We have developed a safe, noninvasive imaging-guided localized antivascular method, namely photo-mediated ultrasound therapy (PUT), by applying synchronized laser and ultrasound pulses. Through our experimental and theoretical studies, we demonstrate that cavitation plays a key role in PUT. PUT promotes cavitation activity in blood vessels by concurrently applying ultrasound bursts and nanosecond laser pulses. The collapse of cavitation can induce damage to blood vessel endothelial cells, resulting in occlusion of microvessels. This study presents the effect of laser pulse energy, laser pulse length, ultrasound intensity, and synchronization time between laser and ultrasound. We found that, in order to produce controllable blood vessel occlusion, linear oscillation of cavitation (or non-inertial cavitation) might be the key, while strong collapse of cavitation (inertial cavitation) might induce bleeding. Under the guidance an optical coherence tomography (OCT) system, we utilized PUT to remove microvessels in the rabbit choroid. We were able to monitor cavitation activity in real-time in vivo during PUT treatment, and predict treatment outcome. Histology findings confirmed that fibrin clots were developed in the microvessels in the treated region, while no damage was found in the surrounding tissue.
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