Development and validation of MRI-based measurements of microvessel structure in the brain

Damage of the smallest blood vessels in the brain is common and is thought to contribute to a wide range of diseases including neurodegenerative disorders. For example there is evidence for thickening of vessel walls, reductions in vessel density and increased vessel tortuosity in neurodegenerative disease. These microstructural changes may lead to reduced oxygen supply thus causing damage to neurons, but the ordering and nature of events is unclear. Open questions remain as to whether structural changes to vessels are themselves purely detrimental or possibly compensatory, for example micro-collaterals may preserve blood supply. One gap in probing such questions is the lack of accurate, precise validated measurements of microvessel structure in vivo. MRI has the potential to provide these measurements but validation is critical.

A number of innovative microvascular MR imaging approaches are under development here in Manchester. For example, capillary segment length derived from diffusion-weighted images, arterial arrival time (the time taken for blood to travel along vessels) derived from arterial spin labelling MRI, along with more established techniques such as vessel size imaging. While these imaging approaches are readily translatable into clinical practice, the values of the microvascular parameters obtained rely on complex modelling and incorporate a number of assumptions. The techniques therefore require substantial technical validation before acceptance by the wider clinical community for use as diagnostic or predictive biomarkers. One promising approach to validation is via 3D X-ray microscopy of vascular corrosion casts, a technique that has been developed in Manchester on tumours which we now wish to extend to the brain. The 3D microscopy image is segmented and skeletonised allowing extraction of statistics on vessel radius and segment length which can be used to validate the MR measurements.

The aim of this PhD project is to develop and comprehensively validate MRI-based microvascular measurements using 3D X-ray microscopy of vascular corrosion casts. The successful student will join our growing team of scientists working on a programme of EPSRC-funded work in Manchester developing novel measurements of neuronal and vascular pathology for accurate characterisation of disease burden in dementia. This PhD project will take the next crucial step by developing quantitative, validated microvascular measures which will help clinical researchers understand the link between microvascular change and neurodegeneration.