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Histotripsy-mediated reactive oxygen species generation in vitro
Gregory J Anthony1, Steffen Sammet1, Jeffrey S Souris1
15835 S Cottage Grove, Department of Radiology, University of Chicago, Chicago, IL 60637, USA.
Ultrasonics
|November 15, 2025
Summary
Histotripsy, a focused ultrasound therapy, generates hydroxyl radicals without microbubbles, enhancing sonodynamic therapy. This method shows promise for activating sonosensitizers and can be monitored via acoustic emissions.
Area of Science:
- Biomedical Engineering
- Acoustic Physics
- Chemical Engineering
Background:
- Sonodynamic therapy (SDT) uses microbubbles and agents to produce reactive oxygen species (ROS).
- Microbubble-based SDT has limited therapeutic range due to intravascular agent distribution.
- Histotripsy offers an alternative by ablating tissue through spontaneous bubble cloud generation, eliminating the need for microbubbles.
Purpose of the Study:
- To investigate histotripsy's capacity to generate hydroxyl radicals.
- To assess histotripsy's efficacy in activating sonodynamic agents.
- To correlate sonochemical reactions with acoustic emissions.
Main Methods:
- Histotripsy was employed to generate hydroxyl radicals with and without sonodynamic agents.
- Passive cavitation imaging was used to track acoustic emissions.
- Sonosensitizer activation was evaluated using varying ultrasound pulse durations.
Main Results:
- Histotripsy produced hydroxyl radicals at three times the rate of other therapeutic ultrasound methods, even without sonodynamic agents.
- Sonochemical reactions strongly correlated with acoustic emissions.
- Histotripsy enhanced hydroxyl radical production for sonosensitizers, especially with ultrasound pulses exceeding 20 microseconds.
Conclusions:
- Histotripsy demonstrates potential as a viable method for activating sonosensitive agents.
- The activation process can be effectively monitored using acoustic emission tracking.
- Histotripsy expands the possibilities for targeted ROS generation in therapy.

