Indirectly probing Ca 2+ handling alterations following myocardial infarction in a murine model using T 1 ‐mapping manganese‐enhanced magnetic resonance imaging

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