Longitudinal alterations in brain microstructure surrounding subcortical ischemic stroke lesions detected by free-water imaging

BackgroundFree-water imaging identifies subtle changes in white matter microstructure indicative of cellular and extracellular pathologies not visible on conventional stroke MRI. We explore the spatial extent and temporal trajectory of free-water changes in patients with subcortical stroke and their relationship to symptoms, as well as lesion evolution. MethodsTwenty-seven patients with isolated subcortical infarct with mean age of 66.73 (SD 11.57) and median initial NIHSS score of 4 (IQR 4) received MRI 3-5 days, 1 month, 3 months and 12 months after symptom-onset. After lesion segmentation, 8 unique tissue shells (2 mm distance) surrounding stroke lesions were created. Extracellular freewater and fractional anisotropy of the tissue (FAT), derived from diffusion-weighted MRI, were averaged within tissue shells/stroke lesions, and normalized to corresponding contralateral regions. Linear mixed-effects models and t-tests were used for statistics. Baseline imaging measures were correlated with clinical outcomes 3 months after stroke. ResultsWe found increased free-water and decreased FAT in the stroke lesion, as well as the surrounding tissue with a characteristic spatio-temporal distribution. Free-water and FAT changes were most prominent within the lesion and gradually became less with increasing distance from the lesion. Free-water elevations continuously increased over time and peaked after 12 months. In contrast, FAT decreases were most pronounced 1 month after stroke, after which there was a steady increase leading to similarly reduced FAT levels 12 months compared to 3-5 days after stroke. Higher perilesional free-water and higher lesional FAT at baseline were correlated with greater reductions in lesion size, while there were no associations with clinical measures. ConclusionsBoth free-water and FAT are altered beyond isolated subcortical stroke lesions. The spatial extent of these extracellular and cellular changes varies differentially over time indicating a dynamic parenchymal response to the initial insult characterized by vasogenic edema, cellular damage and white matter atrophy.