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  • Damian Tyler

About the Research

The role of abnormal cardiac substrate metabolism in the development of a wide array of cardiovascular diseases and the therapeutic potential of interventions targeting cardiac substrate metabolism are unclear. Magnetic Resonance Imaging and Spectroscopy (MRI/MRS) have long been used to monitor cardiac structure and function. However, the application of MRI/MRS for metabolic imaging has been limited by an intrinsically low sensitivity. Hyperpolarized Magnetic Resonance (MR) is a new technique that yields greater than 10,000-fold signal increases in MR images and enables unprecedented real-time visualization of the biochemical mechanisms of abnormal metabolism. This allows measurement of instantaneous rates of substrate uptake and enzymatic transformation in vivo, providing a sensitive assessment of disease and a new means to monitor treatment response. We hypothesise that cardiac dysfunction results from the impairment of cardiac metabolism in the diseased heart and that treatments that normalise myocardial metabolism will reverse the cardiac dysfunction.

Therefore, a key feature of the project will focus on the development of new imaging approaches and their application in the measurement of rates of cardiac metabolism and assessment of how it can be modulated as a therapeutic target in cardiovascular disease.

Training Opportunities

During your time in the lab, you’ll be trained in the running of clinical studies, the processing of imaging and clinical data and the understanding of metabolic pathways and medical imaging approaches.

You’ll have chance to learn to how to use an MRI scanner, as well as to scan volunteers and patients in your studies.

You’ll also be given the opportunity to learn and develop skills in Matlab and Python programming languages for data reconstruction, postprocessing, and analysis.

 

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.

 Additional supervisors

1

Dr James Grist

2

Prof Ladislav Valkovic

Publications

1

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

2

Noninvasive In Vivo Assessment of Cardiac Metabolism in the Healthy and Diabetic Human Heart Using Hyperpolarized 13C MRI. 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. Circ Res. 2020 Mar 13;126(6):725-736. PMID: 32078413

3

Early detection of doxorubicin-induced cardiotoxicity in rats by its cardiac metabolic signature assessed with hyperpolarized MRI. 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. Commun Biol. 2020 Nov 19;3(1):692. PMID: 33214680

4

Non-invasive Immunometabolic Cardiac Inflammation Imaging Using Hyperpolarized Magnetic Resonance. Lewis AJM, Miller JJ, Lau AZ, Curtis MK, Rider OJ, Choudhury RP, Neubauer S, Cunningham CH, Carr CA, Tyler DJ. 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