Quantitative bone imaging biomarkers to diagnose temporomandibular joint osteoarthritis.

Bone degradation of the condylar surface is seen in temporomandibular joint osteoarthritis (TMJ OA); however, the initial changes occur in the subchondral bone. This cross-sectional study was performed to evaluate 23 subchondral bone imaging biomarkers for TMJ OA. The sample consisted of high-resolution cone beam computed tomography scans of 84 subjects, divided into two groups: TMJ OA (45 patients with TMJ OA) and control (39 asymptomatic subjects). Six regions of each mandibular condyle scan were extracted for computation of five bone morphometric and 18 grey-level texture-based variables. The groups were compared using the Mann-Whitney U-test, and the receiver operating characteristics (ROC) curve was determined for each variable that showed a statically significance difference. The results showed statistically significant differences in the subchondral bone microstructure in the lateral and central condylar regions between the control and TMJ OA groups (P< 0.05). The area under the ROC curve (AUC) for these variables was between 0.620 and 0.710. In conclusion, 13 imaging bone biomarkers presented an acceptable diagnostic performance for the diagnosis of TMJ OA, indicating that the texture and geometry of the subchondral bone microarchitecture may be useful for quantitative grading of the disease.

Three-dimensional analysis of condylar changes in surgical correction for open bite patients with skeletal class II and class III malocclusions.

The aim of this study was to quantify three-dimensional condylar displacements as a result of two-jaw surgery for open bite correction in patients with skeletal class II and class III malocclusion. Pre-surgical (T1) and post-surgical (T2) cone beam computed tomography scans were taken for 16 patients with skeletal class II (mean age 22.3±9.47years) and 14 patients with skeletal class III (mean age 25.6±6.27years). T2 scans were registered to T1 scans at the cranial base. Translational and rotational condylar changes were calculated by x,y,z coordinates of corresponding landmarks. The directions and amounts of condylar displacement were assessed by intra- and inter-class Mann-Whitney U-test or t-test. Class II patients presented significantly greater amounts of lateral (P=0.002) and inferior (P=0.038) translation than class III patients. The magnitudes of condylar translational displacements were small for both groups. Skeletal class III patients had predominantly medial (P=0.024) and superior (P=0.047) condylar translation. Skeletal class II patients presented greater condylar counterclockwise pitch (P=0.007) than class III patients. Two-jaw surgery for the correction of open bite led to different directions and amounts of condylar rotational displacement in patients with skeletal class II compared to class III malocclusion, with greater rotational than translational displacements.

Cone beam computed tomography evaluation of midpalatal suture maturation in adults.

The aim of this study was to evaluate midpalatal suture maturation in adults, as observed in cone beam computed tomography (CBCT) images. CBCT scans from 78 subjects (64 female and 14 male, age range from 18 to 66 years) were evaluated. Midpalatal suture maturation was verified on the central cross-sectional axial slice in the superior-inferior dimension of the palate, using methods validated previously. Intra-examiner agreement was analyzed by weighted kappa test. Multinomial logistic regression was used to test whether sex and chronological age (adults <30 years or ≥30 years) could be used as a predictor for the maturational stages of the midpalatal suture. The majority of the adults presented a fused midpalatal suture in the palatine (stage D) and/or maxillary bones (stage E). However, the midpalatal suture was not fused in 12% of the subjects. Sex and chronological age were not significant predictors of the maturational stages of the midpalatal suture. The individual assessment of midpalatal suture maturation by way of CBCT images may provide reliable information critical to making the clinical decision between rapid maxillary expansion and surgically assisted rapid maxillary expansion for the treatment of maxillary atresia in adults.

Zygomaticomaxillary suture maturation: Part II-The influence of sutural maturation on the response to maxillary protraction.

