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Harmonized Connectome Resampling for Variance in Voxel Sizes

Posted by on Monday, November 24, 2025 in News.

Diffusion tensor imaging (DTI), fiber orientation distributions (FODs), tractography, and connectomics present exciting opportunities to deepen our knowledge of human brain connectivity and discover novel alterations in white matter. To date, there has been no comprehensive study characterizing the effect of diffusion-weighted magnetic resonance imaging (dMRI) voxel resolution on the resulting connectome for high resolution subject data. We assessed the statistical significance of graph measures derived from dMRI data by comparing connectomes from the same scans across different resolutions with 44 subjects (32 female) from the Human Connectome Project – Young Adult dataset (HCP-YA) with scan/rescan data (88 scans). We explored 15 isotropic and anisotropic resolutions, generated tractography and connectomes, and compared graph measures between each resolution and its nearest larger and smaller resolutions. Graph measures exhibited instability for images with voxels larger than 3 mm isotropic. Nearly all pairwise comparisons yielded statistically significant differences in graph measures (p ≤ 0.05, Wilcoxon Sign-Rank Test). Upon up sampling the 14 down sampled resolutions in 0.5 mm increments, we observed mitigation of the spatial sampling effect on both the tractography and the connectome’s complex graph measures. To investigate translational impact, we down sampled a subject from the HCP-YA data to the resolutions of three major national studies and up-sampled this data back to 1 mm isotropic. We observed Cohen’s d effect size of at least 1 for all graph measures when comparing study resolution with 1mm isotropic resolution data. Similarity in results improved with higher resolution, even after initial down-sampling. To ensure robust tractography and connectomes, we advise resampling data to 1mm isotropic resolution.