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Tyler Group

Division of Cardiovascular Medicine Oxford Centre for Clinical Magnetic Resonance Research

Development and Application of Cardiac Magnetic Resonance Imaging and Spectroscopy

Metabolic images of the conversion of hyperpolarized pyruvate into bicarbonate and lactate in the normal and infarcted heart. A/F show standard proton images of the perfused heart, B/G show late gadolinium images highlighting the infarct area with a region of hypointensity, C/H show the distribution of the infused hyperpolarized pyruvate whilst D/I and E/J show the distribution of bicarbonate and lactate respectively. An area of reduced bicarbonate and enhanced lactate signal can be seen in the region of the infarct.
Metabolic images of the conversion of hyperpolarized pyruvate into bicarbonate and lactate in the normal and infarcted heart. A/F show standard proton images of the perfused heart, B/G show late gadolinium images highlighting the infarct area with a region of hypointensity, C/H show the distribution of the infused hyperpolarized pyruvate whilst D/I and E/J show the distribution of bicarbonate and lactate respectively. An area of reduced bicarbonate and enhanced lactate signal can be seen in the region of the infarct.

Using metabolic imaging to transform 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. 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.

Our team

DPhil research opportunity 2023

Imaging Cardiac Metabolism Using Hyperpolarized MRI

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Selected publications

COLLABORATORS

Dr Kerstin Timm

Related research themes

We aim to better understand, diagnose and treat heart and vascular disease through our extensive cutting edge research programmes. We have a particular focus on understanding disease mechanisms and on new approaches to stratifying patients. Our expertise encompasses genetic studies to identify causative and risk genes, cardiovascular physiology and cellular biology to understand health and disease, the development and application of advanced imaging, experimental medicine and clinical trials.
Cardiovascular Science
We have world-class clinical imaging facilities aimed at better understanding, diagnosing and treating disease. Our clinical studies feedback into molecular research, taking learnings from the clinical setting to ask further questions in model systems. We have particular strengths in cardiovascular imaging and our facilities integrate clinical care with the latest research.
Clinical Imaging
Using a range of imaging modalities, our researchers can probe – at the molecular level – the events that underpin cellular health and dysfunction.
Cellular and Preclinical Imaging
We seek to bridge the ‘innovation gap’ between ‘basic’ research in the laboratory and tangible benefits for patients. Our researchers aim to develop novel approaches to treating disease and we have particular strengths in evaluating technologies such as antibody therapy and gene therapy, and using new techniques for target discovery. Many of our researchers collaborate with biotech and industry partners to accelerate progress along the drug discovery pipeline and assess these new treatments in the clinic.
Emerging Therapies and Drug Discovery
Metabolism in Molecular Medicine