Blood-Brain Barrier Imaging in Cerebral Small Vessel Disease

Maskery, Mark and Emsley, Hedley and Knight, Joanne and Rennie, Nicola and Parkes, Laura M. (2024) Blood-Brain Barrier Imaging in Cerebral Small Vessel Disease. PhD thesis, Lancaster University.

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Abstract

Cerebral small vessel disease (cSVD) refers to a group of conditions associated with impaired functioning of the smallest blood vessels supplying the brain. Whilst cSVD causes around a quarter of all strokes and contributes to approximately half of all cases of dementia – as well as disturbances in gait, mood and cognition - the condition is often overlooked and treatment options are limited. We found evidence of white matter hyperintensities (WMHs), often indicative of cSVD, on over 40% of routinely performed brain scans locally. Recent evidence suggests that changes in the highly specialised blood-brain barrier (BBB) underlie the early pathophysiology of cSVD. Measuring water exchange across the BBB using magnetic resonance imaging may be a sensitive marker for BBB dysfunction. Our systematic scoping review identified 38 clinical BBB water exchange studies in a number of disorders, with seven focussed on cSVD. Studies were heterogeneous, as expected with exploratory research, but with encouraging trends across several pathologies including measures of repeatability. We performed an exploratory study of filter-exchange imaging (FEXI) in patients with cSVD, compared with healthy volunteers. Whilst the imaging protocol was well tolerated, there was no significant difference between BBB water exchange between groups nor correlation with WMH volume. However, we demonstrate important associations between WMH volume, cognition and QRISK3 as well as an interesting difference in extra-vascular diffusivity (thought to reflect altered microstructural integrity) between groups. Larger, longitudinal studies are required to determine the sensitivity of these novel measurements as markers of cSVD and to assess their prognostic value for clinical parameters such as cognitive decline.