Microstructural and dynamic biomarkers of neurodegeneration

Lead supervisor: Professor Vanessa Raymont

Co-supervisor: Dr Ivan Koychev

Commercial partner: Oxford Brain Diagnostics

Dementia is a leading cause of death globally, and a primary cause of UK mortality. The lack of effective diagnostics has affected clinical pathways and management, and the failure of meaningful therapeutic development.

The project will be affiliated with the MRC-funded Dementias Platform UK (DPUK). We will work with the Oxford University start-up company Oxford Brain Diagnostics (OBD) to develop novel neuroimaging biomarkers. Specifically, we will use two highly complementary techniques to study neurodegeneration in a sample of at-risk and clinically diagnosed individuals. Firstly, we will deploy diffusion tensor imaging to derive microstructural measurements using methodologies for which OBD has FDA clearance and FDA Breakthrough Device Designation. Secondly, we use an experimental medicine model to apply intranasal insulin and record the cortical responsiveness using functional MRI and arterial spin labelling. This measure is hypothesised to be reflective of neuroplasticity reserve given the known role of insulin as a neural growth factor. The study will recruit individuals with a range of biomarker profiles from two leading blood biomarker studies; the READ-OUT programme (co-leads Raymont and Koychev) and FAST study (CI Koychev). The former will provide access to those with existing memory disorders, while the latter individuals at-risk for dementia. The PhD student will collaborate with OBD to gain experience in advanced neuroimaging analysis. 

The objectives are to:

1. Establish novel microstructural and dynamic neuroimaging biomarkers for various dementia pathologies (i.e. Alzheimer’s disease, Lewy Body dementia, vascular dementia) and at-risk states for dementia

2.  Create multi-modal algorithms of disease progression using fluid (i.e. blood) and neuroimaging biomarkers the generation of novel analytic pipelines

3. Translate insights gained from objectives 1 and 2 to design a clinical validation framework for care pathway change that will utilise multi-modal biomarker assessments for complex neurodegeneration presentations, allowing generation of novel analytic pipelines made available via the DPUK data portal.

Apply using course: DPhil in Psychiatry