In human neuroimaging studies, atlas registration enables mapping MRI scans to a common coordinate frame, which is necessary to aggregate data from multiple subjects. Machine learning registration methods have achieved excellent speed and accuracy but lack interpretability. More recently, keypoint-based methods have been proposed to tackle this issue, but their accuracy is still subpar, particularly when fitting nonlinear transforms. Here we propose Registration by Regression (RbR), a novel atlas registration framework that is highly robust and flexible, conceptually simple, and can be trained with cheaply obtained data. RbR predicts the (x,y,z) atlas coordinates for every voxel of the input scan (i.e., every voxel is a keypoint), and then uses closed-form expressions to quickly fit transforms using a wide array of possible deformation models, including affine and nonlinear (e.g., Bspline, Demons, invertible diffeomorphic models, etc.). Robustness is provided by the large number of voxels informing the registration and can be further increased by robust estimators like RANSAC. Experiments on independent public datasets show that RbR yields more accurate registration than competing keypoint approaches, while providing full control of the deformation model.
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