Anatomy-aware and acquisition-agnostic joint registration with SynthMorph

Affine image registration is a cornerstone of medical-image analysis. While classical algorithms can achieve excellent accuracy, they solve a time-consuming optimization for every image pair. Deep-learning (DL) methods learn a function that maps an image pair to an output transform. Evaluating the function is fast, but capturing large transforms can be challenging, and networks tend to struggle if a test-image characteristic shifts from the training domain, such as resolution. Most affine methods are agnostic to anatomy, meaning the registration will be inaccurate if algorithms consider all structures in the image. We address these shortcomings with SynthMorph, an easy-to-use DL tool for joint affine-deformable registration of any brain image without preprocessing, right off the MRI scanner. First, we leverage a strategy to train networks with wildly varying images synthesized from label maps, yielding robust performance across acquisition specifics unseen at training. Second, we optimize the spatial overlap of select anatomical labels. This enables networks to distinguish anatomy of interest from irrelevant structures, removing the need for preprocessing that excludes content which would impinge on anatomy-specific registration. Third, we combine the affine model with a deformable hypernetwork that lets users choose the optimal deformation-field regularity for their specific data, at registration time, in a fraction of the time required by classical methods. We rigorously analyze how competing architectures learn affine transforms and compare state-of-the-art registration tools across an extremely diverse set of neuroimaging data, aiming to truly capture the behavior of methods in the real world. SynthMorph demonstrates consistent and improved accuracy. It is available at https://w3id.org/synthmorph, as a single complete end-to-end solution for registration of brain MRI.