ShapeAXI: Shape Analysis Explainability and Interpretability.

ShapeAXI represents a cutting-edge framework for shape analysis that leverages a multi-view approach, capturing 3D objects from diverse viewpoints and subsequently analyzing them via 2D Convolutional Neural Networks (CNNs). We implement an automatic N-fold cross-validation process and aggregate the results across all folds. This ensures insightful explainability heat-maps for each class across every shape, enhancing interpretability and contributing to a more nuanced understanding of the underlying phenomena. We demonstrate the versatility of ShapeAXI through two targeted classification experiments. The first experiment categorizes condyles into healthy and degenerative states. The second, more intricate experiment, engages with shapes extracted from CBCT scans of cleft patients, efficiently classifying them into four severity classes. This innovative application not only aligns with existing medical research but also opens new avenues for specialized cleft patient analysis, holding considerable promise for both scientific exploration and clinical practice. The rich insights derived from ShapeAXI's explainability images reinforce existing knowledge and provide a platform for fresh discovery in the fields of condyle assessment and cleft patient severity classification. As a versatile and interpretative tool, ShapeAXI sets a new benchmark in 3D object interpretation and classification, and its groundbreaking approach hopes to make significant contributions to research and practical applications across various domains. ShapeAXI is available in our GitHub repository https://github.com/DCBIA-OrthoLab/ShapeAXI.

A comprehensive patient-specific prediction model for temporomandibular joint osteoarthritis progression.

Temporomandibular joint osteoarthritis (TMJ OA) is a prevalent degenerative disease characterized by chronic pain and impaired jaw function. The complexity of TMJ OA has hindered the development of prognostic tools, posing a significant challenge in timely, patient-specific management. Addressing this gap, our research employs a comprehensive, multidimensional approach to advance TMJ OA prognostication. We conducted a prospective study with 106 subjects, 74 of whom were followed up after 2 to 3 y of conservative treatment. Central to our methodology is the development of an innovative, open-source predictive modeling framework, the Ensemble via Hierarchical Predictions through Nested cross-validation tool (EHPN). This framework synergistically integrates 18 feature selection, statistical, and machine learning methods to yield an accuracy of 0.87, with an area under the ROC curve of 0.72 and an F1 score of 0.82. Our study, beyond technical advancements, emphasizes the global impact of TMJ OA, recognizing its unique demographic occurrence. We highlight key factors influencing TMJ OA progression. Using SHAP analysis, we identified personalized prognostic predictors: lower values of headache, lower back pain, restless sleep, condyle high gray level-GL-run emphasis, articular fossa GL nonuniformity, and long-run low GL emphasis; and higher values of superior joint space, mouth opening, saliva Vascular-endothelium-growth-factor, Matrix-metalloproteinase-7, serum Epithelial-neutrophil-activating-peptide, and age indicate recovery likelihood. Our multidimensional and multimodal EHPN tool enhances clinicians' decision-making, offering a transformative translational infrastructure. The EHPN model stands as a significant contribution to precision medicine, offering a paradigm shift in the management of temporomandibular disorders and potentially influencing broader applications in personalized healthcare.

Automated artificial intelligence-based three-dimensional comparison of orthodontic treatment outcomes with and without piezocision surgery.

OBJECTIVE(S): This study aims to evaluate the influence of the piezocision surgery in the orthodontic biomechanics, as well as in the magnitude and direction of tooth movement in the mandibular arch using novel artificial intelligence (AI)-automated tools. MATERIALS AND METHODS: Nineteen patients, who had piezocision performed in the lower arch at the beginning of treatment with the goal of accelerating tooth movement, were compared to 19 patients who did not receive piezocision. Cone beam computed tomography (CBCT) and intraoral scans (IOS) were acquired before and after orthodontic treatment. AI-automated dental tools were used to segment and locate landmarks in dental crowns from IOS and root canals from CBCT scans to quantify 3D tooth movement. Differences in mesial-distal, buccolingual, intrusion and extrusion linear movements, as well as tooth long axis angulation and rotation were compared. RESULTS: The treatment time for the control and experimental groups were 13.2 ± 5.06 and 13 ± 5.52 months respectively (P = .176). Overall, anterior and posterior tooth movement presented similar 3D linear and angular changes in the groups. The piezocision group demonstrated greater (P = .01) mesial long axis angulation of lower right first premolar (4.4 ± 6°) compared with control group (0.02 ± 4.9°), while the mesial rotation was significantly smaller (P = .008) in the experimental group (0.5 ± 7.8°) than in the control (8.5 ± 9.8°) considering the same tooth. CONCLUSION: The open source-automated dental tools facilitated the clinicians' assessment of piezocision treatment outcomes. The piezocision surgery prior to the orthodontic treatment did not decrease the treatment time and did not influence in the orthodontic biomechanics, leading to similar tooth movements compared to conventional treatment.

