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

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 7 days (acute MI, n = 8) or 8 weeks (chronic MI, n = 6) after surgery with sequential injection of 0.15 mmol/kg Gd³⁺ and Mn²⁺ chelate. The biodistribution of Mn²⁺ in tissues and blood was measured at 1.5 and 24 h. 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 1.5 h, with low tissue uptake and urine residue at 24 h 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.