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

TY - JOUR

T1 - Longitudinal microstructural alterations surrounding subcortical ischemic stroke lesions detected by free-water imaging

AU - Nägele, Felix L

AU - Petersen, Marvin

AU - Mayer, Carola

AU - Bönstrup, Marlene

AU - Schulz, Robert

AU - Gerloff, Christian

AU - Thomalla, Götz

AU - Cheng, Bastian

N1 - © 2024 The Author(s). Human Brain Mapping published by Wiley Periodicals LLC.

PY - 2024/6/1

Y1 - 2024/6/1

N2 - In 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.

AB - In 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.

KW - Humans

KW - Male

KW - Aged

KW - Female

KW - Middle Aged

KW - Ischemic Stroke/diagnostic imaging

KW - White Matter/diagnostic imaging

KW - Diffusion Magnetic Resonance Imaging/methods

KW - Longitudinal Studies

KW - Water

KW - Brain/diagnostic imaging

KW - Anisotropy

U2 - 10.1002/hbm.26722

DO - 10.1002/hbm.26722

M3 - SCORING: Journal article

C2 - 38780442

VL - 45

SP - e26722

JO - HUM BRAIN MAPP

JF - HUM BRAIN MAPP

SN - 1065-9471

IS - 8

ER -