We developed a novel localized antivascular method, namely photo-mediated ultrasound therapy (PUT), by applying synchronized laser and ultrasound pulses. PUT relies on high optical contrast among biological tissues. Taking advantage of the high optical absorption of hemoglobin, PUT can selectively target microvessels without causing unwanted damages to the surrounding tissue. Moreover, PUT working at different optical wavelengths can selectively treat veins or arteries by utilizing the contrast in the optical spectra between deoxy- and oxy-hemoglobin. Through our experiments, we demonstrated that cavitation might have played a key role in PUT. The addition of a laser pulse to an existing ultrasound field can significantly improve the likelihood of inertial cavitation, which can induce microvessel damage through its mechanical effect. In comparison with conventional laser therapies, such as photothermolysis and photocoagulation, the laser energy level needed in PUT is significantly lower. When a nanosecond laser was used, our in vivo experiments showed that the needed laser fluence was in the range of 4 to 40 mJ/cm2.
Laser-induced thermotherapy (LITT), i.e. tissue destruction induced by a local increase of temperature by means of laser light energy transmission, has been frequently used for minimally invasive treatments of various diseases such as benign thyroid nodules and liver cancer. The emerging photoacoustic (PA) imaging, when integrated with ultrasound (US), could contribute to LITT procedure. PA can enable a good visualization of percutaneous apparatus deep inside tissue and, therefore, can offer accurate guidance of the optical fibers to the target tissue. Our initial experiment demonstrated that, by picking the strong photoacoustic signals generated at the tips of optical fibers as a needle, the trajectory and position of the fibers could be visualized clearly using a commercial available US unit. When working the conventional US Bscan mode, the fibers disappeared when the angle between the fibers and the probe surface was larger than 60 degree; while working on the new PA mode, the fibers could be visualized without any problem even when the angle between the fibers and the probe surface was larger than 75 degree. Moreover, with PA imaging function integrated, the optical fibers positioned into the target tissue, besides delivering optical energy for thermotherapy, can also be used to generate PA signals for on-line evaluation of LITT. Powered by our recently developed PA physio-chemical analysis, PA measurements from the tissue can provide a direct and accurate feedback of the tissue responses to laser ablation, including the changes in not only chemical compositions but also histological microstructures. The initial experiment on the rat liver model has demonstrated the excellent sensitivity of PA imaging to the changes in tissue temperature rise and tissue status (from native to coagulated) when the tissue is treated in vivo with LITT.