Department of Cardiology and Angiology I, Heart Center Freiburg University, Faculty of Medicine, University of Freiburg, Hugstetter Strasse 55, 79106, Freiburg, Germany.
Department of Radiology, Medical Physics, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Sci Rep. 2020 Aug 6;10(1):13211. doi: 10.1038/s41598-020-70043-9.
MRI sensitivity for diagnosis and localization of early myocarditis is limited, although it is of central clinical interest. The aim of this project was to test a contrast agent targeting activated platelets consisting of microparticles of iron oxide (MPIO) conjugated to a single-chain antibody directed against ligand-induced binding sites (LIBS) of activated glycoprotein IIb/IIIa (= LIBS-MPIO). Myocarditis was induced by subcutaneous injection of an emulsion of porcine cardiac myosin and complete Freund's adjuvant in mice. 3D 7 T in-vivo MRI showed focal signal effects in LIBS-MPIO injected mice 2 days after induction of myocarditis, whereas in control-MPIO injected mice no signal was detectable. Histology confirmed CD41-positive staining, indicating platelet involvement in myocarditis in mice as well as in human specimens with significantly higher LIBS-MPIO binding compared to control-MPIO in both species. Quantification of the myocardial MRI signal confirmed a signal decrease after LIBS-MPIO injection and significant less signal in comparison to control-MPIO injection. These data show, that platelets are involved in inflammation during the course of myocarditis in mice and humans. They can be imaged non-invasively with LIBS-MPIO by molecular MRI at an early time point of the inflammation in mice, which is a valuable approach for preclinical models and of interest for both diagnostic and prognostic purposes.
MRI 对早期心肌炎的诊断和定位的敏感性有限，尽管这是临床关注的焦点。本项目的目的是测试一种针对激活血小板的造影剂，该造影剂由与针对激活糖蛋白 IIb/IIIa（=LIBS）的配体诱导结合位点的单链抗体偶联的氧化铁微粒（MPIO）组成。心肌炎是通过在小鼠皮下注射猪心肌肌球蛋白和完全弗氏佐剂的乳液诱导的。3D 7T 体内 MRI 显示，在心肌炎诱导后 2 天，LIBS-MPIO 注射小鼠出现局灶性信号效应，而在对照-MPIO 注射小鼠中则无法检测到信号。组织学证实 CD41 阳性染色，表明在心肌炎小鼠以及与对照-MPIO 相比，在两种物种中均具有明显更高的 LIBS-MPIO 结合的人类标本中，血小板参与了心肌炎。LIBS-MPIO 注射后的心肌 MRI 信号定量证实信号降低，与对照-MPIO 注射相比信号明显降低。这些数据表明，血小板在小鼠和人类心肌炎的炎症过程中被激活。通过分子 MRI 可以在炎症的早期阶段非侵入性地对 LIBS-MPIO 进行成像，这是一种有价值的临床前模型方法，对于诊断和预后均具有重要意义。
