# Transcranial Magnetic Resonance guided Histotripsy (tcMRgHt)

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2021 · $628,297

## Abstract

Transcranial Magnetic Resonance guided Histotripsy (tcMRgHt)
Project Summary
The goal of this proposal is to develop the first integrated tcMRgHt system for treatment
of brain tumors. Approximately 256,000 new patients are diagnosed with primary brain tumor
annually worldwide, and many more patients are diagnosed with brain metastases. The current
clinical treatment for brain tumors is a highly invasive surgery. The five-year survival rate is only
33% with many surviving patients suffering from cognitive deficits. Transcranial magnetic
resonance guided focused ultrasound (tcMRgFUS) has been investigated as a noninvasive
ablation method in the brain. However, due to the overheating of the skull, tcMRgFUS cannot
treat a target volume >1 cm diameter in the brain or locations within 2 cm from the skull surface,
rendering inoperable up to ~90% of the cortex regions where brain tumors often reside. We
hypothesize that transcranial MR guided histotripsy (tcMRgHt) can overcome the
treatment location and volume limitations of tcMRgFUS and provide a non-invasive
ablation technique to improve the treatment of brain tumors. Using microsecond-length,
high-amplitude ultrasound pulses applied from outside the skull, cavitation can be precisely
generated to disrupt cells within the targeted brain region. The heating to the skull and
surrounding tissue can be avoided by using a very low duty cycle (<0.1%). Our preliminary data
show that histotripsy applied through excised human skulls was used to ablate a wide range of
locations and brain volumes inside the skull, while keeping the temperature increase in the skull
under 4°C. Although the feasibility of transcranial histotripsy and MRI guidance has been shown
separately, developing and building an integrated tcMRgHt system is a substantial technical
challenge. We propose the following three specific aims. 1) Design and construct an integrated
tcMRgHt system. 2) Develop and optimize specialized RF pulse sequences for MRI guidance of
tcMRgHt. 3) Validate the performance of the tcMRgHt system in ex vivo brain phantom and
human cadaver. An integrated tcMRgHt system that can noninvasively treat a wide range of
locations and volumes in the brain and validated in human cadavers would be a critical
milestone to advance this promising technology for future clinical translation for treatment of
brain tumors.

## Key facts

- **NIH application ID:** 10183248
- **Project number:** 5R01EB028309-03
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Zhen Xu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $628,297
- **Award type:** 5
- **Project period:** 2019-08-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10183248

## Citation

> US National Institutes of Health, RePORTER application 10183248, Transcranial Magnetic Resonance guided Histotripsy (tcMRgHt) (5R01EB028309-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10183248. Licensed CC0.

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