, specifically for the airway 1+2 area (mm2) The mean (+ 1 sd) of the size of each cluster is graphed. Cluster 1 contained the most cases (n = 48), cluster 2 was n = 2, cluster 3 was 15, cluster 4 was 5, and cluster 5 contained just 1 case (thus, no standard deviation). 66 Figure 4-26. Results of cluster analysis using the 11 pharyngeal dimensions, specifically for the airway 2 volume (mm3) The mean (+ 1 sd) of the size of each cluster is graphed. Cluster 1 contained the most cases (n = 48), cluster 2 was n = 2, cluster 3 was 15, cluster 4 was 5, and cluster 5 contained just 1 case (thus, no standard deviation). 67 Figure 4-27. Results of cluster analysis using the 11 pharyngeal dimensions, specifically for the airway 2 area (mm2) The mean (+ 1 sd) of the size of each cluster is graphed. Cluster 1 contained the most cases (n = 48), cluster 2 was n = 2, cluster 3 was 15, cluster 4 was 5, and cluster 5 contained just 1 case (thus, no standard deviation). 68 Figure 4-28. Results of cluster analysis using the 11 pharyngeal dimensions, specifically for the airway 1+2+3 volume (mm3) The mean (+ 1 sd) of the size of each cluster is graphed. Cluster 1 contained the most cases (n = 48), cluster 2 was n = 2, cluster 3 was 15, cluster 4 was 5, and cluster 5 contained just 1 case (thus, no standard deviation). 69 Figure 4-29. Results of cluster analysis using the 11 pharyngeal dimensions, specifically for the airway 2 area (mm2) The mean (+ 1 sd) of the size of each cluster is graphed. Cluster 1 contained the most cases (n = 48), cluster 2 was n = 2, cluster 3 was 15, cluster 4 was 5, and cluster 5 contained just 1 case (thus, no standard deviation). 70 Figure 4-30. Results of cluster analysis using the 11 pharyngeal dimensions, specifically for the airway 1+2+3 volume (mm3) The mean (+ 1 sd) of the size of each cluster is graphed. Cluster 1 contained the most cases (n = 48), cluster 2 was n = 2, cluster 3 was 15, cluster 4 was 5, and cluster 5 contained just 1 case (thus, no standard deviation). 71 Figure 4-31. Results of cluster analysis using the 11 pharyngeal dimensions, specifically for the airway 3 area (mm2) The mean (+ 1 sd) of the size of each cluster is graphed. Cluster 1 contained the most cases (n = 48), cluster 2 was n = 2, cluster 3 was 15, cluster 4 was 5, and cluster 5 contained just 1 case (thus, no standard deviation). 72 Figure 4-32. Results of cluster analysis using the 11 pharyngeal dimensions, specifically for the total airway (mm3) The mean (+ 1 sd) of the size of each cluster is graphed. Cluster 1 contained the most cases (n = 48), cluster 2 was n = 2, cluster 3 was 15, cluster 4 was 5, and cluster 5 contained just 1 case (thus, no standard deviation). 73 12. B-Nasion-perpendicular 13. Anterior Facial Height 14. Posterior Facial Height 15. Gonion-Menton 16. Sella-vertical-to-A point 17. Sella-vertical-to-B point 18. Sella-vertical-to-Pogonion 19. Sella-vertical-to-M point The scree plot for this cluster analysis suggested that there are just two clusters (Figure 4-33). The dendrogram itself is illustrated in Figure 4-34. One other investigation was the use of variables that reflect the degree of maxillamandibular discrepancy. There were four dimensions in this approach, namely SNA, SNB, ANB, and Wits appraisal (AOBO). The first three of these were measured in degrees, while the Wits appraisal was recorded in millimeters. A benefit of these angular variables is that they are not as strongly correlated with size and age as are linear dimensions (e.g., Proffit 2000). Inspection of the scree plot for this dendrogram suggested there were eight recognizable clusters (Figures 4-35 and 4-36). The dendrograms presented here produce different results, of course, depending on the variables used to construct them and the assumptions chosen. Using the raw sizes of the cephalometrics is unlikely to be particularly meaningful because these subjects— examined in late childhood and early adolescence—are actively growing and increasing their cephalometric dimensions (e.g., Riolo et al. 1974). As such, the subjects’ ages are reflected in the dimensions, which importantly influenced the results. Though too laborintense for a sidelight of the present study, one solution would have been to standardize all of the data by age and sex. That is, in place of using the raw data, if the z-scores based on age- and sex-specific standards had been entered into the clustering algorithm; the relative sizes of the variables would have been appropriately highlighted. The simplest and time-honored method of standardization probably is the z-score (or “Tscore”) as described, for instance, in the text by Garn and Shamir (1958). The z-score is where X is an individual’s measurement and x and s are, respectively, the mean and standard deviation for that subject’s age and sex. This formula expresses the measurement as the number of standard deviations away from the group mean, and of course, this is desirable because it is the relative sizes of the dimensions that determine the kind of Class II malocclusion and modulate treatment. The influence of each variable in this cluster analysis was tested using a one-way factorial ANOVA (alpha = 0.05) (Tables 4-2 through 4-6), and the HSD post-hoc test (e.g., Abdi et al. 2009) was used to identify the source of statistical significance within 74 Figure 4-33. The scree plot for the cluster analysis based on 19 skeletal dimensions The inflection point in the scree pattern seems to be toward the far right side, with just two groups. 75 Figure 4-34. Cluster analysis (dendrogram) of the 71 Class II cases based on 19 skeletal dimensions The scree plot suggested that there were just two clusters, as defined by the vertical red line. 76 Figure 4-35. The scree plot resulting from clustering of four cephalometric dimensions (SNA, SNB, ANB, and AOBO) The division of the dendrogram using this inflection point produced eight clusters. 77 Figure 4-36. The dendrogram produced by four cephalometric variables (SNA, SNB, ANB, and Wits) According to the scree plot (shown here by the red vertical line) there are 8 distinguishable clusters among these 71 cases. That is, there are 8 clusters of Class II cases emanating from the left of the vertical red line. 78 Table 4-2. Results of one-way ANOVAs testing for differences in mean sizes among the 8 clusters developed using 4 maxillo-mandibular discrepancies Variable SNA SNB ANB Wits df 7 7 7 7 Sum of Squares 665.43 510.19 123.99 339.50 Mean Square 95.06 72.88 17.71 48.50 F Ratio 76.99 43.01 26.33 22.24 P Value <0.0001 <0.0001 <0.0001 <0.0001 Adjusted R-Square 0.88 0.81 0.72 0.68 Table 4-3. Descriptive statistics for SNA among the 8 groupings generated by cluster analysis Cluster Mean Standard Deviation 1 2 3 4 5 6 7 8 77.3 81.3 86.8 84.2 84.3 85.7 87.5 82.2 1.57660 0.70017 0.56821 0.76659 1.01083 1.60375 1.55027 1.58902 SEM 0.45513 0.16063 0.21476 0.24242 0.31965 0.71722 0.89505 0.71063 79 Lower 95% Confidence 76.323 80.999 86.317 83.642 83.597 83.729 83.616 80.227 Upper 95% Confidence 78.327 81.674 87.368 84.738 85.043 87.711 91.318 84.173 Table 4-4. Descriptive statistics for SNB among the 8 groupings generated by cluster analysis Cluster 1 2 3 4 5 6 7 8 Mean Standard Deviation SEM Lower 95% Confidence Upper 95% Confidence 72.7 76.0 81.6 78.4 79.5 77.7 77.8 74.3 1.16421 1.04951 1.10518 1.09565 1.39000 2.01420 1.34288 2.04157 0.33608 0.24077 0.41772 0.34647 0.43956 0.90078 0.77531 0.91302 72.002 75.452 80.592 77.656 78.516 75.179 74.497 71.805 73.481 76.464 82.636 79.224 80.504 80.181 81.169 76.875 Table 4-5. Descriptive statistics for ANB among the 8 groupings generated by cluster analysis Cluster Mean Standard Deviation 1 2 3 4 5 6 7 8 4.59 5.38 5.23 5.77 4.81 8.06 9.63 7.88 0.820707 0.792509 0.760952 0.928619 0.966609 0.450555 0.950438 0.593296 SEM Lower 95% Confidence 0.23692 0.18181 0.28761 0.29366 0.30567 0.20149 0.54874 0.26533 4.0702 5.0022 4.5248 5.1057 4.1185 7.5006 7.2723 7.1433 80 Upper 95% Confidence 5.113 5.766 5.932 6.434 5.501 8.619 11.994 8.617 Table 4-6. Descriptive statistics for Wits among the 8 groupings generated by cluster analysis Cluster 1 2 3 4 5 6 7 8 Mean 2.37 3.75 3.86 4.30 -0.12 2.30 7.07 8.78 Standard Deviation 1.91849 1.37936 1.03579 1.33583 1.04009 1.10680 1.61658 2.25322 SEM 0.5538 0.3164 0.3915 0.4224 0.3289 0.4950 0.9333 1.0077 81 Lower 95% Confidence 1.148 3.083 2.899 3.344 -0.864 0.926 3.051 5.982 Upper 95% Confidence 3.586 4.412 4.815 5.256 0.624 3.674 11.082 11.578 each ANOVA. If—as here—only pairwise comparisons are made, this Tukey-Kramer HSD method results in a narrower confidence limit (which is preferable and more powerful) than Scheffé's method. Calculation of the HSD multiple comparisons were calculated as an option in the JMP program. The F-ratio for SNA was 77. (df = 7 and 70; P < 0.0001). The HSD indicated that the source of statistical significance was due to four differences between the 8 clusters, that is (7-3-6) < (6-5-4) < (8-2) < 1 (Figure 4-37). The F-ratio for SNB was 43 (P < 0.0001) with 7 and 70 df (Figure 4-38). The HSD results show that the significance is due to four breaks among five groups, namely 3 > (5-4-7-6) > (2-8) > 1. Some of these cluster numbers are duplicated because, after the group means were sequenced some of the adjacent groups were not strictly significant, though farther separations did attain statistical significance. This stated grouping (3 > (5-4-7-6) > (2-8) > 1), then, is the best available interpretation of the results. The F-ratio for ANB was 17 (P < 0.0001) with 7 and 70 df (Figure 4-39). The HSD analysis indicates there are three distinctive groupings of the 8 clusters, namely (7-6-8) > (4-2-3-5) > 1. Fourthly, the Wits appraisal produced an F-ratio of 22 (P < 0.0001) with 7 and 70 df (Figure 4-40). The Wits appraisal (AOBO) was smaller (mean < 4 mm) in six of the eight groups, while the average was above 6 mm in clusters 7 and 8. The HSD analysis disclosed three breaks among the eight clusters that resulted in four groups, namely (8-7) > (7-4) > (3-2-1-6) > (6-5). To attempt to summarize, clusters 3 and 7 were characterized by high SNA angles (i.e., maxillary excess). SNB was lowest in cluster 8 (i.e., mandibular insufficiency). The ANB angle was highest in clusters 6, 7, and 8, but for different reasons. ANB was large in clusters 6 and 7 because of maxillary excess, but large in cluster 8 because of an underdeveloped mandible. Finer discriminations would seem to await larger sample sizes and more complete cephalometric measurements aimed at capturing various Class II characteristics. Notably, cluster analysis is suggestive (e.g., Blackith and Reyment 1971): It develops a perspective of possible solutions. It does not provide any sort of definitive results; instead, the result depends on the assumptions made and the methods chosen. It also typically depends on a large sample size in order to increase assurances of including all of the relevant groupings (“types” of Class II malocclusions in the present study). Consequently, the tentative applications discussed here require more thorough study of a larger sample. 