Background and purpose: The pathogenesis of cerebral small vessel disease (SVD) is incompletely understood. Endothelial dysfunction has been implicated and may result in increased blood-brain barrier (BBB) permeability with leakage of blood constituents into the vessel wall and white matter. We used contrast enhanced magnetic resonance imaging (MRI) to determine whether there was evidence for BBB permeability in the white matter of patients with SVD, and whether this was present not only in areas of leukoaraiosis (white matter lesions,WML) but also in normal appearing white matter (NAWM).
Methods: Subjects underwent T1 volumetric MRI before and after bolus injection of contrast. Scanning was continued for 30 minutes post injection to determine the contrast enhancement time course. Mean signal intensity change was plotted against time to calculate area under curve (AUC) values, a parameter related to BBB permeability. Automated brain segmentation and regions of interest analysis were performed to determine “permeability” in different brain compartments.
Results: Compared to controls (n=15), the SVD patient group (n=24) had signal changes consistent with increased BBB permeability in NAWM (P = 0.033). Multivariate regression analyses identified leukoaraiosis grade as an independent predictor of these permeability related signal changes in NAWM after adjustment for age, gender, weight, brain volume, AUC in the internal carotid arteries, and cardiovascular risk factors.
Conclusion: This study provides evidence for increased BBB permeability in SVD, and this is particularly seen in SVD with leukoaraiosis. Its presence in NAWM would be consistent with it playing a causal role in disease pathophysiology.