Development of a Novel Gas Embolotherapy Technique

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DESCRIPTION (provided by applicant): The delivery of emboli to arterial blood flow with the goal of flow occlusion, or embolotherapy, is a potential means to treat a variety of cancers, such as heptatocellular carcinoma (HCC) and renal carcinoma. HCC, the most common form of liver cancer, occurs in 2-30 per 100,000 males each year, resulting in approximately 1,250,000 deaths worldwide annually. The accompanying liver cirrhosis makes the treatment of HCC by traditional methods difficult. Systemic chemotherapy has no appreciable impact on survival rates. In addition to these types of cancer, many other types could potentially be treated using embototherapy. Previous attempts at embolotherapy have used solid emboli, such as blood clot, gelatin sponge, particulates, balloons and streamers. A major difficulty in embolotherapy is restricting delivery of the emboli to the tumor, i.e. minimizing ischemia of healthy tissue, without extremely invasive procedures. Here, we propose an acoustically activated gas embolotherapy. While gas bubbles have been used as ultrasonic contrast agents, they have not previously been used to occlude flow to tumors. Moreover, this novel approach involves introducing liquid droplets, which are small enough to pass through capillaries, into the vascular flow. The droplets could be tracked using ultrasound and vaporized via high intensity ultrasound near the tumor allowing gas bubbles, which are considerably larger than the liquid drops from which they originated, to occlude flow in the tumor. This minimally invasive technique would allow selective delivery of gas emboli to the tumor, and is well suited to repeated doses and long term use. The proposed research uses computational and experimental (animal and bench top) studies to provide proof of concept of this technique. This work will investigate the physical phenomena of vessel occlusion by gas emboli and vessel deformation due to the vaporization of liquid droplets. The proposed research is a collaboration of engineers, physicists, and clinicians with expertise in expertise in fluid dynamics, gas transport, and diagnostic and therapeutic ultrasound. The proposed research is an essential first step in developing this potentially revolutionary technique.