82 Figure 4-37. Box plots of the arrangement of the angle SNA among the 8 clusters 83 Figure 4-38. Box plots of the arrangement of the angle SNB among the 8 clusters 84 Figure 4-39. Box plots of the arrangement of the angle ANB among the 8 clusters 85 Figure 4-40. Box plots of the arrangement of the Wits measurement among the 8 clusters AOBO) was smaller (mean < 4 mm) in six of the eight groups, while the average was above 6 mm in clusters 7 and 8. 86 CHAPTER 5. DISCUSSION There is debate over what degree of relationship exists between the pharynx and the craniofacial structures. Evidence to date implies that the type and severity of Class II malocclusion affects the size and shape of the pharynx. Several authors contend that smaller airways are associated with Class II malocclusions. It is also proposed that small airways can be caused by nasal obstruction, an anatomical circumstance that can lead to weakened muscle action with a consequently altered facial growth pattern. This scenario suggests that small airways and small mandibles are developmentally coincident. The present study questions this claim, and analysis shows that there is likely no correlation between pharyngeal size and malocclusion type. There is, however, in the conventional teenage orthodontic patient, linear pharyngeal growth concurrent with age and sex. Various researchers have classified Class II malocclusions into groups based on size and positioning of the maxilla and mandible. If there exists a difference in the airway size and shape between Class II and Class I patients, it is of interest to determine what specific combination of skeletal presentations causes the greatest airway differences. For example, if a child at age 11 has a skeletal malocclusion that causes a concurrent small airway, and if that small airway causes a clinically significant reduction in respiration, or increases the future likelihood of a condition like sleep apnea, then correction of the skeletal malocclusion would seem warranted. However, this hypothetical scenario must first be documented before being given merit. There have been many research projects conducted on three-dimensional analysis of the pharynx. Kim et al. (2010) studied the three-dimensional airway volume and cross-sectional areas of 27 children with a mean age of 11 years. Total airway volume was significantly smaller in the Class II subjects. However, this is likely a type II statistical error due to small sample sizes. A sample size of only 27 patients does not carry enough statistical power to confirm a difference between two groups. Grauer et al. (2009) studied the CBCT records of 62 nongrowing subjects (aged 17-46 years) to evaluate pharyngeal airway volume and shape. Class II subjects had significantly smaller inferior airways than Class I subjects. As with the previous study, 62 is likely not a large enough sample size to sufficiently differentiate between two groups. Furthermore, the authors used the C3 vertebrae as a landmark for dividing the airway. The position of the C3 vertebrae varies greatly from patient to patient in its relation to the soft tissue that comprises the pharynx. So, it is likely that the airway was inconsistently measured from patient to patient. Also, the use of patients that range in age from 17 to 46 is troubling, given that growth of the pharynx begins to level off after the age of 20, and even tends to decrease in size in some individuals around the age of 40 (Streight 2011). Furthermore, studying the pharyngeal airway in adults is less reliable since the quality of the soft tissues of the pharynx is more variable as a result of the aging process (Johnston and Richardson 1999). 87 In contrast to the studies of Kim and Grauer, Alves et al. (2008) found that the majority of airway measurements were not affected by malocclusion type, with volume and area measurements that were statistically equivalent between Class II and Class III groups. Findings did indicate increased airway volume and area for males when compared to females. However, as with the studies of Kim and Grauer, small sample sizes cast doubt on the results. Streight (2011) analyzed the CBCT images of 263 routine dental patients to develop normative standards of pharyngeal dimensions by sex and age. They found that pharyngeal volume, midsagittal area, and craniocaudal height are significantly larger in men, and that several pharyngeal variables continued to increase during adulthood in men, but not women. There were a few issues with the methodology of the study, including an extremely wide age range of 5 to 85 years of age, a sample that includes both whites and non-whites, and a cross-sectional research design. A few studies have looked at the relationship between mandibular position and the pharynx. Park et al. (2010) studied the pharyngeal airways of 12 subjects who underwent mandibular setback surgery. 2-D and 3-D analysis of images taken before surgery and 6 months after surgery showed a decrease in oropharyngeal volume, but the change was not statistically significant. The volume of the nasopharynx, however, remained relatively constant, which suggests that deformation occurs to preserve the airway capacity in the changed environment following mandibular setback surgery. It might also suggest that nasopharyngeal volume is independent of mandibular positioning. These results should be viewed with caution, due to the extremely small sample size. Pierre Robin Sequence (PRS) is a clinical entity consisting of micrognathia, cleft of the secondary palate, with glossoptosis, and upper airway obstruction (Figueroa et al. 1991). Figueroa and associates compared the lateral cephalograms of 17 infants with PRS to groups of 26 normal infants and 26 infants with isolated cleft palate. While the groups were distinct throughout the 2-year period of study, differences were greater at the earliest age. Initially, the PRS infant had a shorter mandibular length and narrower airway. PRS infants did experience “partial mandibular catch-up growth” leading to improved airway dimensions and concurrent resolution of respiratory distress. The increased growth rate, however, did not allow PRS infants to recover to values equal to normal. It is rational to assume that Class II patients with smaller than normal mandibles, might exhibit similar characteristics. However, PRS patients exhibited the confounding factors of cleft of the secondary palate, glossoptosis, and upper airway obstruction, whereas Class II patients, by definition, may not. Based on the studies of Harvold, Miller, and Vargervik, it is reasonable to assume that a small pharyngeal airway could be the product of a past airway obstruction that led to subsequent altered respiration, skeletal muscle adaptation, and then altered craniofacial growth (i.e.. Class II malocclusion). However, this supposition has not been documented and should not be applied to the issue at hand, especially since the presence of airway obstruction in our sample is unknown. 88 Two growth studies, demonstrate that, surprisingly, little growth occured in the anteroposterior dimension of the nasopharynx. King (1949) studied the serial cephalometric radiographs of 24 boys and 26 girls that had been taken at three months of age, six months, one year, and then annually to six years, and biennially from 6 to 16 years. He found that most of the sagittal growth of the pharynx occurred in the first year of life. More inferiorly, in the oropharynx, the distance between the cervical vertebrae and the hyoid bone was relatively constant until puberty when the hyoid bone moved slightly forward. This suggests that the anteroposterior dimensions of the pharynx are established in early infancy. Linder-Aronson and Woodside (1979), with a sample size of 260, also concluded that the sagittal increase of the pharynx was unrelated to other cephalometric dimensions of the facial complex. This finding coincides with our results, which suggest that craniofacial positioning has little effect on the pharyngeal dimensions. The majority of orthodontic research on airway health is restricted by the technological limitations of cephalometric imaging (Lowe et al. 1986; Finkelstein et al. 2001; Hanggi et al. 2008; Abramson et al. 2009). Using 2-dimensional radiography, no reliable conclusions can be made about the effects of orthodontic treatment on airway volume because mediolateral widths are unknown. The advantage of the present study and other current airway studies that capitalize on CBCT technology is that these previously unknown widths, areas, and volumes can now be quantified. 