# First Report of Histotripsy-Induced Survival Benefit in Murine Glioblastomas

## TL;DR

A noninvasive ultrasound technique called histotripsy was shown to improve survival in mice with brain tumors, with no major side effects.

## Contribution

This is the first report demonstrating a survival benefit from histotripsy in a murine glioblastoma model.

## Key findings

- Histotripsy treatment increased median survival by 18.5% in mice with glioblastoma.
- MRI and histology confirmed tumor volume reduction and increased tumor necrosis after treatment.
- The treatment was well tolerated with no significant acute or chronic adverse effects.

## Abstract

Histotripsy is a noninvasive soft tissue ablation technique that uses high-pressure ultrasound to generate precise regions of cellular destruction within tumors while sparing surrounding healthy tissue. This study evaluated the survival benefit of a single transcranial histotripsy treatment in glioblastoma-bearing mice using a raster-scanning pattern with varying numbers of histotripsy pulses. Histotripsy resulted in an 18.5% increase in survival compared with untreated controls and was well tolerated with no significant acute or chronic adverse effects. These findings support further investigation of histotripsy as a potential therapeutic approach for brain tumors.

Background: Glioblastoma (GBM) is a lethal, highly invasive, and recurrent brain tumor. Standard treatment combines maximal surgical resection, radiation, and chemotherapy; however, such approaches are often infeasible for tumors in eloquent brain regions. Objective: Histotripsy is a noninvasive, nonthermal ultrasound-based mechanical ablation modality that employs focused acoustic energy for targeted tissue destruction. This study aimed to investigate the feasibility, safety, and therapeutic effect of a one-time transcranial histotripsy treatment in a pre-clinical murine GBM model. Methods: GL261 GBM cells were orthotopically implanted into C56BL/6 mouse brains. Transcranial histotripsy was performed using a stereotactically guided 2 MHz transducer targeting either lower (25%) or higher (75%) tumor volume, with 5 or 10 pulses per location (PPL) administered. Tumor growth and cerebral injury were monitored with weekly magnetic resonance imaging (MRI) following treatment. At the study endpoint, hematoxylin and eosin (H&E) histology assessed residual tumor burden and histotripsy-induced tissue changes. Results: Mice receiving 5 PPL high-percent treatment (>30 sites) showed a statistically significant median survival extension of 5 days (18.5%) compared to untreated controls. MRI demonstrated marked tumor volume reduction in the high-percent treatment group at week 4, while H&E confirmed increased tumor necrosis and cellular damage in the treated cohort. Conclusions: Single-session, incisionless transcranial histotripsy was well tolerated and conferred mild yet meaningful survival advantages in this GBM model. These results support ongoing exploration of histotripsy, alone or in combination with existing therapies, for safe and effective treatment of challenging brain tumors.