Microstructural and microvascular features of white matter hyperintensities and their association with small vessel disease markers
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 neurova...
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| Published in | Scientific reports Vol. 15; no. 1; pp. 18567 - 11 |
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| Main Authors | , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
London
Nature Publishing Group UK
27.05.2025
Nature Publishing Group Nature Portfolio |
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| Online Access | Get full text |
| ISSN | 2045-2322 2045-2322 |
| DOI | 10.1038/s41598-025-03885-w |
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| 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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| AbstractList | 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. 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.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. 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. 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. |
| ArticleNumber | 18567 |
| Author | DiFrancesco, Mark W. Wang, Lily L. Sriwastawa, Aakanksha Williamson, Brady J. Aziz, Yasmin N. Antzoulatos, Eleni Khatri, Pooja Zhang, Bin Stephens, Cody B. Vagal, Achala |
| Author_xml | – sequence: 1 givenname: Lily L. surname: Wang fullname: Wang, Lily L. organization: Department of Radiology, University of Cincinnati College of Medicine – sequence: 2 givenname: Brady J. surname: Williamson fullname: Williamson, Brady J. organization: Department of Radiology, University of Cincinnati College of Medicine – sequence: 3 givenname: Bin surname: Zhang fullname: Zhang, Bin organization: Division of Biostatistics and Epidemiology, Cincinnati Children’s Hospital Medical Center – sequence: 4 givenname: Aakanksha surname: Sriwastawa fullname: Sriwastawa, Aakanksha organization: Department of Radiology, University of Cincinnati College of Medicine – sequence: 5 givenname: Yasmin N. surname: Aziz fullname: Aziz, Yasmin N. organization: Department of Neurology and Rehabilitation Medicine, University of Cincinnati College of Medicine – sequence: 6 givenname: Eleni surname: Antzoulatos fullname: Antzoulatos, Eleni organization: Department of Neurology, Emory University School of Medicine – sequence: 7 givenname: Cody B. surname: Stephens fullname: Stephens, Cody B. organization: Department of Radiology, University of Cincinnati College of Medicine – sequence: 8 givenname: Achala surname: Vagal fullname: Vagal, Achala organization: Department of Radiology, University of Cincinnati College of Medicine – sequence: 9 givenname: Pooja surname: Khatri fullname: Khatri, Pooja organization: Department of Neurology and Rehabilitation Medicine, University of Cincinnati College of Medicine – sequence: 10 givenname: Mark W. surname: DiFrancesco fullname: DiFrancesco, Mark W. email: mark.difrancesco@cchmc.org organization: Department of Radiology, University of Cincinnati College of Medicine, Department of Radiology, Cincinnati Children’s Hospital Medical Center |
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| Keywords | Diffusion-weighted imaging White matter hyperintensities Small Vessel Disease Blood–brain-barrier Brain microvasculature Arterial spin labeling |
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| Snippet | 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... Abstract White matter hyperintensities (WMH) are the most prominent imaging feature of small vessel disease (SVD). WMH and other imaging features of SVD are... |
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| Title | Microstructural and microvascular features of white matter hyperintensities and their association with small vessel disease markers |
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