Characterizing post-stroke changes in brain microstructure using the mean apparent propagator model

This study investigated regional and whole-brain microstructural alterations following stroke using diffusion tensor imaging (DTI) and Mean Apparent Propagator MRI (MAP-MRI). Multi-shell diffusion and T1-weighted MRI data were analyzed from participants with chronic stroke and healthy controls. DTI-derived fractional anisotropy (FA) and mean diffusivity (MD), and MAP-MRI-derived return-to-origin (RTOP), return-to-axis (RTAP), and return-to-plane (RTPP) probabilities were quantified across 13 predefined regions in native diffusion space. Regional group differences were assessed using participant-level median values with Benjamini-Hochberg false discovery rate (BH-FDR) correction across all 65 ROI × diffusion-metric comparisons and age- and sex-adjusted sensitivity analyses. Complementary lesion-relative whole-brain analyses used nonparametric permutation testing with threshold-free cluster enhancement and family-wise error correction. MAP-MRI demonstrated widespread regional abnormalities, with significant group differences in 11 of 13 regions for RTOP, 12 of 13 for RTAP, and 10 of 13 for RTPP, compared with 8 of 13 for FA and all 13 regions for MD. After adjustment for age and sex, significant differences remained in 11, 10, and 9 regions for RTOP, RTAP, and RTPP, respectively, compared with 6 for FA and all 13 for MD. Whole-brain analyses demonstrated significant corrected abnormalities across all five diffusion metrics, with RTOP and RTAP showing the most spatially extensive Control > Stroke effects, followed by RTPP and FA, whereas MD showed extensive effects in the opposite, Stroke > Control direction. Regional discrimination varied by anatomical region and metric, without a uniform advantage of MAP-MRI over DTI. Exploratory diffusion-function analyses identified several nominal associations, but none survived correction across all comparisons. These findings demonstrate complementary, region- and metric-specific sensitivity of MAP-MRI and DTI to chronic stroke-related microstructural abnormalities. MAP-MRI identified distributed abnormalities across regional and whole-brain analyses, while MD remained highly sensitive to widespread tissue differences. The differing spatial distributions and regional discriminative performance of MAP-MRI and DTI suggest that these approaches capture partially distinct features of the post-stroke diffusion environment. Together, these findings support their complementary use for characterizing distributed microstructural abnormalities following chronic stroke.