Cross-sectional and longitudinal quantification of total white matter perivascular space volume fraction in Dutch-type Cerebral Amyloid Angiopathy

Enlarged perivascular spaces (PVS) in the centrum semiovale are an important marker of Cerebral Amyloid Angiopathy (CAA) and are thought to reflect brain clearance dysfunction. However, the current golden standard for assessing PVS is limited to a unilateral, single slice, qualitative analysis, whic...

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Main Authors: Manon R. Schipper, Thijs W. van Harten, Arie-Tjerk Razoux-Schultz, Kanishk Kaushik, Lydiane Hirschler, Sabine Voigt, Ingeborg Rasing, Emma A. Koemans, Rosemarie van Dort, Reinier G.J. van der Zwet, Sanne E. Schriemer, Erik W. van Zwet, Jeroen van der Grond, Mark A. van Buchem, Steven M. Greenberg, Marieke J.H. Wermer, Matthias J.P. van Osch, Marianne A.A. van Walderveen, Sanneke van Rooden
Format: Article
Language:English
Published: Elsevier 2025-01-01
Series:NeuroImage: Clinical
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Online Access:http://www.sciencedirect.com/science/article/pii/S2213158225000488
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author Manon R. Schipper
Thijs W. van Harten
Arie-Tjerk Razoux-Schultz
Kanishk Kaushik
Lydiane Hirschler
Sabine Voigt
Ingeborg Rasing
Emma A. Koemans
Rosemarie van Dort
Reinier G.J. van der Zwet
Sanne E. Schriemer
Erik W. van Zwet
Jeroen van der Grond
Mark A. van Buchem
Steven M. Greenberg
Marieke J.H. Wermer
Matthias J.P. van Osch
Marianne A.A. van Walderveen
Sanneke van Rooden
author_facet Manon R. Schipper
Thijs W. van Harten
Arie-Tjerk Razoux-Schultz
Kanishk Kaushik
Lydiane Hirschler
Sabine Voigt
Ingeborg Rasing
Emma A. Koemans
Rosemarie van Dort
Reinier G.J. van der Zwet
Sanne E. Schriemer
Erik W. van Zwet
Jeroen van der Grond
Mark A. van Buchem
Steven M. Greenberg
Marieke J.H. Wermer
Matthias J.P. van Osch
Marianne A.A. van Walderveen
Sanneke van Rooden
author_sort Manon R. Schipper
collection DOAJ
description Enlarged perivascular spaces (PVS) in the centrum semiovale are an important marker of Cerebral Amyloid Angiopathy (CAA) and are thought to reflect brain clearance dysfunction. However, the current golden standard for assessing PVS is limited to a unilateral, single slice, qualitative analysis, which has the disadvantage of a strong ceiling effect. We aim to introduce a whole-brain PVS volume fraction (PVSvf) measurement to assess cross-sectional and longitudinal PVSvf differences between pre-symptomatic and symptomatic Dutch-type CAA (D-CAA) mutation carriers and similar-age controls. PVSvf was assessed with a Frangi-vesselness filter-based, segmentation tool developed in-house and was compared cross-sectionally in 70 participants (28 symptomatic D-CAA, 17 pre-symptomatic D-CAA, 10 controls > 50 years, 17 controls ≤ 50 years) and longitudinally in 40 participants (16 symptomatic D-CAA, 13 pre-symptomatic D-CAA, 11 controls combined from both age groups). We found a higher baseline PVSvf in symptomatic D-CAA compared to controls ≤ 50 years (p < 0.0001, 95% CI [−0.051, −0.025]) and controls > 50 years (p < 0.0001, 95% CI [-0.042, −0.016]), in pre-symptomatic D-CAA compared to controls ≤ 50 years (p = 0.023, 95% CI [−0.035, −0.002]), and in controls > 50 years compared to controls ≤ 50 years (p < 0.001, 95% CI [0.004, 0.014]). We found no group differences in PVSvf change over time. The introduction of this quantitative measure of PVS volume in D-CAA showed cross-sectional differences already in pre-symptomatic D-CAA, indicating increased PVSvf in the early stages of D-CAA. We did not observe longitudinal differences over a four-year follow-up when analyzed at group level.
