Serial Multimodality Assessment of Myocardial Infarction in Mice Using Magnetic Resonance Imaging and Micro–Positron Emission Tomography Provides Complementary Information on the Progression of Scar Formation
Recent technological advances have made imaging the mouse heart possible using both 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) and magnetic resonance imaging (MRI),1–4 thus facilitating the investigation of mechanisms underlying the progression toward heart failure after myocardial infarction (MI). These imaging modalities provide complementary information regarding cellular metabolism and infarct location, respectively. To demonstrate this, we used FDG PET and MRI in a serial study of male C57Bl/6 mice that were subjected to a 1-hour coronary occlusion and then 30 days of reperfusion. Imaging was performed 1, 7, and 28 days after coronary occlusion. Gd-enhanced ECG-gated cardiac MRI was performed using a 4.7-T MRI scanner (Varian, Inc, Palo Alto, Calif) with a physiological monitoring/gating system (Model 1025, SA Instruments, Inc, Stony Brook, NY). ECG-gated PET was completed within 2 hours after the intravenous injection of 1.0-mCi FDG using a Focus 120 micro-PET system (Siemens Medical Solutions USA, Inc, Malvern, Pa) with a Model 1025L monitoring/gating system (SA Instruments, Stony Brook, NY). Midventricular, short-axis image planes were compared over time between the 2 modalities. Hearts from parallel mice were used in immunohistochemistry studies of neutrophil and macrophage infiltration. Gd-enhanced MRI revealed MI expansion and left ventricular wall thinning between post-MI days 1 (Figure, D) and 7 (Figure, E). FDG PET revealed a signal void in the infarcted anterior left ventricle when imaged on post-MI day 1 (Figure, A). Interestingly, this signal void became hyperintense relative to normal myocardium when imaged 7 days after MI (Figure, B). By 28 days after MI, the signal void in the infarcted anterior left ventricle had largely returned (Figure, C). Immunohistochemistry using an anti-Mac2 antibody revealed few macrophages in the infarcted anterior wall on post-MI days 1 or 28 but abundant macrophages in the infarct zone on post-MI day 7 (Figure, F). This study shows that macrophage uptake of FDG outstrips that of either cardiomyocytes or neutrophils in mice after MI. The use of MRI for infarct sizing (via Gd-DTPA–delayed hyperenhancement) and volumetrics (via end diastolic and end systolic volumes, ejection fraction, and cardiac output), combined with FDG PET for glucose metabolism, provides considerable information regarding the progression of wound healing and scar formation in the left ventricle after MI.
Sources of Funding
This work was carried out in the University of Virginia Molecular Imaging Core Laboratory and was supported by the UVA Pratt Fund and by National Institutes of Health R01 grants HL 058582 and HL 069494 to Dr French.
The online-only Data Supplement, consisting of a movie, is available with this article at http://circ.ahajournals.org/cgi/content/full/115/17/e428/DC1.