Persistent inflammation following myocardial infarction (MI) precipitates adverse outcome including acute ventricular rupture and chronic heart failure. Molecular imaging allows longitudinal assessment of immune cell activity in the infarct territory and predicts severity of remodeling. We utilized a multiparametric imaging platform to assess the immune response and cardiac healing following MI in mice. Suppression of circulating macrophages prior to MI paradoxically resulted in higher total leukocyte content in the heart, demonstrated by increased CXC motif chemokine receptor 4 (CXCR4) positron emission tomography imaging. This supported the formation of a thrombus overlying the injured region, as identified by magnetic resonance imaging. The injured and thrombotic region in macrophage depeleted mice subsequently showed active calcification, as evidenced by accumulation of ¹⁸F-fluoride and by cardiac computed tomography. Importantly, macrophage suppression triggered a prolonged inflammatory response confirmed by post-mortem tissue analysis that was associated with higher mortality from ventricular rupture early after occlusion and with increased infarct size and worse chronic contractile function at 6 weeks after reperfusion. These findings establish a molecular imaging toolbox for monitoring the interplay between adverse immune response and tissue repair after MI. This may serve as a foundation for development and monitoring of novel targeted therapies that may include immune modulation and endogenous healing support.

心肌梗死 (MI) 后的持续炎症会导致不良后果，包括急性心室破裂和慢性心力衰竭。分子成像允许纵向评估梗死区域内的免疫细胞活性并预测重塑的严重程度。我们利用多参数成像平台来评估小鼠 MI 后的免疫反应和心脏愈合。矛盾的是，在 MI 之前抑制循环巨噬细胞会导致心脏中总白细胞含量升高，这通过增加的 CXC 基序趋化因子受体 4 (CXCR4) 正电子发射断层扫描成像得到证实。这支持了覆盖受伤区域的血栓形成，如磁共振成像所识别的那样。去除巨噬细胞的小鼠中受伤和血栓形成的区域随后显示出活跃的钙化，¹⁸ F-氟化物和心脏计算机断层扫描。重要的是，巨噬细胞抑制引发了长期的炎症反应，死后组织分析证实了这种反应与闭塞后早期心室破裂死亡率较高以及梗死面积增加和再灌注后 6 周慢性收缩功能恶化有关。这些发现建立了一个分子成像工具箱，用于监测 MI 后不良免疫反应和组织修复之间的相互作用。这可以作为开发和监测新型靶向疗法的基础，这些疗法可能包括免疫调节和内源性愈合支持。