OBJECTIVE: To evaluate the influence of the maturational stages of zygomaticomaxillary sutures (ZMS) on the response to maxillary protraction. SUBJECTS AND METHODS: A total of 40 Class III patients were treated retrospectively with either a combination of rapid maxillary expansion and facial mask (RME/FM) or bone-anchored maxillary protraction (BAMP). The RME/FM group consisted of 18 patients (mean age 8.3 years), while the BAMP group was comprised of 22 patients (mean age 11.8 years). The initial CBCT images (T1) of the ZMSs were classified blindly. 3D models from CBCT images at the start and at the end of orthopaedic treatment were registered on the anterior cranial base, and corresponding structures were measured on colour-coded maps and semitransparent overlays. The amounts of protraction of the maxilla, zygoma, orbitale and maxillary first molars for both groups were analysed with two-way ANOVA with Holm-Sidak post hoc test for multiple comparisons. RESULTS: A significant association was found between the early maturation stages of the ZMSs and the amount of maxillary protraction, regardless of the protraction method used. Class III patients with ZMS stages A and B showed greater maxillary protraction than patients at stage C. CONCLUSION: The maturational stages of ZMS are associated with the response maxillary protraction.

Zygomaticomaxillary suture maturation: A predictor of maxillary protraction? Part I - A classification method.

OBJECTIVE: The aim of this study was to present a method of classifying the maturational level of the zygomaticomaxillary sutures (ZMSs). METHODS: Cone-beam CT (CBCT) images from 74 subjects (5.6-58.4 years) were examined to define the radiographic stages of ZMS maturation. Five stages of maturation of the ZMS were identified and defined: Stage A-uniform high-density sutural line, with no or little interdigitation; Stage B-scalloped appearance of the high-density sutural line; Stage C-two parallel, scalloped, high-density lines, separated in some areas by small low-density spaces; Stage D-fusion in the inferior portion of the suture; and Stage E-complete fusion. Intra- and inter-examiner agreements were evaluated by weighted kappa tests. RESULTS: The intra- and inter-examiners reproducibility values demonstrated substantial to almost perfect agreement. No fusion of ZMSs was observed in patients up to 10 years of age. From 10 to 15 years, all maturational stages were identified. After 15 years of age, the majority of patients showed fusion of ZMSs. CONCLUSIONS: The classification of ZMS maturation using CBCT is a reliable method that allows the assessment of the morphology of the ZMSs in the individual patient.

Three-dimensional skeletal mandibular changes associated with Herbst appliance treatment.

OBJECTIVES: Three-dimensional evaluation of skeletal mandibular changes following Herbst appliance treatment. SETTING AND SAMPLE POPULATION: Retrospective case-control study, based on a sample size calculation. Twenty-five pubertal patients treated with Herbst appliance (HAG), and 25 matched Class II patients who received other non-orthopaedic dental treatments (CG). MATERIAL AND METHODS: Three-dimensional models were generated from pre-treatment (T0) and post-treatment (T1) cone beam computed tomograms. Volumetric registration on the cranial base was used to assess mandibular displacement; volumetric regional registration was performed to evaluate mandibular growth. Quantitative measurements of X, Y, Z and 3D Euclidian changes, and also qualitative visualization by colour-mapping and semi-transparent overlays were obtained. RESULTS: Downward displacement of the mandible was observed in both HAG and CG (2.4 mm and 1.5 mm, respectively). Significant forward displacement of the mandible was observed in the HAG (1.7 mm). HAG showed greater 3D superior and posterior condylar growth than the CG (3.5 mm and 2.0 mm, respectively). Greater posterior growth of the ramus was noted in the HAG than in CG. CONCLUSIONS: Immediately after Herbst therapy, a significant mandibular forward displacement was achieved, due to increased bone remodelling of the condyles and rami compared to a comparison group. Three-dimensional changes in the direction and magnitude of condylar growth were observed in Herbst patients.

Three-dimensional regional displacement after surgical-orthodontic correction of Class III malocclusion.

