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A novel non-rigid image registration algorithm is built upon fully convolutional networks (FCNs) to optimize and learn spatial transformations between pairs of images to be registered in a self-supervised learning framework. Different from most existing deep learning based image registration methods that learn spatial transformations from training data with known corresponding spatial transformations, our method directly estimates spatial transformations between pairs of images by maximizing an image-wise similarity metric between fixed and deformed moving images, similar to conventional image registration algorithms. The image registration is implemented in a multi-resolution image registration framework to jointly optimize and learn spatial transformations and FCNs at different spatial resolutions with deep self-supervision through typical feedforward and backpropagation computation. The proposed method …