Registration quality filtering improves robustness of voxel-wise analyses to the choice of brain template

Motivation: Many clinical and scientific conclusions that rely on voxel-wise analyses of neuroimaging depend on the accurate comparison of corresponding anatomical regions. Such comparisons are made possible by registration of the images of subjects of interest onto a common brain template, such as the Johns Hopkins University (JHU) template. However, current image registration algorithms are prone to errors that are distributed in a template-dependent manner. Therefore, the results of voxel-wise analyses can be sensitive to template choice. Despite this problem, the issue of appropriate template choice for voxel-wise analyses is not generally addressed in contemporary neuroimaging studies, which may lead to the reporting of spurious results. Results: We present a novel approach to determine the suitability of a brain template for voxel-wise analysis. The approach is based on computing a “distance” between automatically-generated atlases of the subjects of interest and templates that is indicative of the extent of subject-to-template registration errors. This allows for the filtering of subjects and candidate templates based on a quantitative measure of registration quality. We benchmark our approach by evaluating alternative templates for a voxel-wise analysis that reproduces the well-known decline in fractional anisotropy (FA) with age. Our results show that filtering registrations minimizes errors and decreases the sensitivity of voxel-wise analysis to template choice. In addition to carrying important implications for future neuroimaging studies, the developed framework of template induction can be used to evaluate robustness of data analysis methods to template choice.