The goal of this SBIR project is to develop an integrated, image-guided ultrasound therapy system for soft tissue ablation, including cancer therapy. The motivation for this approach, based on extensive preliminary data, is that image guided bulk ablation using intense ultrasound (IUS) has several benefits compared with currently employed ablation methods, which include: Localization and targeting: the ability to image while positioning the probe, such as during a minimally invasive approach; Treatment planning: the capability to map out therapy based on interstitial, real-time visualization of target tissue; Precise energy deposition: the ability to selectively direct energy to spare critical structures or intervening tissue; and Procedure monitoring: the facility to ultrasonically monitor tissue effects during treatment; and Low cost and complexity compared to noninvasive approaches (e.g., MRI-guided HIFU). Our system will perform ultrasound bulk ablation of liver cancer and other soft tissue tumors using dual functionality (image and ablate) interstitial ultrasound arrays, a recently developed, innovative technology that provides precise image guidance for tumor ablation. Interstitial ultrasound ablation also offers greatly improved selectivity and reduced sensitivity to blood flow cooling effects that limit other thermal ablation methods. In our Phase I study, new image-ablate arrays with improved imaging and focusing capabilities will be designed, developed, and integrated into probes suitable for interstitial ablation. The capability of these probes for intense ultrasound ablation will be specified based on systematic simulation and tissue experiments. Treatment methods for clinically relevant ablation performance, as measured by ablation defect diameter, volumetric ablation rate, and capability for selective ablation with tissue sparing, will thus be specified. An in vivo study using VX2 tumor tissue implanted in rabbit liver will test the feasibility of image-guided ablation of cancer, with pathologic analysis that will provide insight into the effects of our ultrasound bulk ablation methods on malignant vs. normal tissue. Milestones evaluated based on the in vivo results will assess the clinically relevant capabilities of our system for treatment targeting, planning, and selective image-guided ablation of planned treatment zones. This Phase I research will provide the foundation for the thorough preclinical and pilot clinical studies to be performed in a later Phase II project, expected to culminate in development of a clinically and commercially successful ultrasound imaging and ablation system that will significantly improve treatment of focal tumors. Liver cancer, both primary and metastatic, is a major public health problem, accounting for the largest cancer- related mortality in the world. Only a small fraction of patients are eligible for curative resection or transplantation; minimally invasive ablation methods provide an important alternative but have significant problems with incomplete treatment, tumor recurrence, and complications caused by imprecise treatment. Our integrated, image-guided ultrasound ablation system will provide more precise, selective, predictable, and consistent ablation of liver cancer as well as other soft tissue tumors, resulting in fewer complications, reduced tumor recurrence, and thus improved outcomes for cancer patients.
