UniReg: Conditional Unified Model for Medical Image Registration

We propose a new probabilistic model for general-purpose medical image registration that builds upon the mutual information registration criterion. It centers around a spatial interpolation technique that assumes latent voxel-wise correspondences between the images being registered. By exploiting these latent variables, we derive dedicated optimization and MCMC sampling techniques that only involve closed-form iterative updates. When applied to nonlinear registration, an efficient demons-like optimization algorithm is obtained that shows robust out-of-the-box performance across a variety of monomodal and multimodal registration tasks. We also demonstrate a corresponding sampler that can quantify, for the first time, uncertainty in multimodal registration scenarios with very high-dimensional 3D deformations. Our code, which we call BINDER (Bayesian INference for DEformable Registration), is freely available at https://github.com/ste93ste/BINDER.

Quantitative cardiac magnetic resonance imaging (MRI) enables non-invasive myocardial tissue characterization but relies on robust motion correction within these variable-length, variable-contrast image sequences. Groupwise registration, which simultaneously aligns all images, has shown greater robustness than pairwise registration for motion correction. However, current deep-learning-based groupwise registration methods cannot generalize across MRI sequences: the architecture typically encodes input data as a fixed-length channel stack, which rigidly couples network design to protocol-specific sequence length, input ordering, and contrast dynamics. At inference time, any change in imaging protocols will render the network unusable. In this work, we introduce \emph{\AnyTwoReg}, a new set-based groupwise registration framework that takes a quantitative MRI sequence as an unordered set. This set formulation fundamentally decouples network design from sequence length and input ordering. By utilizing a shared encoder and correlation-guided feature aggregation, \emph{\AnyTwoReg} constructs a permutation-invariant canonical reference for registration, and learns a permutation-equivariant mapping from images to deformation fields. Additionally, we extract contrast-insensitive image features from an existing foundation model to handle extreme contrast variations. Trained exclusively on a single public $T_1$ mapping dataset (STONE, sequence length $L=11$), \AnyTwoReg generalizes to two unseen quantitative MRI datasets (MOLLI, ASL) with variable lengths ($L \in [11, 60]$) and different contrast dynamics. It achieves strong cross-protocol generalization in a zero-shot manner, and consistently improves downstream quantitative mapping quality. Notably, while designed for quantitative MRI sequences, our framework is directly applicable to Cine MRI sequences for inter-cardiac-phase registration.

3D/2D registration serves as a cornerstone technique in surgical navigation. Traditional iterative optimization algorithms suffer from low efficiency and high failure rates in intraoperative settings. Deep learning-based methods reformulate registration from iterative optimization to a regression problem that maps image appearance features to spatial pose, typically achieving improved real-time performance and accuracy. However, such learnable methods are confined to memory-driven retrieval of specific pose features rather than understanding the task of image alignment itself, which limits their generalization in complex scenarios. We propose LayersReg, a pioneering regression paradigm that endows the model with 3D anatomical awareness and searches for the correct pose in a progressive, layer-by-layer manner. Inspired by the iterative pose-searching optimization criterion of classical registration, LayersReg searches for correlations between the moving and fixed images in feature space, capturing the trend of pixel flow and thereby converging iteratively toward the correct spatial pose transformation. We further design a coupling of node-wise regression with the progressive registration framework to enhance the model's perception of spatial pose changes. Experimental results demonstrate that under large offsets and multimodality conditions, LayersReg achieves high accuracy on both X-ray/CT registration (0.68°, 1.41 mm) and slice localization (0.73°, 1.55 mm) tasks, outperforming existing state-of-the-art methods while meeting the intraoperative demands for precision and real-time capability.