Siddharth Vora

Background: Facial asymmetries have been reported with a prevalence range of 6% - 34% of the population. Unfortunately, there is no gold standard method for assessing facial asymmetry. Computational tools which utilize 3D-data to objectively quantify facial asymmetry, are needed. Purpose: Evaluate the reliability of examiners to assess facial asymmetry in set of 3D images of normal orthodontic population. Use an image-based computational tool - Dense Correspondence Analysis (DeCA), to objectively score facial asymmetry, and study its distribution in the different region of the face. Research Design: Facial surfaces were captured from CBCT records of 178 Orthodontic patients and 21 soft tissue landmarks were annotated. 12 subjects were selected which represented a range of facial asymmetry. 30 examiners belonging to 3 groups (laypersons, dental students, and orthodontists) were asked to rank the 12 subjects from most symmetric to asymmetric twice to calculate intra-rater and inter-rater reliability. The DeCA tool was used to calculate asymmetry scores in the overall facial surface and regional areas of the nose, upper lip, zygomatic region, and mandible. Descriptive statistics were performed to analyze distribution patterns of asymmetry.Results: Intra-examiner reliability was strong and Inter-examiner reliability was moderate for laypersons (0.36) and DMD students (0.44), but strong for the Orthodontist group (0.78). Quantification of asymmetry using DeCA indicated strong asymmetry in the zygomatic and mandibular regions, which were strongly correlated to each other (0.79), and to the overall facial asymmetry scores (r=0.92 and 0.93 respectively). No covariance between asymmetry scores and patients’ age or Angle’s Classification of malocclusion were noted. However, increased facial asymmetry was found in males compared to female subjects in the overall, zygomatic, and facial regions. There was weak-moderate concordance between the DeCA scores and averaged scores of the Orthodontist Group.Conclusion: Individual examiners are consistent at assessing facial asymmetry. There is poor agreement between examiners (except for the Orthodontist group) indicating a high degree of subjectivity in the assessment of this facial feature. The computational tool used here (DeCA) provides robust visualization of facial asymmetry in both the local and global regions of the face and allows for objective quantification.

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Objective: Colony stimulating factor 1 receptor (CSF1R) binds its ligand CSF1 and regulates the formation of osteoclasts. Mice nullizgyous for CSF1 (Csf1op/op) or CSF1R (Csf1r-/-) fail to erupt teeth due to defective osteoclast formation. Dental abnormalities have also been observed postnatally in the unerupted teeth of these mouse models. However, it is not understood if these dental abnormalities are caused by direct effects of CSF1R or defects in bone remodeling. Therefore, the aim of this thesis was to identify a direct role of CSF1R in early tooth development.Methods: Immunostaining techniques were used to show CSF1R expression during early stages of odontogenesis. CSF1R was inhibited in utero during key odontogenic stages. Teeth from embryos and offspring were collected at different ages and studied for phenotypic abnormalities using histological techniques. Teeth from adult mice were analyzed using high-resolution micro-computed tomography.Results: CSF1R expression was found in ectomesenchymal tissues around normally developing incisors and molars. Osteoclasts had similar localization patterns. Prenatal CSF1R inhibition during odontogenesis led to significant dental abnormalities observed prenatally and postnatally due to altered bone remodeling. Ultimately, continuous tooth growth of mouse incisors postnatally was not impacted.Conclusion: These results indicate that CSF1R regulates tooth morphology during the bell stage, likely by remodeling the bony crypts at the tooth-bone interface.

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BACKGROUND: Growth characteristics of the human craniofacial region during the fetal stages of development remain largely unexplored. This project investigates the growth of the human tongue, mandible and hyoid cartilage, during the early fetal stage, using a rare collection of preserved fetal head tissues. These structures differ in the tissue types that they are comprised of, however, they share common developmental origins. We hypothesized that the growth of these tissues exhibits a strong positive correlation during prenatal human life.MATERIALS AND METHODS: Human fetal heads were obtained from elective terminations between nine and nineteen postconceptional weeks (n=16). They were contrast-enhanced with phosphotungstic acid (PTA) and imaged with high-resolution micro-CT. Segmentation of the tongue, mandible, and hyoid cartilage was performed, three-dimensional models were constructed, and their volumes were calculated. To assess the relationship between the variables, correlations between different tissues were determined. Additionally, regression analyses were performed after normalization of data to permit comparisons between the different tissues. A single-rater interclass correlation coefficient was performed for 5 randomly selected samples, to study the measurement reliability.iiiRESULTS: PTA contrast enhancement provides excellent visualization and allows for accurate digital segmentation of hard and soft tissues of the craniofacial regions in the fetal head samples. Pearson’s correlation coefficients of 0.96, 0.85, and 0.91 were calculated between the growth of the tongue – hyoid, tongue – mandible, and mandible-hyoid, respectively. The mandibular bone showed a similar growth trajectory as the tongue and the hyoid cartilage. However, the growth of the tongue was found to precede the mandibular growth, albeit slightly, at day 109.6 pc. Interclass correlation coefficient for all repeated measurements were > 0.9 with a P .001.CONCLUSION: Contrast-enhancement followed by high-resolution 3D scanning provides an important resource to study hard-soft tissue correlations within the fetal craniofacial region during development. Our data indicate a strong positive correlation between the tongue, mandible, and hyoid cartilage, during the early fetal stage of human growth. These structures seem to begin a growth spurt between the end of the 13th to the 15th postconceptional weeks.

