Financiado para publicación en acceso aberto: Universidade da Coruña/CISUG[Abstract] Medical imaging, and particularly retinal imaging, allows to accurately diagnose many eye pathologies as well as some systemic diseases such as hypertension or diabetes. Registering these images is crucial to correctly compare key structures, not only within patients, but also to contrast data with a model or among a population. Currently, this field is dominated by complex classical methods because the novel deep learning methods cannot compete yet in terms of results and commonly used methods are difficult to adapt to the retinal domain. In this work, we propose a novel method to register color fundus images based on previous works which employed classical approaches to detect domain-specific landmarks. Instead, we propose to use deep learning methods for the detection of these highly-specific domain-related landmarks. Our method uses a neural network to detect the bifurcations and crossovers of the retinal blood vessels, whose arrangement and location are unique to each eye and person. This proposal is the first deep learning feature-based registration method in fundus imaging. These keypoints are matched using a method based on RANSAC (Random Sample Consensus) without the requirement to calculate complex descriptors. Our method was tested using the public FIRE dataset, although the landmark detection network was trained using the DRIVE dataset. Our method provides accurate results, a registration score of 0.657 for the whole FIRE dataset (0.908 for category S, 0.293 for category P and 0.660 for category A). Therefore, our proposal can compete with complex classical methods and beat the deep learning methods in the state of the art.This research was funded by Instituto de Salud Carlos III, Government of Spain, DTS18/00 136 research project; Ministerio de Ciencia e Innovación y Universidades, Government of Spain, RTI2018-095 894-B-I00 research project; Consellería de Cultura, Educación e Universidade, Xunta de Galicia through the predoctoral grant contract ref. ED481A 2021/147 and Grupos de Referencia Competitiva, grant ref. ED431C 2020/24; CITIC, Centro de Investigación de Galicia ref. ED431G 2019/01, receives financial support from Consellería de Educación, Universidade e Formación Profesional, Xunta de Galicia, through the ERDF (80%) and Secretaría Xeral de Universidades (20%). The funding institutions had no involvement in the study design, in the collection, analysis and interpretation of data; in the writing of the manuscript; or in the decision to submit the manuscript for publication. Funding for open access charge: Universidade da Coruña/CISUGXunta de Galicia; ED481A 2021/147Xunta de Galicia; ED431C 2020/24Xunta de Galicia; ED431G 2019/0