Interpretable artificial intelligence for classification of alveolar bone defect in patients with cleft lip and palate.

Cleft lip and/or palate (CLP) is the most common congenital craniofacial anomaly and requires bone grafting of the alveolar cleft. This study aimed to develop a novel classification algorithm to assess the severity of alveolar bone defects in patients with CLP using three-dimensional (3D) surface models and to demonstrate through an interpretable artificial intelligence (AI)-based algorithm the decisions provided by the classifier. Cone-beam computed tomography scans of 194 patients with CLP were used to train and test the performance of an automatic classification of the severity of alveolar bone defect. The shape, height, and width of the alveolar bone defect were assessed in automatically segmented maxillary 3D surface models to determine the ground truth classification index of its severity. The novel classifier algorithm renders the 3D surface models from different viewpoints and captures 2D image snapshots fed into a 2D Convolutional Neural Network. An interpretable AI algorithm was developed that uses features from each view and aggregated via Attention Layers to explain the classification. The precision, recall and F-1 score were 0.823, 0.816, and 0.817, respectively, with agreement ranging from 97.4 to 100% on the severity index within 1 group difference. The new classifier and interpretable AI algorithm presented satisfactory accuracy to classify the severity of alveolar bone defect morphology using 3D surface models of patients with CLP and graphically displaying the features that were considered during the deep learning model's classification decision.

Semaphorin 4D Induces Vasculogenic Differentiation of Dental Pulp Stem Cells.

This work aimed to evaluate the effect of Semaphorin 4D (SEMA4D) signaling through Plexin B1 on the vasculogenic differentiation of dental pulp stem cells. We assessed the protein expression of SEMA4D and Plexin B1 in dental pulp stem cells (DPSC) from permanent human teeth and stem cells from human exfoliated deciduous (SHED) teeth using Western blots. Their expression in human dental pulp tissues and DPSC-engineered dental pulps was determined using immunofluorescence. We then exposed dental pulp stem cells to recombinant human SEMA4D (rhSEMA4D), evaluated the expression of endothelial cell differentiation markers, and assessed the vasculogenic potential of rhSEMA4D using an in vitro sprouting assay. Lastly, Plexin B1 was silenced to ascertain its role in SEMA4D-mediated vasculogenic differentiation. We found that SEMA4D and Plexin B1 are expressed in DPSC, SHED, and human dental pulp tissues. rhSEMA4D (25-100 ng/mL) induced the expression of endothelial markers, i.e., vascular endothelial growth factor receptor (VEGFR)-2, cluster of differentiation (CD)-31, and tyrosine kinase with immunoglobulin-like and EGF-like domains (Tie)-2, in dental pulp stem cells and promoted capillary-like sprouting in vitro (p < 0.05). Furthermore, Plexin B1 silencing abrogated the vasculogenic differentiation of dental pulp stem cells and significantly inhibited capillary sprouting upon exposure to rhSEMA4D. Collectively, these data provide evidence that SEMA4D induces vasculogenic differentiation of dental pulp stem cells through Plexin B1 signaling.

Automatic landmark identification in cone-beam computed tomography.

