Abstract

To facilitate the comparison of white matter morphologic connectivity across target populations, it is invaluable to map the data to a standardized neuroanatomical space. Here, we evaluated direct streamline normalization (DSN), where the warping was applied directly to the streamlines, with two publically available approaches that spatially normalize the diffusion data and then reconstruct the streamlines. Prior work has shown that streamlines generated after normalization from reoriented diffusion data do not reliably match the streamlines generated in native space. To test the impact of these different normalization methods on quantitative tractography measures, we compared the reproducibility of the resulting normalized connectivity matrices and network metrics with those originally obtained in native space. The two methods that reconstruct streamlines after normalization led to significant differences in network metrics with large to huge standardized effect sizes, reflecting a dramatic alteration of the same subject’s native connectivity. In contrast, after normalizing with DSN we found no significant difference in network metrics compared with native space with only very small-to-small standardized effect sizes. DSN readily outperformed the other methods at preserving native space connectivity and introduced novel opportunities to define connectome networks without relying on gray matter parcellations.