OBJECTIVES: To investigate how displacements of maxillo-mandibular structures are associated with each other at splint removal and 1 year post-surgery following 1-jaw and 2-jaw surgeries for correction of Class III malocclusion. SETTING AND SAMPLE POPULATION: Fifty patients who underwent surgical correction with maxillary advancement only (n = 25) or combined with mandibular setback (n = 25) were prospectively enrolled in this study. METHODS: Cone-beam computed tomographies were taken pre-surgery, at splint removal and at 1 year post-surgery. Three-dimensional cranial base superimpositions and shape correspondence were used to measure the outcomes from pre-surgery to splint removal (surgical changes) and splint removal to 1 year post-surgery (post-surgical adaptations). Pearson's correlation coefficients were used to evaluate the association between the regional displacements. RESULTS: Both surgery groups presented mandibular clockwise rotation with surgery and post-surgical adaptive counterclockwise rotation. In patients treated with maxillary advancement only, the surgical changes of the maxilla were significantly correlated with chin changes. The amount and direction of chin autorotation were significantly correlated with right and left ramus autorotation. Right and left condylar displacements were significantly correlated. One year post-surgery, adaptive displacements and bone remodeling of both rami were correlated with the chin and condylar changes. For the 2-jaw group, the few correlations between the positional and remodeling changes in the anatomic regions of interest observed due to the surgery were different than those observed after post-surgical adaptations, suggesting that these changes occurred independently. CONCLUSION: Our results indicate that surgical displacements and post-surgical adaptations are often correlated in one-jaw surgery and are, in general, independent in two-jaw surgery.

Fast three-dimensional superimposition of cone beam computed tomography for orthopaedics and orthognathic surgery evaluation.

The aim of this study was to validate a method for fast three-dimensional (3D) superimposition of cone beam computed tomography (CBCT) in growing patients and adults (surgical cases). The sample consisted of CBCT scans of 18 patients. For 10 patients, as the gold standard, the spatial position of the pretreatment CBCT was reoriented, saved as a reoriented volume, and then superimposed on the original image. For eight patients, four non-growing and four growing, the pre- and post-treatment scans were superimposed. Fast voxel-based superimposition was performed, with registration at the anterior cranial base. This superimposition process took 10-15s. The fit of the cranial base superimposition was verified by qualitative visualization of the semi-transparent axial, sagittal, and coronal cross-sectional slices of all corresponding anatomical structures. Virtual 3D surface models of the skull were generated via threshold segmentation, and superimposition errors in the reoriented models and the results of treatment for the treated cases were evaluated by 3D surface distances on colour-coded maps. The superimposition error of the spatial reorientation and for growing and non-growing patients was <0.5mm, which is acceptable and clinically insignificant. The voxel-based superimposition method evaluated was reproducible in different clinical conditions, rapid, and applicable for research and clinical practice.

3D superimposition and understanding temporomandibular joint arthritis.

OBJECTIVES: To investigate the 3D morphological variations in 169 temporomandibular ioint (TMJ) condyles, using novel imaging statistical modeling approaches. SETTING AND SAMPLE POPULATION: The Department of Orthodontics and Pediatric Dentistry at the University of Michigan. Cone beam CT scans were acquired from 69 subjects with long-term TMJ osteoarthritis (OA, mean age 39.1±15.7 years), 15 subjects at initial consult diagnosis of OA (mean age 44.9±14.8 years), and seven healthy controls (mean age 43±12.4 years). MATERIALS AND METHODS: 3D surface models of the condyles were constructed, and homologous correspondent points on each model were established. The statistical framework included Direction-Projection-Permutation (DiProPerm) for testing statistical significance of the differences between healthy controls and the OA groups determined by clinical and radiographic diagnoses. RESULTS: Condylar morphology in OA and healthy subjects varied widely with categorization from mild to severe bone degeneration or overgrowth. DiProPerm statistics supported a significant difference between the healthy control group and the initial diagnosis of OA group (t=6.6, empirical p-value=0.006) and between healthy and long-term diagnosis of OA group (t=7.2, empirical p-value=0). Compared with healthy controls, the average condyle in OA subjects was significantly smaller in all dimensions, except its anterior surface, even in subjects with initial diagnosis of OA. CONCLUSION: This new statistical modeling of condylar morphology allows the development of more targeted classifications of this condition than previously possible.