3-D imaging is also preferred because it produces an image that is a true 1:1 representation of the anatomical structure in question (Mah et al. 2011). Recent criticisms of the radiation dose of a CBCT scan seem sensible, given that the average dose varies from ~40 to 135 microsieverts. This is two to 14 times greater than the dose administered by the typical lateral cephalogram plus panoramic image (~8 to 18 microsieverts). However, newer technology (including the iCAT machines used in this study) claim radiation doses closer to 35 to 40 microsieverts. Another issue concerns the risk and responsibility for diagnosing pathology present on CBCT scans. In the present study, no new CBCT images were taken, but rather existing CBCT images were studied. Thus, the issues of radiation exposure and pathology diagnosis were not a direct concern. The present study analyzed 131 patients with pretreatment CBCT records from orthodontic practices in Jackson, Tennessee, and Wichita, Kansas. Identical, Next Generation iCAT® CBCT machines were used to collect all samples and each scan recorded patients in an upright position, with a 12-inch field of view to include full craniofacial anatomy. Samples were selected from private practices, with an age range of 9 to 13, in order to reflect current orthodontic practice in the United States. Of the 131 patients (65 males; 66 females) 71 exhibited a Class II malocclusion while 60 exhibited a Class I malocclusion. The study was limited to Class II, division 1 malocclusions by confirming labioverted maxillary central incisors, a sign indicated by an overjet of at least 3.5 mm. 89 It was suggested that the geography of Jackson, TN (being approximately 170 miles further south than Wichita, Kansas, and thus experiencing a warmer climate) might have some environmental effect on the patients from those areas. Additionally, since Wichita is located on the Arkansas River, there might exist some environmental effect on the patients’ respiratory development. However, there was no difference in airway volume or area between geographical sites. As such, geographical location did not factor significantly. Nasopharyngeal volume grows faster with age in Class II patients than in Class I patients. By this, we mean that the tempo of nasopharyngeal growth was faster in Class II patients. However, the two groups are similar in size around the end of childhood. This could represent a form of catch-up growth for the Class II patients. However, it seems strange that the faster growth tempo presents in the nasopharynx but not in either section of the oropharynx, nor does the trend appear when considering the Total Airway Volume. Another possible explanation is the potential variation caused by tonsils and adenoid tissue in the nasopharynx or from measuring errors caused by the difficulty in finding the pterygomaxillary fissure, one of three points used to outline the nasopharynx. There was a positive, statistically significant association between chronological age and Total Airway Volume (a combination of nasopharyngeal and oropharyngeal volumes). Figure 5-1 shows this relationship, partitioning the sample by Angle Class and sex. By visual assessment, these four regression slopes appeared to be homogemeous, and, by two-way ANOVA (Table 5-1), this was confirmened in that none of the three F ratios was statistically significant at alpha = 0.05. Because of the nonsignicance of Class and sex, the sample was reintegrated to recoup degrees of freedom. Figure 5-2 shows the positive relationship between the age at the start of treatment and size of Total Airway Volume for the entire sample. Within the age interval of 9 to 14, the Total Airway Volume increases almost 1,400 mm3 per year. The same can be said of Total Airway Area, as significant increases in size were seen with age. There was also a linear increase in oropharyngeal dimensions in the observed age interval. One aspect of orthodontic treatment that cannot be ignored is that the majority of orthodontic patients are growing adolescents. In growing patients, structural dimensions expand as the face grows downward and forward. Normal growth, then, seems like the best explanation for the increase in pharyngeal size with age. There was a highly significant difference between Class I and Class II patients in degree of facial convexity (Na A-Pg). This is not at all surprising, though, since facial retrognathism is one of the dependent variables used for case selection. This finding works as vindication that the two samples were appropriately divided into Class I and Class II groups. The same principle applied to significant Class differences between Wits appraisal and ANB. Similarly, both SNA and SNB were significantly different between Classes. Interestingly, there was a significant increase in SNA angle with age in the Class I sample, whereas the SNA angle does not change with age in the Class II sample. The same finding is true with SNB angle between Classes. It is clear from these bivariate 90 Figure 5-1. (mm3) Bivariate plots by Angle Class and sex for Total Airway Volume The least squares regression line was fit to each scatter of points, and the 95% confidence limits are shown by the blue bands. Table 5-1. Results of two-way ANOVA tests for Total Airway Volume factored by Angle Class and sex Source df SSQ F Ratio P Value Class 1 15096864 0.5201 0.4721 Sex 1 11206226 0.3861 0.5355 Class-by-Sex 1 42581289 1.4671 0.2281 Neither class, sex, nor the interaction term was statistically significant. 91 Figure 5-2. Bivariate plot between the patient’s age at the start of treatment and Total Airway Volume for the complete sample (n = 131) The 95% confidence limits are shown by the blue band. 92 plots that the average Class II patient has a less developed maxilla and mandible in relation to their cranial base when compared with a Class I patient. It would seem also that the colloquial, orthodontic approach of describing patients as “haves” and “havenots” applies to Class I and Class II patients. In clearer terms, it seems that patients exhibiting small SNA and SNB values at a young age, do not outgrow these skeletal conditions. It was originally anticipated that there would be a size difference in the pharyngeal airway variables by Angle’s Class. Class II cases were supposed to have smaller airway dimensions because the mandible was smaller, leaving less space for the pharynx. This difference had been suggested in the literatrure, and it was speculated that the present study, with a larger sample size (n = 131) and better statistical control of the subject’s age and sex, a size difference by Class would be evident. The specifics of the statistical lack of any difference were detailed in the Results chapter. As a single, summary graph (Figure 5-3) displays this overall overlap of sizes between Class I and Class II orthodontic samples. None of the 11 variables differed significantly between Classes. Our attempt to separate Class II patients into groups using cluster analysis did not produce any clinically relevant findings. The primary cause was our relatively small sample size of 71 Class II patients. Moyers classic study on the subject included a much larger sample of 497 patients. Future research on Class II groups will require a more thorough study of a larger sample. While sleep apnea is a clinically significant topic, it is impractical to apply conclusions from these findings to sleep apnea since patients were seated during the CBCT image capture process and not supine. Patients were also awake during image capture process with no standard tongue position and no way to tell whether patients swallowed or not. Future airway studies need to image patients in a supine position, during sleep, and in conjunction with sleep studies. Combining this information with BMI, nasal airflow measures, and even a pharyngeal flaccidity measure would be helpful in better understanding sleep apnea. After measuring 131 airways, there seems to be variability in airway morphology. Due to the nature of pharyngeal anatomy, the most common airway division methods require a combination of soft and hard tissue landmarks. Other proposed landmarks such as vertebrae and the hyoid bone show significant variation from patient to patient and were eliminated as possibilities. Another limitation is in splitting the oropharynx, since the dividing line between superior and inferior is determined by position of the soft palate, which can vary because the patient was swallowing or due to normal physiological variation in size or shape of the soft palate. Also, positions of most soft tissue pharyngeal landmarks vary as you move transversely through slices of the pharynx. We attempted to make all measurements in the midsagittal plane of each patient, by measuring the slice that was located between the maxillary central incisors. 93 Figure 5-3. A stacked chart of the average sizes of the 11 measures of pharyngeal size analyzed in the present study Visually, there is no evident (clinically important) difference in size by Angle’s Class. 