Minimally invasive tumour treatment done via histotripsy
Focused ultrasound waves can be used to destroy tissue with millimetre precision. The innovative technology is being tested in the 'HOPE4LIVER' study.
Histotripsy in brief
- Histotripsy is an ultrasound-based treatment method based on the generation of targeted cavitation bubble clouds (exploding microbubbles) that mechanically fractionate tissue.
- In animal experiments, even liver tumours from which only a partial volume was ablated by histotripsy showed complete regression without recurrence or metastasis.
- Histotripsy was also shown to stimulate the tumour immune response, which may have contributed to the regression of the untreated tumour regions.
- By contrast, 100% of untreated control animals developed local tumour progression and intrahepatic metastases.
Gas bubbles with sound waves against tumours
A relatively new procedure is histotripsy, which can be used to destroy tumour tissue by ultrasound. High-amplitude ultrasound pulses in the microsecond range create microbubbles in the target tissue that expand and collapse rapidly: when the beam hits the target site, it activates thousands of gas bubbles that naturally occur in tissues throughout the body, including tumours, as a result of the respiratory process. These tiny gas bubbles are normally inert, but when bombarded with the sound waves, they expand, vibrate, explode and form a high-energy cloud of microbubbles in the tumour.2 These violent but extremely localised mechanical stress forces kill cancer cells and break down the tumour structure. This is called controlled acoustic cavitation (cavitation = creation of a cavity within a solid material). The impulses can be concentrated specifically on the tumour. Conventional ultrasound machines for imaging use pulses with a lower amplitude.
Ablation of tumours possible even under suboptimal conditions
A laboratory at the University of Michigan, which has pioneered the use of histotripsy in cancer since 2001 and has also developed a special transducer for this application, recently published exciting results in the journal 'Cancer' of the first in vivo study of the effect of partial histotripsy ablation on survival and metastasis development in rats with liver cancer.3,4
Size, location or tumour stage sometimes do not allow direct targeting of the tumour in its entirety. To investigate the effect of partial ablation by sound, the current study removed only a portion of the tumour mass (50-75%), leaving a viable, intact tumour. Apparently, the animals' immune system was able to eliminate the remaining tumour cells. In 9 out of 11 (81%) of the treated experimental animals, MRI showed complete local regression of the tumour without recurrence or metastasis, and the survival of the animals was significantly prolonged compared to the untreated controls.
Histotripsy stimulates local immune response
The antitumour immune response is also considered an important prognostic factor. Two and seven days after histotripsy, an increased infiltration of immune cells (monocytic CD11b+, cytotoxic CD8+ and natural killer cells) into the tumour was observed compared to controls, which may have contributed to the regression of the non-treated tumour parts.
"Histotripsy is a promising option that may overcome the limitations of currently available ablation techniques and provide safe and effective non-invasive ablation of liver tumours," said main author Tejaswi Worlikar, a biomedical engineer at UM.
More studies underway
More recently, the group's research has also led to, among other things, the development of a transcranial MR-guided histotripsy system for use in various brain surgery applications5.
Clinical applications are still in their infancy. To date, four adults with liver cancer have been treated with histotripsy at two hospitals in the UK. Four other hospitals in Europe are also participating in this 'HOPE4LIVER' trial, involving 40 people with the disease.2
- Siegel, R. L., Miller, K. D., Fuchs, H. E. & Jemal, A. Cancer Statistics, 2021. CA Cancer J Clin 71, 7–33 (2021).
- Monti, A. Radical new therapy uses tiny bubbles of gas to destroy tumours. Mail Online https://www.dailymail.co.uk/health/article-10612197/Radical-new-therapy-uses-tiny-bubbles-gas-destroy-tumours.html (2022).
- Worlikar, T. et al. Impact of Histotripsy on Development of Intrahepatic Metastases in a Rodent Liver Tumor Model. Cancers 14, 1612 (2022).
- Tumors partially destroyed with sound don’t come back. University of Michigan News https://news.umich.edu/tumors-partially-destroyed-with-sound-dont-come-back/ (2022).
- A New System for Brain Histotripsy. Focused Ultrasound Foundation https://www.fusfoundation.org/news/a-new-system-for-brain-histotripsy.