Department of Radiology, University Hospital (CHUV), Lausanne, Switzerland.
Circ Cardiovasc Imaging. 2013 Mar 1;6(2):277-84. doi: 10.1161/CIRCIMAGING.112.000125. Epub 2013 Jan 23.
BACKGROUND: The goal of this study was to characterize the performance of fluorine-19 ((19)F) cardiac magnetic resonance (CMR) for the specific detection of inflammatory cells in a mouse model of myocarditis. Intravenously administered perfluorocarbons are taken up by infiltrating inflammatory cells and can be detected by (19)F-CMR. (19)F-labeled cells should, therefore, generate an exclusive signal at the inflamed regions within the myocardium. METHODS AND RESULTS: Experimental autoimmune myocarditis was induced in BALB/c mice. After intravenous injection of 2×200 µL of a perfluorocarbon on day 19 and 20 (n=9) after immunization, in vivo (19)F-CMR was performed at the peak of myocardial inflammation (day 21). In 5 additional animals, perfluorocarbon combined with FITC (fluorescein isothiocyanate) was administered for postmortem immunofluorescence and flow-cytometry analyses. Control experiments were performed in 9 animals. In vivo (19)F-CMR detected myocardial inflammation in all experimental autoimmune myocarditis-positive animals. Its resolution was sufficient to identify even small inflammatory foci, that is, at the surface of the right ventricle. Postmortem immunohistochemistry and flow cytometry confirmed the presence of perfluorocarbon in macrophages, dendritic cells, and granulocytes, but not in lymphocytes. The myocardial volume of elevated (19)F signal (rs=0.96; P<0.001), the (19)F signal-to-noise ratio (rs=0.92; P<0.001), and the (19)F signal integral (rs=0.96; P<0.001) at day 21 correlated with the histological myocarditis severity score. CONCLUSIONS: In vivo (19)F-CMR was successfully used to visualize the inflammation specifically and robustly in experimental autoimmune myocarditis, and thus allowed for an unprecedented insight into the involvement of inflammatory cells in the disease process.
背景:本研究旨在描述氟-19(19F)心脏磁共振(CMR)在心肌炎小鼠模型中对炎症细胞的特异性检测性能。静脉内给予的全氟化碳被浸润的炎症细胞摄取,并可通过 19F-CMR 检测到。(19)F 标记的细胞应因此在心肌内炎症区域产生独特的信号。
方法和结果:在 BALB/c 小鼠中诱导实验性自身免疫性心肌炎。在免疫后第 19 天和第 20 天(n=9)静脉注射 2×200 µL 全氟化碳后,在心肌炎症高峰期(第 21 天)进行体内 19F-CMR。在另外 5 只动物中,全氟化碳与 FITC(异硫氰酸荧光素)联合给药,用于死后免疫荧光和流式细胞术分析。在 9 只动物中进行对照实验。体内 19F-CMR 在所有实验性自身免疫性心肌炎阳性动物中均检测到心肌炎症。其分辨率足以识别甚至小的炎症灶,即右心室表面。死后免疫组织化学和流式细胞术证实全氟化碳存在于巨噬细胞、树突状细胞和粒细胞中,但不存在于淋巴细胞中。第 21 天,升高的 19F 信号的心肌体积(rs=0.96;P<0.001)、19F 信号-噪声比(rs=0.92;P<0.001)和 19F 信号积分(rs=0.96;P<0.001)与组织学心肌炎严重程度评分相关。
结论:体内 19F-CMR 成功地用于可视化实验性自身免疫性心肌炎中的炎症,特异性强且稳健,从而使人们对炎症细胞在疾病过程中的参与有了前所未有的深入了解。
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