BINDER: A Latent Variable Model for Probabilistic Medical Image Registration

Learning-based medical image registration has matched the accuracy of conventional methods while offering superior computational efficiency. However, existing approaches suffer from poor generalization across diverse clinical scenarios, requiring the laborious development of multiple isolated networks for specific registration tasks, \emph{e.g.}, inter-/intra-subject registration or anatomical region-specific alignment, leading to cumbersome development pipelines. To overcome this limitation, we propose \textbf{UniReg}, the first conditional unified model for multi-scenario medical image registration, which combines the precision advantages of task-specific learning methods with the generalization of traditional optimization methods. Our key innovation is a unified registration framework that adaptively estimates deformation fields conditioned on: (1) anatomical structure priors, (2) registration type constraints (inter/intra-subject), and (3) instance-specific features, enabling effective alignment across heterogeneous CT and MR registration scenarios within a single model. Through comprehensive experiments on multiple CT/MR registration datasets, UniReg achieves superior average registration accuracy compared with current state-of-the-art learning-based methods while exhibiting strong cross-scenario generalization. Moreover, by replacing multiple isolated task-specific models with a compact unified model, UniReg substantially reduces the overall training burden in terms of total training cost and model redundancy.

Image registration is an ill-posed dense vision task, where multiple solutions achieve similar loss values, motivating probabilistic inference. Variational inference has previously been employed to capture these distributions, however restrictive assumptions about the posterior form can lead to poor characterisation, overconfidence and low-quality samples. More flexible posteriors are typically bottlenecked by the complexity of high-dimensional covariance matrices required for dense 3D image registration. In this work, we present a memory and computationally efficient inference method, Structured SIR, that enables expressive, multi-modal, characterisation of uncertainty with high quality samples. We propose the use of a Sampled Importance Resampling (SIR) algorithm with a novel memory-efficient high-dimensional covariance parameterisation as the sum of a low-rank covariance and a sparse, spatially structured Cholesky precision factor. This structure enables capturing complex spatial correlations while remaining computationally tractable. We evaluate the efficacy of this approach in 3D dense image registration of brain MRI data, which is a very high-dimensional problem. We demonstrate that our proposed method produces uncertainty estimates that are significantly better calibrated than those produced by variational methods, achieving equivalent or better accuracy. Crucially, we show that the model yields highly structured multi-modal posterior distributions, enable effective and efficient uncertainty quantification.

Medical image registration benefits significantly from deep learning, yet existing approaches often lack physical explainability and fine-grained deformation control. Motivated by Demons algorithms, we propose a novel DrivenMorph framework that bridges attention mechanisms with variational image registration by incorporating difference modeling as a physically inspired inductive bias. The resulting driving force, computed from local differences in the latent feature space, provides explicit semantic guidance throughout the registration process. It directly drives the registration process through a neural Demons layer that simulates force-displacement interactions to generate smooth and anatomically consistent deformation. Unlike previous methods, our approach not only integrates traditional registration principles with popular deep networks, providing an explainable and efficient solution for learning-based medical image registration, but also separates difference modeling from deformation, improving modularity and explainability. Extensive experiments on multiple 3D brain MRI datasets demonstrate superior performance over state of-the-art learning-based and optimization-based methods. Furthermore, visualizations and statistical analyses confirm that the learned driving force aligns closely with actual deformation patterns, supporting its explanatory value.