Expedient assessment of post-infarct remodeling by native cardiac magnetic resonance imaging in mice.

Novel therapeutic strategies aiming at improving the healing process after an acute myocardial infarction are currently under intense investigation. The mouse model plays a central role for deciphering the underlying mechanisms on a molecular and cellular level. Therefore, we intended to assess in-vivo post-infarct remodeling as comprehensively as possible using an expedient native magnetic resonance imaging (MRI) in the two most prominent infarct models, permanent ligation (PL) of the left anterior descending artery (LAD) versus ischemia reperfusion (I/R). Mice were subjected to either permanent or transient (45 min) occlusion of the LAD. After 3 weeks, examinations were performed with a 7-Tesla small animal MRI system. Data analysis was performed with the freely available software Segment. PL resulted in a massive dilation of the left ventricle, accompanied by hypertrophy of the non-infarcted myocardium and a decline of contractile function. These effects were less pronounced following I/R compared to healthy animals. Single plane assessments were not sufficient to capture the specific differences of left ventricular (LV) properties between the two infarct models. Bulls-eye plots were found to be an ideal tool for qualitative LV wall assessment, whereas a multi-slice sector-based analysis of wall regions is ideal to determine differences in hypertrophy, lateral wall thinning and wall thickening on a quantitative level. We combine the use of polar map-based analysis of LV wall properties with volumetric measurements using simple CINE CMR imaging. Our strategy represents a versatile and easily available tool for serial assessment of the LV during the remodeling process. Our study contributes to a better understanding of the effects of novel therapies targeting the healing of damaged myocardium.

[68Ga]-NODAGA-RGD Positron Emission Tomography (PET) for Assessment of Post Myocardial Infarction Angiogenesis as a Predictor for Left Ventricular Remodeling in Mice after Cardiac Stem Cell Therapy.

Angiogenesis plays a central role in the healing process following acute myocardial infarction. The PET tracer [68Ga]-NODAGA-RGD, which is a ligand for the αvß3 integrin, has been investigated for imaging angiogenesis in the process of healing myocardium in both animal and clinical studies. It´s value as a prognostic marker of functional outcome remains unclear. Therefore, the aim of this work was to establish [68Ga]-NODAGA-RGD for imaging angiogenesis in the murine infarct model and evaluate the tracer as a predictor for cardiac remodeling in the context of cardiac stem cell therapy. [68Ga]-NODAGA-RGD PET performed seven days after left anterior descending coronary artery (LAD) occlusion in 129S6 mice showed intense tracer accumulation within the infarct region. The specificity was shown in a sub-group of animals by application of the competitive inhibitor cilengitide prior to tracer injection in a subgroup of animals. Myocardial infarction (MI) significantly reduced cardiac function and resulted in pronounced left ventricular remodeling after three weeks, as measured by cardiac MRI in a separate group. Cardiac induced cells (CiC) that were derived from mESC injected intramyocardially in the therapy group significantly improved left ventricular ejection fraction (LVEF). Surprisingly, CiC transplantation resulted in significantly lower tracer accumulation seven days after MI induction. Accordingly, we successfully established the PET tracer [68Ga]-NODAGA-RGD for the assessment of αvß3 integrin expression in the healing process after MI in the mouse model. Yet, our results indicate that the mere extent of angiogenesis following MI does not serve as a sufficient prognostic marker for functional outcome.