94 Another limitation of the present study was that there were possible methodological differences between the different geographical sites. Both sites used the same iCAT CBCT machine, with the same settings and exposure time. However, it is impossible to know, given the retrospective nature of the study, whether the images were captured in an identical fashion. Since respiratory health histories were unavailable, it is impossible to know what effect, if any, a history of tonsillectomy had on the results. All patients with visibly large tonsils or adenoids were removed from the study. According to Rowe (1982), enlarged tonsils and adenoids are the primary source of upper airway obstruction in young patients, so a better knowledge of the patients’ respiratory history would have been beneficial. Future research should focus on differences between Class I, Class II, and Class III patients. A prospective, longitudinal study would best show differences in growth between Classes. While the current study has the largest sample size to date, a larger sample (especially of different Class II types) would potentially illustrate airway differences. 95 CHAPTER 6. SUMMARY AND CONCLUSIONS Morphology of the pharynx affects the volume of airflow and facial growth patterns, the risk of sleep apnea, and swallowing patterns. Since the pharynx is housed within the facial structures, there may well be an association between the two. Preliminary works by Kim et al. (2010) and Grauer et al. (2009) suggest a link between craniofacial dimensions and pharyngeal shape. However, sample sizes have been small. The three dimensions of height, width, and depth determine the size and shape of the pharynx. Studies by Brodie (1941) and King (1952) found that the total depth of the nasopharynx is established in infancy, with little change thereafter. Linder-Aronson and Woodside (1979) reported that sagittal depth of the nasopharynx increases in small increments up to 16 years of age for females and 20 years of age for males. Streight and Harris (2011) found that growth of the pharynx did not decline during childhood, but was linear throughout the child-to-adult age interval. Class II malocclusions are some of the most common facial disharmonies encountered in orthodontics. A Class II malocclusion can be a dental problem, a skeletal problem, or some combination of the two (Graber 2005). Evidence to date implies that the type and severity of Class II malocclusion affects the size and shape of the pharynx. The purpose of the present, retrospective, cross sectional study was to determine if there is a difference in pharyngeal dimensions between Class I and Class II orthodontic patients. Oropharyngeal structures were analyzed in 131 healthy adolescents (71 Class II, 60 Class I) before orthodontic treatment. Using CBCT technology, cephalometric variables and volumetric measurements were analyzed. Major findings are: 1. Pharyngeal growth, as measured by retrospective, cross sectional CBCT images, occurs at a linear pace during the key orthodontic ages of 9 to 13 years and is significantly faster in boys. 2. Total Airway Volume (a combination of nasopharyngeal, superior oropharyngeal, and inferior oropharyngeal volumes) is statistically equivalent between Class I and Class II adolescent whites. 3. 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Results of ANCOVA test for geographical site difference, while controlling for patient’s age, sex and class; the dependent variable is Airway 1 Volume (Nasopharyngeal) Source df SSQ F Ratio P Value Geographical Site 1 1043311 0.54 0.4623 Class 1 11214369 5.84 0.0171 Sex 1 110276 0.06 0.8109 Chronological Age Initial 1 31626602 16.48 <0.0001 Geographical Site-x-Class 1 35843 0.02 0.8915 Geographical Site-x-Sex 1 2574500 1.34 0.2490 Geographical Site-xChronological Age Initial 1 9855800 5.14 0.0252 Geographical Site-x-Class-x-Sex 1 31278 0.02 0.8986 Geographical Site-x-Class-xChronological Age Initial 1 1845043 0.96 0.3288 Geographical Site-x-Class-xChronological Age Initial-x-Sex 1 1739538 0.91 0.3429 108 Table A-2. Results of ANCOVA test for geographical site difference, while controlling for patient’s age, sex and class; the dependent variable is Airway 1 Volume (Nasopharyngeal) Source df SSQ F Ratio P Value Geographical Site 1 0.002 0.00 0.9994 Class 1 11618.035 2.95 0.0884 Sex 1 832.610 0.21 0.6464 Chronological Age Initial 1 26927.100 6.84 0.0101 Geographical Site-x-Class 1 56.550 0.01 0.9048 Geographical Site-x-Sex 1 4620.581 1.17 0.2808 Geographical Site-xChronological Age Initial 1 10150.910 2.58 0.1109 Geographical Site-x-Class-x-Sex 1 954.347 0.24 0.6234 Geographical Site-x-Class-xChronological Age Initial 1 11334.805 2.88 0.0923 Geographical Site-x-Class-xChronological Age Initial-x-Sex 1 644.180 0.16 0.6865 109 Table A-3. Results of ANCOVA test for geographical site difference, while controlling for patient’s age, sex and class; the dependent variable is Airway 1+2 Volume Source df SSQ F Ratio P Value Geographical Site 1 9364133 0.72 0.3973 Class 1 10559133 0.81 0.3688 Sex 1 1282546 0.10 0.7538 Chronological Age Initial 1 198513481 15.30 0.0002 Geographical Site-x-Class 1 882019 0.07 0.7948 Geographical Site-x-Sex 1 20487332 1.58 0.2114 Geographical Site-xChronological Age Initial 1 78140831 6.02 0.0156 Geographical Site-x-Class-x-Sex 1 24836414 1.91 0.1691 Geographical Site-x-Class-xChronological Age Initial 1 13017865 1.00 0.3185 Geographical Site-x-Class-xChronological Age Initial-x-Sex 1 25836576 1.99 0.1608 110 Table A-4. Results of ANCOVA test for geographical site difference, while controlling for patient’s age, sex and class; the dependent variable is Airway 1+2 Area Source df Geographical Site 1 Class F Ratio P Value 9921.08 0.77 0.3815 1 29189.95 2.27 0.1345 Sex 1 754.64 0.06 0.8090 Chronological Age Initial 1 11.94 0.0008 Geographical Site-x-Class 1 1744.97 0.14 0.7132 Geographical Site-x-Sex 1 29297.72 2.28 0.1338 Geographical Site-xChronological Age Initial 1 33792.14 2.63 0.1076 Geographical Site-x-Class-x-Sex 1 4051.53 0.32 0.5756 Geographical Site-x-Class-xChronological Age Initial 1 13074.69 1.02 0.3153 Geographical Site-x-Class-xChronological Age Initial-x-Sex 1 23072.63 1.79 0.1829 111 SSQ 153533.9 Table A-5. Results of ANCOVA test for geographical site difference, while controlling for patient’s age, sex and class; the dependent variable is Airway 2 Volume (Superior) Source df SSQ F Ratio P Value Geographical Site 1 4156139 0.47 0.4956 Class 1 9861 0.00 0.9735 Sex 1 640666 0.07 0.7889 Chronological Age Initial 1 71668549 8.06 0.0053 Geographical Site-x-Class 1 562256 0.06 0.8019 Geographical Site-x-Sex 1 8536731 0.96 0.3292 Geographical Site-xChronological Age Initial 1 32493824 3.65 0.0584 Geographical Site-x-Class-x-Sex 1 23104939 2.60 0.1097 Geographical Site-x-Class-xChronological Age Initial 1 5061170 0.57 0.4522 Geographical Site-x-Class-xChronological Age Initial-x-Sex 1 14168101 1.59 0.2094 112 Table A-6. Results of ANCOVA test for geographical site difference, while controlling for patient’s age, sex and class; the dependent variable is Airway 2 Area (Superior) Source df SSQ F Ratio P Value Geographical Site 1 9930.539 1.25 0.2667 Class 1 3977.026 0.50 0.4814 Sex 1 1.916 0.00 0.9877 Chronological Age Initial 1 51865.157 6.50 0.0120 Geographical Site-x-Class 1 1173.262 0.15 0.7020 Geographical Site-x-Sex 1 10648.366 1.34 0.2502 Geographical Site-xChronological Age Initial 1 6901.4 0.87 0.3541 Geographical Site-x-Class-x-Sex 1 8938.599 1.12 0.2918 Geographical Site-x-Class-xChronological Age Initial 1 62.088 0.01 0.9298 Geographical Site-x-Class-xChronological Age Initial-x-Sex 1 16006.314 2.01 0.1591 113 Table A-7. Results of ANCOVA test for geographical site difference, while controlling for patient’s age, sex and class; the dependent variable is Airway 1+2+3 Volume Source df Geographical Site 1 Class F Ratio P Value 26740339 1.05 0.3065 1 23716420 0.94 0.3355 Sex 1 2646800 0.10 0.7472 Chronological Age Initial 1 465903647 18.37 <0.0001 Geographical Site-x-Class 1 3196561 0.13 0.7232 Geographical Site-x-Sex 1 24464564 0.96 0.3280 Geographical Site-xChronological Age Initial 1 148044999 5.84 0.0172 Geographical Site-x-Class-x-Sex 1 32945144 1.30 0.2566 Geographical Site-x-Class-xChronological Age Initial 1 15978448 0.63 0.4289 Geographical Site-x-Class-xChronological Age Initial-x-Sex 1 42567536 1.68 0.1976 114 SSQ Table A-8. Results of ANCOVA test for geographical site difference, while controlling for patient’s age, sex and class; the dependent variable is Airway 1+2+3 Area Source df SSQ F Ratio P Value Geographical Site 1 38420.13 1.54 0.2176 Class 1 54135.32 2.16 0.1439 Sex 1 15890.57 0.64 0.4270 Chronological Age Initial 1 13.97 0.0003 Geographical Site-x-Class 1 47149.75 1.89 0.1723 Geographical Site-x-Sex 1 38732.37 1.55 0.2158 Geographical Site-xChronological Age Initial 1 68659.84 2.75 0.1002 Geographical Site-x-Class-x-Sex 1 19484.9 0.78 0.3792 Geographical Site-x-Class-xChronological Age Initial 1 15200.33 0.61 0.4372 Geographical Site-x-Class-xChronological Age Initial-x-Sex 1 43733.57 1.75 0.1886 115 349436.8 Table A-9. Results of ANCOVA test for geographical site difference, while controlling for patient’s age, sex and class; the dependent variable is Airway 3 Volume (Inferior) Source df SSQ F Ratio P Value Geographical Site 1 4456401 1.03 0.3125 Class 1 2625919 0.61 0.4378 Sex 1 7614257 1.76 0.1874 Chronological Age Initial 1 56179823 12.97 0.0005 Geographical Site-x-Class 1 720350 0.17 0.6842 Geographical Site-x-Sex 1 176293 0.04 0.8405 Geographical Site-xChronological Age Initial 1 11073215 2.56 0.1125 Geographical Site-x-Class-x-Sex 1 571795 0.13 0.7170 Geographical Site-xClass-x-Chronological Age Initial 1 151537 0.04 0.8520 Geographical Site-x-Class-xChronological Age Initial-x-Sex 1 2077666 0.48 0.4900 116 Table A-10. Results of ANCOVA test for geographical site difference, while controlling for patient’s age, sex and class; the dependent variable is Airway 3 Area (Inferior) Source df SSQ F Ratio P Value Geographical Site 1 9294.102 1.39 0.2410 Class 1 3821.63 0.57 0.4514 Sex 1 23571.007 3.52 0.0630 Chronological Age Initial 1 39719.604 5.93 0.0163 Geographical