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The role of abnormal cardiac substrate metabolism in the development of many 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 (hp-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. This project will explore the application of hp-MR in the study of cardiovascular disease, enabling the assessment of pyruvate metabolism through the key metabolic enzyme, pyruvate dehydrogenase, and how it can be modulated as a therapeutic target.

Relevant References

  1. Rider OJ, Tyler DJ et al. Non-Invasive In Vivo Assessment of Cardiac Metabolism in the Healthy and Diabetic Human Heart Using Hyperpolarized 13C MRI. Circ Res. 2020. PMID: 32078413
  2. Lewis AJ, Tyler DJ et al. Non-Invasive Immuno-Metabolic Cardiac Inflammation Imaging Using Hyperpolarized MRI. Circ Res. 2018. PMID:29440071 

 

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