Longitudinal microstructural alterations surrounding subcortical ischemic stroke lesions detected by free‐water imaging

Abstract

AbstractIn this study we explore the spatio‐temporal trajectory and clinical relevance of microstructural white matter changes within and beyond subcortical stroke lesions detected by free‐water imaging. Twenty‐seven patients with subcortical infarct with mean age of 66.73 (SD 11.57) and median initial NIHSS score of 4 (IQR 3–7) received diffusion MRI 3–5 days, 1 month, 3 months, and 12 months after symptom‐onset. Extracellular free‐water and fractional anisotropy of the tissue (FAT) were averaged within stroke lesions and the surrounding tissue. Linear models showed increased free‐water and decreased FAT in the white matter of patients with subcortical stroke (lesion [free‐water/FAT, mean relative difference in %, ipsilesional vs. contralesional hemisphere at 3–5 days, 1 month, 3 months, and 12 months after symptom‐onset]: +41/−34, +111/−37, +208/−26, +251/−18; perilesional tissue [range in %]: +[5–24]/−[0.2–7], +[2–20]/−[3–16], +[5–43]/−[2–16], +[10–110]/−[2–12]). Microstructural changes were most prominent within the lesion and gradually became less pronounced with increasing distance from the lesion. While free‐water elevations continuously increased over time and peaked after 12 months, FAT decreases were most evident 1 month post‐stroke, gradually returning to baseline values thereafter. Higher perilesional free‐water and higher lesional FAT at baseline were correlated with greater reductions in lesion size (rho = −0.51, p = .03) in unadjusted analyses only, while there were no associations with clinical measures. In summary, we find a characteristic spatio‐temporal pattern of extracellular and cellular alterations beyond subcortical stroke lesions, indicating a dynamic parenchymal response to ischemia characterized by vasogenic edema, cellular damage, and white matter atrophy.