Nonlinear registration of brain MRI scans is often used to quantify morphological differences associated with disease or genetic factors. Recently, surface-guided fully 3D volumetric registrations have been developed that combine intensity-guided volume registrations with cortical surface constraints. In this paper, we compare one such algorithm to two popular high-dimensional volumetric registration methods: large-deformation viscous fluid registration, formulated in a Riemannian framework, and the diffeomorphic “Demons” algorithm. We performed an objective morphometric comparison, by using a large MRI dataset from 340 young adult twin subjects to examine 3D patterns of correlations in anatomical volumes. Surface-constrained volume registration gave greater effect sizes for detecting morphometric associations near the cortex, while the other two approaches gave greater effects sizes subcortically. These findings suggest novel ways to combine the advantages of multiple methods in the future.
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