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Generalizable Multimodal Retinal Image Registration via Label-free Vessel Segmentation
Utkarsh Doshi1, Elli Davis2, Mayss Al-Sheikh3
1Department of Ophthalmology, University of Pittsburgh, School of Medicine, Pittsburgh, Pennsylvania, United States.
Biomedical Signal Processing and Control
|November 3, 2025
Summary
This study introduces a novel, label-free method for registering multimodal retinal images using vessel structures. This approach enhances diagnostic accuracy for retinal diseases like diabetic retinopathy and AMD by integrating diverse imaging data.
Area of Science:
- Ophthalmology
- Medical Imaging
- Computer Vision
Background:
- Multimodal retinal imaging is vital for diagnosing and managing diseases like diabetic retinopathy and age-related macular degeneration (AMD).
- Accurate registration of images from different modalities (CF, FAG, FAF, ICG, OCT, IR) is essential for integrating complementary pathological insights.
- Existing registration methods often require labeled datasets, limiting their generalizability and application.
Purpose of the Study:
- To develop a generalizable, label-free retinal image registration algorithm applicable across multiple imaging modalities.
- To improve the accuracy of disease quantification, monitoring, and automated diagnosis through integrated multimodal retinal data.
- To overcome the limitations of existing methods by eliminating the need for large labeled training datasets.
Main Methods:
- A novel, label-free retinal image registration approach was developed.
- Vessel structures were extracted using the DexiNed algorithm to facilitate registration.
- The method was evaluated across various multimodal pairings (CF-IR, CF-FAF, CF-FAG, CF-ICG, FAF-FAG, FAF-ICG, FAG-ICG).
Main Results:
- The proposed method achieved a mean landmark error (MLE) between 1.91±0.44 and 4.9±2.32 pixels across different modality combinations.
- Registration of Color Fundus (CF) and Infrared (IR) images yielded an MLE of 3.08±1.47 pixels.
- Registration of CF and Fundus Autofluorescence (FAF) images resulted in an MLE of 4.9±2.32 pixels, comparable to human annotations.
Conclusions:
- The developed label-free registration method effectively integrates multimodal retinal imaging data.
- This approach enhances diagnostic precision and disease monitoring for various retinal conditions.
- The elimination of the need for labeled training data increases the method's practicality and broad applicability.

