Non-Invasive In Vivo Assessment of Cardiac Metabolism in the Healthy and Diabetic Human Heart Using Hyperpolarized 13C MRI

Oliver Rider, Andrew Apps, Jack Miller, Justin Lau, Andrew Lewis, Mark Peterzan, Michael Dodd, Angus Lau, Claire Trumper, Ferdia Gallagher, James Grist, Kevin Brindle, Stefan Neubauer, Damian J Tyler

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    119 Citations (Scopus)
    96 Downloads (Pure)

    Abstract

    RATIONALE: The recent development of hyperpolarized 13C magnetic resonance spectroscopy has made it possible to measure cellular metabolism in vivo, in real time. OBJECTIVE: By comparing participants with and without type 2 diabetes mellitus (T2DM), we report the first case-control study to use this technique to record changes in cardiac metabolism in the healthy and diseased human heart. METHODS AND RESULTS: Thirteen people with T2DM (glycated hemoglobin, 6.9±1.0%) and 12 age-matched healthy controls underwent assessment of cardiac systolic and diastolic function, myocardial energetics ( 31P-magnetic resonance spectroscopy), and lipid content ( 1H-magnetic resonance spectroscopy) in the fasted state. In a subset (5 T2DM, 5 control), hyperpolarized [1- 13C]pyruvate magnetic resonance spectra were also acquired and in 5 of these participants (3 T2DM, 2 controls), this was successfully repeated 45 minutes after a 75 g oral glucose challenge. Downstream metabolism of [1- 13C]pyruvate via PDH (pyruvate dehydrogenase, [ 13C]bicarbonate), lactate dehydrogenase ([1- 13C]lactate), and alanine transaminase ([1- 13C]alanine) was assessed. Metabolic flux through cardiac PDH was significantly reduced in the people with T2DM (Fasted: 0.0084±0.0067 [Control] versus 0.0016±0.0014 [T2DM], Fed: 0.0184±0.0109 versus 0.0053±0.0041; P=0.013). In addition, a significant increase in metabolic flux through PDH was observed after the oral glucose challenge (P<0.001). As is characteristic of diabetes mellitus, impaired myocardial energetics, myocardial lipid content, and diastolic function were also demonstrated in the wider study cohort. CONCLUSIONS: This work represents the first demonstration of the ability of hyperpolarized 13C magnetic resonance spectroscopy to noninvasively assess physiological and pathological changes in cardiac metabolism in the human heart. In doing so, we highlight the potential of the technique to detect and quantify metabolic alterations in the setting of cardiovascular disease. VISUAL OVERVIEW: An online visual overview is available for this article.

    Original languageEnglish
    Pages (from-to)725-736
    Number of pages12
    JournalCirculation Research
    Volume126
    Issue number6
    Early online date5 Feb 2020
    DOIs
    Publication statusPublished - 13 Mar 2020

    Bibliographical note

    © 2020 The Authors. Circulation is published on behalf of the American Heart Association, Inc., by Wolters Kluwer Health, Inc. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution, and reproduction in any medium, provided that the original work is properly cited.

    Funding

    FundersFunder number
    Wellcome Trust
    NIHR Bristol Biomedical Research Centre
    Engineering and Physical Sciences Research Council
    British Heart FoundationFS/15/80/31803, FS/14/54/30946, FS/14/17/30634, FS/17/18/32449, RE/08/004/23915, RG/11/9/28921
    British Heart Foundation
    Cancer Research UK
    Novo Nordisk
    University of OxfordRE/13/1/30181
    University of Oxford
    NIHR University College London Hospitals Biomedical Research Centre

    Keywords

    • Hyperpolarized Magnetic Resonance Spectroscopy
    • Pyruvate Dehydrogenase
    • pyruvate dehydrogenase
    • magnetic resonance imaging
    • hyperpolarized magnetic resonance spectroscopy
    • diabetes mellitus
    • metabolism
    • diabetic cardiomyopathy

    ASJC Scopus subject areas

    • Cardiology and Cardiovascular Medicine
    • Physiology

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