DCE-MRI reveals spatial pattern in heterogeneous blood-brain barrier leakage within white matter in cerebral small vessel disease

Damon Verstappen; Joost J.A. de Jong; Paulien H.M. Voorter; Maud van Dinther; Robert J. van Oostenbrugge; Julie Staals; Jacobus F.A. Jansen; Walter H. Backes

doi:10.1177/0271678X251364151

DCE-MRI reveals spatial pattern in heterogeneous blood-brain barrier leakage within white matter in cerebral small vessel disease

Damon Verstappen
, Joost J.A. de Jong
, Paulien H.M. Voorter
, Maud van Dinther
, Robert J. van Oostenbrugge
, Julie Staals
, Jacobus F.A. Jansen
, Walter H. Backes (Corresponding author)

Research output: Contribution to journal › Article › Academic › peer-review

1 Citation (Scopus)

21 Downloads (Pure)

Abstract

Cerebral small vessel disease (cSVD) is associated with vascular cognitive impairment, dementia, and stroke. Blood-brain barrier (BBB) dysfunction is central to its pathophysiology and is involved in the formation of tissue lesions. The spatial heterogeneity of BBB leakage remains largely unclear. This cross-sectional study assessed BBB leakage rate (K_i), fractional volume of leaking tissue (v_l), and blood plasma volume (v_p) in various tissue regions, including gray matter (GM), normal appearing white matter (NAWM), and white matter hyperintensities (WMH) of 59 patients with cSVD and 32 controls using a high spatial resolution dynamic-contrast enhanced MRI protocol. Using regionally averaged measures, patients with cSVD had higher v_l(p = 0.020) and lower v_p(p < 0.001) within WMH compared to controls, K_idid not differ in any region. To evaluate the spatial heterogeneity of leakage in the NAWM, we analyzed 2-mm-wide shells extending outward from WMH edges. This revealed stronger BBB leakage in perilesional NAWM (p = 0.032) of cSVD patients compared to controls, with a striking dip close to the WMH. K_i, v_l, and v_pincreased with distance from WMH edges (all p < 0.001). This pattern of lower BBB leakage in the perilesional NAWM could be caused by local reductions in microvascular blood flow or vessel surface area.

Original language	English
Pages (from-to)	2104-2114
Number of pages	11
Journal	Journal of Cerebral Blood Flow and Metabolism
Volume	45
Issue number	11
DOIs	https://doi.org/10.1177/0271678X251364151
Publication status	Published - Nov 2025

Bibliographical note

Publisher Copyright:
© The Author(s) 2025. This article is distributed under the terms of the Creative Commons Attribution 4.0 License (https://creativecommons.org/licenses/by/4.0/) which permits any use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).

Keywords

Blood-brain barrier
Cerebral small vessel disease
Dynamic contrast-enhanced MRI
Vascular cognitive impairment
White matter hyperintensities

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10.1177/0271678X251364151

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Verstappen, D., de Jong, J. J. A., Voorter, P. H. M., van Dinther, M., van Oostenbrugge, R. J., Staals, J., Jansen, J. F. A., & Backes, W. H. (2025). DCE-MRI reveals spatial pattern in heterogeneous blood-brain barrier leakage within white matter in cerebral small vessel disease. Journal of Cerebral Blood Flow and Metabolism, 45(11), 2104-2114. https://doi.org/10.1177/0271678X251364151

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title = "DCE-MRI reveals spatial pattern in heterogeneous blood-brain barrier leakage within white matter in cerebral small vessel disease",

abstract = "Cerebral small vessel disease (cSVD) is associated with vascular cognitive impairment, dementia, and stroke. Blood-brain barrier (BBB) dysfunction is central to its pathophysiology and is involved in the formation of tissue lesions. The spatial heterogeneity of BBB leakage remains largely unclear. This cross-sectional study assessed BBB leakage rate (Ki), fractional volume of leaking tissue (vl), and blood plasma volume (vp) in various tissue regions, including gray matter (GM), normal appearing white matter (NAWM), and white matter hyperintensities (WMH) of 59 patients with cSVD and 32 controls using a high spatial resolution dynamic-contrast enhanced MRI protocol. Using regionally averaged measures, patients with cSVD had higher vl(p = 0.020) and lower vp(p < 0.001) within WMH compared to controls, Kidid not differ in any region. To evaluate the spatial heterogeneity of leakage in the NAWM, we analyzed 2-mm-wide shells extending outward from WMH edges. This revealed stronger BBB leakage in perilesional NAWM (p = 0.032) of cSVD patients compared to controls, with a striking dip close to the WMH. Ki, vl, and vpincreased with distance from WMH edges (all p < 0.001). This pattern of lower BBB leakage in the perilesional NAWM could be caused by local reductions in microvascular blood flow or vessel surface area.",

keywords = "Blood-brain barrier, Cerebral small vessel disease, Dynamic contrast-enhanced MRI, Vascular cognitive impairment, White matter hyperintensities",