3D osteoarthritic changes in TMJ condylar morphology correlates with specific systemic and local biomarkers of disease.

OBJECTIVE: To assess 3D morphological variations and local and systemic biomarker profiles in subjects with a diagnosis of temporomandibular joint osteoarthritis (TMJ OA). DESIGN: Twenty-eight patients with long-term TMJ OA (39.9 ± 16 years), 12 patients at initial diagnosis of OA (47.4 ± 16.1 years), and 12 healthy controls (41.8 ± 12.2 years) were recruited. All patients were female and had cone beam CT scans taken. TMJ arthrocentesis and venipuncture were performed on 12 OA and 12 age-matched healthy controls. Serum and synovial fluid levels of 50 biomarkers of arthritic inflammation were quantified by protein microarrays. Shape Analysis MANCOVA tested statistical correlations between biomarker levels and variations in condylar morphology. RESULTS: Compared with healthy controls, the OA average condyle was significantly smaller in all dimensions except its anterior surface, with areas indicative of bone resorption along the articular surface, particularly in the lateral pole. Synovial fluid levels of ANG, GDF15, TIMP-1, CXCL16, MMP-3 and MMP-7 were significantly correlated with bone apposition of the condylar anterior surface. Serum levels of ENA-78, MMP-3, PAI-1, VE-Cadherin, VEGF, GM-CSF, TGFßb1, IFNγg, TNFαa, IL-1αa, and IL-6 were significantly correlated with flattening of the lateral pole. Expression levels of ANG were significantly correlated with the articular morphology in healthy controls. CONCLUSIONS: Bone resorption at the articular surface, particularly at the lateral pole was statistically significant at initial diagnosis of TMJ OA. Synovial fluid levels of ANG, GDF15, TIMP-1, CXCL16, MMP-3 and MMP-7 were correlated with bone apposition. Serum levels of ENA-78, MMP-3, PAI-1, VE-Cadherin, VEGF, GM-CSF, TGFß1, IFNγ, TNFα, IL-1α, and IL-6 were correlated with bone resorption.

Regional 3D superimposition to assess temporomandibular joint condylar morphology.

OBJECTIVES: To investigate the reliability of regional three-dimensional registration and superimposition methods for assessment of temporomandibular joint condylar morphology across subjects and longitudinally. METHODS: The sample consisted of cone beam CT scans of 36 patients. The across-subject comparisons included 12 controls, mean age 41.3 ± 12.0 years, and 12 patients with temporomandibular joint osteoarthritis, mean age 41.3 ± 14.7 years. The individual longitudinal assessments included 12 patients with temporomandibular joint osteoarthritis, mean age 37.8 ± 16.7 years, followed up at pre-operative jaw surgery, immediately after and one-year post-operative. Surface models of all condyles were constructed from the cone beam CT scans. Two previously calibrated observers independently performed all registration methods. A landmark-based approach was used for the registration of across-subject condylar models, and temporomandibular joint osteoarthritis vs control group differences were computed with shape analysis. A voxel-based approach was used for registration of longitudinal scans calculated x, y, z degrees of freedom for translation and rotation. Two-way random intraclass correlation coefficients tested the interobserver reliability. RESULTS: Statistically significant differences between the control group and the osteoarthritis group were consistently located on the lateral and medial poles for both observers. The interobserver differences were ≤0.2 mm. For individual longitudinal comparisons, the mean interobserver differences were ≤0.6 mm in translation errors and 1.2° in rotation errors, with excellent reliability (intraclass correlation coefficient >0.75). CONCLUSIONS: Condylar registration for across-subjects and longitudinal assessments is reliable and can be used to quantify subtle bony differences in the three-dimensional condylar morphology.

