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

doi:10.1161/CIRCRESAHA.119.316260

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

Research output: Contribution to journal › Article › peer-review

119 Citations (Scopus)

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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 language	English
Pages (from-to)	725-736
Number of pages	12
Journal	Circulation Research
Volume	126
Issue number	6
Early online date	5 Feb 2020
DOIs	https://doi.org/10.1161/CIRCRESAHA.119.316260
Publication status	Published - 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

Funders	Funder number
Wellcome Trust
NIHR Bristol Biomedical Research Centre
Engineering and Physical Sciences Research Council
British Heart Foundation	FS/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 Oxford	RE/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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1161/CIRCRESAHA.119.316260Licence: CC BY

PublishedFinal published version, 1.87 MBLicence: CC BY

Cite this

Rider, O., Apps, A., Miller, J., Lau, J., Lewis, A., Peterzan, M., Dodd, M., Lau, A., Trumper, C., Gallagher, F., Grist, J., Brindle, K., Neubauer, S., & Tyler, D. J. (2020). Non-Invasive In Vivo Assessment of Cardiac Metabolism in the Healthy and Diabetic Human Heart Using Hyperpolarized 13C MRI. Circulation Research, 126(6), 725-736. https://doi.org/10.1161/CIRCRESAHA.119.316260

Rider, O, Apps, A, Miller, J, Lau, J, Lewis, A, Peterzan, M, Dodd, M, Lau, A, Trumper, C, Gallagher, F, Grist, J, Brindle, K, Neubauer, S & Tyler, DJ 2020, 'Non-Invasive In Vivo Assessment of Cardiac Metabolism in the Healthy and Diabetic Human Heart Using Hyperpolarized 13C MRI', Circulation Research, vol. 126, no. 6, pp. 725-736. https://doi.org/10.1161/CIRCRESAHA.119.316260

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

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. ",

keywords = "Hyperpolarized Magnetic Resonance Spectroscopy, Pyruvate Dehydrogenase, pyruvate dehydrogenase, magnetic resonance imaging, hyperpolarized magnetic resonance spectroscopy, diabetes mellitus, metabolism, diabetic cardiomyopathy",

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

note = "{\textcopyright} 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.",

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doi = "10.1161/CIRCRESAHA.119.316260",

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T1 - Non-Invasive In Vivo Assessment of Cardiac Metabolism in the Healthy and Diabetic Human Heart Using Hyperpolarized 13C MRI

AU - Rider, Oliver

AU - Apps, Andrew

AU - Miller, Jack

AU - Lau, Justin

AU - Lewis, Andrew

AU - Peterzan, Mark

AU - Dodd, Michael

AU - Lau, Angus

AU - Trumper, Claire

AU - Gallagher, Ferdia

AU - Grist, James

AU - Brindle, Kevin

AU - Neubauer, Stefan

AU - Tyler, Damian J

N1 - © 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.

PY - 2020/3/13

Y1 - 2020/3/13

N2 - 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.

AB - 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.

KW - Hyperpolarized Magnetic Resonance Spectroscopy

KW - Pyruvate Dehydrogenase

KW - pyruvate dehydrogenase

KW - magnetic resonance imaging

KW - hyperpolarized magnetic resonance spectroscopy

KW - diabetes mellitus

KW - metabolism

KW - diabetic cardiomyopathy

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

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

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Mike Dodd

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

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

Fingerprint

Profiles

Mike Dodd

Cite this