Abstract 17344: Serial Quantitative Cellular MRI of Macrophage Infiltration in the Post-Infarct Heart Using T1-Mapping and Gd-Liposomes
Introduction: Following myocardial infarction (MI), macrophages infiltrate the infarct zone to clear necrotic debris and modulate angiogenesis and infarct healing. Previously, in vivo MRI of post-MI macrophage infiltration used iron oxide particles and T2*-weighted imaging. However, these Methods produce negative contrast which persists after macrophage departure and pose challenges to quantitation. We hypothesized that T1 mapping after labeling macrophages with a T1-shortening contrast agent would enable the measurement of macrophage arrival to and departure from the infarct zone.
Methods: Liposomes incorporating gadolinium-DPTA-bis(stearylamide) (Gd-liposomes) were prepared by a slightly modified standard reverse-phase evaporation procedure. Gd-liposomes were injected intravenously (50–100μL) in 5 mice at day -2 before MI to label monocytes. MI was induced at day 0 by a 1-hour occlusion of the left anterior descending coronary artery, followed by reperfusion. T1-mapping of the heart and spleen was performed using a 7T MRI system at days −3 and −1 before MI, and days 1, 4 and 7 post-MI. Cine DENSE MRI assessed myocardial strain.
Results: T1 mapping after monocyte labeling detected macrophage infiltration of the infarcted anterolateral wall at day 4 post-MI (Figure, A, arrows). The time course of T1 shortening due to labeled macrophages (B) demonstrated a decrease in infarct-zone T1 on day 4 (p<0.05 vs. all other days) and a return to baseline T1 on day 7. Spatially, T1 shortening was confined to the dysfunctional infarct zone as defined by reduced myocardial strain. T1 mapping of the spleen showed that monocytes remain labeled with Gd-liposomes through day 7 post-MI.
Conclusions: T1-mapping after labeling monocytes with Gd-liposomes enables the quantitative measurement of macrophage infiltration of the infarct zone after MI. The spatiotemporal macrophage kinetics measured in vivo by these methods agrees with prior in vitro histological studies.
- © 2010 by American Heart Association, Inc.