Self-supervised Disentanglement of Disease Effects from Aging in 3D Medical Shapes

Accurately isolating disease-related features from confounding covariates (e.g., age, gender, site) and individual variations remains a fundamental challenge in medical image classification. Traditional regression-based approaches may ignore non-linear relations between image features and true covariates. To overcome this issue, we present a generalized Medical Imaging Disentanglement Learning (MedIDL) framework. MedIDL maps image features into three mutually orthogonal latent spaces through specialized disentanglement heads: a disease classification head guided by a supervised loss, a covariate-alignment head constrained by cross-subject similarity matching, and a Gaussian head absorbing individual variations. We evaluated our framework across 7 datasets encompassing diverse imaging modalities. MedIDL outperforms state-of-the-art supervised and self-supervised classification methods in accuracy across all datasets. Association analyses demonstrate that MedIDL successfully isolates target-specific latent representations. Gradient-based interpretability mappings localize pathognomonic patterns aligning with established clinical literature.

The corpus callosum (CC) is a major white-matter structure and a well-established marker of brain aging, but most studies quantify it using scalar summaries that discard its boundary geometry. We present a Riemannian shape-space framework \cite{fletcher2013geodesic-regression} for analyzing age-related morphological change in the midsagittal CC, applied to the OASIS-1 cohort. Each contour is represented by $128$ landmarks and embedded into Kendall shape space, where translation, rotation, and scale are removed. We derive a multivariate geodesic regression with exact Riemannian gradients and use the fitted age-velocity field to localize age-related deformation to five anatomical sub-regions. In the cognitively normal cohort ($n = 252$), geodesic regression outperforms the Euclidean linear benchmark ($R^2 = 0.1355$ vs.\ $0.1216$). Regional energy is anterior-dominant: the Genu carries $46.1\%$ and the Anterior Body $23.3\%$ of total age-related shape change, together accounting for $\sim 69\%$ despite comprising only $\sim 41\%$ of landmarks. Signed projections confirm the ordering (Genu $r = 0.562$; Anterior Body $r = 0.507$). In contrast, age explains less than $0.5\%$ of shape variance in Alzheimer's disease ($n = 88$), indicating that the disease disrupts the healthy aging trajectory. A tangent-space classifier achieves an age-group AUC of $0.791$ from the 2D contour alone, exceeding a recent volumetric benchmark ($0.67$).

Unsupervised Domain Adaptation (UDA) is essential for deploying medical segmentation models across diverse clinical environments. Existing methods are fundamentally limited, suffering from semantically unaware feature alignment that results in poor distributional fidelity and from pseudo-label validation that disregards global anatomical constraints, thus failing to prevent the formation of globally implausible structures. To address these issues, we propose SHAPE (Structure-aware Hierarchical Unsupervised Domain Adaptation with Plausibility Evaluation), a framework that reframes adaptation towards global anatomical plausibility. Built on a DINOv3 foundation, its Hierarchical Feature Modulation (HFM) module first generates features with both high fidelity and class-awareness. This shifts the core challenge to robustly validating pseudo-labels. To augment conventional pixel-level validation, we introduce Hypergraph Plausibility Estimation (HPE), which leverages hypergraphs to assess the global anatomical plausibility that standard graphs cannot capture. This is complemented by Structural Anomaly Pruning (SAP) to purge remaining artifacts via cross-view stability. SHAPE significantly outperforms prior methods on cardiac and abdominal cross-modality benchmarks, achieving state-of-the-art average Dice scores of 90.08% (MRI->CT) and 78.51% (CT->MRI) on cardiac data, and 87.48% (MRI->CT) and 86.89% (CT->MRI) on abdominal data. The code is available at https://github.com/BioMedIA-repo/SHAPE.