The Effect of Laser and Ultrasound Synchronization in Photo-Mediated Ultrasound Therapy

Objective: Photo-mediated ultrasound therapy (PUT) is a novel, non-invasive, agent-free, highly selective, and precise anti-vascular technique. PUT removes microvessels through promoting cavitation activity precisely in targeted microvessels by applying synchronized nanosecond laser pulses and ultrasound bursts. The synchronization between laser and ultrasound is critical to the outcome of PUT. Methods: Through theoretical simulation and experimental study, the effect of synchronization between laser pulses and ultrasound bursts on cavitation activity during PUT is evaluated. Results: By using a theoretical model, we found that cavitation activity was enhanced when laser pulses and ultrasound bursts were synchronized such that the produced photoacoustic wave overlaid the rarefactional phase of the ultrasound wave. This finding was then verified through in vitro studies where cavitation was monitored by using a passive cavitation detector. Furthermore, we demonstrated that the in vivo treatment outcome of PUT in rabbits was directly related to the synchronization between laser and ultrasound. The anti-vascular effect could only be observed when laser and ultrasound were properly synchronized in vivo. Conclusion: PUT is more efficient when the laser-induced photoacoustic wave overlays the rarefactional phase of the ultrasonic wave. Significance: This is a systematic study to investigate the synchronization effect of PUT, which would be significant for further understanding the mechanism and further improving the treatment efficiency of PUT.