One-year assessment of surgical outcomes in Class III patients using cone beam computed tomography.

The purpose of this study was to apply a novel method to evaluate surgical outcomes at 1 year after orthognathic surgery for Class III patients undergoing two different surgical protocols. Fifty patients divided equally into two groups (maxillary advancement only and combined with mandibular setback) had cone beam computed tomography (CBCT) scans taken pre-surgery, at splint removal, and at 1-year post-surgery. An automatic cranial base superimposition method was used to register, and shape correspondence was applied to assess, the overall changes between pre-surgery and splint removal (surgical changes) and between splint removal and 1-year post-surgery at the end of orthodontic treatment (post-surgical adaptations). Post-surgical maxillary adaptations were exactly the same for both groups, with 52% of the patients having changes >2mm. Approximately half of the post-surgical changes in the maxilla for both groups were vertical. The two-jaw group showed significantly greater surgical and post-surgical changes in the ramus, chin, and most of the condylar surfaces (P<0.05). Post-surgical adaptation on the anterior part of the chin was also more significant in the two-jaw group (P<0.05). Regardless of the type of surgery, marked post-surgical adaptations were observed in the regions evaluated, which explain the adequate maxillary-mandibular relationship at 1-year post-surgery on average, with individual variability.

Transversal maxillary dento-alveolar changes in patients treated with active and passive self-ligating brackets: a randomized clinical trial using CBCT-scans and digital models.

OBJECTIVE: To assess transversal tooth movements and buccal bone modeling of maxillary lateral segments achieved with active or passive self-ligating bracket systems in a randomized clinical trial. MATERIALS AND METHODS: Sixty-four patients, with Class I, II, and mild Class III malocclusions, were randomly assigned to treatment with passive (Damon 3 MX) or active (In-Ovation R) SLBs. Impressions and cone-beam CT-scans were taken before (T0) and after treatment (T1). Displacement of maxillary canines, premolars and molars, and buccal alveolar bone modeling were blindly assessed. RESULTS: Twenty-one patients in the Damon and 20 in the In-Ovation group completed treatment according to the prescribed protocol. Eight Damon and 10 In-Ovation patients were excluded as the treatment approach had to be changed because of deviation from the recommended initial plan, while three Damon and two In-Ovation patients did not complete the treatment. Transversal expansion of the upper arch was achieved by buccal tipping in all but one patient in each group. No statistical significant difference in inter-premolar bucco-lingual inclination was found between the two groups from T0 to T1. The bone area buccal to the 2nd premolar decreased on average of 20% in the Damon and 14% in the In-Ovation group. Only few patients exhibited widening of the alveolar process. CONCLUSION: The anticipated translation and buccal bone modeling using active or passive SLBs could not be confirmed. Because of the large interindividual variation, a patient-specific analysis seems to be mandatory as individual factors like pre-treatment teeth inclination and occlusion influenced the treatment outcome of the individual patients.

Comparison of two methods for quantitative assessment of mandibular asymmetry using cone beam computed tomography image volumes.

OBJECTIVES: The aim of this study was to compare two methods of measuring mandibular asymmetry. The first method uses mirroring of the mandible in the midsagittal plane; the second uses mirroring of the mandible and registration on the cranial base. METHODS: Surface models were constructed from cone beam CT (CBCT) scans of 50 patients with asymmetry. For the first approach, a midsagittal plane was defined for each patient as the plane passing through nasion, anterior nasal spine and basion. Mirrors for both halves of the mandible were created. The second approach consisted of mirroring the image volume by flipping the left and right sides and then registering the mirrored image onto the cranial base using a mutual information maximization method. Surface distances between hemimandibles and mirrors were calculated for nine regions. RESULTS: There was no statistically significant difference between the mean surface distance measurements obtained with the two approaches and when comparing both halves in most areas. CONCLUSION: Both mirroring techniques provided similar quantification of mandibular asymmetry in this cohort.

