Multi-modal retinal image registration plays an important role in the ophthalmological diagnosis process. The conventional methods lack robustness in aligning multi-modal images of various imaging qualities. Deep-learning methods have not been widely developed for this task, especially for the coarse-to-fine registration pipeline. To handle this task, we propose a two-step method based on deep convolutional networks, including a coarse alignment step and a fine alignment step. In the coarse alignment step, a global registration matrix is estimated by three sequentially connected networks for vessel segmentation, feature detection and description, and outlier rejection, respectively. In the fine alignment step, a deformable registration network is set up to find pixel-wise correspondence between a target image and a coarsely aligned image from the previous step to further improve the alignment accuracy. Particularly, an unsupervised learning framework is proposed to handle the difficulties of inconsistent modalities and lack of labeled training data for the fine alignment step. The proposed framework first changes multi-modal images into a same modality through modality transformers, and then adopts photometric consistency loss and smoothness loss to train the deformable registration network. The experimental results show that the proposed method achieves state-of-the-art results in Dice metrics and is more robust in challenging cases.
