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Updated: Sep 12, 2025
Identification of Disease-related Spatial Covariance Patterns using Neuroimaging Data
Published on: June 26, 2013
DCE-MRI reveals spatial pattern in heterogeneous blood-brain barrier leakage within white matter in cerebral small
Damon Verstappen1,2, Joost J A de Jong1,2, Paulien H M Voorter1,2
1Department of Radiology & Nuclear Medicine, Maastricht University Medical Centre+, Maastricht, Netherlands.
Insights
Cerebral small vessel disease (cSVD) shows varied blood-brain barrier (BBB) leakage. Leakage is higher in white matter lesions and surrounding tissue, but lower near lesions in normal-appearing white matter.
Area of Science:
- Neurology
- Radiology
- Vascular Biology
Background:
- Cerebral small vessel disease (cSVD) is a key factor in cognitive decline, dementia, and stroke.
- Blood-brain barrier (BBB) dysfunction is central to cSVD pathophysiology, contributing to lesion formation.
- The spatial distribution of BBB leakage in cSVD is not well understood.
Purpose of the Study:
- To investigate the spatial heterogeneity of BBB leakage in different brain tissue regions in patients with cSVD.
- To quantify BBB leakage rate (Ki), fractional volume of leaking tissue (vl), and blood plasma volume (vp) in gray matter (GM), normal-appearing white matter (NAWM), and white matter hyperintensities (WMH).
Main Methods:
- Cross-sectional study involving 59 cSVD patients and 32 controls.
- High-spatial-resolution dynamic-contrast enhanced MRI protocol used to assess BBB parameters.
- Analysis included regionally averaged measures and 2-mm-wide shells extending from WMH edges to evaluate perilesional NAWM.
Main Results:
- Patients with cSVD exhibited higher vl and lower vp in WMH compared to controls.
- BBB leakage was elevated in perilesional NAWM of cSVD patients but showed a dip immediately adjacent to WMH.
- Ki, vl, and vp increased with distance from WMH edges in cSVD patients.
Conclusions:
- BBB dysfunction in cSVD is spatially heterogeneous, with distinct patterns in WMH, perilesional NAWM, and distant NAWM.
- The observed leakage pattern near WMH may relate to local changes in microvascular blood flow or vessel surface area.
- Understanding this heterogeneity is crucial for elucidating cSVD mechanisms and developing targeted therapies.
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, Ki 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. Ki, vl, and vp 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.
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