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Myocardial Viability Imaging using Manganese-Enhanced MRI in the First Hours after Myocardial Infarction

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Nur Hayati Jasmin, May Zaw Thin, Robert D. Johnson, Laurence H. Jackson, Thomas A. Roberts, Anna L. David, Mark F. Lythgoe, Philip C. Yang, Sean M. Davidson, Patrizia Camelliti, Daniel J. Stuckey

Original languageEnglish
Article number2003987
JournalAdvanced Science
Volume8
Issue number11
DOIs
Accepted/In press2021
Published9 Jun 2021

Bibliographical note

Funding Information: The authors acknowledge the technical support of Mrs. Valerie Taylor. D.J.S. was supported by a British Heart Foundation Intermediate Basic Science Research Fellowship (FS/15/33/31608), BHF Centre for Regenerative Medicine RM/17/1/33377, MRC MR/R026416/1, and Wellcome Trust 212937/Z/18/Z. P.C. acknowledges support from the British Heart Foundation (FS/17/33/32931) and the Royal Society (RSG?R1?180198). S.M.D. was supported by the National Institute of Health Research (NIHR), Biomedical Research Council (BRC233/CM/SD/101320), and the British Heart Foundation (PG/18/44/33790, PG/19/51/34493). Publisher Copyright: © 2021 The Authors. Advanced Science published by Wiley-VCH GmbH Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

King's Authors

Abstract

Early measurements of tissue viability after myocardial infarction (MI) are essential for accurate diagnosis and treatment planning but are challenging to obtain. Here, manganese, a calcium analogue and clinically approved magnetic resonance imaging (MRI) contrast agent, is used as an imaging biomarker of myocardial viability in the first hours after experimental MI. Safe Mn2+ dosing is confirmed by measuring in vitro beating rates, calcium transients, and action potentials in cardiomyocytes, and in vivo heart rates and cardiac contractility in mice. Quantitative T1 mapping-manganese-enhanced MRI (MEMRI) reveals elevated and increasing Mn2+ uptake in viable myocardium remote from the infarct, suggesting MEMRI offers a quantitative biomarker of cardiac inotropy. MEMRI evaluation of infarct size at 1 h, 1 and 14 days after MI quantifies myocardial viability earlier than the current gold-standard technique, late-gadolinium-enhanced MRI. These data, coupled with the re-emergence of clinical Mn2+-based contrast agents open the possibility of using MEMRI for direct evaluation of myocardial viability early after ischemic onset in patients.

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