The National Cancer Institute awarded Virginia Polytechnic Institute & State University (Virginia Tech) a $628,220 Project Grant under the Cancer Detection and Diagnosis Research program (CFDA 93.394) to develop an integrated image-guided histotripsy system for the non-invasive treatment of heterogeneous osteosarcoma (OS) tumors. The 4-year project aims to design an advanced histotripsy system with 3D cavitation imaging and image-fusion targeting capabilities to enable complete, uniform, and tissue-selective ablation of complex OS tumors. This includes optimizing treatment parameters and validating the safety and efficacy of the system through in vivo testing in canine OS patients. The project involves a sub-award to the University of Michigan to collaborate on this initiative. The goal is to create a human prototype histotripsy system with unique ablation and monitoring abilities tailored for the complex challenges of treating OS, thereby improving treatment options and outcomes for this devastating form of cancer.