Histotripsy – using ultrasound to destroy liver tumors

A non-invasive sound technology that breaks down liver tumors in mice, killing cancer cells and stimulating the immune system to prevent further spread (metastasis), was developed by biomedical engineers at the University of Michigan (UM) in the USA.

The treatment, called histotripsy, focuses ultrasound waves to mechanically destroy the target tissue with millimeter precision.

In a new study, the team showed that by destroying just 50% to 75% of the liver tumor volume with sound, the mice’s immune system was able to eliminate the rest, and there was no evidence of recurrence or metastases in 81% of animals. after 12 weeks.

“Even if we don’t target the entire tumor, we can still cause the tumor to regress and also reduce the risk of future metastasis,” says Zhen Xu, a professor of biomedical engineering at UM and senior author of the new research published in Cancers.

Liver cancer is one of the top 10 causes of cancer-related deaths worldwide, and while there are several treatment options available, the prognosis remains poor. Five-year survival rates are less than 18% in the US.

Due to the high incidence of tumor recurrence and metastasis after initial treatment, there is a great clinical need to improve these results. Histotripsy, a relatively new technique pioneered by engineers at UM, is being tested on human liver cancer in the US and Europe.

It relies on a process known as acoustic cavitation, in which high-energy, microsecond pulses of ultrasound generate microbubbles within target tissues that rapidly expand and collapse.

These violent but extremely localized mechanical stresses kill cancer cells and destroy the tumor’s structure so that it can be eliminated by the body, without the harmful side effects associated with other currently available treatments (chemotherapy, radiation therapy, ablation).

“Our transducer, designed and built at UM, delivers high-amplitude microsecond ultrasound pulses – acoustic cavitation – to focus the tumor specifically to break it up,” explains Xu. “Traditional ultrasound devices use lower amplitude pulses for imaging.”

histotripsy
Zhen Xu, a professor of biomedical engineering at the University of Michigan (left) and Tejaswi Worlikar, a doctoral student in biomedical engineering, discuss the 700 kHz, 260-element histotripsy ultrasound array transducer they use in Prof. Xu.

Engineers were interested in investigating the effect of only partially destroying tumors with histotripsy because, in many clinical situations, the entirety of a cancerous tumor cannot be directly targeted due to the size, location, or stage of progression of the mass.

In mice, they only targeted a part of each mass and left behind a viable intact tumor to show the effectiveness of the approach under less-than-ideal conditions.

The treatment stimulated the mice’s immune responses, indicated by increased infiltration of immune cells into the tumor tissue, which possibly contributed to the eventual regression of the non-target portion of the tumor and prevented the cancer from spreading.

“Histotripsy is a promising option that can overcome the limitations of currently available ablation modalities and provide safe and effective non-invasive liver tumor ablation,” says Tejaswi Worlikar, a PhD student in biomedical engineering at UM.

“We hope that our learnings from this study will motivate future preclinical and clinical histotripsy investigations towards the ultimate goal of clinical adoption of histotripsy treatment for patients with liver cancer.”



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