Recursive Uncertainty-Gated Image Registration for Learning-based Algorithms

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.

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.

This paper describes a new spatial correspondence representation based on paired regions-of-interest (ROIs), for medical image registration. The distinct properties of the proposed ROI-based correspondence are discussed, in the context of potential benefits in clinical applications following image registration, compared with alternative correspondence-representing approaches, such as those based on sampled displacements and spatial transformation functions. These benefits include a clear connection between learning-based image registration and segmentation, which in turn motivates two cases of image registration approaches using (pre-)trained segmentation networks. Based on the segment anything model (SAM), a vision foundation model for segmentation, we develop a new registration algorithm SAMReg, which does not require any training (or training data), gradient-based fine-tuning or prompt engineering. The proposed SAMReg models are evaluated across five real-world applications, including intra-subject registration tasks with cardiac MR and lung CT, challenging inter-subject registration scenarios with prostate MR and retinal imaging, and an additional evaluation with a non-clinical example with aerial image registration. The proposed methods outperform both intensity-based iterative algorithms and DDF-predicting learning-based networks across tested metrics including Dice and target registration errors on anatomical structures, and further demonstrates competitive performance compared to weakly-supervised registration approaches that rely on fully-segmented training data. Open source code and examples are available at: https://github.com/sqhuang0103/SAMReg.git.