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Background: Prior to operative correction of a cleft lip, presurgical orthopaedics (PSO) with facial taping is used to improve pre-maxillary and soft tissue alignment. Two commercially available taping systems, Dynacleft and 3MTM taping are used at the British Columbia Children’s Hospital for this purpose. The aim of this study was to evaluate 3MTM and Dynacleft tape, for their ability to impact nasolabial shape during the treatment of the cleft lip deformity. Methods: A retrospective cohort study of 93 cleft lip +/- palate patients (69 unilateral, 24 bilateral) that had received either Dynacleft or 3MTM facial taping was conducted. 3D stereophotogrammetry images were obtained at three time-points: prior to treatment, after receiving taping but prior to surgery and after surgical repair. 3D photos were annotated with landmarks on the nasolabial region using 3DMD Vultus software. The landmarks were then used in conventional morphometric analysis with previously validated facial measurements to describe and compare the two cohorts at each stage. Geometric morphometrics using Procrustes ANOVA analysis was also conducted to compare the nasolabial shape between the two taping groups. Unilateral cleft patients were additionally compared by their presenting cleft severity using both morphometric analyses to evaluate the impact of presenting severity on cleft outcomes. Results: Both taping devices demonstrated progressive improvement in multiple facial metrics after taping and after surgery. Although variability in the degree of improvement was noted in the evaluated facial metrics after pre-surgical orthopedics between the two taping groups, no differences were found between these metrics after surgery. ANOVA comparison of the nasolabial region after Procrustes analysis also found no significant difference between the two taping cohorts after surgical cleft lip repair (p-value =0.57). Unilateral cleft patients classified as severe at presentation had residual facial shape differences after lip repair compared to milder presenting clefts (p-value=0.005)Conclusions: PSO with facial taping reduces the cleft facial deformity prior to surgical correction across multiple facial measurements. However, both 3M and Dynacleft taping devices result in similar facial alignment post-operatively suggesting either can be successfully utilized and that differences prior to surgery have limited influence on the post-operative result.

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Introduction: Growth of the facial skeleton is integrated to growth of the cranial base. This relationship is highlighted in patients with craniosynostosis syndromes in whom premature fusion of cranial base synchondroses, including the spheno-occipital synchondrosis (SOS), is associated with severe midface deficiency. Objectives: To evaluate the relationship between SOS fusion and craniofacial morphology in non-syndromic individuals – specifically midface projection and skeletal Class III phenotype. Methods: 250 pre-treatment cone-beam computed tomography images were studied from a collection of orthodontic patients’ records, aged 5-11 years (M = 99, F = 151, average age = 8.77 years). SOS fusion was scored using a 6-stage SOS fusion scale utilizing InVivoDental (v6). 3D Slicer (v4.10.2) was used to place three-dimensional landmarks. Error analysis was performed by repeat landmarking of 12 volumes (mean error = 0.23 mm). X, Y, Z coordinates for landmarks were used to determine linear and angular craniofacial measurements. Geometric morphometric (GM) analyses were used to describe facial shape variation. Results: There is a large variation in SOS fusion stage, with older children tending to have a higher fusion stage than younger children. While SOS stage is correlated with subject age, no statistically significant relationships were noted in the age of SOS stages between the Skeletal Class I, II, and III groups for males or females. There were no statistically significant findings of SOS stage as it relates to age or the linear and angular craniofacial measurements in this study, except A Point – Nasion – B point angle being decreased in SOS stage 3 compared to SOS stage 2. The GM analyses suggests that SOS stage, sex, and skeletal class do correlate with craniofacial morphology. Conclusions: This data suggests that younger children with early fusion of the SOS may display a skeletal pattern which is similar to a skeletal Class III morphology. SOS stage is more closely correlated to facial morphology differences of increased mandibular length and transverse facial width. Maxillary projection is also found to be correlated with sex and skeletal class. Further investigation is needed to assess how fusion of the SOS may affect orthodontic and orthopedic treatments for midface deficiency.

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