OBJECTIVE: To present and validate an open-source fully automated landmark placement (ALICBCT) tool for cone-beam computed tomography scans. MATERIALS AND METHODS: One hundred and forty-three large and medium field of view cone-beam computed tomography (CBCT) were used to train and test a novel approach, called ALICBCT that reformulates landmark detection as a classification problem through a virtual agent placed inside volumetric images. The landmark agents were trained to navigate in a multi-scale volumetric space to reach the estimated landmark position. The agent movements decision relies on a combination of DenseNet feature network and fully connected layers. For each CBCT, 32 ground truth landmark positions were identified by 2 clinician experts. After validation of the 32 landmarks, new models were trained to identify a total of 119 landmarks that are commonly used in clinical studies for the quantification of changes in bone morphology and tooth position. RESULTS: Our method achieved a high accuracy with an average of 1.54 ± 0.87 mm error for the 32 landmark positions with rare failures, taking an average of 4.2 second computation time to identify each landmark in one large 3D-CBCT scan using a conventional GPU. CONCLUSION: The ALICBCT algorithm is a robust automatic identification tool that has been deployed for clinical and research use as an extension in the 3D Slicer platform allowing continuous updates for increased precision.

Three-dimensional comparison of bone-borne and tooth-bone-borne maxillary expansion in young adults with maxillary skeletal deficiency.

OBJECTIVE: To compare the transverse dental and skeletal changes in patients treated with bone-anchored palatal expander (bone-borne, BB) compared to patients treated with tooth and bone-anchored palatal expanders (tooth-bone-borne, TBB) using cone-beam computer tomography (CBCT) and 3D image analysis. METHODS: The sample comprised 30 patients with transverse maxillary discrepancy treated with two different types of appliances: bone-borne (Group BB) and tooth-bone-borne (Group TBB) expanders. CBCT scans were acquired before (T1) and after completion of maxillary expansion (T2); the interval was 5.4 ± 3.4 and 6.2 ± 2.1 months between the T1 and the T2 scans of Group TBB (tooth-bone-borne) and Group BB (bone-borne), respectively. Transverse, anteroposterior and vertical linear and angular three-dimensional dentoskeletal changes were assessed after cranial base superimposition. RESULTS: Both groups displayed marked transverse skeletal expansion with a greater ratio of skeletal to dental changes. Greater changes at the nasal cavity, zygoma and orbital levels were found in Group BB. A relatively parallel sutural opening in an anterior-posterior direction was observed in Group TBB; however, the Group BB presented a somewhat triangular (V-shaped) opening of the suture that was wider anteriorly. Small downward-forward displacements were observed in both groups. Asymmetric expansion occurred in approximately 50% of the patients in both groups. CONCLUSION: Greater skeletal vs dental expansion ratio and expansion of the circummaxillary regions were found in Group BB, the group in which a bone-borne expander was used. Both groups presented skeletal and dental changes, with a similar amount of posterior palate expansion. Asymmetric expansion was observed in both groups.

Automated Orientation and Registration of Cone-Beam Computed Tomography Scans.

Automated clinical decision support systems rely on accurate analysis of three-dimensional (3D) medical and dental images to assist clinicians in diagnosis, treatment planning, intervention, and assessment of growth and treatment effects. However, analyzing longitudinal 3D images requires standardized orientation and registration, which can be laborious and error-prone tasks dependent on structures of reference for registration. This paper proposes two novel tools to automatically perform the orientation and registration of 3D Cone-Beam Computed Tomography (CBCT) scans with high accuracy (<3° and <2mm of angular and linear errors when compared to expert clinicians). These tools have undergone rigorous testing, and are currently being evaluated by clinicians who utilize the 3D Slicer open-source platform. Our work aims to reduce the sources of error in the 3D medical image analysis workflow by automating these operations. These methods combine conventional image processing approaches and Artificial Intelligence (AI) based models trained and tested on de-identified CBCT volumetric images. Our results showed robust performance for standardized and reproducible image orientation and registration that provide a more complete understanding of individual patient facial growth and response to orthopedic treatment in less than 5 min.

Integrative Risk Predictors of Temporomandibular Joint Osteoarthritis Progression.

In this paper we propose feature selection and machine learning approaches to identify a combination of features for risk prediction of Temporomandibular Joint (TMJ) disease progression. In a sample of 32 TMJ osteoarthritis and 38 controls, feature selection of 5 clinical comorbidities, 43 quantitative imaging, 28 biological features and was performed using Maximum Relevance Minimum Redundancy, Chi-Square and Least Absolute Shrinkage and Selection Operator (LASSO) and Recursive Feature Elimination. We compared the performance of learning using concave and convex kernels (LUCCK), Support Vector Machine (SVM) and Random Forest (RF) approaches to predict disease cure/improvement or persistence/worsening. We show that the SVM model using LASSO achieves area under the curve (AUC), sensitivity and precision of 0.92±0.08, 0.85±0.19 and 0.76 ±0.18, respectively. Baseline levels of headaches, lower back pain, restless sleep, muscle soreness, articular fossa bone surface/bone volume and trabecular separation, condylar High Gray Level Run Emphasis and Short Run High Gray Level Emphasis, saliva levels of 6Ckine, Osteoprotegerin (OPG) and Angiogenin, and serum levels of 6ckine and Brain Derived Neurotrophic Factor (BDNF) were the most frequently occurring features to predict more severe TMJ osteoarthritis prognosis.

