Geometric microstructural damage of white matter with functional compensation in post-stroke

Background and purpose: Subcortical ischemic stroke usually leads to the geometric microstructural changes in the orientation of peri-infarct white matter fiber. We conducted the study to determine the microstructural changes in the white matter fiber orientation in post stroke patients with and without cognitive impairment (PSCI, NPSCI), and to investigate the impact of peri-infarct white matter damage on the morphology and functional connectivity of their projective cerebral regions. Methods: A novel mathematical framework called Director Field Analysis (DFA) was applied to study the microstructural changes in the orientation of white matter fiber in PSCI (n = 23), NPSCI (n = 17), and cognitively normal (CN, n = 29) individuals. Results: PSCI patients had extensive abnormalities in the orientation of white matter fiber in the corpus callosum, bilateral internal capsule, external capsule, forceps major, forceps minor, and corticospinal tract in comparison with NPSCI and CN. NPSCI patients also showed significant increases in bend and twist of white matter fiber orientation in the internal capsule in comparison with CN. Seed-based functional connectivity analysis showed that peri-infarct white matter deficits indicate a significant impact on functional connectivity with related cortical regions, suggesting the coexistence of impairment and compensation in post-stroke. In addition, these peri-infarct white matter damages and abnormal functional connectivity were significantly correlated with cognitive scores. Machine learning model also indicated that these changes in white matter fiber orientation and functional connectivity can predict the cognitive status in post-stroke. Conclusions: Post-stroke patients experienced pathological damage in the orientation of peri-infarct white matter fiber. The peri-infarct white matter damage may further induce the abnormal functional connectivity in projective cerebral regions. These degenerations of peri-infarct white matter fiber and associated functional connectivity changes may mediate the cognitive impairment in post-stroke.