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

Magn Reson Med. 2011 Jan;65(1):239-49. doi: 10.1002/mrm.22597.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / metabolism*
  • Calcium Signaling*
  • Chlorides / pharmacokinetics*
  • Contrast Media / pharmacokinetics
  • Disease Models, Animal*
  • Humans
  • Magnetic Resonance Imaging / methods*
  • Male
  • Manganese Compounds / pharmacokinetics*
  • Mice
  • Mice, Inbred C57BL
  • Molecular Probe Techniques
  • Myocardial Infarction / metabolism*
  • Myocardium / metabolism*


  • Chlorides
  • Contrast Media
  • Manganese Compounds
  • manganese chloride
  • Calcium