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


Neuroscience Institute

Sheffield United Kingdom Biomedical Engineering Electrical Engineering Medical Physics Mathematics

About the Project

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.

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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.


Funding Notes

• 3.5 years PhD studentship commencing October 2021
• UKRI equivalent home stipend rate per annum for 3.5 years
• Tuition fees for 3.5 years
• EPSRC studentships come with a £4,500 Research Training Support Grant over the course of the award.
Additional cost towards RF components and hyperpolarised xenon gas that is in addition to EPSRC studentship will be co-funded by the POLARIS research group and GE healthcare. For international students, we will able to cover additional fees incurred due to international student fee rates and offer an enhanced stipend subjected to the merit of the candidate.

References



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