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

Abstract 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 th...

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Main Authors: Lily L. Wang, Brady J. Williamson, Bin Zhang, Aakanksha Sriwastawa, Yasmin N. Aziz, Eleni Antzoulatos, Cody B. Stephens, Achala Vagal, Pooja Khatri, Mark W. DiFrancesco
Format: Article
Language:English
Published: Nature Portfolio 2025-05-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-03885-w
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author Lily L. Wang
Brady J. Williamson
Bin Zhang
Aakanksha Sriwastawa
Yasmin N. Aziz
Eleni Antzoulatos
Cody B. Stephens
Achala Vagal
Pooja Khatri
Mark W. DiFrancesco
author_facet Lily L. Wang
Brady J. Williamson
Bin Zhang
Aakanksha Sriwastawa
Yasmin N. Aziz
Eleni Antzoulatos
Cody B. Stephens
Achala Vagal
Pooja Khatri
Mark W. DiFrancesco
author_sort Lily L. Wang
collection DOAJ
description Abstract 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.
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spelling doaj-art-ca0ea3d8bdd14e258eecd8c4971d3c8e2025-08-20T02:03:35ZengNature PortfolioScientific Reports2045-23222025-05-0115111110.1038/s41598-025-03885-wMicrostructural and microvascular features of white matter hyperintensities and their association with small vessel disease markersLily L. Wang0Brady J. Williamson1Bin Zhang2Aakanksha Sriwastawa3Yasmin N. Aziz4Eleni Antzoulatos5Cody B. Stephens6Achala Vagal7Pooja Khatri8Mark W. DiFrancesco9Department of Radiology, University of Cincinnati College of MedicineDepartment of Radiology, University of Cincinnati College of MedicineDivision of Biostatistics and Epidemiology, Cincinnati Children’s Hospital Medical CenterDepartment of Radiology, University of Cincinnati College of MedicineDepartment of Neurology and Rehabilitation Medicine, University of Cincinnati College of MedicineDepartment of Neurology, Emory University School of MedicineDepartment of Radiology, University of Cincinnati College of MedicineDepartment of Radiology, University of Cincinnati College of MedicineDepartment of Neurology and Rehabilitation Medicine, University of Cincinnati College of MedicineDepartment of Radiology, University of Cincinnati College of MedicineAbstract 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.https://doi.org/10.1038/s41598-025-03885-wSmall Vessel DiseaseArterial spin labelingDiffusion-weighted imagingBlood–brain-barrierBrain microvasculatureWhite matter hyperintensities
spellingShingle Lily L. Wang
Brady J. Williamson
Bin Zhang
Aakanksha Sriwastawa
Yasmin N. Aziz
Eleni Antzoulatos
Cody B. Stephens
Achala Vagal
Pooja Khatri
Mark W. DiFrancesco
Microstructural and microvascular features of white matter hyperintensities and their association with small vessel disease markers
Scientific Reports
Small Vessel Disease
Arterial spin labeling
Diffusion-weighted imaging
Blood–brain-barrier
Brain microvasculature
White matter hyperintensities
title Microstructural and microvascular features of white matter hyperintensities and their association with small vessel disease markers
title_full Microstructural and microvascular features of white matter hyperintensities and their association with small vessel disease markers
title_fullStr Microstructural and microvascular features of white matter hyperintensities and their association with small vessel disease markers
title_full_unstemmed Microstructural and microvascular features of white matter hyperintensities and their association with small vessel disease markers
title_short Microstructural and microvascular features of white matter hyperintensities and their association with small vessel disease markers
title_sort microstructural and microvascular features of white matter hyperintensities and their association with small vessel disease markers
topic Small Vessel Disease
Arterial spin labeling
Diffusion-weighted imaging
Blood–brain-barrier
Brain microvasculature
White matter hyperintensities
url https://doi.org/10.1038/s41598-025-03885-w
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