Saturday, May 31, 2025
5/31/2025
Image-guided Histotripsy System for Complete, Uniform, and Non-Invasive Ablation of Heterogeneous Osteosarcoma Tumors - Summary The goal of this project is to develop a novel histotripsy device for non-invasive treatment of heterogeneous osteosarcoma tumors (OS). OS are malignant bone tumors that develop in both children and adults. Long-term survival rates for patients with metastatic and non-metastatic OS are around 20% and 70%, respectively, highlighting the devastating nature of this disease. Limb salvage surgery or amputation are first-line treatments for primary appendicular OS, but these remain associated with high complication rates and decreased mobility and function. Novel treatments for OS are needed to improve outcomes. Histotripsy is a non-invasive ultrasound therapy that mechanically ablates tumors into acellular debris via controlled acoustic cavitation. Histotripsy can be tissue-selective, where neurovascular bundles, vessels, and bone can be preserved while the tumor is completely disrupted to acellular debris. Histotripsy appears to be well-suited for OS with the ability to serve as a non-surgical limb salvage treatment option, with promising results noted in preliminary studies. Despite this promise, OS treatment with histotripsy presents unique challenges: 1) OS tumors exhibit high inter- and intra- tumoral heterogeneity, with varying proportions of lytic and proliferative bone and soft tissue tumor proliferation, requiring optimized treatment strategies for complete and uniform ablation of all OS phenotypes. 2) OS tumors grow close to critical structures. While histotripsy has been shown to be tissue-selective for other applications, there remains a need to develop methods for selectively ablating OS tumors while preserving healthy bone, nerves, vessels, and connective tissue. 3) Histotripsy is typically guided by real-time ultrasound imaging, which is not feasible for a subset of OS tumors due to bone obstruction, requiring improved targeting and monitoring techniques. In this proposal, we will develop an integrated image-guided histotripsy system for the precise targeting and ablation of OS tumors. The system will consist of a phased array transducer with transmit-receive capability for 3D cavitation monitoring, image-fusion targeting (CT/MRI), and a fully automated robotic treatment technique with strategies for achieving uniform and complete ablation of heterogeneous OS tumors. We propose the following three aims. Aim 1: Design and construct an integrated histotripsy OS system consisting of an array transducer with transmit-receive capabilities for 3D cavitation imaging and image-fusion targeting. Aim 2: Develop patient specific treatment methods with optimized parameters for complete, uniform, and tissue- selective OS ablation. Aim 3: Test the in vivo safety and efficacy of the integrated OS system (Aim 1) and optimized parameters for uniform and safe treatment of OS (Aim 2) in canine OS patients at the Virginia Tech Animal Cancer Care and Research Center. This project will result in a human prototype histotripsy system with unique treatment and monitoring capabilities as well as parameters optimized for OS. The canine patients are the best large animal model to test the safety and efficacy of histotripsy and accelerate clinical translation, and the veterinary treatment is another application for histotripsy OS therapy before the FDA approval of human use.
HHS’ Tracking Accountability in Government Grants System (TAGGS) website provides access to detailed descriptions of grants, loans, aggregated direct payments and other types of financial assistance awarded by the HHS Operating Divisions (OPDIVs) and the Office of the Secretary Staff Divisions (STAFFDIVs).