Hall C S, Marsh J N, Scott M J, Gaffney P J, Wickline S A, Lanza G M
Washington University School of Medicine, St. Louis, Missouri 63110, USA.
J Acoust Soc Am. 2000 Dec;108(6):3049-57. doi: 10.1121/1.1322566.
Complex molecular signaling heralds the early stages of pathologies such as angiogenesis, inflammation, unstable atherosclerotic plaques, and areas of remote thrombi. In previous studies, acoustic enhancement of blood clot morphology was demonstrated with the use of a nongaseous, fibrin-targeted acoustic nanoparticle emulsion delivered to areas of thrombosis both in vitro and in vivo. In this study, a system was designed and constructed that allows visualization of the evolution of acoustic contrast enhancement. To evaluate the system, two targets were examined: avidin-complexed nitrocellulose membrane and human plasma clots. The time evolution of enhancement was visualized in 10-min increments for 1 h. A monotonic increase was observed in ultrasonic reflection enhancement from specially treated nitrocellulose membranes for targeted emulsions containing perfluorooctylbromide (1.30+/-0.3 dB) and for perfluorooctane (2.64+/-0.5 dB) within the first 60 min of imaging. In comparison, the inherently nonechogenic plasma clots showed a substantial increase of 12.0+/-0.9 dB when targeted with a perfluoro-octane emulsion. This study demonstrates the concept of molecular imaging and provides the first quantifiable time-evolution report of the binding of a site-targeted ultrasonic contrast agent. Moreover, with the incorporation of specific drug treatments into the nanoparticulate contrast agent, ultrasonic molecular imaging may yield reliable detection and quantification of nascent pathologies and facilitate targeted drug therapy.
复杂的分子信号预示着诸如血管生成、炎症、不稳定动脉粥样硬化斑块和远处血栓区域等病理过程的早期阶段。在先前的研究中，通过将一种非气态、靶向纤维蛋白的声学纳米颗粒乳剂递送至血栓形成区域，在体外和体内均证明了血凝块形态的声学增强。在本研究中，设计并构建了一个系统，该系统能够可视化声学造影增强的演变过程。为了评估该系统，研究了两个靶点：抗生物素蛋白复合硝酸纤维素膜和人血浆凝块。以10分钟为增量，持续1小时观察增强的时间演变。在成像的前60分钟内，对于含有全氟辛基溴（1.30±0.3 dB）和全氟辛烷（2.64±0.5 dB）的靶向乳剂，经特殊处理的硝酸纤维素膜的超声反射增强呈现单调增加。相比之下，当用全氟辛烷乳剂靶向时，本质上无回声的血浆凝块显示出大幅增加，为12.0±0.9 dB。本研究证明了分子成像的概念，并提供了首个关于位点靶向超声造影剂结合的可量化时间演变报告。此外，通过将特定药物治疗纳入纳米颗粒造影剂中，超声分子成像可能实现对新生病变的可靠检测和定量，并促进靶向药物治疗。
