Introduction
Angiogenesis plays a critical role in the pathogenesis of numerous pathological conditions, including cancer, inflammation, and eye diseases. Currently available anti-vascular treatments such as anti-VEGF agents and photodynamic therapy have several drawbacks. We have developed a novel, selective, localized anti-vascular technique, namely photo-mediated ultrasound therapy (PUT), by applying synchronized nanosecond laser irradiation and ultrasound pulses. Taking advantage of the high optical absorption of hemoglobin, PUT can selectively target microvessels without causing unwanted damages to the surrounding tissue. Moreover, PUT is totally noninvasive and agent-free.
The mechanism of PUT is thought to be cavitation activities in microvessels. Cavitation is produced via photospallation due to transient thermoelastic stress following short pulse duration laser and is driven by concurrent ultrasound. The addition of a laser pulse to an existing ultrasound field can significantly improve the likelihood of localized inertial cavitation, which can induce micro-vessel damage through its mechanical effect. In PUT, the required energy levels of both ultrasound and laser are significant lower than those used in previous therapeutic effects. Therefore, no significant temperature rise is induced and thermal damage can be effectively avoided.
We are developing PUT as a novel method to selectively treat pathologic microvasculature in retinal vascular diseases, in addition to investigating other applications in tumors and dermatologic applications, including port wine stains and tattoo removal.
Example results
The vein on a chicken yolk sac membrane before treatment with PUT (a). The vein after being treated by PUT with 0.45 MPa ultrasound and 4 mJ/cm2 laser fluence at 532 nm (b). The black circle corresponds to the region of treatment. Change in blood vessel diameter after laser only, ultrasound only, and PUT at 2, 4 and 6 mJ/cm2 fluence (c). Vertical bars demonstrate standard deviation. The relative change of the vessel size shows that statistical significances exist between 4 and 6 mJ/cm2 PUT and any other group (d). Higher laser fluence can result in vessel rupture (e,f,g). Repeated 10 times for each group. *p < 0.05; **p < 0.01, ***p < 0.001. Scale bar: 200 µm. Courtesy of the Authors.
Fundus photos of rabbit eye before and after PUT treatment. The rabbit choroidal vasculature is treated by PUT with 2 MPa ultrasound + 75 mJ/cm2 laser, which caused edema immediately after treatment. By 1 week, pallor occurred in the region of treatment with greatly diminished choroidal vessels which persisted to 4 weeks.