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Evaluation of blood-brain barrier dysfunction in cerebral small vessel disease

Project Description

Project Description

Blood-brain barrier (BBB) dysfunction is implicated in neurological conditions including cerebral small vessel disease (CSVD) – a condition that accounts for 25% of ischaemic stroke and makes a major contribution to dementia. BBB dysfunction plays a role in numerous other neurological disorders.

Currently, methods to quantify BBB dysfunction are either invasive, potentially harmful or not sufficiently sensitive to detect regional abnormalities of clinical significance. Novel MRI methods to measure water exchange across the BBB are in development but have not yet been clinically evaluated.

This fellowship will be closely aligned to a grant-funded imaging study co-ordinated by an established team of internationally recognised experts within the field of novel MRI markers (including co-supervisor Parkes), that will start with a discovery phase building upon current knowledge of contrast-enhanced and non-contrast arterial spin labelling sequences to identify the most sensitive markers of BBB dysfunction in preclinical models.

The PhD will focus on an evaluation phase in which BBB markers will be tested for the first time clinically. After completing a systematic review of current CSVD MRI markers, the PhD student will then trial the measurements using an existing dataset before recruiting 40 stroke patients and 20 healthy volunteers to undergo 3T MR imaging. Participants will also undergo cognitive assessment at baseline, repeated at 12 months to assess for radiological correlation with cognitive impairment, and potential radiological predictors of cognitive decline.

This project will permit further understanding of the pathophysiology of BBB dysfunction and its relationship to cognition. This will support researchers characterising the delivery of therapeutic agents across the BBB to help develop new treatments. Ultimately, this will enable clinicians to guide individualised care.

This project would suit a clinically qualified applicant with an interest in neurology.

Funding Notes

Applications should be made directly to Professor Jo Knight and should include:

CV (max 2 A4 sides), including details of two academic references
A cover letter outlining your qualifications and interest in the studentship (max 2 A4 sides)

How good is research at Lancaster University in Allied Health Professions, Dentistry, Nursing and Pharmacy?

FTE Category A staff submitted: 64.40

Research output data provided by the Research Excellence Framework (REF)

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