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Image registration with deep neural networks has become an active field of research and exciting avenue for a long standing problem in medical imaging. The goal is to learn a complex function that maps the appearance of input image pairs to parameters of a spatial transformation in order to align corresponding anatomical structures. We argue and show that the current direct, non-iterative approaches are sub-optimal, in particular if we seek accurate alignment of Structures-of-Interest (SoI). Information about SoI is often available at training time, for example, in form of segmentations or landmarks. We introduce a novel, generic framework, Image-and-Spatial Transformer Networks (ISTNs), to leverage SoI information allowing us to learn new image representations that are optimised for the downstream registration task. Thanks to these representations we can employ a test-specific, iterative refinement over …