Left ventricular functional assessment in murine models of ischemic and dilated cardiomyopathy using [18 F]FDG-PET: comparison with cardiac MRI and monitoring erythropoietin therapy

Abstract

BackgroundWe performed an initial evaluation of non-invasive ECG-gated [18 F]FDG-positron emission tomography (FDG-PET) for serial measurements of left ventricular volumes and function in murine models of dilated (DCM) and ischemic cardiomyopathy (ICM), and then tested the effect of erythropoietin (EPO) treatment on DCM mice in a preliminary FDG-PET therapy monitoring study.MethodsMice developed DCM 8 weeks after injection with Coxsackievirus B3 (CVB3), whereas ICM was induced by ligation of the left anterior descending artery. LV volumes (EDV and ESV) and the ejection fraction (LVEF) of DCM, ICM and healthy control mice were measured by FDG-PET and compared with reference standard results obtained with 1.5 T magnetic resonance imaging (MRI). In the subsequent monitoring study, LVEF of DCM mice was evaluated by FDG-PET at baseline, and after 4 weeks of treatment, with EPO or saline.ResultsLV volumes and the LVEF as measured by FDG-PET correlated significantly with the MRI results. These correlations were higher in healthy and DCM mice than in ICM mice, in which LVEF measurements were somewhat compromised by absence of FDG uptake in the area of infarction. LV volumes (EDV and ESV) were systematically underestimated by FDG-PET, with net bias such that LVEF measurements in both models of heart disease exceeded by 15% to 20% results obtained by MRI. In our subsequent monitoring study of DCM mice, we found a significant decrease of LVEF in the EPO group, but not in the saline-treated mice. Moreover, LVEF in the EPO and saline mice significantly correlated with histological scores of fibrosis.ConclusionsLVEF estimated by ECG-gated FDG-PET significantly correlated with the reference standard MRI, most notably in healthy mice and mice with DCM. FDG-PET served for longitudinal monitoring of effects of EPO treatment in DCM mice.

Developing a rat model of dilated cardiomyopathy with improved survival

“…Cardiomyocyte damages, leading to necrosis, edema, inflammatory cell infiltration, and fibrosis, were similar in both models. Similarly, 18 FDG-PET myocardial metabolism imaging revealed decreased myocardial viability, which was consistent with the findings reported by another study (Brunner et al, 2012). Similar to echocardiography, 18 FDG-PET imaging is a useful and minimally invasive evaluation method that can be used to detect pathological changes, offering the benefit of being useful for serial evaluations.…”

Autophagy inhibition of hsa-miR-19a-3p/19b-3p by targeting TGF-β R II during TGF-β1-induced fibrogenesis in human cardiac fibroblasts

“…HF is characterized by left ventricular (LV) remodeling and dilatation, with activation of a fetal gene program that triggers pathological changes in the myocardium associated with progressive dysfunction 55 . Tissue biopsy and cardiac radionuclide scan showed that there was no necrosis of cardiac muscle cells in the early stage of HF, but the degeneration, apoptosis and interstitial fibrosis of myocardial cells 56 57 58 59 60 61 . Therefore, most of the early HF patients firstly exhibit heart cavity expansion without obvious cardiac function insufficiency.…”

In Vivo Monitoring of Parathyroid Hormone Treatment after Myocardial Infarction in Mice with [68Ga]Annexin A5 and [18F]Fluorodeoxyglucose Positron Emission Tomography

“…The electrocardiogram (ECG)-gated FDG data were divided into 16 equal intervals and iteratively reconstructed using OSEM 3D (four iterations) and MAP (32 iterations), as previously described by our group. 9 All PET data were normalized and corrected for randoms, dead time and decay, and attenuation ( Figure 1). Right after the PET scan, the accuracy of the ECG trigger signals in the listmode data were verified using in-house software programmed in MATLAB (The Mathworks, Natick, MA) and in C programming language, and erroneous trigger events were removed as previously described.…”

“…An automated wall recognition algorithm was applied to delineate left ventricular contours, and the left ventricular ejection fraction (LVEF) was calculated as described by Brunner and colleagues. 9 The voxel size of the FDG images analyzed with QPS 2012 and QGS 2012 software packages had to be magnified by a factor of 10, as required for compatibility of smallanimal PET data with software designed for humans, as previously described. 12,13 Histologic Fluorescein Staining A separate group of mice was sacrificed on day 2 after LAD artery occlusion for histologic correlation of apoptosis and [ 68 Ga]annexin A5 uptake ex vivo (n 5 5 in the treatment group, n 5 5 in the control group).…”