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spelling doaj-art-da8d8cc7b4f948d3bbef5123542378af2025-08-20T02:34:43ZengElsevierNeuroImage: Clinical2213-15822025-01-014610377810.1016/j.nicl.2025.103778Cross-sectional and longitudinal quantification of total white matter perivascular space volume fraction in Dutch-type Cerebral Amyloid AngiopathyManon R. Schipper0Thijs W. van Harten1Arie-Tjerk Razoux-Schultz2Kanishk Kaushik3Lydiane Hirschler4Sabine Voigt5Ingeborg Rasing6Emma A. Koemans7Rosemarie van Dort8Reinier G.J. van der Zwet9Sanne E. Schriemer10Erik W. van Zwet11Jeroen van der Grond12Mark A. van Buchem13Steven M. Greenberg14Marieke J.H. Wermer15Matthias J.P. van Osch16Marianne A.A. van Walderveen17Sanneke van Rooden18Department of Radiology, Leiden University Medical Center, Leiden, the Netherlands; Corresponding author at: Leiden University Medical Center, Albinusdreef 2, 2300 RC Leiden, The Netherlands.Department of Radiology, Leiden University Medical Center, Leiden, the NetherlandsDepartment of Radiology, Leiden University Medical Center, Leiden, the NetherlandsDepartment of Neurology, Leiden University Medical Center, Leiden, the NetherlandsDepartment of Radiology, Leiden University Medical Center, Leiden, the NetherlandsDepartment of Radiology, Leiden University Medical Center, Leiden, the Netherlands; Department of Neurology, Leiden University Medical Center, Leiden, the NetherlandsDepartment of Neurology, Leiden University Medical Center, Leiden, the NetherlandsDepartment of Neurology, Leiden University Medical Center, Leiden, the NetherlandsDepartment of Neurology, Leiden University Medical Center, Leiden, the NetherlandsDepartment of Neurology, Leiden University Medical Center, Leiden, the NetherlandsDepartment of Neurology, Leiden University Medical Center, Leiden, the NetherlandsDepartment of Biostatistics, Leiden University Medical Center, Leiden, the NetherlandsDepartment of Radiology, Leiden University Medical Center, Leiden, the NetherlandsDepartment of Radiology, Leiden University Medical Center, Leiden, the NetherlandsHemorrhagic Stroke Research Program, J Philip Kistler Research Center, Department of Neurology, Massachusetts General Hospital, Boston, MA, USADepartment of Neurology, Leiden University Medical Center, Leiden, the Netherlands; Department of Neurology, University Medical Center Groningen, Groningen, the NetherlandsDepartment of Radiology, Leiden University Medical Center, Leiden, the NetherlandsDepartment of Radiology, Leiden University Medical Center, Leiden, the NetherlandsDepartment of Radiology, Leiden University Medical Center, Leiden, the NetherlandsEnlarged perivascular spaces (PVS) in the centrum semiovale are an important marker of Cerebral Amyloid Angiopathy (CAA) and are thought to reflect brain clearance dysfunction. However, the current golden standard for assessing PVS is limited to a unilateral, single slice, qualitative analysis, which has the disadvantage of a strong ceiling effect. We aim to introduce a whole-brain PVS volume fraction (PVSvf) measurement to assess cross-sectional and longitudinal PVSvf differences between pre-symptomatic and symptomatic Dutch-type CAA (D-CAA) mutation carriers and similar-age controls. PVSvf was assessed with a Frangi-vesselness filter-based, segmentation tool developed in-house and was compared cross-sectionally in 70 participants (28 symptomatic D-CAA, 17 pre-symptomatic D-CAA, 10 controls > 50 years, 17 controls ≤ 50 years) and longitudinally in 40 participants (16 symptomatic D-CAA, 13 pre-symptomatic D-CAA, 11 controls combined from both age groups). We found a higher baseline PVSvf in symptomatic D-CAA compared to controls ≤ 50 years (p < 0.0001, 95% CI [−0.051, −0.025]) and controls > 50 years (p < 0.0001, 95% CI [-0.042, −0.016]), in pre-symptomatic D-CAA compared to controls ≤ 50 years (p = 0.023, 95% CI [−0.035, −0.002]), and in controls > 50 years compared to controls ≤ 50 years (p < 0.001, 95% CI [0.004, 0.014]). We found no group differences in PVSvf change over time. The introduction of this quantitative measure of PVS volume in D-CAA showed cross-sectional differences already in pre-symptomatic D-CAA, indicating increased PVSvf in the early stages of D-CAA. We did not observe longitudinal differences over a four-year follow-up when analyzed at group level.http://www.sciencedirect.com/science/article/pii/S2213158225000488Perivascular spacesBrain clearanceAmyloid-βCerebral amyloid angiopathyDutch-type cerebral amyloid angiopathyHereditary cerebral hemorrhage with amyloidosis Dutch-type
spellingShingle Manon R. Schipper
Thijs W. van Harten
Arie-Tjerk Razoux-Schultz
Kanishk Kaushik
Lydiane Hirschler
Sabine Voigt
Ingeborg Rasing
Emma A. Koemans
Rosemarie van Dort
Reinier G.J. van der Zwet
Sanne E. Schriemer
Erik W. van Zwet
Jeroen van der Grond
Mark A. van Buchem
Steven M. Greenberg
Marieke J.H. Wermer
Matthias J.P. van Osch
Marianne A.A. van Walderveen
Sanneke van Rooden
Cross-sectional and longitudinal quantification of total white matter perivascular space volume fraction in Dutch-type Cerebral Amyloid Angiopathy
NeuroImage: Clinical
Perivascular spaces
Brain clearance
Amyloid-β
Cerebral amyloid angiopathy
Dutch-type cerebral amyloid angiopathy
Hereditary cerebral hemorrhage with amyloidosis Dutch-type
title Cross-sectional and longitudinal quantification of total white matter perivascular space volume fraction in Dutch-type Cerebral Amyloid Angiopathy
title_full Cross-sectional and longitudinal quantification of total white matter perivascular space volume fraction in Dutch-type Cerebral Amyloid Angiopathy
title_fullStr Cross-sectional and longitudinal quantification of total white matter perivascular space volume fraction in Dutch-type Cerebral Amyloid Angiopathy
title_full_unstemmed Cross-sectional and longitudinal quantification of total white matter perivascular space volume fraction in Dutch-type Cerebral Amyloid Angiopathy
title_short Cross-sectional and longitudinal quantification of total white matter perivascular space volume fraction in Dutch-type Cerebral Amyloid Angiopathy
title_sort cross sectional and longitudinal quantification of total white matter perivascular space volume fraction in dutch type cerebral amyloid angiopathy
topic Perivascular spaces
Brain clearance
Amyloid-β
Cerebral amyloid angiopathy
Dutch-type cerebral amyloid angiopathy
Hereditary cerebral hemorrhage with amyloidosis Dutch-type
url http://www.sciencedirect.com/science/article/pii/S2213158225000488
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