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

Lead Research Organisation: University of Manchester
Department Name: School of Biological Sciences

Abstract

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.

Publications

10 25 50
 
Description ISMRM Educational Stipend
Amount $675 (USD)
Organisation International Society for Magnetic Resonance in Medicine (ISMRM) 
Sector Charity/Non Profit
Country United States
Start 05/2019 
End 05/2019
 
Description ISMRM New Entrant Stipend
Amount $675 (USD)
Organisation International Society for Magnetic Resonance in Medicine (ISMRM) 
Sector Charity/Non Profit
Country United States
Start 05/2018 
End 05/2018
 
Title SIDD data 
Description Collecting simultaneous PET-MR data from 40 volunteers - 20 healthy controls and 20 volunteers with a clinical diagnosis of mild cognitive impairment. 
Type Of Material Database/Collection of data 
Year Produced 2019 
Provided To Others? No  
Impact Data collection is not yet complete. 
 
Description Big Brain 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact Schools attended several workshops learning about the brain - I helped in running a section of the neuroimaging workshop.
Year(s) Of Engagement Activity 2018
 
Description British Science Week 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Schools
Results and Impact Running a stall on neuroimaging methods where students could learn about ongoing research and the fundamental science behind the imaging techniques, ask any questions in a friendly and fun environment, and get hands on with interactive games/ equipment. High school students from across the Manchester area attended.
Year(s) Of Engagement Activity 2018,2019
URL http://www.engagement.manchester.ac.uk/highlights/national_science_engineering_week/index.html
 
Description Science Spectacular 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact A science event for the general public to learn about the research happening at the university and the science behind the imaging techniques. Children and adults attended, and were equally interested in the interactive activities.
Year(s) Of Engagement Activity 2018
URL http://www.engagement.manchester.ac.uk/highlights/manchester_science_festival/science_spectacular/