Indirectly probing Ca2+ handling alterations following myocardial infarction in a murine model using T1-mapping manganese-enhanced magnetic resonance imaging

Prolonged ischemia causes cellular necrosis and myocardial infarction (MI) via intracellular calcium (Ca2+) overload. Manganese‐enhanced MRI indirectly assesses Ca2+ influx movement in vivo as manganese (Mn2+) is a Ca2+ analog. To characterize myocardial Mn2+ efflux properties, T1‐mapping manganese‐enhanced MRI studies were performed on adult male C57Bl/6 mice in which Ca2+ efflux was altered using pharmacological intervention agents or MI‐inducing surgery. Results showed that (1) Mn2+ efflux rate increased exponentially with increasing Mn2+ doses; (2) SEA0400 (a sodium–calcium exchanger inhibitor) decreased the rate of Mn2+ efflux; and (3) dobutamine (a positive inotropic agent) increased the Mn2+ efflux rate. A novel analysis technique also delineated regional features in the MI mice, which showed an increased Mn2+ efflux rate in the necrosed and peri‐infarcted tissue zones. The T1‐mapping manganese‐enhanced MRI technique characterized alterations in myocardial Mn2+ efflux rates following both pharmacologic intervention and an acute MI. The Mn2+ efflux results were consistent with those in ex vivo studies showing an increased Ca2+ concentration under similar conditions. Thus, T1‐mapping manganese‐enhanced MRI has the potential to indirectly identify and quantify intracellular Ca2+ handling in the peri‐infarcted tissue zones, which may reveal salvageable tissue in the post‐MI myocardium. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.