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MRC DiMeN Doctoral Training Partnership: Development and application of fast Magnetic Resonance Spectroscopic Imaging methods for neuro-chemical profiling


Project Description

While Magnetic Resonance Imaging is well established to assess anatomy, structure and function in patients and in animal models of human disease alike, (routine) MR Spectroscopy tools to investigate metabolic alterations are far less common. Long scan times and low spatial resolution (i.e. typically single voxel MRS of large volumes) associated with MRS experiments limit the applicability of this versatile technique, particularly in critically ill patients. SPectroscopic Imaging by exploiting spatiospectral CorrElation (SPICE) is a novel and emerging technique that promises to overcome some of the limitations and achieves high-resolution MR spectroscopic imaging (MRSI). We propose to develop SPICE for application in an orthotopic murine brain tumour model and to translate this into the clinic. SPICE has so far only been reported as proof of concept studies in healthy human volunteers at 3T, but not in small animals. The supervisors and their teams have initiated a major multi-modal imaging study in patients with glioblastoma, which is complemented by preclinical investigations in a representative murine model. Metabolic information is presently not obtained but would be highly desirable, and ultimately pave the way for novel (pre-)clinical applications. The overall aim of this project is to extend SPICE to both a preclinical ultra-high MR system and to patients, paving the way for a more comprehensive, neuro-chemical profiling. More specifically, the plan is to implement and optimise the appropriate measurement sequences on a preclinical MR system, to validate it in synthetic phantoms (resembling the metabolic profile of the brain), and apply it to healthy mice. To demonstrate applicability, a longitudinal investigation of a murine glioblastoma model with / without radiotherapy treatment will be performed. It is ultimately planned to translate this technique to a clinical 3T scanner, for which a preliminary measurement sequence already exists.


The student will be, as member of the Preclinical and Experimental Imaging Centre (ePIC) at the University of Leeds, trained in preclinical MR imaging and sequence development, using the preclinical 7T MR system in ePIC. In the initial stage of the project it is also planned for the student to visit a lab at the University of Illinois, US, to receive training in SPICE and the required analysis / post-processing. The student will also work with the translational neuro oncology team on the St James’s hospital site learning about the clinical and biological challenges inherent in managing glioma patients and becoming familiar with establishment, treatment and assessment of pre-clinical models of this disease.

Benefits of being in the DiMeN DTP:
This project is part of the Discovery Medicine North Doctoral Training Partnership (DiMeN DTP), a diverse community of PhD students across the North of England researching the major health problems facing the world today. Our partner institutions (Universities of Leeds, Liverpool, Newcastle and Sheffield) are internationally recognised as centres of research excellence and can offer you access to state-of the-art facilities to deliver high impact research.
We are very proud of our student-centred ethos and committed to supporting you throughout your PhD. As part of the DTP, we offer bespoke training in key skills sought after in early career researchers, as well as opportunities to broaden your career horizons in a range of non-academic sectors.
Being funded by the MRC means you can access additional funding for research placements, international training opportunities or internships in science policy, science communication and beyond. See how our current DiMeN students have benefited from this funding here: http://www.dimen.org.uk/overview/student-profiles/flexible-supplement-awards
Further information on the programme can be found on our website:
http://www.dimen.org.uk/

Funding Notes

Funding notes
Studentships are fully funded by the Medical Research Council (MRC) for 3.5yrs
Includes:
Stipend at national UKRI standard rate
Tuition fees
Research training and support grant (RTSG)
Travel allowance
Studentships commence: 1st October 2019.

To qualify, you must be a UK or EU citizen who has been resident in the UK/EU for 3 years prior to commencement. Applicants must have obtained, or be about to obtain, at least a 2.1 honours degree (or equivalent) in a relevant subject. All applications are scored blindly based on merit. Please read additional guidance here: View Website
Good luck!

References

1. Liang ZP. Spatiotemporal imaging with partially separable functions. 2007 4th Ieee International Symposium on Biomedical Imaging : Macro to Nano, Vols 1-3 2007:988-991.
2. Lam F, Ma C, Clifford B, Johnson CL, Liang ZP. High-resolution (1) H-MRSI of the brain using SPICE: Data acquisition and image reconstruction. Magn Reson Med 2016;76(4):1059-1070.

3. Ma C, Lam F, Ning Q, Johnson CL, Liang ZP. High-resolution 1 H-MRSI of the brain using short-TE SPICE. Magn Reson Med 2017;77(2):467-479.

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