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

Molecular imaging with targeted contrast agents is emerging as an important technological advance for diagnostic ultrasound. In vivo, these agents must bind to and acoustically enhance their targets before the agents are cleared or destroyed. In this study, we present results using a system that was designed and constructed for 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-minute increments for one hour. A monotonic increase was observed in ultrasonic reflection enhancement from specially treated nitrocellulose membranes for targeted emulsions containing perfluorooctylbromide (1.3±0.3 dB) and perfluorooctane (2.6±0.5 dB) within the first 60 minutes of imaging. In comparison, the inherently non-echogenic plasma clots showed a substantial increase of 12.0±0.9 dB when targeted with a perfluorooctane 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.