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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 Voorter, Maud van Dinther, Robert J. van Oostenbrugge, Julie Staals, Jacobus F.A. Jansen, Walter H. Backes. Journal of Cerebral Blood Flow & Metabolism, 2025-08-04
Topic: Brain proteins, microglia and lab models
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 i did 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 p increased 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.
Key findings
- Cerebral small vessel disease (cSVD) is associated with vascular cognitive impairment, dementia, and stroke.
- 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 i did not differ in any region.
- 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.
Why it matters
In this cross-sectional study, patients with cerebral small vessel disease had higher leakage tissue volume and lower blood plasma volume within white matter hyperintensities compared to controls, but the leakage rate itself did not differ in any region. The findings describe a spatial pattern of blood-brain barrier leakage that may be caused by local reductions in microvascular blood flow or vessel surface area, but they do not test any treatment, cure, or prevention.
Study details
- Study designcross-sectional
- Participants59
- Evidence strengthLow
How this study scored 47/100
Published in a peer-reviewed journal, and it is a snapshot of people at one point in time. Scored zero for effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Journal of Cerebral Blood Flow & Metabolism) |
| Journal's citation record | 3 / 4 | Journal of Cerebral Blood Flow & Metabolism: journal h-index 285 (OpenAlex, 2026-10-29) |
| Study design | 4 / 12 | A snapshot of people at one point in time |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 4 / 5 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 1 / 4 | 59 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 1 / 7 | Cited 3 times (OpenAlex, 2026-10-10) |
| Citations per year | 1 / 5 | 1.0 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 2 / 6 | Cited 1.7× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 1 / 4 | Cited 3 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Walter H. Backes: h-index 71 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | Maastricht University: institution h-index 876 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40757800) |
| Free to read | 2 / 2 | Free to read |
| Total | 47 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1177/0271678x251364151
- PubMed: 40757800
- Original source →
- Free full text: Journal of Cerebral Blood Flow & Metabolism →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record names 8 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
APA 7th
Verstappen, D., de Jong, J. J., Voorter, P., van Dinther, M., van Oostenbrugge, R. J., Staals, J., et al. (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 & Metabolism. https://doi.org/10.1177/0271678x251364151
Vancouver
Verstappen D, de Jong JJ, Voorter P, van Dinther M, van Oostenbrugge RJ, Staals J, et al. DCE-MRI reveals spatial pattern in heterogeneous blood-brain barrier leakage within white matter in cerebral small vessel disease. Journal of Cerebral Blood Flow & Metabolism. 2025. doi:10.1177/0271678x251364151. PMID: 40757800.
BibTeX
@article{verstappen2025-40757800,
author = {Verstappen, Damon and de Jong, Joost J.A. and Voorter, Paulien and van Dinther, Maud and van Oostenbrugge, Robert J. and Staals, Julie and Jansen, Jacobus F.A. and Backes, Walter H.},
title = {{DCE-MRI reveals spatial pattern in heterogeneous blood-brain barrier leakage within white matter in cerebral small vessel disease}},
journal = {Journal of Cerebral Blood Flow \& Metabolism},
year = {2025},
doi = {10.1177/0271678x251364151},
pmid = {40757800},
url = {https://doi.org/10.1177/0271678x251364151}
}
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