Monitoring of Cardiac Remodeling in a Mouse Model of Pressure-Overload Left Ventricular Hypertrophy with [18F]FDG MicroPET
- 158 Downloads
This study aims to analyze the left ventricular function parameters, scar load, and hypertrophy in a mouse model of pressure-overload left ventricular (LV) hypertrophy over the course of 8 weeks using 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) micro-positron emission tomography (microPET) imaging.
LV hypertrophy was induced in C57BL/6 mice by transverse aortic constriction (TAC). Myocardial hypertrophy developed after 2–4 weeks. ECG-gated microPET scans with [18F]FDG were performed 4 and 8 weeks after surgery. The extent of fibrosis was measured by histopathologic analysis. LV function parameters and scar load were calculated using QGS®/QPS®. LV metabolic volume (LVMV) and percentage injected dose per gram were estimated by threshold-based analysis.
The fibrotic tissue volume increased significantly from 4 to 8 weeks after TAC (1.67 vs. 3.91 mm3; P = 0.044). There was a significant increase of the EDV (4 weeks: 54 ± 15 μl, 8 weeks: 79 ± 32 μl, P < 0.01) and LVMV (4 weeks: 222 ± 24 μl, 8 weeks: 276 ± 52 μl, P < 0.01) as well as a significant decrease of the LVEF (4 weeks: 56 ± 17 %, 8 weeks: 44 ± 20 %, P < 0.01). The increase of LVMV had a high predictive value regarding the amount of ex vivo measured fibrotic tissue (R = 0.905, P < 0.001). The myocardial metabolic defects increased within 4 weeks (P = 0.055) but only moderately correlated with the fibrosis volume (R = 0.502, P = 0.021). The increase in end-diastolic volume showed a positive correlation with the fibrosis at 8 weeks (R = 0.763, P = 0.017).
[18F]FDG-PET is applicable for serial in vivo monitoring of the TAC mouse model. Myocardial hypertrophy, the dilation of the left ventricle, and the decrease in LVEF could be reliably quantified over time, as well as the developing localized scar. The increase in volume over time is predictive of a high fibrosis load.
Key words[18F]FDG-PET Hypertrophy Mice Pressure overload Cardiac remodeling
A part of this work originated from the doctoral thesis of Nick L. Beetz.
Compliance with Ethical Standards
Conflict of Interest
The authors declare that they have no conflict of interest.
- 14.Brunner S, Todica A, Boning G et al (2012) 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. Eur J Nucl Med Mol Iimaging Res 2:43Google Scholar
- 16.Lehner S, Todica A, Vanchev Y et al (2014) In vivo monitoring of parathyroid hormone treatment after myocardial infarction in mice with [68Ga]annexin A5 and [18F]fluorodeoxyglucose positron emission tomography. Mol Imaging 13Google Scholar
- 30.Bishop SP, Altschuld RA (1970) Increased glycolytic metabolism in cardiac hypertrophy and congestive failure. Am J Phys 218:153–159Google Scholar
- 35.Kreissl MC, Stout DB, Wong KP et al (2011) Influence of dietary state and insulin on myocardial, skeletal muscle and brain [F]-fluorodeoxyglucose kinetics in mice. Eur J Nucl Med Mol Imaging Res 1:8Google Scholar