Modality-Invariant Coarse-to-Fine Retinal Image Registration

We present Consistent-Recurrent Feature Flow Transformer (CRFT), a unified coarse-to-fine framework based on feature flow learning for robust cross-modal image registration. CRFT learns a modality-independent feature flow representation within a transformer-based architecture that jointly performs feature alignment and flow estimation. The coarse stage establishes global correspondences through multi-scale feature correlation, while the fine stage refines local details via hierarchical feature fusion and adaptive spatial reasoning. To enhance geometric adaptability, an iterative discrepancy-guided attention mechanism with a Spatial Geometric Transform (SGT) recurrently refines the flow field, progressively capturing subtle spatial inconsistencies and enforcing feature-level consistency. This design enables accurate alignment under large affine and scale variations while maintaining structural coherence across modalities. Extensive experiments on diverse cross-modal datasets demonstrate that CRFT consistently outperforms state-of-the-art registration methods in both accuracy and robustness. Beyond registration, CRFT provides a generalizable paradigm for multimodal spatial correspondence, offering broad applicability to remote sensing, autonomous navigation, and medical imaging. Code and datasets are publicly available at https://github.com/NEU-Liuxuecong/CRFT.

Deformable image registration remains a central challenge in medical image analysis, particularly under multi-modal scenarios where intensity distributions vary significantly across scans. While deep learning methods provide efficient feed-forward predictions, they often fail to generalize robustly under distribution shifts at test time. A straightforward remedy is full network fine-tuning, yet for modern architectures such as Transformers or deep U-Nets, this adaptation is prohibitively expensive in both memory and runtime when operating in 3D. Meanwhile, the naive fine-tuning struggles more with potential degradation in performance in the existence of drastic domain shifts. In this work, we propose a registration framework that integrates a frozen pretrained mono-modal registration model with a lightweight adaptation pipeline for multi-modal image registration. Specifically, we employ style transfer based on contrast-agnostic representation generation and refinement modules to bridge modality and domain gaps with instance optimization at test time. This design is orthogonal to the choice of backbone mono-modal model, thus avoids the computational burden of full fine-tuning while retaining the flexibility to adapt to unseen domains. We evaluate our approach on the Learn2Reg 2025 LUMIR validation set and observe consistent improvements over the pretrained state-of-the-art mono-modal backbone. In particular, the method ranks second on the multi-modal subset, third on the out-of-domain subset, and achieves fourth place overall in Dice score. These results demonstrate that combining frozen mono-modal models with modality adaptation and lightweight instance optimization offers an effective and practical pathway toward robust multi-modal registration.

Multi-modal image registration plays a critical role in precision medicine but faces challenges from non-linear intensity relationships and local optima. While deep learning models enable rapid inference, they often suffer from generalization collapse on unseen modalities. To address this, we propose Search-MIND, a training-free, iterative optimization framework for instance-specific registration. Our pipeline utilizes a coarse-to-fine strategy: a hierarchical coarse alignment stage followed by deformable refinement. We introduce two novel loss functions: Variance-Weighted Mutual Information (VWMI), which prioritizes informative tissue regions to shield global alignment from background noise and uniform regions, and Search-MIND (S-MIND), which broadens the convergence basin of structural descriptors by considering larger local search range. Evaluations on CARE Liver 2025 and CHAOS Challenge datasets show that Search-MIND consistently outperforms classical baselines like ANTs and foundation model-based approaches like DINO-reg, offering superior stability across diverse modalities.