# Developing Methods for Precise, Safe and Target-location Specific Histotripsy of Liver Tumors

> **NIH NIH R01** · UNIVERSITY OF WISCONSIN-MADISON · 2021 · $552,836

## Abstract

PROJECT SUMMARY
The goal of this grant is to optimize hepatic histotripsy to create safe and effective ablation in any
location in a large animal, human-scale model. Liver cancer is a leading cause of death with
ablation one of the limited curative options in select patients. Unfortunately, currently available
ablation procedures have a variable local failure rate of ~10-40%. Also, tumors located near
critical structures, such as bile ducts and bowel, often do not receive curative treatment as thermal
ablation is associated with increased risk of injury. Histotripsy is the first non-invasive, non-
thermal, and non-ionizing ablation modality, using focused ultrasound energy to create cavitation,
resulting in mechanical tissue disruption. In preliminary studies, histotripsy has shown an ability
to cause tissue disruption that spares certain structures with collagenous architecture, including
bile ducts and bowel, and to create ablation zones with a thin margin between treated and normal
tissues. To catalyze the clinical translation of histotripsy and potentially increase the
number of patients eligible for curative treatment, a key question needs to be answered:
Can we leverage the potential safety advantages of histotripsy while maintaining efficacy
such that more tumors will be eligible for curative treatment? First, strategies to mitigate the
effects of respiratory motion by decreasing liver motion with high-frequency jet ventilation or using
in-suite cone-beam CT to model liver motion and modify prescriptions will be trialed in Aim 1. In
Aim 2 we will determine dose thresholds to treat excised HCC while sparing critical structures to
identify a safe, effective treatment dose for tumors of any location and then validate this dose in
a survival, in vivo swine liver model. Finally, in Aim 3 we will advance a SCID-like HCC porcine
liver tumor model, which will allow us to apply these strategies to tumors located within specific
high-risk locations of the liver to confirm safety and efficacy, ultimately, proving our hypothesis
that histotripsy can treat tumors in any liver location safely. The three Specific Aims are the
following. Aim 1: Determine the best strategy to mitigate the effects of respiratory motion to
increase the precision and safety of histotripsy ablation. Aim 2: To determine dose thresholds for
liver cancer and critical structures ex vivo, allowing a trial of safe, effective treatment parameters
for in vivo treatment in critical locations. Aim 3: Advance a highly relevant large animal liver HCC
model for medical devices and confirm safety and efficacy in this large animal model. This project
will yield critical preclinical data which will be necessary before the widespread adoption of
histotripsy to treat patients with non-surgical hepatocellular carcinoma.

## Key facts

- **NIH application ID:** 10276750
- **Project number:** 1R01CA262474-01
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** Timothy J Ziemlewicz
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $552,836
- **Award type:** 1
- **Project period:** 2021-09-23 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10276750

## Citation

> US National Institutes of Health, RePORTER application 10276750, Developing Methods for Precise, Safe and Target-location Specific Histotripsy of Liver Tumors (1R01CA262474-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10276750. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*