Site-x-Class 1 30753.602 4.59 0.0341 Geographical Site-x-Sex 1 657.39 0.10 0.7545 Geographical Site-xChronological Age Initial 1 6115.839 0.91 0.3411 Geographical Site-x-Class-x-Sex 1 5766.377 0.86 0.3552 Geographical Site-x-Class-xChronological Age Initial 1 80.013 0.01 0.9131 Geographical Site-x-Class-xChronological Age Initial-x-Sex 1 3275.154 0.49 0.4856 117 Table A-11. Results of ANCOVA test for geographical site difference, while controlling for patient’s age, sex and class; the dependent variable is Total Airway Source df SSQ F Ratio P Value Geographical Site 1 26740339 1.05 0.3065 Class 1 23716420 0.94 0.3355 Sex 1 2646800 0.10 0.7472 Chronological Age Initial 1 465903647 18.37 <0.0001 Geographical Site-x-Class 1 3196561 0.13 0.7232 Geographical Site-x-Sex 1 24464564 0.96 0.3280 Geographical Site-xChronological Age Initial 1 148044999 5.84 0.0172 Geographical Site-x-Class-x-Sex 1 32945144 1.30 0.2566 Geographical Site-x-Class-xChronological Age Initial 1 15978448 0.63 0.4289 Geographical Site-x-Class-xChronological Age Initial-x-Sex 1 42567536 1.68 0.1976 118 Table A-12. Results of ANCOVA test for geographical site difference, while controlling for patient’s age, sex and class; the dependent variable is Minimum Constriction Source df SSQ F Ratio P Value Geographical Site 1 4834.495 0.74 0.3916 Class 1 2189.200 0.33 0.5639 Sex 1 627.303 0.10 0.7573 Chronological Age Initial 1 20704.299 3.17 0.0777 Geographical Site-x-Class 1 5900.122 0.90 0.3441 Geographical Site-x-Sex 1 1695.615 0.26 0.6115 Geographical Site-xChronological Age Initial 1 13095.106 2.00 0.1596 Geographical Site-x-Class-x-Sex 1 4234.174 0.65 0.4226 Geographical Site-xClass-x-Chronological Age Initial 1 298.402 0.05 0.8312 Geographical Site-x-Class-xChronological Age Initial-x-Sex 1 5106.071 0.78 0.3787 119 Table A-13. Results of ANCOVA test for geographical site difference, while controlling for patient’s age, sex and class; the dependent variable is PFH/AFH % Source df SSQ F Ratio P Value Geographical Site 1 0.01550063 6.20 0.0142 Class 1 0.00081710 0.33 0.5687 Sex 1 0.00034223 0.14 0.7122 Chronological Age Initial 1 0.00438553 1.75 0.1880 Geographical Site-x-Class 1 0.00592204 2.37 0.1266 Geographical Site-x-Sex 1 0.00012734 0.05 0.8219 Geographical Site-xChronological Age Initial 1 0.00449156 1.80 0.1828 Geographical Site-x-Class-x-Sex 1 0.00122842 0.49 0.4848 Geographical Site-x-Class-xChronological Age Initial 1 0.00007517 0.03 0.8627 Geographical Site-x-Class-xChronological Age Initial-x-Sex 1 0.00505426 2.02 0.1578 120 Table A-14. Results of ANCOVA test for geographical site difference, while controlling for patient’s age, sex and class; the dependent variable is Y-Axis Source df SSQ F Ratio P Value Geographical Site 1 0.000352 0.00 0.9951 Class 1 0.033717 0.00 0.9525 Sex 1 19.074137 2.02 0.1580 Chronological Age Initial 1 8.614583 0.91 0.3416 Geographical Site-x-Class 1 35.837276 3.79 0.0538 Geographical Site-x-Sex 1 0.971568 0.10 0.7490 Geographical Site-xChronological Age Initial 1 23.52121 2.49 0.1173 Geographical Site-x-Class-x-Sex 1 71.993714 7.62 0.0067 Geographical Site-x-Class-xChronological Age Initial 1 7.231705 0.77 0.3834 Geographical Site-x-Class-xChronological Age Initial-x-Sex 1 25.651882 2.71 0.1020 121 Table A-15. Results of ANCOVA test for geographical site difference, while controlling for patient’s age, sex and class; the dependent variable is Facial Convexity Source df SSQ F Ratio P Value Geographical Site 1 3.0705 0.21 0.6466 Class 1 2495.8537 171.69 <0.0001 Sex 1 0.1042 0.01 0.9327 Chronological Age Initial 1 24.2037 1.66 0.1994 Geographical Site-x-Class 1 11.5209 0.79 0.3751 Geographical Site-x-Sex 1 0.2375 0.02 0.8985 Geographical Site-xChronological Age Initial 1 1.104 0.08 0.7833 Geographical Site-x-Class-x-Sex 1 0.1018 0.01 0.9335 Geographical Site-x-Class-xChronological Age Initial 1 0.4701 0.03 0.8576 Geographical Site-x-Class-xChronological Age Initial-x-Sex 1 1.66 0.2005 122 24.088 Table A-16. Results of ANCOVA test for geographical site difference, while controlling for patient’s age, sex and class; the dependent variable is SNA Source df SSQ F Ratio P Value Geographical Site 1 17.40294 1.55 0.2159 Class 1 104.32574 9.28 0.0028 Sex 1 0.00062 0.00 0.9941 Chronological Age Initial 1 35.66934 3.17 0.0774 Geographical Site-x-Class 1 18.56333 1.65 0.2013 Geographical Site-x-Sex 1 0.2334 0.02 0.8857 Geographical Site-xChronological Age Initial 1 20.63072 1.84 0.1781 Geographical Site-x-Class-x-Sex 1 6.95004 0.62 0.4333 Geographical Site-x-Class-xChronological Age Initial 1 11.95348 1.06 0.3046 Geographical Site-x-Class-xChronological Age Initial-x-Sex 1 0.28167 0.03 0.8745 123 Table A-17. Results of ANCOVA test for geographical site difference, while controlling for patient’s age, sex and class; the dependent variable is SNB Source df SSQ Geographical Site 1 20.81163 2.20 0.1407 Class 1 145.73328 15.40 0.0001 Sex 1 0.00157 0.00 0.9898 Chronological Age Initial 1 52.5042 5.55 0.0201 Geographical Site-x-Class 1 19.80158 2.09 0.1506 Geographical Site-x-Sex 1 1.8482 0.20 0.6593 Geographical Site-xChronological Age Initial 1 23.55167 2.49 0.1173 Geographical Site-x-Class-x-Sex 1 7.52618 0.80 0.3742 Geographical Site-x-Class-xChronological Age Initial 1 13.55011 1.43 0.2338 Geographical Site-x-Class-xChronological Age Initial-x-Sex 1 4.5927 0.49 0.4873 124 F Ratio P Value Table A-18. Results of ANCOVA test for geographical site difference, while controlling for patient’s age, sex and class; the dependent variable is ANB Source df SSQ F Ratio P Value Geographical Site 1 0.2609 0.12 0.7287 Class 1 497.52721 230.50 <0.0001 Sex 1 0.00098 0.00 0.9830 Chronological Age Initial 1 1.68894 0.78 0.3782 Geographical Site-x-Class 1 0.0336 0.02 0.9009 Geographical Site-x-Sex 1 0.69583 0.32 0.5712 Geographical Site-xChronological Age Initial 1 0.13348 0.06 0.8040 Geographical Site-x-Class-x-Sex 1 0.00675 0.00 0.9555 Geographical Site-x-Class-xChronological Age Initial 1 0.02457 0.01 0.9152 Geographical Site-x-Class-xChronological Age Initial-x-Sex 1 2.7247 1.26 0.2635 125 Table A-19. Results of ANCOVA test for geographical site difference, while controlling for patient’s age, sex and class; the dependent variable is Wits Source df SSQ F Ratio P Value Geographical Site 1 8.66728 1.43 0.2335 Class 1 727.50065 120.37 <0.0001 Sex 1 3.11177 0.51 0.4744 Chronological Age Initial 1 8.76920 1.45 0.2308 Geographical Site-x-Class 1 11.56402 1.91 0.1692 Geographical Site-x-Sex 1 0.30888 0.05 0.8215 Geographical Site-xChronological Age Initial 1 0.14569 0.02 0.8769 Geographical Site-x-Class-x-Sex 1 0.66225 0.11 0.7412 Geographical Site-x-Class-xChronological Age Initial 1 9.46431 1.57 0.2132 Geographical Site-x-Class-xChronological Age Initial-x-Sex 1 1.16106 0.19 0.6620 126 Table A-20. Results of ANCOVA test for geographical site difference, while controlling for patient’s age, sex and class; the dependent variable is FMA Source df SSQ Geographical Site 1 100.40455 3.83 0.0527 Class 1 18.70501 0.71 0.4001 Sex 1 9.97563 0.38 0.5386 Chronological Age Initial 1 50.66647 1.93 0.1671 Geographical Site-x-Class 1 54.92266 2.09 0.1505 Geographical Site-x-Sex 1 0.00092 0.00 0.9953 Geographical Site-xChronological Age Initial 1 28.18389 1.07 0.3020 Geographical Site-x-Class-x-Sex 1 28.319 1.08 0.3008 Geographical Site-x-Class-xChronological Age Initial 1 112.99182 4.31 0.0401 Geographical Site-x-Class-xChronological Age Initial-x-Sex 1 13.09782 0.50 0.4811 127 F Ratio P Value Table A-21. Results of ANCOVA test for geographical site difference, while controlling for patient’s age, sex and class; the dependent variable is IMPA Source df SSQ F Ratio P Value Geographical Site 1 454.8385 8.88 0.0035 Class 1 1085.4772 21.19 <0.0001 Sex 1 7.8076 0.15 0.6969 Chronological Age Initial 1 9.0952 0.18 0.6742 Geographical Site-x-Class 1 10.9927 0.21 0.6440 Geographical Site-x-Sex 1 24.7854 0.48 0.4880 Geographical Site-xChronological Age Initial 1 8.311 0.16 0.6878 Geographical Site-x-Class-x-Sex 1 5.8934 0.12 0.7350 Geographical Site-x-Class-xChronological Age Initial 1 62.9062 1.23 0.2700 Geographical Site-x-Class-xChronological Age Initial-x-Sex 1 0.0049 0.00 0.9922 128 Table A-22. Results of ANCOVA test for geographical site difference, while controlling for patient’s age, sex and class; the dependent variable is FMIA Source df SSQ F Ratio P Value Geographical Site 1 103.6907 2.30 0.1323 Class 1 763.80475 16.91 <0.0001 Sex 1 0.08545 0.00 0.9654 Chronological Age Initial 1 17.30632 0.38 0.5371 Geographical Site-x-Class 1 24.33953 0.54 0.4643 Geographical Site-x-Sex 1 35.81901 0.79 0.3749 Geographical Site-xChronological Age Initial 1 8.266 0.18 0.6696 Geographical Site-x-Class-x-Sex 1 3.64892 0.08 0.7767 Geographical Site-x-Class-xChronological Age Initial 1 9.72725 0.22 0.6434 Geographical Site-x-Class-xChronological Age Initial-x-Sex 1 15.74274 0.35 0.5560 129 Table A-23. Results of ANCOVA test for geographical site difference, while controlling for patient’s age, sex and class; the dependent variable is Interincisal angle Source df SSQ Geographical Site 1 672.17291 5.92 0.0164 Class 1 549.61256 4.84 0.0297 Sex 1 106.92944 0.94 0.3337 Chronological Age Initial 1 41.35659 0.36 0.5473 Geographical Site-x-Class 1 117.60457 1.04 0.3108 Geographical Site-x-Sex 1 61.53509 0.54 0.4630 Geographical Site-xChronological Age Initial 1 246.40615 2.17 0.1433 Geographical Site-x-Class-x-Sex 1 136.91952 1.21 0.2743 Geographical Site-x-Class-xChronological Age Initial 1 274.41772 2.42 0.1226 Geographical Site-x-Class-xChronological Age Initial-x-Sex 1 2.43683 0.02 0.8838 130 F Ratio P Value Table A-24. Results of ANCOVA test for geographical site difference, while controlling for patient’s age, sex and class; the dependent variable is U1-SN Source