Molecular Imaging Of Ventricular Function And Myocardial Injury

Objective:Duramycin represents a unique class of imaging agents, where a compact peptide structure (2kDa) supports a well defined binding pocket. Duramycin binds phosphatidylethanolamine (PE) with high affinity and specificity. When pathologically externalized, PE is a surrogate marker for detecting cell death. Given its robust binding mechanism plus favorable pharmacokinetics, the goal was to investigate99mTc-labeled Duramycin for detecting acute cardiac cell death in a pig model of myocardial ischemia-reperfusion injury.Methods:The clearance and distribution profiles of intravenously injected99mTc-duramycin was characterized in sham-operated animals (n=5). Ischemia of20-30min was induced by balloon angioplasty in anterior coronary artery (n=5) and circumflex branch (n=4).99mTc-Duramycin was injected intravenously at1hour after reperfusion. SPECT/CT was acquired at1and3hours after injection. Target-to-background ratios were determined using ROI analysis. Myocardial perfusion imaging with99mTc-Tetrofosmin was performed on day2. Cardiac tissues were analyzed postmortem for the presence of apoptosis, necrosis and ultrastructural changes associated with acute cellular injuries.Results:Intravenously injected99mTc-Duramycin rapidly cleared from circulation via the renal/urinary tract, with an a-phase half-life of2.1±0.2minutes (n=5) and B-phase half-life of150.6±57.7minutes (n=5). Dynamic whole-body planar images indicated that the systemic background was relatively low. In the group with coronary occlusion followed by reperfusion, avid uptake in the ischemic myocardium combined with a fast receding background enabled a conspicuous visualization of the target tissue within1hour post injection. The ischemic-to-normal myocardial wall uptake ratios were3.57±0.74and3.69±0.91(P>0.05) at1and3hours post injection, respectively. Ischemic-to-lung ratios were4.89±0.85and4.93±0.57(P>0.05), at1and3hours, respectively. Ischemic-to-liver ratios were2.05±0.30and3.23±0.78(P<0.05), at1and3hours, respectively. The focal uptake of99mTc-Duramycin corresponded to a perfusion defect in99mTc-Tetrofosmin scan. The colocalization of99mTc-Duramycin radioactivity with ischemic tissues was validated using autoradiography and histological analyses. Additionally, the tissue area positive for99mTc-Duramycin was23.7±6.1%greater than the infarct size as determined by autoradiography versus tetrazolium staining.Conclusion:The in vivo properties of99mTc-Duramycin are suitable for a positive imaging agent for detecting acute cell death in the heart. The current investigation using an established large animal model marked an important milestone toward clinical translation. Objective:The aim of this study is to evaluate the agreement between myocardial18F-FDG PET imaging and cardiac magnetic resonance imaging (cMRI) in assessing cardiac function and relationship of cMRI late-gadolinium enhancement (cMRI-LGE) and myocardial perfusion-metabolism pattern in patients with idiopathic dilated cardiomyopathy (IDCM).Methods:42consecutive patients diagnosed with IDCM were enrolled. All patients underwent99mTc-MIBI SPECT, gated18F-FDG PET imaging and cMRI within3-7days. Cardiac function parameters were calculated using PET and cMRI. The segments analysis was performed using17-segment model. Patterns of perfusion/metabolism were classified as normal, mismatch, mild-to-moderate match and severe match, and cMRI-LGE was classified into3categories (non-LGE, mid-wall LGE and transmural LGE).Results:The correlation between gated PET and cMRI was excellent for EDV(r=0,948, P<0.001), ESV(r=0.939, P<0.001) and LVEF(r=0.685, P<0.001). EDV and ESV were underestimated, whereas LVEF was slightly overestimated by gated PET in comparison to cMRI. Perfusion/metabolism patterns varied in three different categories of non-LGE, mid-wall LGE and transmural LGE (χ2=14.216, P<0.001).71.0%(44/62) segments with mid-wall LGE had normal perfusion/metabolism patterns, and75.9%(63/83) perfusion/metabolism mismatch segments were shown non-LGE. The incidence of LGE was significantly higher in segments with severe match than other3segment groups (χ2=12.53, P<0.001).Conclusion:There is an excellent agreement between gated PET and cMRI in assessment of cardiac function. The LGE-cMRI is much more sensitive in detecting moderate fibrosis, while PET could detect more impaired but viable myocardium. Combining the two imaging modalities is useful for providing more comprehensive evaluations of myocardial injury in patients with IDCM. Background Right ventricular function is a powerful predictor of survival in patients with pulmonary hypertension, but noninvasively assessing right ventricular function remains a challenge. The aim of this study was to prospectively compare gated18F-FDG PET myocardial imaging (gated PET), cardiac magnetic resonance (CMR) and cardiac computed tomography (CCT) for the assessment of right ventricular volume and ejection fraction in patients with pulmonary hypertension.Methods Twenty-three consecutive patients aged over16years diagnosed with pulmonary hypertension were included. All patients underwent gated PET, CMR and CCT within7days. Right ventricular end-diastolic volume (RVEDV), right ventricular end-systolic volume (RVESV) and right ventricular ejection fraction (RVEF) were calculated by three imaging modalities. RV18F-FDG uptake was determined as RV corrected standardized uptake value (SUV) and the ratio of RV to LV corrected SUV (Corrected SUV R/L).Results Gated PET showed a moderate correlation (r=0.680, P<0.001) for RVEDV, good correlation for RVESV (r=0.757, P<0.001) and RVEF (r=0.788, P<0.001) with CMR, and good correlation for RVEDV (r=0.767, P<0.001), RVESV (r=0.837, P<0.001) and RVEF (r=0.730, P<0.001) with CCT. Bland-Altman analysis revealed systematic underestimation of RVEDV and RVESV and overestimation of RVEF with gated PET compared with CMR and CCT. The correlation between RVESV (r=0.863, P<0.001), RVESV (r=0.903, P<0.001) and RVEF (r=0.853, P<0.001) of CMR and those of CCT was excellent, Bland-Altman analysis showed only a slight systematic variation between CMR and CCT. There were statistically significant negative correlations between RV corrected SUV and RVEF-CMR (r=-0.543, P<0.01), Corrected SUV R/L and RVEF-CMR (r=-0.521, P<0.05), RV corrected SUV and RVEF-CCT (r=-0.429, P<0.05), Corrected SUV R/L and RVEF-CCT (r=-0.580, P<0.01), respectively.Conclusion Gated PET had moderate to high correlation with CMR and CCT in assessment of right ventricular volume and ejection fraction. It is an available method for simultaneous assessing of right ventricular function and myocardial glucose metabolism in patients with pulmonary hypertension.