Key Points
- Researchers recently completed a project to develop and validate a transcranial histotripsy system.
- The team evaluated several regions of the brain and gathered data to inform the design of a next-generation device.
Right: Simulated pressure field maps for superior target 10 mm from skull interior surface with and without aberration correction (AC).
The biomedical engineering team led by Zhen Xu, PhD, at the University of Michigan recently published results from a Foundation-funded research project to develop and test a transcranial (brain) histotripsy system. While histotripsy clinical trials are already underway for liver cancer, pancreatic cancer, and veterinary applications, this study sought to design and test a histotripsy system for treating brain tumors, intracerebral hemorrhages, and more.
Methods
A novel 360-element histotripsy device for delivering mechanical ultrasound energy across the skull was tested using skulls from two different medical research cadavers. The team evaluated the device across a range of brain locations, including shallow targets. Passive cavitation mapping was used to track cavitation generation. Additional data were gathered by conducting simulation studies on imported computed tomography scans from eight different deidentified patients.
Results
Regarding the treatment envelope, histotripsy delivery was successful in both deep and shallow targets, but the shallow target range varied based on the skull density ratio (SDR) and skull thickness measurement of each subject. If the SDR was high and the skull thickness was small, targets within 5 mm of the skull surface could be reached; however, when the SDR was low and the skull thickness was large, the target needed to be at least 16 mm from the skull surface to be successful. This limitation, namely due to the high attenuation for shallow targets, could be addressed through the development of new transducer designs with sufficiently high output power.
The simulation studies confirmed that the acoustic properties of each skull determined its treatment envelope. Similar to thermal ablation, targeting near the skull created hotspots and a loss of acoustic pressure caused by high attenuation, large incident angles, and pre-focal pressure.
Next Steps
The capabilities and limitations that were discovered will inform the design of a next-generation translational research device. Going forward, the team will redesign the array, optimize pose, and design new amplitude correction strategies to increase the treatment envelope for transcranial histotripsy. Each challenge identified – along with its proposed solution – is outlined in the publication’s Discussion section.
“The results from this study will help us design and construct a transcranial ultrasound array that can perform noninvasive histotripsy treatment in all brain locations,” said Dr. Xu.
Funding
This work was supported by funding from both the National Institutes of Health and the Focused Ultrasound Foundation.