MRI with gadofosveset: A potential marker for permeability in myocardial infarction

Background and aims: Acute ischemia is associated with myocardial endothelial damage and microvessel formation, resulting in leakage of plasma albumin into the myocardial extravascular space. In this study, we tested whether an albumin-binding intravascular contrast agent (gadofosveset) allows for improved quantification of myocardial permeability compared to the conventional extracellular contrast agent Gd-DTPA using late gadolinium enhancement (LGE) and T1 mapping in vivo. Methods: MI was induced in C57BL/6 mice (n = 6) and cardiac magnetic resonance imaging (CMR) was performed at 3, 10 and 21 days post-MI using Gd-DTPA and 24 h later using gadofosveset. Functional, LGE and T1 mapping protocols were performed 45 min post-injection of the contrast agent. Results: LGE images showed that both contrast agents provided similar measurements of infarct area at all time points following MI. Importantly, the myocardial R-1 measurements after administration of gadofosveset were higher in the acute phase-day 3 (R1 [s(-1)] = 6.29 +/- 0.29) compared to the maturation phase-days 10 and 21 (R1 [s(-1)] = 4.76 +/- 0.30 and 4.48 +/- 0.14), suggesting that the uptake of this agent could be used to stage myocardial remodeling. No differences in myocardial R1 were observed after administration of Gd-DTPA at different time points post-MI (R1 [s(-1)] = 3d: 3.77 +/- 0.37; 10d: 2.74 +/- 0.06; 21d: 3.35 +/- 0.26). The MRI results were validated by ex vivo histology that showed albumin leakage in the myocardium in the acute phase and microvessel formation at later stages. Conclusions: We demonstrate the merits of an albumin-binding contrast agent for monitoring changes in myocardial permeability between acute ischemia and chronic post-MI myocardial remodeling. (C) 2018 The Authors. Published by Elsevier B.V.