The relation between cerebral small vessel function and white matter microstructure in monogenic and sporadic small vessel disease - the ZOOM@SVDs study

In cerebral small vessel disease (cSVD), vascular dysfunction has been associated with cSVD-lesions across the brain. Here we further explore the relation between vascular dysfunction and cSVD-related brain injury. We tested two hypotheses: (1) that complementary measures of abnormal small vessel fu...

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Main Authors: Naomi Vlegels, Hilde van den Brink, Anna Kopczak, Tine Arts, Stanley D.T. Pham, Jeroen C.W. Siero, Benno Gesierich, Alberto De Luca, Marco Duering, Jaco J.M. Zwanenburg, Martin Dichgans, Geert Jan Biessels
Format: Article
Language:English
Published: Elsevier 2025-01-01
Series:Cerebral Circulation - Cognition and Behavior
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Online Access:http://www.sciencedirect.com/science/article/pii/S2666245025000078
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author Naomi Vlegels
Hilde van den Brink
Anna Kopczak
Tine Arts
Stanley D.T. Pham
Jeroen C.W. Siero
Benno Gesierich
Alberto De Luca
Marco Duering
Jaco J.M. Zwanenburg
Martin Dichgans
Geert Jan Biessels
author_facet Naomi Vlegels
Hilde van den Brink
Anna Kopczak
Tine Arts
Stanley D.T. Pham
Jeroen C.W. Siero
Benno Gesierich
Alberto De Luca
Marco Duering
Jaco J.M. Zwanenburg
Martin Dichgans
Geert Jan Biessels
author_sort Naomi Vlegels
collection DOAJ
description In cerebral small vessel disease (cSVD), vascular dysfunction has been associated with cSVD-lesions across the brain. Here we further explore the relation between vascular dysfunction and cSVD-related brain injury. We tested two hypotheses: (1) that complementary measures of abnormal small vessel function relate to decreased white matter integrity, and (2) that local variance in vascular dysfunction relates to local variance in white matter integrity within individual patients.We included 23 patients with monogenic cSVD (i.e. CADASIL) and 46 patients with sporadic cSVD. With whole-brain analyses, we tested if small vessel flow velocity and reactivity measures from 7T-MRI were associated with global peak-width-of-skeletonized-mean-diffusivity (PSMD). We also tested voxel-wise correlations between reactivity to hypercapnia and mean diffusivity (MD) in white matter.Whole-brain analyses showed a negative association between blood flow velocity and PSMD for the perforating arteries in the centrum semiovale in CADASIL (p = 0.04) and in the basal ganglia in sporadic cSVD (p = 0.002). Global white matter reactivity to hypercapnia was not associated with PSMD. Within patients, both in CADASIL and sporadic cSVD, we observed significant voxel-wise negative correlations for endothelial-independent vascular reactivity and MD in the white matter.These findings confirm our hypothesis that small vessel dysfunction in patients with cSVD is associated with microstructural white matter alterations, also at voxel level. The latter may reflect a direct relationship between local small vessel dysfunction and tissue injury.
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spelling doaj-art-9d388090afd04bd18f6f7a7aeee154812025-08-20T02:10:17ZengElsevierCerebral Circulation - Cognition and Behavior2666-24502025-01-01810038310.1016/j.cccb.2025.100383The relation between cerebral small vessel function and white matter microstructure in monogenic and sporadic small vessel disease - the ZOOM@SVDs studyNaomi Vlegels0Hilde van den Brink1Anna Kopczak2Tine Arts3Stanley D.T. Pham4Jeroen C.W. Siero5Benno Gesierich6Alberto De Luca7Marco Duering8Jaco J.M. Zwanenburg9Martin Dichgans10Geert Jan Biessels11Department of Neurology and Neurosurgery, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht University, Utrecht, The NetherlandsDepartment of Neurology and Neurosurgery, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht University, Utrecht, The NetherlandsInstitute for Stroke and Dementia Research, University Hospital, LMU Munich, Munich, GermanyTranslational Neuroimaging Group, Center for Image Sciences, University Medical Center Utrecht, Utrecht, The NetherlandsTranslational Neuroimaging Group, Center for Image Sciences, University Medical Center Utrecht, Utrecht, The NetherlandsTranslational Neuroimaging Group, Center for Image Sciences, University Medical Center Utrecht, Utrecht, The Netherlands; Spinoza Centre for Neuroimaging Amsterdam, Amsterdam, The NetherlandsInstitute for Stroke and Dementia Research, University Hospital, LMU Munich, Munich, Germany; Medical Image Analysis Center (MIAC) and Department of Biomedical Engineering, University of Basel, Basel, SwitzerlandDepartment