Harnessing bioeffects of ultrasound triggered microbubble cavitation in medicine

The use of gas-filled microbubbles (1-10 mm in diameter) for ultrasound imaging is well established. Such contrast agents are used worldwide to improve the diagnostic capabilities of contrast enhanced ultrasound imaging (CEUS). At higher acoustic pressures (albeit well within United States Food and Drug Administration limits), the microbubbles undergo stable cavitation followed by destruction via gas diffusion and inertial cavitation, which produces numerous, localized bioeffects. Among these bioeffects, microbubble cavitation can improve drug delivery and sensitize solid tumors to radiation. This talk will discuss the variety of applications in which our laboratory investigates these bioeffects. Our pre-clinical and clinical trials to investigate the safety and therapeutic benefits of combining radioembolization and ultrasound-triggered microbubble destruction (UTMD) in patients with hepatocellular carcinoma (HCC) as well as the possibility of improving antibiotic treatment of joint infections with UTMD will be discussed. The current status of our ongoing trial of sonoporation in patients with pancreatic ductal adenocarcinoma (PDAC) will be presented. Moreover, we have developed a noninvasive pressure measurement technique, known as subharmonic-aided pressure estimation (SHAPE), which was used to acquire intra-tumoral pressure measurements. The use of SHAPE and other quantitative ultrasound techniques as biomarkers for predicting treatment response will also be presented.