P846, a new gadolinium based low diffusion magnetic resonance contrast agent, in characterizing occlusive infarcts, reperfused ischemic myocardium and reperfused infarcts in rats

Abstract

This study has two objectives: (1) to compare the kinetics of low diffusion P846 with Gd-DOTA using inversion recovery echo planar (IR-EPI) magnetic resonance (MR) imaging and (2) to determine the potential of P846 in defining myocardial viability in hearts subjected to various injuries using T1-weighted spin echo (T1-SE). Rats were subjected to (1) occlusive infarcts (n = 16), (2) reperfused ischemic injuries (n = 8) or (3) reperfused infarcts (n = 16). A dose of 0.05 mmol/kg P846 was compared to 0.1 mmol/kg Gd-DOTA. IR-EPI and T1-SE images were obtained during 60 min. T(1), DeltaR(1) and DeltaR(1) ratio were measured on IR-EPI. Infarct extents were evaluated on T1-SE and compared with histochemical staining. Blood DeltaR(1) was higher at 5 min after P846 (6.36 +/- 0.32 s(-1)) than after Gd-DOTA (1.30 +/- 0.14 s(-1); P < 0.001). With P846, occlusive infarcts appeared as a hypoenhanced region surrounded by a hyperenhanced rim that lasted for 60 min. The increase in the DeltaR(1) ratio value was slower after P846 than with Gd-DOTA in the reperfused infarcts, suggesting low diffusion/convection of P846. Gd-DOTA homogenously enhanced both occlusive and reperfused infarcts at 30 min. P846 provides better contrast and extended discrimination between occlusive and reperfused infarcts compared with Gd-DOTA. The gadolinium dose could be reduced with P846.