Microstructural and microvascular features of white matter hyperintensities and their association with small vessel disease markers

• Published in: Scientific reports Vol. 15; no. 1; pp. 18567 - 11
• Main Authors: Wang, Lily L., Williamson, Brady J., Zhang, Bin, Sriwastawa, Aakanksha, Aziz, Yasmin N., Antzoulatos, Eleni, Stephens, Cody B., Vagal, Achala, Khatri, Pooja, DiFrancesco, Mark W.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 27.05.2025; Nature Publishing Group; Nature Portfolio
• Subjects: 631/378/1341; 631/378/1689; 692/617/375/1370; 692/699/375/1370; 692/699/375/380; 692/699/375/534; Aged; Aged, 80 and over; Arterial spin labeling; Biomarkers; Blood; Blood-brain barrier; Blood-Brain Barrier - diagnostic imaging; Brain injury; Brain microvasculature; Cardiovascular disease; Cerebral Small Vessel Diseases - diagnostic imaging; Cerebral Small Vessel Diseases - pathology; Cognitive ability; Diffusion Magnetic Resonance Imaging; Diffusion-weighted imaging; Female; Gray Matter - blood supply; Gray Matter - diagnostic imaging; Gray Matter - pathology; Humanities and Social Sciences; Humans; Magnetic Resonance Imaging; Male; Medicine; Membrane permeability; Microvasculature; Microvessels - diagnostic imaging; Microvessels - pathology; Middle Aged; multidisciplinary; Neuroimaging; Pathogenesis; Patients; Permeability; Pilot Projects; Prospective Studies; Regions; Science; Science (multidisciplinary); Small Vessel Disease; Spin labeling; Stroke; Substantia alba; Substantia grisea; Vascularization; White Matter - blood supply; White Matter - diagnostic imaging; White Matter - pathology; White matter hyperintensities; Diffusion-weighted imaging; White matter hyperintensities; Small Vessel Disease; Blood–brain-barrier; Brain microvasculature; Arterial spin labeling
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-025-03885-w

White matter hyperintensities (WMH) are the most prominent imaging feature of small vessel disease (SVD). WMH and other imaging features of SVD are likely the result of ongoing insults associated with cognitive decline and cerebrovascular events. Emerging evidence suggests degradation of the neurovascular unit may underlie the pathogenesis of SVD. This prospective pilot study employed MRI in 19 subjects (68.2 ± 11.5 years of age) for diffusion-weighted imaging, applied to intravoxel incoherent motion (IVIM) modeling, to characterize microstructural and microvascular properties throughout the brain and arterial spin labeling, using multiple labeling and delay times, to measure dynamic perfusion properties including blood–brain barrier permeability (PS) in gray matter (GM). IVIM revealed WMH to have significantly greater blood volume fraction and lower pseudodiffusion and bulk diffusion than normal-appearing white matter (NAWM). IVIM parameters and PS, in canonical GM network regions, correlated with WMH volume with at least moderate effect size. Findings suggest the potential for neovascularization and evidence of restricted diffusion in WMH compared to surrounding NAWM. Regional changes in GM pertaining to the NVU scale in proportion to WMH load. Observed GM changes precede visible MR imaging abnormalities. Their early detection could elucidate SVD mechanisms of brain injury and inform future preventative measures.