Tracer kinetic assessment of blood-brain barrier leakage and blood volume in cerebral small vessel disease: associations with disease burden and vascular risk factors

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