Photo-Mediated Ultrasound Therapy (PUT) for the Treatment of Deep Cutaneous Vasculature

Traditionally, pulsed dye laser (PDL) therapy has been used to treat cutaneous blood vessels in patients with port-wine stain (PWS) birthmarks. PDL therapy, however, has limited treatment depth, and frequently results in suboptimal therapeutic outcomes when used to treat deep cutaneous blood vessels. We have developed photo-mediated ultrasound therapy (PUT), a hybrid cavitation-based anti-vascular technology combining nanosecond light pulses with ultrasound bursts and demonstrated its great potential in treating deep cutaneous vessels. This study explored the feasibility of PUT as an alternative to traditional PDL therapy for deep cutaneous vascular treatment in a clinically relevant chicken wattle model. PUT was employed to induce cavitation in blood vessels by using different light fluence and ultrasound pressure combinations. Theoretical modeling and <i>in vitro</i> experiments were first conducted to validate and optimize parameters for PUT treatment targeting deep vasculature. PUT treatments were then performed in a chicken wattle model using an experimental setup, and outcomes were assessed by using polarized dermoscope, optical coherence tomography angiography (OCT-A) imaging, and histopathological analyses. The results demonstrated that PUT can effectively penetrate the entire thickness of chicken wattle tissue, which is about 3 mm, and significantly reduce blood vessel density by 45.20% with a light fluence 10-100 times less than the fluence used in traditional PDL therapy. OCT-A imaging showed that local blood perfusion was significantly reduced, and the reduced blood perfusion persisted for at least 7 days post-treatment in the treated areas. Histopathological analyses based on H&E, CD31, and Russell-Movat Pentachrome (RMP) stains confirmed effective and selective vascular damage through the entire thickness of chicken wattle without causing collateral thermal damage. In conclusion, PUT can effectively eliminate blood vessels with a treatment depth up to 3 mm whereas the 3 mm treatment depth demonstrated in this study was only limited by the chicken wattle model. By leveraging the deep tissue penetration of ultrasound and the flexibility in treatment parameter selection, PUT can effectively treat deep cutaneous vasculature using reduced light fluence and thereby minimize collateral damage in skin tissues. Thus, PUT holds great potential for treatment of cutaneous vascular anomalies such as PWS.