This article presents a general Bayesian learning framework for multi-modal groupwise image registration. The method builds on probabilistic modelling of the image generative process, where the underlying common anatomy and geometric variations of the observed images are explicitly disentangled as latent variables. Therefore, groupwise image registration is achieved via hierarchical Bayesian inference. We propose a novel hierarchical variational auto-encoding architecture to realise the inference procedure of the latent variables, where the registration parameters can be explicitly estimated in a mathematically interpretable fashion. Remarkably, this new paradigm learns groupwise image registration in an unsupervised closed-loop self-reconstruction process, sparing the burden of designing complex image-based similarity measures. The computationally efficient disentangled network architecture is also inherently scalable and flexible, allowing for groupwise registration on large-scale image groups with variable sizes. Furthermore, the inferred structural representations from multi-modal images via disentanglement learning are capable of capturing the latent anatomy of the observations with visual semantics. Extensive experiments were conducted to validate the proposed framework, including four different datasets from cardiac, brain, and abdominal medical images. The results have demonstrated the superiority of our method over conventional similarity-based approaches in terms of accuracy, efficiency, scalability, and interpretability.

Most prior unsupervised domain adaptation approaches for medical image segmentation are narrowly tailored to either the source-accessible setting, where adaptation is guided by source-target alignment, or the source-free setting, which typically resorts to implicit adaptation mechanisms such as pseudo-labeling and network distillation. This substantial divergence in methodological designs between the two settings reveals an inherent flaw: the lack of an explicit, structured construction of anatomical knowledge that naturally generalizes across domains and settings. To bridge this longstanding divide, we introduce a unified, semantically grounded framework that supports both source-accessible and source-free adaptation. Fundamentally distinct from all prior works, our framework's adaptability emerges naturally as a direct consequence of the model architecture, without relying on explicit cross-domain alignment strategies. Specifically, our model learns a domain-agnostic probabilistic manifold as a global space of anatomical regularities, mirroring how humans establish visual understanding. Thus, the structural content in each image can be interpreted as a canonical anatomy retrieved from the manifold and a spatial transformation capturing individual-specific geometry. This disentangled, interpretable formulation enables semantically meaningful prediction with intrinsic adaptability. Extensive experiments on challenging cardiac and abdominal datasets show that our framework achieves state-of-the-art results in both settings, with source-free performance closely approaching its source-accessible counterpart, a level of consistency rarely observed in prior works. Beyond quantitative improvement, we demonstrate strong interpretability of the proposed framework via manifold traversal for smooth shape manipulation. The results provide a principled foundation for anatomically informed, interpretable, and unified solutions for domain adaptation in medical imaging. The code is available at https://github.com/wxdrizzle/remind.

While total intracranial carotid artery calcification (ICAC) volume is an established stroke biomarker, growing evidence shows this aggregate metric ignores the critical influence of plaque location, since calcification in different segments carries distinct prognostic and procedural risks. However, a finer-grained, segment-specific quantification has remained technically infeasible. Conventional 3D models are forced to process downsampled volumes or isolated patches, sacrificing the global context required to resolve anatomical ambiguity and render reliable landmark localization. To overcome this, we reformulate the 3D challenge as a Parallel Probabilistic Landmark Localization task along the 1D axial dimension. We propose the Depth-Sequence Transformer (DST), a framework that processes full-resolution CT volumes as sequences of 2D slices, learning to predict$N=6$independent probability distributions that pinpoint key anatomical landmarks. Our DST framework demonstrates exceptional accuracy and robustness. Evaluated on a 100-patient clinical cohort with rigorous 5-fold cross-validation, it achieves a Mean Absolute Error (MAE) of 0.1 slices, with$96\%$of predictions falling within a$\pm 1$slice tolerance. Our work delivers the first practical tool for automated segment-specific ICAC analysis. The proposed framework provides a foundation for further studies on the role of location-specific biomarkers in diagnosis, prognosis, and procedural planning. Our code will be made publicly available.