Blood-brain barrier leakage is more widespread in patients with cerebral small vessel disease
C Eleana Zhang1, Sau May Wong2, Harm J van de Haar2
1From the Departments of Neurology (C.E.Z., J.S., R.J.v.O.) and Radiology & Nuclear Medicine (S.M.W., H.J.v.d.H., J.F.A.J., C.R.L.P.N.J., P.A.M.H., W.H.B.), Maastricht University Medical Centre; Cardiovascular Research Institute Maastricht (CARIM) (C.E.Z., R.J.v.O.); and School for Mental Health and Neuroscience (MHeNS) (C.E.Z., S.M.W., H.J.v.d.H., J.S., J.F.A.J., P.A.M.H., R.J.v.O., W.H.B.), Maastricht, the Netherlands. eleana.zhang@mumc.nl.
Objective:
As blood-brain barrier (BBB) dysfunction may occur in normal aging but may also play a pivotal role in the pathophysiology of cerebral small vessel disease (cSVD), we used dynamic contrast-enhanced (DCE)-MRI to quantify the rate and the spatial extent of BBB leakage in patients with cSVD and age- and sex-matched controls to discern cSVD-related BBB leakage from aging-related leakage.
Methods:
We performed structural brain MRI and DCE-MRI in 80 patients with clinically overt cSVD and 40 age- and sex-matched controls. Using the Patlak pharmacokinetic model, we calculated the leakage rate. The mean leakage rate and relative leakage volume were calculated using noise-corrected histogram analysis. Leakage rate and leakage volume were compared between patients with cSVD and controls for the normal-appearing white matter (NAWM), white matter hyperintensities (WMH), cortical gray matter (CGM), and deep gray matter.
Results:
Multivariable linear regression analyses adjusting for age, sex, and cardiovascular risk factors showed that the leakage volume of the NAWM, WMH, and CGM was significantly larger in patients with cSVD compared with controls. No significant difference was found for leakage rate in any of the tissue regions.
Conclusion:
We demonstrated a larger tissue volume with subtle BBB leakage in patients with cSVD than in controls. This was shown in the NAWM, WMH, and CGM, supporting the generalized nature of cSVD.
Insights
Cerebral small vessel disease (cSVD) is linked to increased blood-brain barrier (BBB) leakage in brain tissue, including normal-appearing white matter and gray matter. This subtle BBB dysfunction is more widespread in cSVD patients than in healthy aging.
Area of Science:
- Neurology
- Radiology
- Vascular Biology
Background:
- Blood-brain barrier (BBB) dysfunction is implicated in normal aging and cerebral small vessel disease (cSVD).
- Distinguishing aging-related BBB changes from cSVD-specific pathology is crucial for understanding disease mechanisms.
Purpose of the Study:
- To quantify and compare the rate and spatial extent of BBB leakage in patients with cSVD versus age- and sex-matched controls.
- To differentiate cSVD-related BBB leakage from normal aging-related BBB changes.
Main Methods:
- Dynamic contrast-enhanced MRI (DCE-MRI) was used to assess BBB leakage.
- The Patlak pharmacokinetic model and noise-corrected histogram analysis quantified leakage rate and volume.
- Leakage was analyzed in normal-appearing white matter (NAWM), white matter hyperintensities (WMH), cortical gray matter (CGM), and deep gray matter.
Main Results:
- Patients with cSVD exhibited significantly larger leakage volumes in NAWM, WMH, and CGM compared to controls.
- No significant differences in BBB leakage rate were observed across tissue regions between groups.
- These findings suggest a generalized pattern of subtle BBB leakage in cSVD.
Conclusions:
- Cerebral small vessel disease is associated with a greater volume of subtle blood-brain barrier leakage.
- This leakage extends to normal-appearing white matter and gray matter, indicating a generalized effect in cSVD.
- The study highlights increased BBB permeability as a key feature of cSVD beyond normal aging.