Osteoarthritis Diagnosis Integrating Whole Joint Radiomics and Clinical Features for Robust Learning Models Using Biological Privileged Information.

This paper proposes a machine learning model using privileged information (LUPI) and normalized mutual information feature selection method (NMIFS) to build a robust and accurate framework to diagnose patients with Temporomandibular Joint Osteoarthritis (TMJ OA). To build such a model, we employ clinical, quantitative imaging and additional biological markers as privileged information. We show that clinical features play a leading role in the TMJ OA diagnosis and quantitative imaging features, extracted from cone-beam computerized tomography (CBCT) scans, improve the model performance. As the proposed LUPI model employs biological data in the training phase (which boosted the model performance), this data is unnecessary for the testing stage, indicating the model can be widely used even when only clinical and imaging data are collected. The model was validated using 5-fold stratified cross-validation with hyperparameter tuning to avoid the bias of data splitting. Our method achieved an AUC, specificity and precision of 0.81, 0.79 and 0.77, respectively.

Quantitative bone imaging biomarkers and joint space analysis of the articular Fossa in temporomandibular joint osteoarthritis using artificial intelligence models.

Temporomandibular joint osteoarthritis (TMJ OA) is a disease with a multifactorial etiology, involving many pathophysiological processes, and requiring comprehensive assessments to characterize progressive cartilage degradation, subchondral bone remodeling, and chronic pain. This study aimed to integrate quantitative biomarkers of bone texture and morphometry of the articular fossa and joint space to advance the role of imaging phenotypes for diagnosis of Temporomandibular Joint Osteoarthritis (TMJ OA) in early to moderate stages by improving the performance of machine-learning algorithms to detect TMJ OA status. Ninety-two patients were prospectively enrolled (184 h-CBCT scans of the right and left mandibular condyles), divided into two groups: 46 control and 46 TMJ OA subjects. No significant difference in the articular fossa radiomic biomarkers was found between TMJ OA and control patients. The superior condyle-to-fossa distance (p < 0.05) was significantly smaller in diseased patients. The interaction effects of the articular fossa radiomic biomarkers enhanced the performance of machine-learning algorithms to detect TMJ OA status. The LightGBM model achieved an AUC 0.842 to diagnose the TMJ OA status with Headaches and Range of Mouth Opening Without Pain ranked as top features, and top interactions of VE-cadherin in Serum and Angiogenin in Saliva, TGF-ß1 in Saliva and Headaches, Gender and Muscle Soreness, PA1 in Saliva and Range of Mouth Opening Without Pain, Lateral Condyle Grey Level Non-Uniformity and Lateral Fossa Short Run Emphasis, TGF-ß1 in Serum and Lateral Fossa Trabeculae number, MMP3 in Serum and VEGF in Serum, Headaches and Lateral Fossa Trabecular spacing, Headaches and PA1 in Saliva, and Headaches and BDNF in Saliva. Our preliminary results indicate that condyle imaging features may be more important in regards to main effects, but the fossa imaging features may have a larger contribution in terms of interaction effects. More studies are needed to optimize and further enhance machine-learning algorithms to detect early markers of disease, improve prediction of disease progression and severity to ultimately better serve clinical decision support systems in the treatment of patients with TMJ OA.

Automatic multi-anatomical skull structure segmentation of cone-beam computed tomography scans using 3D UNETR.

