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Background  The exact mechanism of stem cell therapy in augmenting the function of ischemic cardiomyopathy is unclear. In this study, we hypothesized that increased viability of the peri‐infarct region ( PIR ) produces restorative benefits after stem cell engraftment. A novel multimodality imaging approach simultaneously assessed myocardial viability (manganese‐enhanced magnetic resonance imaging [ MEMRI] ), myocardial scar (delayed gadolinium enhancement  MRI ), and transplanted stem cell engraftment (positron emission tomography reporter gene) in the injured porcine hearts.    Methods and Results  Twelve adult swine underwent ischemia–reperfusion injury. Digital subtraction of  MEMRI ‐negative myocardium (intrainfarct region) from delayed gadolinium enhancement  MRI –positive myocardium ( PIR  and intrainfarct region) clearly delineated the  PIR  in which the  MEMRI ‐positive signal reflected  PIR  viability. Human amniotic mesenchymal stem cells ( hAMSC s) represent a unique population of immunomodulatory mesodermal stem cells that restored the murine  PIR . Immediately following  hAMSC  delivery,  MEMRI  demonstrated an increased  PIR  viability signal compared with control. Direct  PIR  viability remained higher in  hAMSC ‐treated hearts for >6 weeks. Increased  PIR  viability correlated with improved regional contractility, left ventricular ejection fraction, infarct size, and  hAMSC  engraftment, as confirmed by immunocytochemistry. Increased  MEMRI  and positron emission tomography reporter gene signal in the intrainfarct region and the  PIR  correlated with sustained functional augmentation (global and regional) within the  hAMSC  group (mean change, left ventricular ejection fraction:  hAMSC  85±60%, control 8±10%;  P <0.05) and reduced chamber dilatation (left ventricular end‐diastole volume increase:  hAMSC  24±8%, control 110±30%;  P <0.05).    Conclusions  The positron emission tomography reporter gene signal of  hAMSC  engraftment correlates with the improved  MEMRI  signal in the  PIR . The increased  MEMRI  signal represents  PIR  viability and the restorative potential of the injured heart. This in vivo multimodality imaging platform represents a novel, real‐time method of tracking  PIR  viability and stem cell engraftment while providing a mechanistic explanation of the therapeutic efficacy of cardiovascular stem cells.

journal of the american heart association

Manganese‐Enhanced Magnetic Resonance Imaging Enables In Vivo Confirmation of Peri‐Infarct Restoration Following Stem Cell Therapy in a Porcine Ischemia–Reperfusion Model