Dr Damian Tyler

Dr Damian Tylerisobel Laing Research Fellow in medicine

Biography

Damian Tyler is a University Research Lecturer in the Department of Physiology, Anatomy and Genetics and the Isobel Laing Research Fellow at Oriel College.  He has been in Oxford since 2001 and has over 10 years experience in the development and application of Magnetic Resonance Imaging and Spectroscopy (MRI/MRS). He gained his MSci in Physics in 1998 and his doctorate in 2001, both from the University of Nottingham. He is an associate member of the Cardiac Metabolism Research Group (CMRG) and leads the Dynamic Nuclear Polarization research group.

Research Interests

Damian’s research in Oxford has been based on the study of cardiac structure, function and metabolism in normal and diseased hearts using MRI/MRS. This has included developing techniques using high spatial and temporal resolution CINE imaging to assess heart function and localized phosphorus and carbon spectroscopy to monitor and investigate abnormalities of metabolism. He has recently been awarded a British Heart Foundation Intermediate Research Fellowship to further develop the technique of Dynamic Nuclear Polarization (DNP) for application to the study of cardiac metabolism. A fundamental limitation of magnetic resonance is its low sensitivity, but the recently developed technique of DNP provides a practical method to gain up to 10,000-fold increases in sensitivity in molecules with an in vivo stability of approximately one minute.  This has enabled visualization of 13C-labelled cellular metabolites in vivo and, more importantly, their enzymatic transformation into other species. This is an important development that could revolutionize spectroscopy using MR.

College Teaching

Damian is responsible for teaching biochemistry to the first year undergraduates on the pre-clinical medicine course and he teaches metabolism to the undergraduate biochemistry students. He is currently supervising three postgraduate students on projects relating to the study of cardiac metabolism.

Key Publications

  1. Atherton HJ, Dodd MS, Heather LC, Schroeder MA, Griffin JL, Radda GK, Clarke K, Tyler DJ. Role of Pyruvate Dehydrogenase Inhibition in the Development of Hypertrophy in the Hyperthyroid Rat Heart: A Combined Magnetic Resonance Imaging and Hyperpolarized Magnetic Resonance Spectroscopy Study. Circulation. 2011 May 23. [Epub ahead of print] PubMed PMID: 21606392.
  2. Tyler DJ. Cardiovascular Applications of Hyperpolarized MRI. Curr Cardiovasc Imaging Rep. 2011 Apr;4(2):108-115. Epub 2011 Jan 19. PubMed PMID: 21475403; PubMed Central PMCID: PMC3047696.
  3. Schroeder MA, Swietach P, Atherton HJ, Gallagher FA, Lee P, Radda GK, Clarke K, Tyler DJ. Measuring intracellular pH in the heart using hyperpolarized carbon dioxide and bicarbonate: a 13C and 31P magnetic resonance spectroscopy study. Cardiovasc Res. 2010 Apr 1;86(1):82-91. Epub 2009 Dec 15. PubMed PMID: 20008827; PubMed Central PMCID: PMC2836261.
  4. Schroeder MA, Atherton HJ, Ball DR, Cole MA, Heather LC, Griffin JL, Clarke K, Radda GK, Tyler DJ. Real-time assessment of Krebs cycle metabolism using hyperpolarized 13C magnetic resonance spectroscopy. FASEB J. 2009 Aug;23(8):2529-38. Epub 2009 Mar 27. PubMed PMID: 19329759; PubMed Central PMCID: PMC2717776.
  5. Schroeder MA, Cochlin LE, Heather LC, Clarke K, Radda GK, Tyler DJ. 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. Epub 2008 Aug 8. PubMed PMID: 18689683; PubMed Central PMCID: PMC2515222.

Current Research Programme

Metabolic imaging, where imaging technology is coupled with metabolic probes to detect disease-specific markers, is transforming our approach to disease detection and treatment. Magnetic Resonance Imaging and Spectroscopy (MRI/MRS) have long been used to monitor structure and function at repeated times and at stages of disease progression. However, the application of MRI/MRS for metabolic imaging has been limited by intrinsically low sensitivity. In standard MRI, the proton concentration in water compensates for low sensitivity; this is not true for low natural abundance magnetic nuclei, such as carbon (13C).

Hyperpolarization using the Dynamic Nuclear Polarization (DNP) technique, first explored and applied in solid-state physics, is a process that yields greater than 10,000-fold signal increases in MR-active nuclei. When used with MR spectroscopy, liquid-state hyperpolarized 13C MR enables unprecedented real-time visualization of the biochemical mechanisms of normal and abnormal metabolism. This allows measurement of instantaneous rates of substrate uptake and enzymatic transformation in vivo, providing a sensitive measurement for the early stages of disease. The aim of our work is to utilize and further these developments to study initial rates of metabolism in the healthy and diseased heart.

The majority of our work focuses on the assessment of rates of pyruvate metabolism through key metabolic enzymes (e.g. Pyruvate Dehydrogenase) and how they are altered in disease (Figures 1 & 2). Through technical developments, our work will also allow the study of other important metabolic molecules and the assessment of pH. Understanding of initial metabolic rates of key molecules will provide insight into disease identification, progression and treatment that will provide new information to the study of cardiac metabolism.

Figure 1
Figure 1
Figure 2
Figure 2