The segmentation of medical and dental images is a fundamental step in automated clinical decision support systems. It supports the entire clinical workflow from diagnosis, therapy planning, intervention, and follow-up. In this paper, we propose a novel tool to accurately process a full-face segmentation in about 5 minutes that would otherwise require an average of 7h of manual work by experienced clinicians. This work focuses on the integration of the state-of-the-art UNEt TRansformers (UNETR) of the Medical Open Network for Artificial Intelligence (MONAI) framework. We trained and tested our models using 618 de-identified Cone-Beam Computed Tomography (CBCT) volumetric images of the head acquired with several parameters from different centers for a generalized clinical application. Our results on a 5-fold cross-validation showed high accuracy and robustness with a Dice score up to 0.962±0.02. Our code is available on our public GitHub repository.

Presurgical orthodontic decompensation with clear aligners.

INTRODUCTION: Orthodontists, surgeons, and patients have taken an interest in using clear aligners in combination with orthognathic surgery. This study aimed to evaluate the accuracy of tooth movements with clear aligners during presurgical orthodontics using novel 3-dimensional superimposition techniques. METHODS: The study sample consisted of 20 patients who have completed presurgical orthodontics using Invisalign clear aligners. Initial (pretreatment) digital dental models, presurgical digital dental models, and ClinCheck prediction models were obtained. Presurgical models were superimposed onto initial ones using stable anatomic landmarks; ClinCheck models were superimposed onto presurgical models using surface best-fit superimposition. Five hundred forty-five teeth were measured for 3 angular movements (buccolingual torque, mesiodistal tip, and rotation) and 4 linear movements (buccolingual, mesiodistal, vertical, and total scalar displacement). The predicted tooth movement was compared with the achieved amount for each movement and tooth, using both percentage accuracy and numerical difference. RESULTS: Average percentage accuracy (63.4% ± 11.5%) was higher than in previously reported literature. The most accurate tooth movements were buccal torque and mesial displacement compared with lingual torque and distal displacement, particularly for mandibular posterior teeth. Clinically significant inaccuracies were found for the buccal displacement of maxillary second molars, lingual displacement of all molars, intrusion of mandibular second molars, the distal tip of molars, second premolars, and mandibular first premolars, buccal torque of maxillary central and lateral incisors, and lingual torque of premolars and molars. CONCLUSIONS: Superimposition techniques used in this study lay the groundwork for future studies to analyze advanced clear aligner patients. Invisalign is a treatment modality that can be considered for presurgical orthodontics-tooth movements involved in arch leveling and decompensation are highly accurate when comparing the simulated and the clinically achieved movements.

Three-dimensional evaluation of skeletal and dental effects of treatment with maxillary skeletal expansion.

INTRODUCTION: The objective was to determine the skeletal and dental changes with microimplant assisted rapid palatal expansion (MARPE) appliances in growing (GR) and nongrowing (NG) patients using cone-beam computed tomography and 3-dimensional imaging analysis. METHODS: The sample consisted of 25 patients with transverse maxillary discrepancy treated with a maxillary skeletal expander, a type of MARPE appliance. Cone-beam computed tomography scans were taken before and after maxillary expansion; the interval was 6.0 ± 4.3 months. The sample was divided into GR and NG groups using cervical vertebral and midpalatal suture maturation. Linear and angular 3-dimensional dentoskeletal changes were assessed after cranial base superimposition. Groups were compared with independent-samples t test (P <0.05). RESULTS: Both groups displayed marked transverse changes with a similar ratio of skeletal to dental transverse changes and parallel sutural opening from the posterior nasal spine-anterior nasal spine; a similar amount of expansion occurred in the anterior and the posterior regions of the maxilla. The maxilla expanded skeletally without rotational displacements in both groups. The small downward-forward displacements were similar in both groups, except that the GR group had a significantly greater vertical displacement of the canines (GR, 1.7 ±1.0 mm; NG, 0.6 ± 0.8 mm; P = 0.02) and anterior nasal spine (GR, 1.1 ± 0.6 mm; NG, 0.5 ± 0.5 mm; P = 0.004). CONCLUSIONS: Treatment of patients with MARPE appliance is effective in GR and NG patients. Although greater skeletal and dental changes were observed in GR patients, a similar ratio of skeletal to dental transverse changes was observed in both groups.

Predicting Osteoarthritis of the Temporomandibular Joint Using Random Forest with Privileged Information.

