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Disruption of the Blood-Brain Barrier Predicts Progression of Cerebral Small Vessel Disease White Matter
Richard Leigh1, Kyle C Kern2, Nae-Yuh Wang3
1Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD.
Insights
Blood-brain barrier (BBB) disruption, measured by dynamic susceptibility contrast (DSC) imaging, predicts white matter hyperintensity (WMH) progression in patients with chronic cerebrovascular disease. More severe BBB disruption indicates a higher risk of WMH worsening over one year.
Area of Science:
- Neurology
- Radiology
- Vascular Biology
Background:
- Chronic cerebrovascular disease is associated with white matter hyperintensities (WMHs).
- The blood-brain barrier (BBB) plays a crucial role in brain health and its disruption is implicated in various neurological conditions.
Purpose of the Study:
- To investigate if blood-brain barrier (BBB) disruption, detected via dynamic susceptibility contrast (DSC) imaging, can predict the progression of white matter hyperintensities (WMHs) over one year.
- To assess the relationship between BBB integrity and WMH volume changes in patients with chronic cerebrovascular disease.
Main Methods:
- Included patients with a history of stroke and WMHs.
- Utilized magnetic resonance imaging (MRI) at baseline and 1-year follow-up to measure WMH volume.
- Assessed BBB disruption using DSC imaging on the baseline MRI, averaging disruption within WMHs and the adjacent 'penumbra' region.
Main Results:
- Fifty patients (median age 69, 46% women) were analyzed.
- More severe BBB disruption in both WMH and penumbra regions was associated with greater WMH progression.
- BBB disruption in the penumbra was the strongest predictor, with a doubling of odds for WMH progression for every 0.1% increase in BBB disruption.
Conclusions:
- Increased blood-brain barrier disruption is a significant predictor of white matter hyperintensity progression in patients with chronic cerebrovascular disease.
- DSC imaging can identify individuals at higher risk for WMH worsening, aiding in understanding disease trajectory.
Objective:
The objective of this study was to test if blood-brain barrier (BBB) disruption, detected using dynamic susceptibility contrast (DSC) imaging, would predict progression of white matter hyperintensities (WMHs) over the subsequent year in patients with chronic cerebrovascular disease.
Methods:
The study included patients with a history of stroke and at least early confluence of WMH. Magnetic resonance imaging (MRI) scans performed at baseline (> 3 months from stroke) and again 1 year later were segmented to calculate the WMH volume expressed as a fraction of the total brain volume. Change in WMH volume between the 2 timepoints and progression of WMH were the outcome measures. BBB disruption was measured using DSC imaging on the baseline MRI. WMH masks were dilated by 3 mm to create a mask of the adjacent normal appearing white matter (penumbra). BBB disruption was averaged within the WMH and the penumbra.
Results:
Fifty patients were included; median age was 69 years, and 46% were women. The mean WMH fraction was 1.25% at baseline and 1.36% at 1 year. The mean baseline BBB disruption was 0.20% in the WMH and 0.22% in the penumbra. More severe BBB disruption was associated with greater WMH progression when measured in the WMH (ß = 0.95, confidence interval [CI] = 0.39-1.51, r2 = 0.19, p = 0.001) and in the penumbra (ß = 0.81, CI = 0.10-1.53, r2 = 0.10, p = 0.027). The best predictor of progression was BBB disruption in the penumbra with an odds ratio (OR) of 2 (OR = 2, CI = 1.01-3.96, p = 0.046) for each 0.1% increase in BBB disruption.
Interpretation:
More severe BBB disruption was predictive of greater WMH progression in patients with chronic cerebrovascular disease. ANN NEUROL 2026;99:437-448.
