Improved normalization of lesioned brains via cohort-specific templates

In MRI studies, spatial normalization is required to infer results at the group level. In the presence of a brain lesion, such as in stroke patients, the normalization process can be affected by tissue loss, spatial deformations, signal intensity changes, and other stroke sequelae that introduce confounds into the group analysis results. Previously, most neuroimaging studies with lesioned brains have used normalization methods optimized for intact brains, raising potential concerns about the accuracy of the resulting transformations and, in turn, their reported group level results. In this study, we demonstrate the benefits of creating an intermediate, cohort-specific template in conjunction with diffeomorphism-based methods to normalize structural MRI images in stroke patients. We show that including this cohort-specific template improves accuracy compared to standard methods for normalizing lesioned brains. Critically, this method reduces overall differences in normalization accuracy between stroke patients and healthy controls, and may improve the localization and connectivity of BOLD signal in functional neuroimaging data.