df SSQ Geographical Site 1 281.60626 5.70 0.0185 Class 1 98.63634 2.00 0.1602 Sex 1 67.19498 1.36 0.2458 Chronological Age Initial 1 154.38768 3.13 0.0796 Geographical Site-x-Class 1 51.31986 1.04 0.3101 Geographical Site-x-Sex 1 4.18302 0.08 0.7715 Geographical Site-xChronological Age Initial 1 269.44896 5.46 0.0212 Geographical Site-x-Class-x-Sex 1 102.13432 2.07 0.1530 Geographical Site-x-Class-xChronological Age Initial 1 184.21223 3.73 0.0558 Geographical Site-x-Class-xChronological Age Initial-x-Sex 1 21.72639 0.44 0.5085 131 F Ratio P Value Table A-25. Results of ANCOVA test for geographical site difference, while controlling for patient’s age, sex and class; the dependent variable is L1-NB (°) Source df SSQ Geographical Site 1 188.99004 4.66 0.0329 Class 1 452.69149 11.16 0.0011 Sex 1 4.82074 0.12 0.7309 Chronological Age Initial 1 1.42955 0.04 0.8514 Geographical Site-x-Class 1 0.62082 0.02 0.9018 Geographical Site-x-Sex 1 51.39847 1.27 0.2626 Geographical Site-xChronological Age Initial 1 17.20489 0.42 0.5162 Geographical Site-x-Class-x-Sex 1 19.12483 0.47 0.4937 Geographical Site-x-Class-xChronological Age Initial 1 42.46696 1.05 0.3084 Geographical Site-x-Class-xChronological Age Initial-x-Sex 1 0.91613 0.02 0.8808 132 F Ratio P Value Table A-26. Results of ANCOVA test for geographical site difference, while controlling for patient’s age, sex and class; the dependent variable is L1-NB (mm) Source df SSQ Geographical Site 1 7.242021 1.57 0.2129 Class 1 46.557004 10.08 0.0019 Sex 1 0.108877 0.02 0.8782 Chronological Age Initial 1 6.526632 1.41 0.2368 Geographical Site-x-Class 1 0.634524 0.14 0.7115 Geographical Site-x-Sex 1 2.254076 0.49 0.4861 Geographical Site-xChronological Age Initial 1 1.321171 0.29 0.5937 Geographical Site-x-Class-x-Sex 1 1.102936 0.24 0.6259 Geographical Site-x-Class-xChronological Age Initial 1 8.366822 1.81 0.1808 Geographical Site-x-Class-xChronological Age Initial-x-Sex 1 0.03 0.8532 133 0.158867 F Ratio P Value Table A-27. Results of ANCOVA test for geographical site difference, while controlling for patient’s age, sex and class; the dependent variable is U1-NA (°) Source df SSQ F Ratio P Value Geographical Site 1 156.60116 3.43 0.0664 Class 1 408.33172 8.95 0.0034 Sex 1 67.66073 1.48 0.2257 Chronological Age Initial 1 42.14946 0.92 0.3384 Geographical Site-x-Class 1 131.13553 2.87 0.0926 Geographical Site-x-Sex 1 2.20659 0.05 0.8263 Geographical Site-xChronological Age Initial 1 141.71777 3.11 0.0806 Geographical Site-x-Class-x-Sex 1 55.76866 1.22 0.2712 Geographical Site-x-Class-xChronological Age Initial 1 102.23842 2.24 0.1371 Geographical Site-x-Class-xChronological Age Initial-x-Sex 1 16.71522 0.37 0.5462 134 Table A-28. Results of ANCOVA test for geographical site difference, while controlling for patient’s age, sex and class; the dependent variable is U1-NA (mm) Source df SSQ F Ratio P Value Geographical Site 1 6.943109 1.66 0.2002 Class 1 49.087982 11.73 0.0008 Sex 1 7.768519 1.86 0.1756 Chronological Age Initial 1 26.196836 6.26 0.0137 Geographical Site-x-Class 1 5.528922 1.32 0.2526 Geographical Site-x-Sex 1 2.47794 0.59 0.4431 Geographical Site-xChronological Age Initial 1 10.775285 2.58 0.1112 Geographical Site-x-Class-x-Sex 1 3.101711 0.74 0.3910 Geographical Site-x-Class-xChronological Age Initial 1 4.26 0.0412 Geographical Site-x-Class-xChronological Age Initial-x-Sex 1 0.27 0.6070 135 17.81626 1.112974 Table A-29. Results of ANCOVA test for geographical site difference, while controlling for patient’s age, sex and class; the dependent variable is Overbite Source df SSQ F Ratio P Value Geographical Site 1 0.034934 0.01 0.9233 Class 1 70.378269 18.73 <0.0001 Sex 1 0.689915 0.18 0.6691 Chronological Age Initial 1 0.012253 0.00 0.9546 Geographical Site-x-Class 1 1.425955 0.38 0.5390 Geographical Site-x-Sex 1 0.000166 0.00 0.9947 Geographical Site-xChronological Age Initial 1 0.379638 0.10 0.7511 Geographical Site-x-Class-x-Sex 1 1.574112 0.42 0.5187 Geographical Site-x-Class-xChronological Age Initial 1 11.871508 3.16 0.0780 Geographical Site-x-Class-xChronological Age Initial-x-Sex 1 1.134376 0.30 0.5837 136 Table A-30. Results of ANCOVA test for geographical site difference, while controlling for patient’s age, sex and class; the dependent variable is Overjet Source df SSQ F Ratio P Value Geographical Site 1 0.48651 0.18 0.6757 Class 1 209.13751 75.62 <0.0001 Sex 1 0.61641 0.22 0.6377 Chronological Age Initial 1 2.78188 1.01 0.3179 Geographical Site-x-Class 1 3.48576 1.26 0.2638 Geographical Site-x-Sex 1 2.21336 0.80 0.3728 Geographical Site-xChronological Age Initial 1 2.83959 1.03 0.3130 Geographical Site-x-Class-x-Sex 1 0.45934 0.17 0.6843 Geographical Site-x-Class-xChronological Age Initial 1 1.54789 0.56 0.4559 Geographical Site-x-Class-xChronological Age Initial-x-Sex 1 0.84448 0.31 0.5816 137 Table A-31. Results of ANCOVA test for geographical site difference, while controlling for patient’s age, sex and class; the dependent variable is Superior Airway Space Source df SSQ F Ratio P Value Geographical Site 1 77.057896 11.76 0.0008 Class 1 0.659427 0.10 0.7516 Sex 1 29.963885 4.57 0.0345 Chronological Age Initial 1 8.870189 1.35 0.2469 Geographical Site-x-Class 1 14.319419 2.19 0.1419 Geographical Site-x-Sex 1 0.831728 0.13 0.7222 Geographical Site-xChronological Age Initial 1 11.661559 1.78 0.1847 Geographical Site-x-Class-x-Sex 1 0.049802 0.01 0.9307 Geographical Site-x-Class-xChronological Age Initial 1 1.281198 0.20 0.6591 Geographical Site-x-Class-xChronological Age Initial-x-Sex 1 21.724871 3.32 0.0711 138 Table A-32. Results of ANCOVA test for geographical site difference, while controlling for patient’s age, sex and class; the dependent variable is Condylion-A Source df SSQ F Ratio P Value Geographical Site 1 482.44406 30.73 <0.0001 Class 1 24.59568 1.57 0.2131 Sex 1 201.17201 12.81 0.0005 Chronological Age Initial 1 408.52103 26.02 <0.0001 Geographical Site-x-Class 1 88.05216 5.61 0.0195 Geographical Site-x-Sex 1 8.69834 0.55 0.4581 Geographical Site-xChronological Age Initial 1 1.05997 0.07 0.7954 Geographical Site-x-Class-x-Sex 1 111.06007 7.07 0.0089 Geographical Site-x-Class-xChronological Age Initial 1 11.14317 0.71 0.4012 Geographical Site-x-Class-xChronological Age Initial-x-Sex 1 2.12465 0.14 0.7136 139 Table A-33. Results of ANCOVA test for geographical site difference, while controlling for patient’s age, sex and class; the dependent variable is CondylionGnathion Source df SSQ F Ratio P Value Geographical Site 1 247.2293 7.98 0.0055 Class 1 968.7018 31.26 <0.0001 Sex 1 271.0429 8.75 0.0037 Chronological Age Initial 1 1332.4733 42.99 <0.0001 Geographical Site-x-Class 1 25.3193 0.82 0.3679 Geographical Site-x-Sex 1 22.4023 0.72 0.3969 Geographical Site-xChronological Age Initial 1 33.3219 1.08 0.3019 Geographical Site-x-Class-x-Sex 1 163.3256 5.27 0.0234 Geographical Site-x-Class-xChronological Age Initial 1 49.2086 1.59 0.2101 Geographical Site-x-Class-xChronological Age Initial-x-Sex 1 7.4634 0.24 0.6245 140 Table A-34. Results of ANCOVA test for geographical site difference, while controlling for patient’s age, sex and class; the dependent variable is A-NasionPerpendicular Source df SSQ F Ratio P Value Geographical Site 1 3.62009 0.40 0.5271 Class 1 194.43423 21.61 <0.0001 Sex 1 6.11035 0.68 0.4115 Chronological Age Initial 1 17.64282 1.96 0.1640 Geographical Site-x-Class 1 17.94349 1.99 0.1605 Geographical Site-x-Sex 1 1.39432 0.16 0.6945 Geographical Site-xChronological Age Initial 1 40.54306 4.51 0.0358 Geographical Site-x-Class-x-Sex 1 46.86571 5.21 0.0242 Geographical Site-x-Class-xChronological Age Initial 1 10.06996 1.12 0.2922 Geographical Site-x-Class-xChronological Age Initial-x-Sex 1 1.13916 0.13 0.7226 141 Table A-35. Results of ANCOVA test for geographical site difference, while controlling for patient’s age, sex and class; the dependent variable is PogonionNasion-Perpendicular Source df SSQ F Ratio P Value Geographical Site 1 11.94612 0.39 0.5322 Class 1 235.13462 7.72 0.0063 Sex 1 37.64117 1.24 0.2684 Chronological Age Initial 1 109.36649 3.59 0.0604 Geographical Site-x-Class 1 93.20221 3.06 0.0827 Geographical Site-x-Sex 1 5.25976 0.17 0.6784 Geographical Site-xChronological Age Initial 1 179.23562 5.89 0.0167 Geographical Site-x-Class-x-Sex 1 155.12886 5.10 0.0258 Geographical Site-x-Class-xChronological Age Initial 1 21.51021 0.71 0.4022 Geographical Site-x-Class-xChronological Age Initial-x-Sex 1 1.11 0.2943 142 33.77933 Table A-36. Results of ANCOVA test for geographical site difference, while controlling for patient’s age, sex and class; the dependent variable is B-NasionPerpendicular Source df SSQ F Ratio P Value 0.00 0.9985 Geographical Site 1 Class 1 1131.4316 204.02 <0.0001 Sex 1 1.5061 0.27 0.6032 Chronological Age Initial 1 0.862 0.16 0.6941 Geographical Site-x-Class 1 1.5677 0.28 0.5959 Geographical Site-x-Sex 1 1.9144 0.35 0.5579 Geographical Site-xChronological Age Initial 1 0.708 0.13 0.7215 Geographical Site-x-Class-x-Sex 1 0.00060994 0.00 0.9916 Geographical Site-x-Class-xChronological Age Initial 1 0.021 0.00 0.9510 Geographical Site-x-Class-xChronological Age Initial-x-Sex 1 6.1606 1.11 0.2940 143 1.88E-05 Table A-37. Results of ANCOVA test for geographical site difference, while controlling for patient’s age, sex and class; the dependent variable is AFH Source df SSQ F Ratio P Value Geographical Site 1 45.2341 1.61 0.2070 Class 1 161.04861 5.73 0.0182 Sex 1 538.91207 19.17 <0.0001 Chronological Age Initial 1 731.47495 26.02 <0.0001 Geographical Site-x-Class 1 11.4517 0.41 0.5245 Geographical Site-x-Sex 1 5.12096 0.18 0.6703 Geographical Site-xChronological Age Initial 1 7.25229 0.26 0.6124 Geographical Site-x-Class-x-Sex 1 6.99403 0.25 0.6188 Geographical Site-x-Class-xChronological