Pittsburgh NMR Center for Biomedical Research, Carnegie Mellon University, Pittsburgh, Pennsylvania, USA.
Magn Reson Med. 2011 Apr;65(4):1144-53. doi: 10.1002/mrm.22702. Epub 2011 Feb 8.
Current diagnosis of organ rejection following transplantation relies on tissue biopsy, which is not ideal due to sampling limitations and risks associated with the invasive procedure.We have previously shown that cellular magnetic resonance imaging (MRI) of iron-oxide labeled immune-cell infiltration can provide a noninvasive measure of rejection status by detecting areas of hypointensity on T 2*-weighted images. In this study, we tested the feasibility of using a fluorine-based cellular tracer agent to detect macrophage accumulation in rodent models of acute allograft rejection by fluorine-19 ((19) F) MRI and magnetic resonance spectroscopy. This study used two rat models of acute rejection, including abdominal heterotopic cardiac transplant and orthotopic kidney transplant models. Following in vivo labeling of monocytes and macrophages with a commercially available agent containing perfluoro-15-crown-5-ether, we observed (19) F-signal intensity in the organs experiencing rejection by (19) F MRI, and conventional (1) H MRI was used for anatomical context. Immunofluorescence and histology confirmed macrophage labeling. These results are consistent with our previous studies and show the complementary nature of the two cellular imaging techniques. With no background signal, (19) F MRI/magnetic resonance spectroscopy can provide unambiguous detection of fluorine labeled cells, and may be a useful technique for detecting and quantifying rejection grade in patients.
目前,移植后器官排斥的诊断依赖于组织活检,但由于取样限制和侵入性操作带来的风险,这种方法并不理想。我们之前已经证明,通过铁氧化物标记免疫细胞浸润的细胞磁共振成像(MRI)可以通过在 T2*-加权图像上检测到低信号区域,提供一种非侵入性的排斥状态测量方法。在这项研究中,我们通过氟-19((19)F)MRI 和磁共振波谱检测,测试了使用基于氟的细胞示踪剂来检测急性同种异体移植排斥反应啮齿动物模型中巨噬细胞积累的可行性。这项研究使用了两种急性排斥的大鼠模型,包括腹部异位心脏移植和原位肾脏移植模型。在使用含有全氟-15-冠-5-醚的市售试剂对单核细胞和巨噬细胞进行体内标记后,我们通过(19)F MRI 观察到经历排斥反应的器官中的(19)F 信号强度,并且使用常规(1)H MRI 提供解剖学背景。免疫荧光和组织学证实了巨噬细胞标记。这些结果与我们之前的研究一致,表明两种细胞成像技术具有互补性。由于没有背景信号,(19)F MRI/磁共振波谱可以提供对氟标记细胞的明确检测,并且可能是一种用于检测和量化患者排斥等级的有用技术。
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