Vibrational sound healing has been recognized across history, beginning with the didgeridoo played by Aboriginal people of Australia to heal ailments. Cats purr at a frequency range shown to decrease stress and heal joints and broken bones. Buddhist monks chant in frequencies that promote wellness. But could sound be targeted more directly, say, to destroy a cancerous tumor?

A research team at the University of Michigan (U-M) recently published a study on their success in treating liver cancer in rats with ultrasound, a high-frequency range of sound waves. This method called “histotripsy” was developed at U-M in collaboration with ten medical research professionals and led to multiple human trials.

Histo-what?

Zhen Xu, professor of biomedical engineering at U-M and co-author of the study, has been developing histotripsy for over two decades. This non-invasive procedure involves using a 700kHz, 260-element ultrasound array transducer.

While ultrasound transducers have traditionally been used to create images of the body, Dr. Xu’s transducer sends microsecond-long sound pulses into cancerous masses with extreme precision. These soundwaves create tiny bubbles that partially break up the tumor.

Even if the tumor is only reduced by half, it’s enough to prevent further growth and stimulate the animal’s immune response to dispel the rest. This procedure is painless and quick and does not require sedation or take-home medication.

The study was funded by the VA Merit Review, U-M’s Forbes Institute for Discovery and Michigan National Institutes of Health, Focused Ultrasound Foundation, Medicine-Peking University Health Sciences Center Joint Institute for Translational and Clinical Research.

Dr. Xu’s method is currently used to treat liver cancer in human trials in Europe and the United States. Histotripsy has also been studied in application to brain cancer and immunotherapy.

Compared to histotripsy, available treatment options for liver cancer are considered more invasive and cause more side effects.

Although it is not yet commercially available, Dr. Xu’s revolutionary method represents a new frontier in oncology where patients can receive effective treatment that doesn’t reduce their quality of life.

Take microwave ablation, for example, an existing treatment for liver cancer that applies a heated probe to cook cancerous cells. Since ablation involves high heat, it can damage surrounding healthy tissue.

Chemotherapy is notorious for its harsh side effects like fatigue, hair loss, appetite changes, anemia, etc. Radiotherapy has similar side effects to chemotherapy and often involves widespread pain.

68-year-old Sheila Riley, one of the first patients to receive histotripsy for liver cancer as part of the #HOPE4LIVER trial program, was delighted with the procedure. In an interview with Daily Mail, Riley explains how the procedure was highly manageable for her.

“‘It was amazing; I didn’t need any medication – not even painkillers afterward. I was able to go shopping the next day, and two days after my treatment, I was out with friends. It didn’t even leave a mark on my skin,” said Riley.

Tejaswi Worlikar, a doctoral student in biomedical engineering at U-M and co-author of the published study on histotripsy, believes a bright future is ahead for the novel method developed in Dr. Xhu’s lab. Worlikar spoke to U-M News to convey her high hopes.

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

The Future of Technological Medicine

The achievements of Dr. Xhu’s lab represent a significant advancement in technological medicine and cancer treatment, already earning her the $75,000 J. Lockhart prize from the Focused Ultrasound Foundation in 2019.

However, Histotripsy developments are just a tiny piece of a more significant movement in the medical world. More researchers invent and apply novel electronic instruments to treat various diseases, specifically ultrasound emitting transducers.

Just this year, a multi-institutional research team led by General Electric (GE) published a study using ultrasound to treat diabetes in rats effectively. While Dr. Xhu’s team at U-M used ultrasound to attack tumors directly, GE’s study applied ultrasound to a specific nerve pathway.

Stimulation of the hepatic neural plexus with high-frequency sound waves stimulated insulin homeostasis. Like Dr. Xhu’s team, GE’s developments have already led to several promising human trials.

The medical applications of ultrasound are diverse and largely unexplored, but they promise a future of non-invasive treatment for many ailments without significant side effects.

For example, the treatment of essential tremors (ET) with ultrasound transducers was approved by the Food and Drug Administration (FDA) in 2016 and finally approved by Medicare in the United States as of 2020. This ultrasound treatment has had successful trials across the globe, with studies in France, the UK, Canada, and Spain.

The University of Maryland Medical Center’s ultrasound device, Exablate Neuro, treats Parkinson’s Disease without incision. The device was approved by the FDA in 2021 and is currently finding great success in reversing and reducing Parkinson’s Disease.

In their 2021 study, researchers found an improvement in the motor skills of the majority of 20 patients.

Some of these new treatments have been in development for decades, but they all seem to be entering human trials in the same time frame. Of course, success is not guaranteed, but new perspectives applied to old problems can only lead to progress for medical researchers.