Age Initial 1 54.17536 1.93 0.1676 Geographical Site-x-Class-xChronological Age Initial-x-Sex 1 3.2697 0.12 0.7336 144 Table A-38. Results of ANCOVA test for geographical site difference, while controlling for patient’s age, sex and class; the dependent variable is Mesial Molar Relation Source df SSQ F Ratio P Value Geographical Site 1 0.51123 0.36 0.5472 Class 1 108.67676 77.48 <0.0001 Sex 1 2.17107 1.55 0.2159 Chronological Age Initial 1 0.03849 0.03 0.8687 Geographical Site-x-Class 1 0.8267 0.59 0.4442 Geographical Site-x-Sex 1 1.8224 1.30 0.2566 Geographical Site-xChronological Age Initial 1 1.77451 1.27 0.2629 Geographical Site-x-Class-x-Sex 1 1.16054 0.83 0.3649 Geographical Site-xClass-x-Chronological Age Initial 1 3.95039 2.82 0.0959 Geographical Site-x-Class-xChronological Age Initial-x-Sex 1 0.01742 0.01 0.9115 145 Table A-39. Results of ANCOVA test for geographical site difference, while controlling for patient’s age, sex and class; the dependent variable is PFH Source df SSQ Geographical Site 1 172.94974 7.81 0.0061 Class 1 123.27556 5.56 0.0200 Sex 1 306.8883 13.85 0.0003 Chronological Age Initial 1 724.89909 32.71 <0.0001 Geographical Site-x-Class 1 77.73309 3.51 0.0635 Geographical Site-x-Sex 1 2.40444 0.11 0.7424 Geographical Site-xChronological Age Initial 1 2.84 0.0943 Geographical Site-x-Class-x-Sex 1 1.60826 0.07 0.7881 Geographical Site-x-Class-xChronological Age Initial 1 0.00014 0.00 0.9980 Geographical Site-x-Class-xChronological Age Initial-x-Sex 1 0.04941 0.00 0.9624 146 63.0314 F Ratio P Value Table A-40. Results of ANCOVA test for geographical site difference, while controlling for patient’s age, sex and class; the dependent variable is GonionMenton Source df SSQ Geographical Site 1 128.31015 6.82 0.0101 Class 1 255.26621 13.57 0.0003 Sex 1 29.84732 1.59 0.2102 Chronological Age Initial 1 541.71625 28.81 <0.0001 Geographical Site-x-Class 1 27.08395 1.44 0.2325 Geographical Site-x-Sex 1 0.10754 0.01 0.9398 Geographical Site-xChronological Age Initial 1 6.16848 0.33 0.5679 Geographical Site-x-Class-x-Sex 1 35.11424 1.87 0.1743 Geographical Site-x-Class-xChronological Age Initial 1 18.23763 0.97 0.3267 Geographical Site-x-Class-xChronological Age Initial-x-Sex 1 1.39763 0.07 0.7856 147 F Ratio P Value Table A-41. Results of ANCOVA test for geographical site difference, while controlling for patient’s age, sex and class; the dependent variable is Sella-VerticalA Source df SSQ F Ratio P Value Geographical Site 1 9.19598 0.69 0.4093 Class 1 244.72081 18.25 <0.0001 Sex 1 85.98894 6.41 0.0126 Chronological Age Initial 1 264.61118 19.73 <0.0001 Geographical Site-x-Class 1 29.38346 2.19 0.1415 Geographical Site-x-Sex 1 1.1664 0.09 0.7686 Geographical Site-xChronological Age Initial 1 32.11841 2.39 0.1244 Geographical Site-x-Class-x-Sex 1 144.23164 10.75 0.0014 Geographical Site-x-Class-xChronological Age Initial 1 2.34955 0.18 0.6763 Geographical Site-x-Class-xChronological Age Initial-x-Sex 1 14.99354 1.12 0.2925 148 Table A-42. Results of ANCOVA test for geographical site difference, while controlling for patient’s age, sex and class; the dependent variable is Sella-VerticalB Source df SSQ Geographical Site 1 21.09166 0.84 0.3602 Class 1 79.36934 3.18 0.0773 Sex 1 42.51379 1.70 0.1947 Chronological Age Initial 1 363.55535 14.54 0.0002 Geographical Site-x-Class 1 91.98738 3.68 0.0575 Geographical Site-x-Sex 1 11.33788 0.45 0.5020 Geographical Site-xChronological Age Initial 1 111.42568 4.46 0.0368 Geographical Site-x-Class-x-Sex 1 260.1867 10.41 0.0016 Geographical Site-x-Class-xChronological Age Initial 1 0.00638 0.00 0.9873 Geographical Site-x-Class-xChronological Age Initial-x-Sex 1 46.77627 1.87 0.1739 149 F Ratio P Value Table A-43. Results of ANCOVA test for geographical site difference, while controlling for patient’s age, sex and class; the dependent variable is Sella-VerticalPogonion Source df SSQ F Ratio P Value Geographical Site 1 181.04294 18.22 <0.0001 Class 1 5.20629 0.52 0.4706 Sex 1 29.25536 2.94 0.0888 Chronological Age Initial 1 0.00 0.9979 Geographical Site-x-Class 1 56.44461 5.68 0.0187 Geographical Site-x-Sex 1 4.992 0.50 0.4798 Geographical Site-xChronological Age Initial 1 46.82989 4.71 0.0319 Geographical Site-x-Class-x-Sex 1 0.02295 0.00 0.9617 Geographical Site-x-Class-xChronological Age Initial 1 3.03934 0.31 0.5812 Geographical Site-x-Class-xChronological Age Initial-x-Sex 1 2.74 0.1002 150 6.84E-05 27.2656 Table A-44. Results of ANCOVA test for geographical site difference, while controlling for patient’s age, sex and class; the dependent variable is Sella-Verticalto M Source df SSQ Geographical Site 1 20.16816 0.82 0.3669 Class 1 118.73855 4.83 0.0299 Sex 1 1.5339 0.06 0.8032 Chronological Age Initial 1 397.1629 16.15 0.0001 Geographical Site-x-Class 1 76.30149 3.10 0.0807 Geographical Site-x-Sex 1 8.85587 0.36 0.5495 Geographical Site-xChronological Age Initial 1 83.13397 3.38 0.0684 Geographical Site-x-Class-x-Sex 1 242.57049 9.87 0.0021 Geographical Site-x-Class-xChronological Age Initial 1 0.01892 0.00 0.9779 Geographical Site-x-Class-xChronological Age Initial-x-Sex 1 79.54221 3.24 0.0746 151 F Ratio P Value APPENDIX B. BIVARIATE PLOTS (REGRESSION OF Y ON X) FOR THE REPEATED MEASUREMENT SESSIONS 152 Figure B-1. Bivariate plot of the repeated measurements for the variable AFH The least squares best fit regression line was Session II = 0.0175052 + 0.9971065 X Session I, where the standard error for the intercept was 5.911417 (P = 0.9977) and for the regression coefficient was 0.056321 (P = <0.0001). 153 Figure B-2. Bivariate plot of the repeated measurements for the variable Airway 1 Area (Nasopharyngeal) The least squares best fit regression line was Session II = 55.999785 + 0.7560649 X Session I, where the standard error for the intercept was19.9166 (P = 0.0092) and for the regression coefficient was 0.101841 P = <0.0001). 154 Figure B-3. Bivariate plot of the repeated measurements for the variable Airway 1 Volume (Nasopharyngeal) The least squares best fit regression line was Difference = -339.5004 + 0.0750509 x Mean Size, where the standard error for the intercept was (P = 0.2955) and for the regression coefficient was 0.063272 (P = 0.2463). 155 Figure B-4. 1+2 Area Bivariate plot of the repeated measurements for the variable Airway The least squares best fit regression line was Difference = -92.52505 + 0.1814351 x Mean Size, where the standard error for the intercept was 74.8658 (P = 0.2276) and for the regression coefficient was 0.147427 (P = 0.2295). 156 Figure B-5. Bivariate plot of the repeated measurements for the variable Airway 1+2 Volume The least squares best fit regression line was Difference = -2286.46 + 0.1799863 x Mean Size, where the standard error for the intercept was 1662.852 (P = 0.1809), and for the regression coefficient was 0.127742 (P = 0.1707). 157 Figure B-6. 1+2+3 Area Bivariate plot of the repeated measurements for the variable Airway The least squares best fit regression line was Difference = -31.75049 + 0.0351726 x Mean Size, where the standard error for the intercept was 40.61369 (P = 0.4414)) and for the regression coefficient was 0.057712 (P = 0.5475). 158 Figure B-7. Bivariate plot of the repeated measurements for the variable Airway 1+2+3 Volume The least squares best fit regression line was Difference = -823.0574 + 0.0206968 x Mean Size, where the standard error for the intercept was 1597.142 (P = 0.6108) and for the regression coefficient was 0.093749 (P = 0.8271). 159 Figure B-8. Bivariate plot of the repeated measurements for the variable Airway 2 Area (Superior) The least squares best fit regression line was Difference = 40.921229 - 0.119589 x Mean Size, where the standard error for the intercept was 51.9017 (P = 0.4379) and for the regression coefficient was 0.165096 (P = 0.4756). 160 Figure B-9. Bivariate plot of the repeated measurements for the variable Airway 2 Volume (Superior) The least squares best fit regression line was Difference = -480.0509 + 0.0558427 x Mean Size, where the standard error for the intercept was 1228.763 (P= 0.6992) and for the regression coefficient was 0.149812 (P = 0.7124). 161 Figure B-10. Bivariate plot of the repeated measurements for the variable Airway 3 Area (Inferior) The least squares best fit regression line was Difference = 35.471599 - 0.2131823 x Mean Size, where the standard error for the intercept was 42.85363 (P = 0.4154) and for the regression coefficient was 0.210705 (P = 0.3210). 162 Figure B-11. Bivariate plot of the repeated measurements for the variable Airway 3 Volume (Inferior) The least squares best fit regression line was Difference = 1620.5168 - 0.4636774 x Mean Size, where the standard error for the intercept was 42.85 (P = 0.4154) and for the regression coefficient was 0.21 (P = 0.3210). 163 Figure B-12. Bivariate plot of the repeated measurements for the variable A-Na Perpendicular The least squares best fit regression line was Difference = -0.321107 - 0.0901378 x Mean Size, where the standard error for the intercept was 0.23 (P = 0.1670) and for the regression coefficient was 0.07 (P = 0.2047). 164 Figure B-13. Bivariate plot of the repeated measurements for the variable ANB The least squares best fit regression line was Difference = -0.187157 - 0.0005804 x Mean Size, where the standard error for the intercept was 0.11 (P = 0.1058) and for the regression coefficient was 0.02 (P = 0.9815). 165 Figure B-14. Bivariate plot of the repeated measurements for the variable B-Na Perpendicular The least squares best fit regression line was Difference = 0.2985847 + 0.0047287 x Mean Size, where the standard error for the intercept was 0.16 (P = 0.0742) and for the regression coefficient was 0.02 mm (P = 0.8366). 