# Non-invasive Transcranial Histotripsy Treatment in a Murine Primary  Malignant Brain Tumor Model

> **NIH NIH R21** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2021 · $383,701

## Abstract

Title: Non-invasive Transcranial Histotripsy Treatment in a Murine Primary Malignant Brain Tumor Model
Abstract
The goal of this proposal is to investigate whether transcranial histotripsy treatment of brain tumors can
lead to survival benefit in a murine primary malignant brain tumor model. Approximately 256,000 new
patients are diagnosed with primary brain tumors annually worldwide, and many more patients have brain
metastases. The first-option treatment is craniotomy-based surgical resection, a highly invasive surgery
associated with high morbidities. Radiation therapy and drug-based therapy have shown limited effectiveness in
treatment of brain tumors. There is a clear unmet clinical need for a noninvasive, safe, and effective treatment
for brain tumors. Histotripsy is a non-invasive, image-guided ultrasound therapy based on acoustic
cavitation. Guided by MRI and using microsecond ultrasound pulses delivered from outside the skull and
focused inside the brain, transcranial histotripsy generates focal cavitation to mechanically liquefy the target
brain tumor into acellular debris with millimeter accuracy. Transcranial histotripsy can be used to treat both
primary brain tumors and brain metastases. Our group has constructed a human-scale transcranial MR guided
histotripsy (tcMRgHt) system and demonstrated its safety and feasibility of non-invasive brain ablation in an in
vivo large animal normal brain through an excised human skull. Unlike transcranial MR guided focused
ultrasound (tcMRgFUS) that has limitations in treatment volume and location in the brain, tcMRgHt can be used
to treat a wide range of volumes and locations in the brain by avoiding skull heating. To advance histotripsy
towards clinical translation for treatment of brain tumors, a key question needs to be answered: Can transcranial
histotripsy result in survival benefit in a clinically relevant brain tumor model? We have achieved very early and
promising preliminary data suggesting that transcranial histotripsy can lengthen survival in a primary malignant
brain tumor model – murine glioma GL261 model. The GL261 model has been widely used in preclinical testing
of brain tumor treatment, however, very few treatment modalities have shown survival benefit in this mode due
to its highly aggressive nature. In this R21, we propose to study the following two specific Aims in the murine
GL261 model. Aim 1: Investigate the transcranial histotripsy parameters that can maximize the tumor kill while
minimizing brain injury. Aim 2: Determine whether histotripsy can achieve survival benefit compared to the
untreated controls. The data yielded here will reveal whether transcranial histotripsy can result in survival benefit
in a preclinical primary malignant brain tumor model. The results are critical to determining the clinical feasibility
of tcMRgHt as an effective, non-invasive treatment of malignant brain tumors and will be combined with our large
animal data for FDA submission to start a fu...

## Key facts

- **NIH application ID:** 10225167
- **Project number:** 1R21CA260684-01
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Aditya S Pandey
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $383,701
- **Award type:** 1
- **Project period:** 2021-04-15 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10225167

## Citation

> US National Institutes of Health, RePORTER application 10225167, Non-invasive Transcranial Histotripsy Treatment in a Murine Primary  Malignant Brain Tumor Model (1R21CA260684-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10225167. Licensed CC0.

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