Abstract
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Objectives Mortality rate of myocarditis remained very high. Due to the invasive nature of endomyocardial biopsy, reliable non-invasive tools to diagnose inflammatory activity are clinically relevant.The aim of this study is to establish an animal experimental platform of non-invasive serial monitoring of acute myocarditis for further insights into the pathological process.
Methods Autoimmune myocarditis was induced in Lewis rats by immunizing twice at a 7day interval with 10mg/mL porcine cardiac myosin with Freund’s complete adjuvant (n=7) or adjuvant alone as controls (n=5). Rats received serial PET imaging at week 1, week 2 and week 3 after first immunization utilizing a micro PET system. At fasting condition (>10h), static 10min chest FDG PET scans were started 1h after FDG intra-peritoenal administrations. 18F-fluorobenzyl triphenyl phosphonium (FBnTP) myocardial perfusion PET imaging was also performed to identify the localization of the FDG signal, followed by post-mortem histological and autoradiographic analysis at week 3.
Results Multiple focal cardiac inflammatory lesions with intense macrophage infiltration were histologically identified after immunization in 5 of 7 animals at week 3. FDG PET showed high contrast multiple focal tracer accumulation in all histologically confirmed myocarditis hearts at week 3, while no focal accumulation in controls (%ID/ml: 1.62±0.93 vs 0.25±0.04, p<0.001). Serial FDG PET imaging provided time course of the uptake signals (%ID/ml: 0.25±0.10, 0.28±0.11, 1.62±0.93, p<0.01 at week 1, 2 and 3, respectively). Ex-vivo analysis confirmed colocalization of the area of FDG accumulation and inflammatory lesions.
Conclusions PET imaging can provide non-invasive serial monitoring of the ative cardiac inflammation in a rat model of acute myocarditis. This experimental platform would be a powerful tool to explore novel diagnostic and therapeutic approaches.