Soft tissue response to mandibular advancement using 3D CBCT scanning.

This prospective longitudinal study assessed the 3D soft tissue changes following mandibular advancement surgery. Cranial base registration was performed for superimposition of virtual models built from cone beam computed tomography (CBCT) volumes. Displacements at the soft and hard tissue chin (n = 20), lower incisors and lower lip (n = 21) were computed for presurgery to splint removal (4-6-week surgical outcome), presurgery to 1 year postsurgery (1-year surgical outcome), and splint removal to 1 year postsurgery (postsurgical adaptation). Qualitative evaluations of color maps illustrated the surgical changes and postsurgical adaptations, but only the lower lip showed statistically significant postsurgical adaptations. Soft and hard tissue chin changes were significantly correlated for each of the intervals evaluated: presurgery to splint removal (r = 0.92), presurgery to 1 year postsurgery (r = 0.86), and splint removal to 1 year postsurgery (r = 0.77). A statistically significant correlation between lower incisor and lower lip was found only between presurgery and 1 year postsurgery (r = 0.55). At 1 year after surgery, 31% of the lower lip changes were explained by changes in the lower incisor position while 73% of the soft tissue chin changes were explained by the hard chin. This study suggests that 3D soft tissue response to mandibular advancement surgery is markedly variable.

Quantification of condylar resorption in temporomandibular joint osteoarthritis.

OBJECTIVE: This study was performed to determine the condylar morphologic variation of osteoarthritic (OA) and asymptomatic temporomandibular joints (TMJs) and to determine its correlation with pain intensity and duration. STUDY DESIGN: Three-dimensional surface models of mandibular condyles were constructed from cone-beam computerized tomography images of 29 female patients with TMJ OA (Research Diagnostic Criteria for Temporomandibular Disorders group III) and 36 female asymptomatic subjects. Shape correspondence was used to localize and quantify the condylar morphology. Statistical analysis was performed with multivariate analysis of covariance analysis, using Hotelling T(2) metric based on covariance matrices, and Pearson correlation. RESULTS: The OA condylar morphology was statistically significantly different from the asymptomatic condyles (P < .05). Three-dimensional morphologic variation of the OA condyles was significantly correlated with pain intensity and duration. CONCLUSION: Three-dimensional quantification of condylar morphology revealed profound differences between OA and asymptomatic condyles, and the extent of the resorptive changes paralleled pain severity and duration.

Superimposition of 3D cone-beam CT models of orthognathic surgery patients.

OBJECTIVES: To evaluate the registration of 3D models from cone-beam CT (CBCT) images taken before and after orthognathic surgery for the assessment of mandibular anatomy and position. METHODS: CBCT scans were taken before and after orthognathic surgery for ten patients with various malocclusions undergoing maxillary surgery only. 3D models were constructed from the CBCT images utilizing semi-automatic segmentation and manual editing. The cranial base was used to register 3D models of pre- and post-surgery scans (1 week). After registration, a novel tool allowed the visual and quantitative assessment of post-operative changes via 2D overlays of superimposed models and 3D coloured displacement maps. RESULTS: 3D changes in mandibular rami position after surgical procedures were clearly illustrated by the 3D colour-coded maps. The average displacement of all surfaces was 0.77 mm (SD=0.17 mm), at the posterior border 0.78 mm (SD=0.25 mm), and at the condyle 0.70 mm (SD=0.07 mm). These displacements were close to the image spatial resolution of 0.60 mm. The average interobserver differences were negligible. The range of the interobserver errors for the average of all mandibular rami surface distances was 0.02 mm (SD=0.01 mm). CONCLUSION: Our results suggest this method provides a valid and reproducible assessment of craniofacial structures for patients undergoing orthognathic surgery. This technique may be used to identify different patterns of ramus and condylar remodelling following orthognathic surgery.