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Explainable deep learning and biomechanical modeling for TMJ disorder morphological risk factors
Shuchun Sun, Pei Xu, Nathan Buchweitz, Cherice N. Hill, Farhad Ahmadi, Marshall B. Wilson, Angela Mei, Xin She, Benedikt Sagl, Elizabeth H. Slate, Janice S. Lee, Yongren Wu, Hai Yao
Shuchun Sun, Pei Xu, Nathan Buchweitz, Cherice N. Hill, Farhad Ahmadi, Marshall B. Wilson, Angela Mei, Xin She, Benedikt Sagl, Elizabeth H. Slate, Janice S. Lee, Yongren Wu, Hai Yao
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Research Article Bone biology Metabolism

Explainable deep learning and biomechanical modeling for TMJ disorder morphological risk factors

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Abstract

Clarifying multifactorial musculoskeletal disorder etiologies supports risk analysis, development of targeted prevention, and treatment modalities. Deep learning enables comprehensive risk factor identification through systematic analyses of disease data sets but does not provide sufficient context for mechanistic understanding, limiting clinical applicability for etiological investigations. Conversely, multiscale biomechanical modeling can evaluate mechanistic etiology within the relevant biomechanical and physiological context. We propose a hybrid approach combining 3D explainable deep learning and multiscale biomechanical modeling; we applied this approach to investigate temporomandibular joint (TMJ) disorder etiology by systematically identifying risk factors and elucidating mechanistic relationships between risk factors and TMJ biomechanics and mechanobiology. Our 3D convolutional neural network recognized TMJ disorder patients through participant-specific morphological features in condylar, ramus, and chin. Driven by deep learning model outputs, biomechanical modeling revealed that small mandibular size and flat condylar shape were associated with increased TMJ disorder risk through increased joint force, decreased tissue nutrient availability and cell ATP production, and increased TMJ disc strain energy density. Combining explainable deep learning and multiscale biomechanical modeling addresses the “mechanism unknown” limitation undermining translational confidence in clinical applications of deep learning and increases methodological accessibility for smaller clinical data sets by providing the crucial biomechanical context.

Authors

Shuchun Sun, Pei Xu, Nathan Buchweitz, Cherice N. Hill, Farhad Ahmadi, Marshall B. Wilson, Angela Mei, Xin She, Benedikt Sagl, Elizabeth H. Slate, Janice S. Lee, Yongren Wu, Hai Yao

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Figure 3

Analysis of mandibular dimensions and their association with TMJ disorders.

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Analysis of mandibular dimensions and their association with TMJ disorde...
(A) Saliency maps generated from deep learning models show key landmarks on the mandible, representing diverse mandibular dimensions. (B) Morphometric measurements extracted from saliency maps (3D mandibular length, 2D mandibular length, ramus width, and ramus height). (C) Comparative analysis of measurements from patients with TMJ disorder (n = 104 derived from 52 individuals, each contributing left and right measurements) and healthy controls (n = 104 derived from 52 individuals, each contributing left and right measurements) with a mixed effects model to account for the correlation between left and right side measurements within participants. The results reveal the differences between the 2 groups. In the figure, asterisks denote the level of statistical significance; * P < 0.05, **P < 0.01, and ***P < 0.001. (D) PCA results with the first principal component (PC1) accounting for 71.5% of the total variance emphasizing the ‘size’ factor in craniofacial morphology. A biplot of the PCA results can be found in Supplemental Figure 2. These analyses underscore the importance of mandibular dimensions in understanding TMJ disorders.

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