Abstract
583
Objectives: Serial non-invasive imaging would provide better understanding of dynamic process of acute autoimmune myocarditis. The aim of this study is to elucidate the time course of cellular expression of adhesion molecules in acute myocarditis in association with the prior inflammatory activities identified by serial non-invasive 18F-FDG imaging.
Methods: Autoimmune myocarditis was induced in Lewis rats by immunizing with porcine cardiac myosin emulsified in complete Freund’s adjuvant. First, serial 18F-FDG PET imaging (2,3,4,5 and 10 weeks after immunization) was performed to determine the time course and feasibility of monitoring acute cardiac inflammation. Next, based on the individual results of serial 18F-FDG imaging, animals were assigned for three inflammatory stages: acute inflammation (Gr-0W) as well as 2 weeks (Gr-2W) and 7 weeks (Gr-7W) after the peak of acute inflammation, respectively. Histological analysis at each stages was conducted for adhesion markers (CD44 and CD34).
Results: Serial 18F-FDG PET imaging revealed focal and temporal increased tracer uptake in the heart peaked at around week 3 in average and decreased rapidly. Localization of CD68 positive cell infiltrations and 18F-FDG uptake signals were well correlated (R=0.91, P<0.0001). To be noted, the cardiac inflammation after the immunization was highly variable between individual animals including no inflammatory induction in 3/23 (13%). Based on the serial individual 18F-FDG findings, different stages of cardiac inflammatory tissue samples were successfully identified (Gr-0W n=4, Gr-2W, n=5, Gr-7W, n=5). High CD44-expressing cells were observed in the entire inflammatory lesions of Gr-0W and decreased time dependently in Gr-2W and Gr-7W. On the other hand, CD34 positive cells were scarce and only observed in the margins in Gr-0W, while strong expression was seen in the sample tissue of Gr-2W and Gr-7W.
Conclusion: Acute autoimmune myocarditis was successfully induced in Lewis rats and identified by non-invasive serial 18F-FDG PET imaging. Furthermore, histological characterization guided by individual 18F-FDG uptake signals revealed time course of adhesion molecules. Research Support: This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement. This work was supported by the Competence Network of Heart Failure funded by the Integrated Research and Treatment Center (IFB) of the Federal Ministry of Education and Research (BMBF) and German Research Council (DFG grant HI 1789/2-1).