Affine image registration is a cornerstone of medical image processing backed by decades of development. While classical algorithms can achieve excellent accuracy, they solve a time-consuming optimization for every new image pair. In contrast, deep-learning (DL) methods learn a function that maps an image pair to an output transform. Evaluating the function is fast, but these methods tend to be susceptible to domain shift. A network trained on a specific image type may perform poorly if an image characteristic changes at test time, such as the imaging contrast or resolution. Secondly, many classical and DL registration algorithms cannot distinguish between relevant and irrelevant anatomy: the global nature of the linear registration problem means that accuracy will suffer if parts of the image deform independently. This is why neuroimage processing, for example, often starts with brain extraction, to enhance the accuracy of brain-specific registration. We address these shortcomings of linear registration by training deep neural networks using a generative strategy that synthesizes wildly varying images from label maps. Optimizing label overlap decouples the loss from the image appearance, encouraging network invariance to acquisition specifics. It also enables the registration model to distinguish between anatomy of interest and irrelevant structures, which alleviates the need for segmenting images prior to registration to remove distracting content. We test brain-specific registration across a variety of magnetic resonance imaging protocols that approximate the diversity of real-world data, demonstrating consistent and improved accuracy relative to state-of-the-art baselines. We freely distribute our easy-to-use tool at https://w3id.org/synthmorph.
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