22 Nov 21. Featured Paper

Tracer kinetic assessment of blood–brain barrier leakage & blood volume in cerebral small vessel disease: Associations with disease burden & vascular risk factors

Link to paper on NeuroImage: Clinical

Authors

Michael S. Stringer, Anna K. Heye, Paul A. Armitage, Francesca Chappell, Maria del C. Valdés Hernández, Stephen D.J. Makin, Eleni Sakka, Michael J. Thrippleton, Joanna M. Wardlaw

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, & 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 & vascular risk factors.

PS increased with WMH severity in grey (B = 0.15, Confidence Interval (CI): [0.001,0.299], p = 0.049) & 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 & vP were lower at older ages in WMH, grey & 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 & WMH.

BBB dysfunction is an important mechanism in SVD, but associations with clinical variables are complex & underlying damage affecting vascular surface area may alter interpretation of tracer kinetic results.

Keywords

• Blood brain barrier
• Cerebrovascular disease
• MRI
• Stroke
• SVD