author = "Damon Verstappen and \{de Jong\}, \{Joost J.A.\} and Voorter, \{Paulien H.M.\} and \{van Dinther\}, Maud and \{van Oostenbrugge\}, \{Robert J.\} and Julie Staals and Jansen, \{Jacobus F.A.\} and Backes, \{Walter H.\}",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2025. This article is distributed under the terms of the Creative Commons Attribution 4.0 License (https://creativecommons.org/licenses/by/4.0/) which permits any use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).",

year = "2025",

month = nov,

doi = "10.1177/0271678X251364151",

language = "English",

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Verstappen, D, de Jong, JJA, Voorter, PHM, van Dinther, M, van Oostenbrugge, RJ, Staals, J, Jansen, JFA & Backes, WH 2025, 'DCE-MRI reveals spatial pattern in heterogeneous blood-brain barrier leakage within white matter in cerebral small vessel disease', Journal of Cerebral Blood Flow and Metabolism, vol. 45, no. 11, pp. 2104-2114. https://doi.org/10.1177/0271678X251364151

DCE-MRI reveals spatial pattern in heterogeneous blood-brain barrier leakage within white matter in cerebral small vessel disease. / Verstappen, Damon; de Jong, Joost J.A.; Voorter, Paulien H.M. et al.
In: Journal of Cerebral Blood Flow and Metabolism, Vol. 45, No. 11, 11.2025, p. 2104-2114.

Research output: Contribution to journal › Article › Academic › peer-review

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AU - Verstappen, Damon

AU - de Jong, Joost J.A.

AU - Voorter, Paulien H.M.

AU - van Dinther, Maud

AU - van Oostenbrugge, Robert J.

AU - Staals, Julie

AU - Jansen, Jacobus F.A.

AU - Backes, Walter H.

N1 - Publisher Copyright: © The Author(s) 2025. This article is distributed under the terms of the Creative Commons Attribution 4.0 License (https://creativecommons.org/licenses/by/4.0/) which permits any use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).

PY - 2025/11

Y1 - 2025/11

N2 - Cerebral small vessel disease (cSVD) is associated with vascular cognitive impairment, dementia, and stroke. Blood-brain barrier (BBB) dysfunction is central to its pathophysiology and is involved in the formation of tissue lesions. The spatial heterogeneity of BBB leakage remains largely unclear. This cross-sectional study assessed BBB leakage rate (Ki), fractional volume of leaking tissue (vl), and blood plasma volume (vp) in various tissue regions, including gray matter (GM), normal appearing white matter (NAWM), and white matter hyperintensities (WMH) of 59 patients with cSVD and 32 controls using a high spatial resolution dynamic-contrast enhanced MRI protocol. Using regionally averaged measures, patients with cSVD had higher vl(p = 0.020) and lower vp(p < 0.001) within WMH compared to controls, Kidid not differ in any region. To evaluate the spatial heterogeneity of leakage in the NAWM, we analyzed 2-mm-wide shells extending outward from WMH edges. This revealed stronger BBB leakage in perilesional NAWM (p = 0.032) of cSVD patients compared to controls, with a striking dip close to the WMH. Ki, vl, and vpincreased with distance from WMH edges (all p < 0.001). This pattern of lower BBB leakage in the perilesional NAWM could be caused by local reductions in microvascular blood flow or vessel surface area.

AB - Cerebral small vessel disease (cSVD) is associated with vascular cognitive impairment, dementia, and stroke. Blood-brain barrier (BBB) dysfunction is central to its pathophysiology and is involved in the formation of tissue lesions. The spatial heterogeneity of BBB leakage remains largely unclear. This cross-sectional study assessed BBB leakage rate (Ki), fractional volume of leaking tissue (vl), and blood plasma volume (vp) in various tissue regions, including gray matter (GM), normal appearing white matter (NAWM), and white matter hyperintensities (WMH) of 59 patients with cSVD and 32 controls using a high spatial resolution dynamic-contrast enhanced MRI protocol. Using regionally averaged measures, patients with cSVD had higher vl(p = 0.020) and lower vp(p < 0.001) within WMH compared to controls, Kidid not differ in any region. To evaluate the spatial heterogeneity of leakage in the NAWM, we analyzed 2-mm-wide shells extending outward from WMH edges. This revealed stronger BBB leakage in perilesional NAWM (p = 0.032) of cSVD patients compared to controls, with a striking dip close to the WMH. Ki, vl, and vpincreased with distance from WMH edges (all p < 0.001). This pattern of lower BBB leakage in the perilesional NAWM could be caused by local reductions in microvascular blood flow or vessel surface area.

KW - Blood-brain barrier

KW - Cerebral small vessel disease

KW - Dynamic contrast-enhanced MRI

KW - Vascular cognitive impairment

KW - White matter hyperintensities

UR - https://www.scopus.com/pages/publications/105012869697

U2 - 10.1177/0271678X251364151

DO - 10.1177/0271678X251364151

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C2 - 40757800

AN - SCOPUS:105012869697

SN - 0271-678X

VL - 45

SP - 2104

EP - 2114

JO - Journal of Cerebral Blood Flow and Metabolism

JF - Journal of Cerebral Blood Flow and Metabolism

IS - 11

ER -

DCE-MRI reveals spatial pattern in heterogeneous blood-brain barrier leakage within white matter in cerebral small vessel disease

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