of Neurology and Neurosurgery, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands; Translational Neuroimaging Group, Center for Image Sciences, University Medical Center Utrecht, Utrecht, The Netherlands; Image Sciences Institute, Division Imaging and Oncology, University Medical Center Utrecht, Utrecht, The NetherlandsInstitute for Stroke and Dementia Research, University Hospital, LMU Munich, Munich, Germany; Medical Image Analysis Center (MIAC) and Department of Biomedical Engineering, University of Basel, Basel, SwitzerlandTranslational Neuroimaging Group, Center for Image Sciences, University Medical Center Utrecht, Utrecht, The NetherlandsInstitute for Stroke and Dementia Research, University Hospital, LMU Munich, Munich, Germany; Munich Cluster for Systems Neurology (SyNergy), Munich, Germany; German Center for Neurodegenerative Disease (DZNE), Munich, GermanyDepartment of Neurology and Neurosurgery, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands; Corresponding author: Department of Neurology and Neurosurgery, University Medical Center Utrecht, Heidelberglaan 100, Utrecht 3508 GA, The Netherlands.In cerebral small vessel disease (cSVD), vascular dysfunction has been associated with cSVD-lesions across the brain. Here we further explore the relation between vascular dysfunction and cSVD-related brain injury. We tested two hypotheses: (1) that complementary measures of abnormal small vessel function relate to decreased white matter integrity, and (2) that local variance in vascular dysfunction relates to local variance in white matter integrity within individual patients.We included 23 patients with monogenic cSVD (i.e. CADASIL) and 46 patients with sporadic cSVD. With whole-brain analyses, we tested if small vessel flow velocity and reactivity measures from 7T-MRI were associated with global peak-width-of-skeletonized-mean-diffusivity (PSMD). We also tested voxel-wise correlations between reactivity to hypercapnia and mean diffusivity (MD) in white matter.Whole-brain analyses showed a negative association between blood flow velocity and PSMD for the perforating arteries in the centrum semiovale in CADASIL (p = 0.04) and in the basal ganglia in sporadic cSVD (p = 0.002). Global white matter reactivity to hypercapnia was not associated with PSMD. Within patients, both in CADASIL and sporadic cSVD, we observed significant voxel-wise negative correlations for endothelial-independent vascular reactivity and MD in the white matter.These findings confirm our hypothesis that small vessel dysfunction in patients with cSVD is associated with microstructural white matter alterations, also at voxel level. The latter may reflect a direct relationship between local small vessel dysfunction and tissue injury.http://www.sciencedirect.com/science/article/pii/S2666245025000078CADASILCerebral small vessel diseaseSmall vessel functionUltra-high field strength MRIWhite matter microstructure
spellingShingle Naomi Vlegels
Hilde van den Brink
Anna Kopczak
Tine Arts
Stanley D.T. Pham
Jeroen C.W. Siero
Benno Gesierich
Alberto De Luca
Marco Duering
Jaco J.M. Zwanenburg
Martin Dichgans
Geert Jan Biessels
The relation between cerebral small vessel function and white matter microstructure in monogenic and sporadic small vessel disease - the ZOOM@SVDs study
Cerebral Circulation - Cognition and Behavior
CADASIL
Cerebral small vessel disease
Small vessel function
Ultra-high field strength MRI
White matter microstructure
title The relation between cerebral small vessel function and white matter microstructure in monogenic and sporadic small vessel disease - the ZOOM@SVDs study
title_full The relation between cerebral small vessel function and white matter microstructure in monogenic and sporadic small vessel disease - the ZOOM@SVDs study
title_fullStr The relation between cerebral small vessel function and white matter microstructure in monogenic and sporadic small vessel disease - the ZOOM@SVDs study
title_full_unstemmed The relation between cerebral small vessel function and white matter microstructure in monogenic and sporadic small vessel disease - the ZOOM@SVDs study
title_short The relation between cerebral small vessel function and white matter microstructure in monogenic and sporadic small vessel disease - the ZOOM@SVDs study
title_sort relation between cerebral small vessel function and white matter microstructure in monogenic and sporadic small vessel disease the zoom svds study
topic CADASIL
Cerebral small vessel disease
Small vessel function
Ultra-high field strength MRI
White matter microstructure
url http://www.sciencedirect.com/science/article/pii/S2666245025000078
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