Jessica Walsh

Supervisor: Professor Hugh Markus

Title: Imaging the Role of Blood Brain Barrier Permeability in Cerebral Small Vessel Disease

Abstract: Cerebral small vessel disease (SVD) occurs within the subcortical vessels of the brain and causes ischemia and haemorrhage. SVD is responsible for around 20% of ischemic strokes worldwide and is a common cause of dementia. The biggest risk factor is hypertension, but much is still unknown about the pathogenesis. The conventional hypothesis is that hypoperfusion occurs due to arteriolar changes and impaired autoregulation. However, more recent studies are indicating an alternative hypothesis, where an increase in blood brain barrier (BBB) permeability may occur to allow leakage of plasma constituents into the brain parenchyma, leading to damage.

This project will investigate this hypothesis using magnetic resonance imaging (MRI) techniques to both quantify and map BBB leakage with damage to brain regions in individual patients. We will also determine whether increased BBB permeability correlates with both clinical parameters and serum markers of endothelial activation and BBB disruption. This study will compare patients with the sporadic form of SVD to patients with a monogenic form of the disease, known as CADASIL. We are interested in how common BBB breakdown is, where it occurs, its relationship to other MRI disease markers and whether it can predict which brain regions will go on to develop permanent damage.