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.
Highlights
Introduction of LGEmagnetic resonance imaging (MRI) early in acute myocardial infarction (AMI),[13] 3) concerns over the safety of Gd-based con-Cardiac imaging has revolutionized our ability to diagnose trast agents have been raised owing to its links to nephrogenic heart disease, quantify mechanisms of pathology, and determine systemic fibrosis[14] and accumulation in the brain.[15]
To investigate the effects of Mn2+ and Ca2+ supplement on cardiomyocyte beating rate and electrophysiology, in vitro studies were performed using mouse HL-1 cardiomyocytes and humaninduced pluripotent stem cell derived cardiomyocytes, with the latter well recognized as the optimal cell type for preclinical compound screening.[38]
Our data indicate that manganese-enhanced MRI offers an important new method for evaluating myocardial viability within the first hour of MI
Summary
Introduction of LGEMRI early in acute myocardial infarction (AMI),[13] 3) concerns over the safety of Gd-based con-Cardiac imaging has revolutionized our ability to diagnose trast agents have been raised owing to its links to nephrogenic heart disease, quantify mechanisms of pathology, and determine systemic fibrosis[14] and accumulation in the brain.[15]. Camelliti School of Biosciences and Medicine University of Surrey Guildford GU2 7XH, UK
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