166 Figure B-15. Bivariate plot of the repeated measurements for the variable Cd-A The least squares best fit regression line was Difference = 5.2895226 - 0.0602985 x Mean Size, where the standard error for the intercept was 4.26 mm(P = 0.2253) and for the regression coefficient was 0.05 mm (P = 0.2555). 167 Figure B-16. Bivariate plot of the repeated measurements for the variable Cd-Gn The least squares best fit regression line was Difference = 7.6075183 - 0.0649372 x Mean Size, where the standard error for the intercept was 4.84 (P = 0.1284) and for the regression coefficient was 0.04 mm (P = 0.1551). 168 Figure B-17. Bivariate plot of the repeated measurements for the variable Facial Convexity The least squares best fit regression line was Difference = -0.393292 + 0.0096249 x Mean Size, where the standard error for the intercept was 0.19 degrees(P = 0.0457) and for the regression coefficient was 0.02 degrees (P = 0.6640). 169 Figure B-18. Bivariate plot of the repeated measurements for the variable FMA The least squares best fit regression line was Difference = 1.2805746 - 0.0519032 x Mean Size, where the standard error for the intercept was 2.20 degrees (P = 0.5657) and for the regression coefficient was 0.09 degrees (P = 0.5599). 170 Figure B-19. Bivariate plot of the repeated measurements for the variable FMIA The least squares best fit regression line was Difference = -0.137551 - 0.0051406 x Mean Size, where the standard error for the intercept was 5.19 degrees (P = 0.9791) and for the regression coefficient was 0.08 degrees (P = 0.9517). 171 Figure B-20. Bivariate plot of the repeated measurements for the variable GonionMenton The least squares best fit regression line was Difference = 0.4785183 - 0.0010991 x Mean Size, where the standard error for the intercept was 5.89 mm (P = 0.9359) and for the regression coefficient was 0.10 mm (P = 0.9914). 172 Figure B-21. Bivariate plot of the repeated measurements for the variable IMPA The least squares best fit regression line was Difference = 5.5772536 - 0.0545874 x Mean Size, where the standard error for the intercept was 10.25 degrees (P = 0.5911) and for the regression coefficient was 0.11 angles (P = 0.6200). 173 Figure B-22. Bivariate plot of the repeated measurements for the variable Interincisal Angle The least squares best fit regression line was Difference = 12.837706 - 0.1030017 x Mean Size, where the standard error for the intercept was 14.86 degrees (P = 0.3957) and for the regression coefficient was 0.11 degrees (P = 0.3745). 174 Figure B-23. Bivariate plot of the repeated measurements for the variable L1-NB (°) The least squares best fit regression line was Difference = 1.8822008 - 0.0645647 x Mean Size, where the standard error for the intercept was 2.13 degrees (P = 0.3849) and for the regression coefficient was 0.08 degrees (P = 0.4451). 175 Figure B-24. Bivariate plot of the repeated measurements for the variable L1-NB (mm) The least squares best fit regression line was Difference = 0.1779251 - 0.0463873 x Mean Size, where the standard error for the intercept was 0.26 (P = 0.5056) and for the regression coefficient was 0.05 degrees (P = 0.3896). 176 Figure B-25. Bivariate plot of the repeated measurements for the variable Mesial Molar Relation The least squares best fit regression line was Difference = 0.0970505 + 0.0059846 x Mean Size, where the standard error for the intercept was 0.09 mm (P = 0.3022) and for the regression coefficient was 0.01 (P = 0.9170). 177 Figure B-26. Bivariate plot of the repeated measurements for the variable Minimum Constriction The least squares best fit regression line was Difference = 4.6784158 - 0.0262055 x Mean Size, where the standard error for the intercept was 9.97 (P = 0.6428) and for the regression coefficient was 0.05 (P = 0.6053). 178 Figure B-27. Bivariate plot of the repeated measurements for the variable Overbite The least squares best fit regression line was Difference = 0.0325709 + 0.0062688*Mean Size, where the standard error for the intercept was 0.03 (P = 0.9070) and for the regression coefficient was 0.07 (P = 0.9276). 179 Figure B-28. Bivariate plot of the repeated measurements for the variable Overjet The least squares best fit regression line was Difference = -0.186635 + 0.012275*Mean Size, where the standard error for the intercept was 0.13 mm (P = 0.1786) and for the regression coefficient was 0.03 mm (P = 0.6624). 180 Figure B-29. Bivariate plot of the repeated measurements for the variable PFH The least squares best fit regression line was Difference = 1.0533452 - 0.0174455*Mean Size, where the standard error for the intercept was 8.82 mm (P = 0.9058) and for the regression coefficient was 0.13 mm (P = 0.8919). 181 Figure B-30. Bivariate plot of the repeated measurements for the variable Pogonion-Nasion-Perpendicular The least squares best fit regression line was Difference = -0.546758 - 0.0287606*Mean Size, where the standard error for the intercept was 0.56 mm (P = 0.3358) and for the regression coefficient was 0.07 mm (P = 0.6965). 182 Figure B-31. Bivariate plot of the repeated measurements for the variable SellaVertical-A The least squares best fit regression line was Difference = 7.5378513 - 0.1032488 x Mean Size, where the standard error for the intercept was 9.11 (P = 0.4157) and for the regression coefficient was 0.14 (P =0.4742). 183 Figure B-32. Bivariate plot of the repeated measurements for the variable SellaVertical-B The least squares best fit regression line was Difference = 8.1391134 - 0.1226247 x Mean Size, where the standard error for the intercept was 7.40 (P = 0.2815) and for the regression coefficient was 0.13 (P = 0.3408). 184 Figure B-33. Bivariate plot of the repeated measurements for the variable SellaVertical-M The least squares best fit regression line was Session II = 2.8404744 + 0.920511 x Session I, where the standard error for the intercept was(P = 0.6628) but for the regression coefficient was statistically significant (t = 6.58; P < 0.0001). 185 Figure B-34. Bivariate plot of the repeated measurements for the variable SellaVertical-Pogonion The least squares best fit regression line was Difference = 11.74378 - 0.5059035 x Mean Size, where the standard error for the intercept was 2.86 (P = 0.0003) and for the regression coefficient was 0.12 (P = 0.0002). 186 Figure B-35. Bivariate plot of the repeated measurements for the variable SNA The least squares best fit regression line was Difference = 3.2733613 - 0.0455283 x Mean Size, where the standard error for the intercept was 4.67 (P = 0.4898) and for the regression coefficient was 0.06 degrees (P = 0.4355). 187 Figure B-36. Bivariate plot of the repeated measurements for the variable SNB The least squares best fit regression line was Difference = -0.56618 + 0.0039832 x Mean Size, where the standard error for the intercept was 5.18 (P = 0.9138) and for the regression coefficient was 0.07 degrees (P = 0.9528). 188 Figure B-37. Bivariate plot of the repeated measurements for the variable Superior Airway Space The least squares best fit regression line was Difference = 0.0050784 + 0.0147391 x Mean Size, where the standard error for the intercept was 0.28 (P = 0.9858) and for the regression coefficient was 0.03 (P = 0.6519). 189 Figure B-38. Bivariate plot of the repeated measurements for the variable Total Airway The least squares best fit regression line was Difference = -1386.849 + 0.0593639 x Mean Size, where the standard error for the intercept was 1,495 (P = 0.3623) and for the regression coefficient was 0.09 (P = 0.4936). 190 Figure B-39. Bivariate plot of the repeated measurements for the variable U1-NA (°) The least squares best fit regression line was Difference = 1.4053703 - 0.0429818 x Mean Size, where the standard error for the intercept was 1.86 degrees (P = 0.4576) and for the regression coefficient was 0.08 degrees (P = 0.6093). 191 Figure B-40. Bivariate plot of the repeated measurements for the variable U1-NA (mm) The least squares best fit regression line was Difference = -0.269704 + 0.069731 x Mean Size, where the standard error for the intercept was 0.42 (P = 0.5309) and for the regression coefficient was 0.10 (P = 0.4718). 192 Figure B-41. Bivariate plot of the repeated measurements for the variable U1-SN The least squares best fit regression line was Session II = 1.827395 + 0.9817392 x Session I, where the standard error for the intercept was 9.20 (P = 0.3179) and for the regression coefficient was 0.09 (P = 0.3191). 193 Figure B-42. Bivariate plot of the repeated measurements for the variable Wits Appraisal The least squares best fit regression line was Session II = 0.0648214 + 1.0536364 x Session I, where the standard error for the intercept was 0.09 (P = 0.5183) and for the regression coefficient was 0.02 mm (P = 0.0223). 194 Figure B-43. Bivariate plot of the repeated measurements for the variable Y-Axis The least squares best fit regression line was Session II = 2.8054939 + 0.9578691 x Session I, where the standard error for the intercept was 8.05 (P =0.1135) and for the regression coefficient was 0.14 degrees (P = 0.1050). 195 VITA Kyle David Fagala was born in 1984 in Jonesboro, Arkansas. Kyle attended school in Paragould, Arkansas and graduated from Crowley’s Ridge Academy in 2002. He attended Harding University in Searcy, Arkansas and then the University of Tennessee College of Dentistry in Memphis, Teneessee, graduating with a Doctor of Dental Surgery degree in May 2010. He is currently completing a residency in orthodontics at the University of Tennessee Health Science Center and plans to graduate with a Master of Dental Science degree in May 2013. He plans to open a private orthodontic practice in Germantown, Tennessee in July 2013. Kyle, his wife Anna, and their son Charlie live in East Memphis. 196