Heidt Timo, Ehrismann Simon, Hövener Jan-Bernd, Neudorfer Irene, Hilgendorf Ingo, Reisert Marco, Hagemeyer Christoph E, Zirlik Andreas, Reinöhl Jochen, Bode Christoph, Peter Karlheinz, von Elverfeldt Dominik, von Zur Muhlen Constantin
Department of Cardiology and Angiology I, Heart Center Freiburg University, Germany.
Department of Radiology, Medical Physics, Medical Center - University of Freiburg, Faculty of Medicine, Germany.
Sci Rep. 2016 May 3;6:25044. doi: 10.1038/srep25044.
Early and reliable detection of pulmonary embolism (PE) is critical for improving patient morbidity and mortality. The desire for low-threshold screening for pulmonary embolism is contradicted by unfavorable radiation of currently used computed tomography or nuclear techniques, while standard magnetic resonance imaging still struggles to provide sufficient diagnostic sensitivity in the lung. In this study we evaluate a molecular-targeted contrast agent against activated platelets for non-invasive detection of murine pulmonary thromboembolism using magnetic resonance imaging. By intravenous injection of human thrombin, pulmonary thromboembolism were consistently induced as confirmed by immunohistochemistry of the lung. Magnetic resonance imaging after thrombin injection showed local tissue edema in weighted images which co-localized with the histological presence of pulmonary thromboembolism. Furthermore, injection of a functionalized contrast agent targeting activated platelets provided sensitive evidence of focal accumulation of activated platelets within the edematous area, which, ex vivo, correlated well with the size of the pulmonary embolism. In summary, we here show delivery and specific binding of a functionalized molecular contrast agent against activated platelets for targeting pulmonary thromboembolism. Going forward, molecular imaging may provide new opportunities to increase sensitivity of magnetic resonance imaging for detection of pulmonary embolism.
早期且可靠地检测肺栓塞(PE)对于改善患者的发病率和死亡率至关重要。目前使用的计算机断层扫描或核技术存在不利的辐射问题,这与低阈值筛查肺栓塞的需求相矛盾,而标准的磁共振成像在肺部仍难以提供足够的诊断敏感性。在本研究中,我们评估了一种针对活化血小板的分子靶向造影剂,用于通过磁共振成像无创检测小鼠肺血栓栓塞。通过静脉注射人凝血酶,经肺组织免疫组化证实可持续诱导肺血栓栓塞。注射凝血酶后的磁共振成像在加权图像中显示局部组织水肿,其与肺血栓栓塞的组织学存在共定位。此外,注射靶向活化血小板的功能化造影剂提供了活化血小板在水肿区域内局灶性聚集的敏感证据,在体外,这与肺栓塞的大小密切相关。总之,我们在此展示了一种针对活化血小板的功能化分子造影剂用于靶向肺血栓栓塞的递送和特异性结合。展望未来,分子成像可能为提高磁共振成像检测肺栓塞的敏感性提供新的机会。