Methods for multi-nuclear magnetic resonance imaging and spectroscopy of the brain using proton, sodium-23, phosphorus-31 and hyperpolarised xenon-129.

To date most neuropathological diseases are diagnosed using conventional structural ¹H MRI techniques such as T₁, T₂, diffusion-weighted MRI and functional ¹H MRI techniques such as dynamic contrast enhanced ¹H MRI and blood oxygen level dependent fMRI. A less explored area of NMR of the brain is the consideration of other nuclei that exhibit NMR properties such as sodium (²³Na) and phosphorus (³¹P). Other non-proton exogenously introduced imaging nuclei that can be used to image the human brain are hyperpolarized (HP) xenon (¹²⁹Xe) and carbon (¹³C). ²³Na, ³¹P and ¹³C MRI can uniquely measure disease related changes in metabolism in the brain, and ¹²⁹Xe MRI can measure perfusion and gas-exchange in the brain irrespective of metabolism, oxygenation or electrolytic balance. Combining the information from each of these non-proton nuclei along with conventional ¹H MRI provides additional functional sensitivity that can be used alongside PET radio tracer imaging to better understand brain disease mechanisms and pathophysiology.

The PhD project is to develop multi-nuclear methods for brain MRI, and there by develop methods to combine the information from all nuclei to investigate novel diagnostic techniques, establish the benefits to estimate specificity and disease severity. Specifically, to develop bespoke RF coil and pulse sequence image acquisition strategies for ²³Na, ¹²⁹Xe, ³¹P and ¹H brain MRI at 3.0 T on PET-MRI scanner. The goal is to create a range of new brain sensing approaches that can be used to study brain metabolism, physiology and gas-exchange alongside ¹H MR and PET. Key research milestones are to (a) establish theoretical limits for sensitivity of ¹²⁹Xe, ³¹P, ²³Na in realistic concentrations and develop phantoms for the same, (b) develop brain MRI protocols to conduct in vivo experiments that include new RF coils, pulse sequence design, image processing and brain computational physiology/disease models, (c) recruit healthy volunteers and (d) conduct in vivo MR experiments. The techniques will be evaluated in healthy volunteers with a scope to further evaluate its feasibility in clinical follow-up studies.

The research requires candidates to have physics or engineering background such as electrical, electronics, computer science or equivalent, and to be excellent in their respective core subjects and mathematics. This opportunity offers students the knowledge and experience of conducting MR research that involve knowledge about MR physics and engineering, developing research protocols, conducting MR studies involving volunteers and academic publication.

About us: Our group has leading expertise in non-proton methods and their application including ¹²⁹Xe and ³¹P brain MRI. Our recent studies with HP ¹²⁹Xe brain MRI have demonstrated a new method to directly image regional brain perfusion and gas-exchange in healthy volunteers. A pilot study in stroke demonstrated image contrast over the infarct region larger than those indicated by conventional ¹H MRI. We have shown that by using quantitative ¹H arterial spin labelling methods, the influence of regional perfusion in ¹²⁹Xe MR image(s) can be compensated such that the image contrast corresponds to regional gas-uptake across BBB. Thus, introducing a new approach to diagnose brain pathologies by combining information from ¹²⁹Xe and ¹H. Recently, we introduced a trace kinetic model to estimate gas-exchange rate between blood and brain tissue across the blood-brain barrier that may aid in quantifying HP ¹²⁹Xe brain MRI. In previous studies working with colleagues in neuroscience, ³¹P MRI has been shown to provide metabolic insight in to motor neurone disease and multiple sclerosis. Thus, the research builds on the investigators record of accomplishment with innovative multinuclear MR imaging research.

--

Please complete a University Postgraduate Research Application form available here: https://www.sheffield.ac.uk/postgradapplication/

Please clearly state the prospective main supervisor in the respective box and select ‘Neuroscience’ as the department.

After the application closing date, we will shortlist applicants for an online interview. We expect to carry out interviews (each lasting approximately 30 minutes) on Tuesday 27th April (am, GMT) and Tuesday 4th May (pm, GMT). If you are shortlisted for interview, we will aim to inform you of this no later than the end of Friday 23rd April. If you are unable to attend at the specified times, please let us know if we confirm that we would like to interview you.