Monitoring of left ventricular function and scar burden in the mouse model of cardiac hypertrophy with F-18 FDG microPET

Objectives Establishment of ECG-gated myocardial FDG PET for sequential analysis of left ventricular functional parameters and scar burden in the mouse model of cardiac hypertrophy.

Methods In 21 C57BL/6 mice a hypertrophy stimulus was induced by transverse aortic constriction. After 2-4 weeks cardiac hypertrophy developed. 4 and 8 weeks post-surgery an ECG-triggered PET was performed. The PET was conducted 20 minutes p.i. with 19 ± 5MBq [18F]FDG over 30min. Subsequently hearts were removed and stained histologically for fibrosis to correlate with PET quantification. In a subgroup (n = 10), the sample was taken after the first scan. The end-diastolic volume (EDV μl), left ventricular ejection fraction (LVEF %) and total perfusion deficit (TPD %) were calculated by means QGS® / QPS®, the metabolic volume (MV mm3) by IRW. The results are given as mean ± SD.

Results Within 4-8 weeks results showed a significant increase in EDV (4 weeks: 54.3 ± 15.9, 8 weeks: 78.8 ± 34.4, p<0.01) and MV (4 weeks: 219.6 ± 25.8, 8 weeks: 276.3 ± 54.71, p<0.01) and a decrease in LVEF (4weeks: 55.6 ± 17.7, 8weeks: 43.4 ± 20.6, p<0.01). The values correlated with the fibrosis volume (mm3): EDV R=0.71, p<0.01; MV R=0.65, p<0.01 and LVEF R=-0.74, p<0.01. The TPD increased within 4 weeks (p=0.06), but only moderately correlated with the fibrosis volume (R=0.45). The increase in end-diastolic volume showed a positive correlation with the fibrosis at 8 weeks (R=0.82, p<0.01).

Conclusions FDG-PET readily applicable for serial in-vivo monitoring of left ventricular changes in the mouse model of cardiac hypertrophy. The dilation of the left ventricle, myocardial hypertrophy and the decrease in LVEF could be reliably quantified and shown over time, as well as the developing localized scar. The increase in volume over time is predictive of a high fibrosis load.