Time evolution of enhanced ultrasonic reflection using a fibrin-targeted nanoparticulate contrast agent

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 mo rphology was demonstrated with the use of a nongaseous, fibrin-targeted aco ustic nanoparticle emulsion delivered to areas of thrombosis both in vitro and in vivo. In this study, a system was designed and constructed that allo ws visualization of the evolution of acoustic contrast enhancement. To eval uate the system, two targets were examined: avidin-complexed nitrocellulose membrane and human plasma clots. The time evolution of enhancement was vis ualized in 10-min increments for 1 h. A monotonic increase was observed in ultrasonic reflection enhancement from specially treated nitrocellulose mem branes for targeted emulsions containing perfluorooctylbromide (1.30+/-0.3 dB) and for perfluorooctane (2.64+/-0.5 dB) within the first 60 min of imag ing. In comparison, the inherently nonechogenic plasma clots showed a subst antial increase of 12.0+/-0.9 dB when targeted with a perfluoro-octane emul sion. This study demonstrates the concept of molecular imaging and provides the first quantifiable time-evolution report of the binding of a site-targ eted ultrasonic contrast agent. Moreover, with the incorporation of specifi c drug treatments into the nanoparticulate contrast agent, ultrasonic molec ular imaging may yield reliable detection and quantification of nascent pat hologies and facilitate targeted drug therapy. (C) 2000 Acoustical Society of America. [S0001-4966(00)02212-8].