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

TY - JOUR

T1 - Myocardial Viability Imaging using Manganese-Enhanced MRI in the First Hours after Myocardial Infarction

AU - Jasmin, Nur Hayati

AU - Thin, May Zaw

AU - Johnson, Robert D.

AU - Jackson, Laurence H.

AU - Roberts, Thomas A.

AU - David, Anna L.

AU - Lythgoe, Mark F.

AU - Yang, Philip C.

AU - Davidson, Sean M.

AU - Camelliti, Patrizia

AU - Stuckey, Daniel J.

N1 - 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.

PY - 2021/6/9

Y1 - 2021/6/9

N2 - 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.

AB - 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.

KW - imaging

KW - manganese

KW - MRI

KW - myocardial infarction

KW - viability

UR - http://www.scopus.com/inward/record.url?scp=85103420788&partnerID=8YFLogxK

U2 - 10.1002/advs.202003987

DO - 10.1002/advs.202003987

M3 - Article

AN - SCOPUS:85103420788

SN - 2198-3844

VL - 8

JO - Advanced Science

JF - Advanced Science

IS - 11

M1 - 2003987

ER -