Abstract 3364: Serial MRI Assessment of Macrophage Activity in the Murine Heart after Myocardial Infarction using Gadolinium-labeled Liposomes as a Positive Contrast Agent

Abstract

Introduction: Macrophage activity in the heart after myocardial infarction (MI) has previously been assessed by iron-particle cardiac magnetic resonance (CMR) that produces negative contrast. We hypothesized that a new multimodal, liposomal agent with both Gd-DTPA and fluorescent DiI dye could be used for positive contrast macrophage tracking. Methods: Multimodal liposomes (ML) were prepared with Gd-DTPA-bis-stearylamide and DiI then filtered to ∼0.3 μm size. Nine C57Bl/6 mice were subjected to 1h coronary occlusion followed by up to 7d of reperfusion. ML volumes of 50μl were injected IV on Day 2 post-MI for monocyte/macrophage phagocytosis. Mice were studied by CMR 2–4h after Day 2 injection and daily until Day 7 post-MI. CMR included inversion-recovery (IR) to image ML followed by IP infusion of Gd-DTPA and more IR to image the entire infarct (IF). After final imaging, hearts were removed for Mac2 immunostaining & fluorescence microscopy. Results: Day 2 IR CMR 2–4h after ML injection revealed strong signal enhancement in the spleen with none in the heart. In all mice from Day 3–7, ML signal enhancement marked the LV anterior wall in IF regions (Fig A ). The ML contrast peaked at Day 5 and decreased by Day 7 post-MI (Fig B ). In mice euthanized at Days 4 & 7, ML-enhanced regions corresponded well with regions containing macrophages as labeled by anti-Mac2 (Fig C ) and DiI (Fig D ) Conclusions: ML can assess the accumulation of macrophages in the heart until at least Day 7 post-MI. The Gd tag provides specific positive contrast and the fluorescent tag expedites histological confirmation. This improves over iron-based agents that preclude complementary CMR imaging in regions containing iron.