Investigating treatment strategies & clinical outcomes of histotripsy for complete ablation of osteosarcoma

Project Summary Osteosarcoma (OS) is a common and devastating primary bone tumor affecting both humans and canines. Histotripsy is an emerging non-thermal ablation modality that uses high-pressure focused ultrasound pulses to induce acoustic cavitation and liquify target tissue with high precision. Our team has pioneered the development of histotripsy for bone tumors with critical ex vivo and in vivo studies using excised canine OS tumors and pet dogs with spontaneous OS, respectively. Dogs have an increased incidence of OS with high similarity to human OS, allowing the pet dog to serve as a valuable comparative oncology model. This proposal seeks to further the development of histotripsy for OS treatment by 1) investigating the treatment parameters & strategies needed for complete ablation in ex vivo canine OS, and 2) testing these strategies in pilot clinical trials with acute and chronic follow-up of pet dogs with histotripsy-treated OS. Throughout these experiments, I will be trained in vital skills in bio-engineering and clinical oncology, including transmit-receive circuitry (Dr. Tim Hall at University of Michigan), histopathological analysis of ablation (Dr. Sheryl Coutermarsh-Ott at Virginia-Maryland College of Veterinary Medicine), and radiological assessment of ablation (Dr. Tim Ziemlewicz at University of Wisconsin). The results of this work will overcome previous technical & engineering barriers in achieving complete ablation of bone tumors and will provide crucial safety & feasibility data to guide and inform the clinical translation of histotripsy as a non-invasive limb salvage treatment for OS.