Active Diffusion Matching: Score-based Iterative Alignment of Cross-Modal Retinal Images

We propose a robust alignment technique for Standard Fundus Images (SFIs) and Ultra-Widefield Fundus Images (UWFIs), which are challenging to align due to differences in scale, appearance, and the scarcity of distinctive features. Our method, termed Particle Diffusion Matching (PDM), performs alignment through an iterative Random Walk Correspondence Search (RWCS) guided by a diffusion model. At each iteration, the model estimates displacement vectors for particle points by considering local appearance, the structural distribution of particles, and an estimated global transformation, enabling progressive refinement of correspondences even under difficult conditions. PDM achieves state-of-the-art performance across multiple retinal image alignment benchmarks, showing substantial improvement on a primary dataset of SFI-UWFI pairs and demonstrating its effectiveness in real-world clinical scenarios. By providing accurate and scalable correspondence estimation, PDM overcomes the limitations of existing methods and facilitates the integration of complementary retinal image modalities. This diffusion-guided search strategy offers a new direction for improving downstream supervised learning, disease diagnosis, and multi-modal image analysis in ophthalmology.

Retinal image registration is essential for ophthalmic diagnosis, longitudinal disease monitoring, and multimodal retinal image analysis. Existing retinal registration methods are typically modality-dependent: they are designed or optimized either for a single imaging modality in mono-modal registration or for a fixed pair of modalities in cross-modal registration. This limits their flexibility and applicability in practical scenarios involving diverse retinal imaging modalities and different combinations of them. In this work, we propose a generalizable two-stage, modality-invariant framework for retinal image registration. First, we introduce a sparse feature-matching model driven by a universal retinal vessel segmentation to achieve robust coarse global alignment across modalities. Second, we develop a modality-invariant optical flow estimation network, termed MI-RAFT, to refine the alignment through dense local registration. Extensive experiments demonstrate that the proposed method can handle diverse combinations of commonly used retinal imaging modalities, exhibiting strong modality invariance while outperforming state-of-the-art modality-dependent registration methods.

Image registration and fusion aim to establish spatial correspondences from misaligned multi-modal source images, and integrate complementary information. However, in real-world imaging scenarios, source images are often affected by complex and diverse degradations, such as low illumination, noise, etc., which severely hinder the effectiveness of registration and fusion. To address this issue, we propose a mutually reinforced image registration and fusion diffusion framework via degradation-aware learning, termed Diff-RF. It explores the intrinsic coupling between registration-fusion and information restoration in the degradation conditions, enabling high-quality fusion of unregistered images under complex degradation conditions. First, the intra-modal restoration module is designed to alleviate modality-specific degradations by leveraging information within each modality, thereby providing more reliable structural representations for registration and facilitating subsequent cross-modal fusion. Second, we develop a cross-modal diffusion registration and fusion module that establishes bidirectional interaction between registration and fusion. By integrating fusion-derived visual cues and correspondence-based geometric conditions into the diffusion process, the proposed framework progressively refines spatial alignment and exploits cross-modal complementary information to achieve collaborative enhancement. Rather than treating them as independent components, degradation-aware information restoration and the collaborative optimization of registration and fusion are tightly coupled, achieving overall performance improvements. Extensive experiments on multiple extended datasets demonstrate that Diff-RF achieves superior registration accuracy and fusion quality under various degraded scenarios, exhibiting strong robustness and generalization ability.