Abstract
Subtle blood–brain barrier (BBB) permeability increases have been shown in small vessel disease (SVD) using various analysis methods. Following recent consensus recommendations, we used Patlak tracer kinetic analysis, considered optimal in low permeability states, to quantify permeability-surface area product (PS), a BBB leakage estimate, and blood plasma volume (vP) in 201 patients with SVD who underwent dynamic contrast-enhanced MRI scans. We ran multivariable regression models with a quantitative or qualitative metric of white matter hyperintensity (WMH) severity, demographic and vascular risk factors. PS increased with WMH severity in grey (B = 0.15, Confidence Interval (CI): [0.001,0.299], p = 0.049) and normal-appearing white matter (B = 0.015, CI: [−0.008,0.308], p = 0.062). Patients with more severe WMH had lower vP in WMH (B = -0.088, CI: [−0.138,-0.039], p < 0.001), but higher vP in normal-appearing white matter (B = 0.031, CI: [−0.004,0.065], p = 0.082). PS and vP were lower at older ages in WMH, grey and white matter. We conclude higher PS in normal-appearing tissue with more severe WMH suggests impaired BBB integrity beyond visible lesions indicating that the microvasculature is compromised in normal-appearing white matter and WMH. BBB dysfunction is an important mechanism in SVD, but associations with clinical variables are complex and underlying damage affecting vascular surface area may alter interpretation of tracer kinetic results.
Highlights
Cerebral small vessel disease (SVD) is an underlying cause in about 25% of strokes and up to 50% of dementias (alone or in combination with Alzheimer’s disease (AD)) (Wardlaw et al, 2019)
PS was highest in recent stroke lesions, followed by white matter hyperintensities (WMH), grey matter (GM) and white matter (WM)
PS decreased with age in WM (B = -0.044, CI: [− 0.07, − 0.018]), GM (B = -0.044, CI: [− 0.068, − 0.019]) and WMH (B = -0.03, CI: [− 0.058, − 0.002]) but not in the recent infarct (B = 0.019, CI: [− 0.067, 0.105])
Summary
Cerebral small vessel disease (SVD) is an underlying cause in about 25% of strokes and up to 50% of dementias (alone or in combination with Alzheimer’s disease (AD)) (Wardlaw et al, 2019). BBB leakiness increases subtly with normal ageing (Erdo et al, 2017; Farrall and Wardlaw, 2009), but has been found in patients with Alzheimer’s disease and in patients with small vessel (lacunar) stroke; leakage was worse in patients with more WMH, and, worse in WMH (Li et al, 2017; Wardlaw et al, 2017; Zhang et al, 2017).
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