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  • Damian Tyler

ABOUT THE RESEARCH

In recent years, the development of cardiac Magnetic Resonance Imaging (MRI) has provided a valuable new approach for the assessment of cardiac structure and function. However, despite the enormous technical developments that have taken place, MRI remains an inherently low sensitivity technique and the low signal levels obtained limit certain applications, e.g., multi-nuclear spectroscopy for the assessment of metabolism. More recently, the development of a range of techniques, which can be gathered under the umbrella term of ‘hyperpolarization’, has offered potential solutions to this low sensitivity.

Dynamic Nuclear Polarization (DNP-MR) is one such hyperpolarization method, which has been demonstrated to increase the sensitivity of MRI to detect metabolic tracers by more than 10,000-fold, thereby allowing in vivo cardiac substrate uptake and metabolism to be measured in real time and at repeated time-points during disease progression. The work in our laboratory aims to develop new imaging techniques and novel metabolic imaging probes to assess metabolism in the heart (See figure). We also apply these techniques to help us understand the mechanisms that control and regulate metabolism in the heart. The exact project can be tailored to the student’s interest i.e., developing new imaging methods, identifying novel hyperpolarized contrast agents or applying developed techniques in model systems or clinical studies.

We work in the Oxford Centre for Clinical Magnetic Resonance Research Centre (OCMR) at the John Radcliffe Hospital where we have three clinical MRI systems and a state-of-the-art hyperpolarizer system, providing all the necessary equipment to undertake studies in various patient groups. We also use pre-clinical MRI equipment in the Department of Physiology, Anatomy & Genetics (DPAG) to study animal models of various cardiovascular diseases.

Additional supervision may be provided by Associate Professor Oliver Rider, Dr James Grist and Dr Aaron Axford.

TRAINING OPPORTUNITIES

The project will allow the student to learn an array of techniques, including in vivo magnetic resonance imaging and spectroscopy for the assessment of cardiac structure and function, as well as the excited new technique of hyperpolarized magnetic resonance imaging

Students are encouraged to attend the MRC Weatherall Institute of Molecular Medicine DPhil Course, which takes place in the autumn of their first year. Running over several days, this course helps students to develop basic research and presentation skills, as well as introducing them to a wide-range of scientific techniques and principles, ensuring that students have the opportunity to build a broad-based understanding of differing research methodologies.

Generic skills training is offered through the Medical Sciences Division's Skills Training Programme. This programme offers a comprehensive range of courses covering many important areas of researcher development: knowledge and intellectual abilities, personal effectiveness, research governance and organisation, and engagement, influence and impact. Students are actively encouraged to take advantage of the training opportunities available to them.

As well as the specific training detailed above, students will have access to a wide-range of seminars and training opportunities through the many research institutes and centres based in Oxford.

The Department has a successful mentoring scheme, open to graduate students, which provides an additional possible channel for personal and professional development outside the regular supervisory framework. We hold an Athena SWAN Silver Award in recognition of our efforts to build a happy and rewarding environment where all staff and students are supported to achieve their full potential.

 

PUBLICATIONS

1

Apps A, Lau JYC, Miller JJJJ, Tyler A, Young LAJ, Lewis AJM, Barnes G, Trumper C, Neubauer S, Rider OJ, Tyler DJ. Proof-of-Principle Demonstration of Direct Metabolic Imaging Following Myocardial Infarction Using Hyperpolarized 13C CMR. JACC Cardiovasc Imaging. 2021 Jun;14(6):1285-1288. PMID: 33582059

2

Timm KN, Perera C, Ball V, Henry JA, Miller JJ, Kerr M, West JA, Sharma E, Broxholme J, Logan A, Savic D, Dodd MS, Griffin JL, Murphy MP, Heather LC, Tyler DJ. Early detection of doxorubicin-induced cardiotoxicity in rats by its cardiac metabolic signature assessed with hyperpolarized MRI. Commun Biol. 2020 Nov 19;3(1):692. PMID: 33214680

3

Rider OJ, Apps A, Miller JJJJ, Lau JYC, Lewis AJM, Peterzan MA, Dodd MS, Lau AZ, Trumper C, Gallagher FA, Grist JT, Brindle KM, Neubauer S, Tyler DJ. Noninvasive In Vivo Assessment of Cardiac Metabolism in the Healthy and Diabetic Human Heart Using Hyperpolarized 13C MRI. Circ Res. 2020 Mar 13;126(6):725-736. PMID: 32078413

4

Lewis AJM, Miller JJ, Lau AZ, Curtis MK, Rider OJ, Choudhury RP, Neubauer S, Cunningham CH, Carr CA, Tyler DJ. Noninvasive Immunometabolic Cardiac Inflammation Imaging Using Hyperpolarized Magnetic Resonance. Circ Res. 2018 Apr 13;122(8):1084-1093. PMID: 29440071

5

Schroeder MA, Clarke K, Neubauer S, Tyler DJ. Hyperpolarized magnetic resonance: a novel technique for the in vivo assessment of cardiovascular disease. Circulation.2011 Oct 4;124(14):1580-94. PMID: 21969318

6

Schroeder MA, Tyler DJ et al. In vivo assessment of pyruvate dehydrogenase flux in the heart using hyperpolarized carbon-13 magnetic resonance. Proc Natl Acad Sci U S A. 2008 Aug 19;105(33):12051-6. PMID: 18689683