# Image-guided Histotripsy System for Complete, Uniform, and Non-Invasive Ablation of Heterogeneous Osteosarcoma Tumors

> **NIH NIH R01** · VIRGINIA POLYTECHNIC INST AND ST UNIV · 2024 · $628,220

## Abstract

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 treatm...

## Key facts

- **NIH application ID:** 10856366
- **Project number:** 1R01CA289288-01
- **Recipient organization:** VIRGINIA POLYTECHNIC INST AND ST UNIV
- **Principal Investigator:** Eli Vlaisavljevich
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $628,220
- **Award type:** 1
- **Project period:** 2024-05-01 → 2028-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10856366

## Citation

> US National Institutes of Health, RePORTER application 10856366, Image-guided Histotripsy System for Complete, Uniform, and Non-Invasive Ablation of Heterogeneous Osteosarcoma Tumors (1R01CA289288-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10856366. Licensed CC0.

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