We develop a low energy ultrasound mechanotherapy method by coupling low frequency ultrasound with nanoscale nanodroplets to remotely detonate tissues, with minimal off target effects.
Histotripsy is a method to fractionate tissues using short yet high intensity ultrasonic bursts. The high energy required is one of the method’s limitations. In order to reduce the required pressure threshold for standard histotripsy we developed a two-step approach for nanodroplet-mediated histotripsy. This technology involves the vaporization of the nanodroplets into gaseous microbubbles via an imaging transducer, followed by low frequency ultrasound application to implode the microbubbles and trigger potent mechanical effects in the surrounding tissues. This method utilizes both the small dimension of the nanodroplets which makes it capable to flow into smaller vessels or extravasate into tumor tissue and the idea that microbubbles oscillations are enhanced under low frequency excitation.
Our next aim is to evaluate the impact of the proposed method in a breast cancer mouse model and combine it with immunotherapy.
- Glickstein, B., Levron, M., Shitrit, S., Aronovich, R., Feng, Y., & Ilovitsh, T. (2022). Nanodroplet-Mediated Low-Energy Mechanical Ultrasound Surgery. Ultrasound in Medicine & Biology. https://doi.org/https://doi.org/10.1016/j.ultrasmedbio.2022.02.018 2.
- Glickstein, B., Aronovich, R., Feng, Y. et al. Development of an ultrasound guided focused ultrasound system for 3D volumetric low energy nanodroplet-mediated histotripsy. Sci Rep 12, 20664 (2022). https://doi.org/10.1038/s41598-022-25129-x