Osteoarthritis of the temporomandibular joint (TMJ OA) is the most common disorder of the TMJ. A clinical decision support (CDS) system designed to detect TMJ OA could function as a useful screening tool as part of regular check-ups to detect early onset. This study implements a CDS concept model based on Random Forest and dubbed RF+ to predict TMJ OA with the hypothesis that a model which leverages high-resolution radiological and biomarker data in training only can improve predictions compared with a baseline model which does not use privileged information. We found that the RF+ model can outperform the baseline model even when privileged features are not of gold standard quality. Additionally, we introduce a novel method for post-hoc feature analysis, finding shortRunHighGreyLevelEmphasis of the lateral condyles and joint distance to be the most important features from the privileged modalities for predicting TMJ OA.

Automatic Segmentation of Dental Root Canal and Merging with Crown Shape.

In this paper, machine learning approaches are proposed to support dental researchers and clinicians to study the shape and position of dental crowns and roots, by implementing a Patient Specific Classification and Prediction tool that includes RootCanalSeg and DentalModelSeg algorithms and then merges the output of these tools for intraoral scanning and volumetric dental imaging. RootCanalSeg combines image processing and machine learning approaches to automatically segment the root canals of the lower and upper jaws from large datasets, providing clinical information on tooth long axis for orthodontics, endodontics, prosthodontic and restorative dentistry procedures. DentalModelSeg includes segmenting the teeth from the crown shape to provide clinical information on each individual tooth. The merging algorithm then allows users to integrate dental models for quantitative assessments. Precision in dentistry has been mainly driven by dental crown surface characteristics, but information on tooth root morphology and position is important for successful root canal preparation, pulp regeneration, planning of orthodontic movement, restorative and implant dentistry. In this paper we propose a patient specific classification and prediction of dental root canal and crown shape analysis workflow that employs image processing and machine learning methods to analyze crown surfaces, obtained by intraoral scanners, and three-dimensional volumetric images of the jaws and teeth root canals, obtained by cone beam computed tomography (CBCT).

Automatic Segmentation of Mandibular Ramus and Condyles.

In order to diagnose TMJ pathologies, we developed and tested a novel algorithm, MandSeg, that combines image processing and machine learning approaches for automatically segmenting the mandibular condyles and ramus. A deep neural network based on the U-Net architecture was trained for this task, using 109 cone-beam computed tomography (CBCT) scans. The ground truth label maps were manually segmented by clinicians. The U-Net takes 2D slices extracted from the 3D volumetric images. All the 3D scans were cropped depending on their size in order to keep only the mandibular region of interest. The same anatomic cropping region was used for every scan in the dataset. The scans were acquired at different centers with different resolutions. Therefore, we resized all scans to 512×512 in the pre-processing step where we also performed contrast adjustment as the original scans had low contrast. After the pre-processing, around 350 slices were extracted from each scan, and used to train the U-Net model. For the cross-validation, the dataset was divided into 10 folds. The training was performed with 60 epochs, a batch size of 8 and a learning rate of 2×10-5. The average performance of the models on the test set presented 0.95 ± 0.05 AUC, 0.93 ± 0.06 sensitivity, 0.9998 ± 0.0001 specificity, 0.9996 ± 0.0003 accuracy, and 0.91 ± 0.03 F1 score. This study findings suggest that fast and efficient CBCT image segmentation of the mandibular condyles and ramus from different clinical data sets and centers can be analyzed effectively. Future studies can now extract radiomic and imaging features as potentially relevant objective diagnostic criteria for TMJ pathologies, such as osteoarthritis (OA). The proposed segmentation will allow large datasets to be analyzed more efficiently for disease classification.

Clinical decision support systems in orthodontics: A narrative review of data science approaches.

Advancements in technology and data collection generated immense amounts of information from various sources such as health records, clinical examination, imaging, medical devices, as well as experimental and biological data. Proper management and analysis of these data via high-end computing solutions, artificial intelligence and machine learning approaches can assist in extracting meaningful information that enhances population health and well-being. Furthermore, the extracted knowledge can provide new avenues for modern healthcare delivery via clinical decision support systems. This manuscript presents a narrative review of data science approaches for clinical decision support systems in orthodontics. We describe the fundamental components of data science approaches including (a) Data collection, storage and management; (b) Data processing; (c) In-depth data analysis; and (d) Data communication. Then, we introduce a web-based data management platform, the Data Storage for Computation and Integration, for temporomandibular joint and dental clinical decision support systems.