Combining radiation force with cavitation for enhanced sonothrombolysis

The use of acoustic radiation force has been suggested for enhancing the delivery of therapeutic substances, whereas sonothrombolysis has been developed for years as treatment by itself, or in combination with thrombolytic agents or ultrasound contrast agents. We have examined the efficacy of using acoustic radiation force to enhance the targeting of microbubbles in cavitation-induced sonothrombolysis in a flow phantom system. A clot was targeted by microbubbles using avidin-biotin binding, and the process was observed using a confocal microscope. We found that the experimental group in which radiation force was combined with cavitation showed an additional 3% to 9% weight reduction of the thrombus relative to the cavitation group. We also found that the fluorescence intensity of the clot increased with the microbubble concentration at each acoustic setting. Microbubbles traveled 10 to 20 μm further than the control group after being exposed to radiation force, cavitation, or both. These observations confirm that radiation force helps microbubbles to distribute into a clot (as does cavitation). Therefore, combining radiation force with cavitation would provide additional thrombolysis effects (based on clot weight measurements) relative to cavitation alone. A local delivery method based on acoustic radiation force has the potential to improve the safety and efficacy of sonothrombolysis.