Accurate identification of myocardial viability after myocardial infarction with novel manganese chelate-based MR imaging.

Abstract

We developed a novel manganese (Mn2+ ) chelate for magnetic resonance imaging (MRI) assessment of myocardial viability in acute and chronic myocardial infarct (MI) models, and compared it with Gadolinium-based delay enhancement MRI (Gd3+ -DEMRI) and histology. MI was induced in 14 rabbits by permanent occlusion of the left circumflex coronary artery. Gd3+ -DEMRI and Mn2+ chelate-based delayed enhancement MRI (Mn2+ chelate-DEMRI) were performed at 7days (acute MI, n=8) or 8weeks (chronic MI, n=6) after surgery with sequential injection of 0.15mmol/kg Gd3+ and Mn2+ chelate. The biodistribution of Mn2+ in tissues and blood was measured at 1.5 and 24h. Blood pressure, heart rate (HR), left ventricular (LV) function, and infarct fraction (IF) were analyzed, and IF was compared with the histology. The Mn2+ chelate group maintained a stable hemodynamic status during experiment. For acute and chronic MI, all rabbits survived without significant differences in HR or LV function before and after injection of Mn2+ chelate or Gd3+ (p>0.05). Mn2+ chelate mainly accumulated in the kidney, liver, spleen, and heart at 1.5h, with low tissue uptake and urine residue at 24h after injection. In the acute MI group, there was no significant difference in IF between Mn2+ chelate-DEMRI and histology (22.92±2.21% vs. 21.79±2.25%, respectively, p=0.87), while Gd3+ -DEMRI overestimated IF, as compared with histology (24.54±1.73%, p=0.04). In the chronic MI group, there was no significant difference in IF between the Mn2+ chelate-DEMRI, Gd3+ -DEMRI, and histology (29.50±11.39%, 29.95±9.40%, and 29.00±10.44%, respectively, p>0.05), and all three were well correlated (r=0.92-0.96, p<0.01). We conclude that the use of Mn2+ chelate-DEMRI is reliable for MI visualization and identifies acute MI more accurately than Gd3+ -DEMRI.