PhD: Imaging vascular dysfunction in dementia using quantitative MRI

Disruption to the brain’s blood supply is a key contributor to dementia. Damage to the inner lining of blood vessels, the endothelium, is a key driver, characterised by i) impaired vasoreactivity resulting in dysfunctional cerebral blood flow (CBF) and hypoxia and ii) a compromised blood-brain barrier (BBB), exposing the brain to blood products, and indicating potentially harmful neuroinflammation. Magnetic Resonance Imaging can measure these physiological processes in vivo in people (Chen et al, 2019).

We are seeking a neuroscience student with an interest in neuroimaging or a physics student with an interest in neuroscience with high motivation to undertake a challenging interdisciplinary topic. You will develop MRI measurements of endothelial dysfunction (vasoreactivity and BBB leakage) and evaluate their sensitivity to cognitive impairment in people with cerebral small vessel disease (cSVD).

Vasoreactivity is generally assessed using a hypercapnic gas challenge. However, use of a neural challenge (e.g. visual stimulation) may improve comfort and repeatability and may be more closely related to cognitive impairment. Reactivity to gas/visual challenge will be compared using Arterial Spin Labelling (Woods et al, 2024) and Quantitative Susceptibility Mapping (McFadden et al, 2021) to quantify changes in CBF and oxygen extraction fraction. The latest advances in simultaneous multi-slice technology, enabling fMRI with sub-second temporal resolution, will capture the dynamics of the vascular response.

BBB leakage is assessed using Dynamic Contrast-Enhanced MRI, tracking the passage of the tracer out of the blood into the brain. You will consider different physics-based models of this system and employ them quantify BBB permeability to the tracer. For example, different physiological constraints in different brain regions may require voxel-wise model selection for accurate permeability estimation.

The association between BBB leakage and impaired vasoreactivity will be tested across individuals and across the brain to understand whether they may have a common cause, for example recent evidence suggests they may both be associated with pericyte loss (Procter et al, 2021).

Improving endothelial cell function may provide a therapeutic route for cSVD, slowing the onset of vascular dementia. You will join a team at Imperial College London and the University of Manchester currently working together to evaluate the action of a new drug aimed at improving endothelial function. You will analyse the imaging data from this ongoing project to evaluate the changes in endothelial function associated with the drug.  Comparisons with plasma markers of endothelial activation will aid evaluation of the specificity of the imaging measurements.

• https://research.manchester.ac.uk/en/persons/laura.parkes
• https://sites.manchester.ac.uk/mcrneuroim/
• https://www.pankhurst.manchester.ac.uk/
• https://gjbrainresearch.org/
• https://profiles.imperial.ac.uk/p.matthews
• https://www.imperial.ac.uk/dementia-research-institute/
• https://profiles.imperial.ac.uk/d.owen

VIDA (Vascular and Immune contributors to DementiA) is a new multi-institutional partnership between Alzheimer’s Society and four world-leading research sites: the University of Manchester, University of Edinburgh, Imperial, and City St George’s University of London. With projects focussing on the importance of vascular and immune mechanisms in dementia, VIDA PhD students will become the next generation of much-needed dementia researchers, contributing to breakthroughs in dementia diagnosis and treatment.

VIDA students will embark upon a 4 year fully-funded PhD project at one of the four institutions above, with access to the state-of-the-art research facilities and interdisciplinary training available at all sites. Students at each site will come together as a cohort at several points during the programme, most importantly for an induction week at the beginning of the programme, followed by annual conferences and residential workshop retreats which will link in with other Alzheimer’s Society Doctoral Training Centres across the UK. Students will also participate in engagement schemes with the Alzheimer’s Society and beyond, sharing the impact of their research in the community. The programme also benefits from built in opportunities for placements with leading industrial partners, and bespoke training plans including schemes to develop teaching, mentoring, and grant writing skills.

https://www.dementiaresearcher.nihr.ac.uk/vascular-and-immune-contributors-to-dementia/

https://www.alzheimers.org.uk/research/our-research/alzheimers-society-doctoral-training-centres/vascular-and-immune-contributors-dementia

Eligibility

Applicants must have obtained or be about to obtain a minimum Upper Second class UK honours degree, or the equivalent qualifications gained outside the UK, in a relevant discipline.

Before you Apply

Applicants must make direct contact with preferred supervisors before applying. It is your responsibility to make arrangements to meet with potential supervisors, prior to submitting a formal online application.

How to Apply

To be considered for this project you MUST submit a formal online application form – on the application form you must select programme: PhD Neuroscience. If you select the incorrect programme your application cannot be considered. Full details on how to apply can be found on the website.

Your application form must be accompanied by a number of supporting documents by the advertised deadlines. Without all the required documents submitted at the time of application, your application will not be processed and we cannot accept responsibility for late or missed deadlines. Incomplete applications will not be considered.  If you have any queries regarding making an application, please contact our admissions team.

Equality, Diversity and Inclusion 

Equality, diversity and inclusion is fundamental to the success of The University of Manchester, and is at the heart of all of our activities. The full Equality, diversity and inclusion statement can be found on the website.