is very precise and avoids damage to surrounding structures.


“At the doses we’re using to break up tumors, structures such as bile ducts, ureters, bowel wall and the liver capsule tend to be resistant to damage by histotripsy,” Dr. Lee says.


The inventors of histotripsy formed a University of Michigan spin-off company called HistoSonics, which is conducting clinical trials with its investigational HistoSonics system. It plans to commercialize the histotripsy technology and its automated delivery platform, called Edison™. The system looks like an ultrasound machine with a robotic arm and a shoebox-sized transducer.


Then-biomedical engineering undergraduate Emily Knott talks with Tim Ziemlewicz, MD, associate professor of radiology in the section of abdominal imaging and intervention at the University of Wisconsin and principal investigator of the #HOPE4LIVER trial.


“That was the first time we observed that ultrasound can be used to literally break tissue into submicron debris and can be used to mechanically remove tissue that way,” she said.


More research showed that cavitation—once considered harmful, uncontrollable and unpredictable— could be controlled and harnessed to destroy tissue. The Michigan team named the technique histotripsy, which means “crushing of tissue.”


“What happens is that these pulses of ultrasound are exquisitely timed, so they arrive at the tissue in such a way that they pull the tissue apart,” Dr. Lee said. “It’s a little bit like pulling taffy apart. When you pull the tissue, you create a very high negative pressure inside of the tissue when you stretch it. The dissolved gas inside the tissues then gets pulled out and forms into gas bubbles.”


The pulling apart of the tissue happens rapidly, with the bubbles quickly


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expanding and collapsing. “It’s that mechanical stress and strain on the tissue by the rapid creation and destruction of these gas bubbles that tears tissue apart at the microscopic level,” Dr. Lee says.


Potential for IR Histotripsy has the most promise in organs that have good ultrasound windows, such as the liver, kidney, pancreas and thyroid, Dr. Lee says. The technique would allow IRs to bypass some of the barriers they face when considering ablation techniques for a patient.


Only a small percentage of patients with liver tumors are considered good candidates for surgery. While minimally invasive ablation therapies can remove tumors in some patients, the therapy also has its limitations. Ablation might not be possible or be considered too risky because of tumor size, location or patient condition. However, histotripsy


The primary role for an IR using histotripsy would be to locate tumors for destruction and set appropriate target parameters. The IR would use test pulses to calculate and personalize the amount of energy required to destroy each tumor. The machine would then take over, using a robot arm to move the transducer over the target at an established speed and time. The procedure time would vary depending on the size and number of tumors to be treated but would be in line with similar therapies.


Liver cancer clinical trials HistoSonics is focusing on liver tumors initially. Liver cancer incidence rates have more than tripled in the U.S. since 1980 and death rates have more than doubled, according to the American Cancer Society (ACS). In 2021, ACS estimated that about 42,230 new cases (29,890 in men and 12,340 in women) will be diagnosed and about 30,230 people will die. The 5-year relative survival rate for liver cancer in 2011–2017 was 20.3%, according to the National Cancer Institute.


Results from HistoSonics’ THERESA Study, a phase 1 liver cancer trial in 2018–2019 in Spain, showed technical success of the system. Physicians in Spain performed histotripsy ablations on 11 liver lesions in eight patients ages 46–87. The trial showed that the technique was able to successfully target the tumors and led to no serious adverse effects.


The company is now conducting the #HOPE4LIVER studies, one in the United


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