The “enormous” promise of focused ultrasound is now a reality

After several years of investigating focused ultrasound as a tool to treat Alzheimer’s, this year the field took a major leap forward.

Elisa Konofagou, PhD, a biomedical engineer who directs the Elasticity Imaging and Ultrasound Laboratory at Columbia University in New York City, published the results of her team’s groundbreaking research in July, demonstrating their non-invasive and fully portable system for administering drugs and immunotherapy to patients with Alzheimer’s disease.

This after West Virginia University researchers established earlier this year how focused ultrasound can be used to sneak medication past the blood-brain barrier, reducing amyloid beta plaques.

But Konofago’s study showed how this treatment can be done without MRI, allowing them to “speed up the procedure while maintaining accuracy and ensuring affordability.” “Our system is also completely portable. The system can be moved to the patient, not the other way around,” Konofago said.

It’s just one example of how focused ultrasound has, according to experts, passed the tipping point.

“The promise of ultrasound is enormous,” said Wynn Legon, PhD, assistant professor at VTC’s Fralin Biomedical Research Institute in Roanoke, Virginia, whose recent study looked at how focused-wave ultrasound low-intensity sounds aimed at the insula of the brain could dramatically. reduce the perception of pain.

“It’s currently the only noninvasive method to transiently alter brain activity virtually anywhere in the brain,” Legon said, adding that it could soon be used to treat everything from chronic pain to addiction to mental health disorders. “I think focused ultrasound has finally gained acceptance and critical mass.”

But the brain is not the only organ that can benefit from focused ultrasound. The technology is already helping doctors treat conditions that normally involve surgery or radiation, such as prostate cancer and essential tremors.

Meanwhile, more than 170 diseases or clinical indications are being investigated that use focused ultrasound as a potential treatment, said Neal F. Kassell, MD, a neurosurgeon at the University of Virginia and founder and president of the Focused Ultrasound Foundation, Charlottesville, Va. . which facilitates and finances research. “That’s how fast this field is growing.”

How we got here

Focused ultrasound is like diagnostic ultrasound, “but with some important differences,” Kassell said. Both use high-frequency sound waves undetectable to the human ear. But instead of using these waves to look at babies in the womb or check for blocked arteries or veins, the technique aims them at precise targets in the body.

It’s like focusing light with a magnifying glass to burn a hole in a leaf. “An acoustic lens is used to focus multiple beams of ultrasound energy with a high degree of precision and accuracy,” Kassell said.

Although ultrasound has been around since the late 19th century, the first focused ultrasound device was invented in 1942 by brothers William and Francis Fry, who used it to perform a partial ablation of the basal ganglia after a craniotomy in the mid-1950s. “It was basically an alternative to the ice pick operation for the frontal lobotomy,” Kassell said.

A focused ultrasound system designed to treat glaucoma was the first use of the technology approved by the US Food and Drug Administration (FDA) in 1988, and during the 1990s, experimental therapeutics used focused ultrasound to a variety of conditions, from brain tumors to prostate. hyperplasia

But the biggest advances have come in the last 10-15 years, with FDA approval of focused ultrasound for a range of conditions, including bone cancer pain, essential tremors, and Alzheimer’s disease. Parkinson’s

And according to medical biophysicist Kullervo Hynynen, PhD, “We’re just scratching the surface of what’s possible.”

So what else is possible? Here are some of the most promising and exciting upcoming applications for focused ultrasound.

Improved drug delivery

Many researchers have combined focused ultrasound with microscopic bubbles, which are filled with drugs for whatever medical condition is being treated. Microbubbles are injected into the patient’s bloodstream and guided by focused ultrasound to an exact target in the body. Because the drugs are trapped inside the nanoparticle, they can circulate through all tissues and organs without being activated.

“Only when it reaches the exact spot where the ultrasound is focused is the microbubbles burst and release their pharmacological payload,” Kassell said. “It increases efficacy because we can deliver drugs at a much higher concentration than conventional means like intravenous or oral, and it also minimizes systemic toxicity or side effects.”

Hynynen, who is vice president of research and innovation at the Sunnybrook Research Institute in Toronto, Ontario, Canada, was one of the first to conduct a successful clinical trial using focused ultrasound in 2015 to deliver chemotherapy to the malignant brain tumor of a patient He also developed a hemispherical helmet, with 1024 ultrasound transducers to deliver the ultrasound.

“It’s customized for each patient because every head is different, every brain is different,” Hynynen said. “It transmits and receives ultrasound and can control it very precisely. It allows us to see where the bubbles are activated and where they are in real time.”

Rebooting the brain

One of the most interesting research fields is depressive disorders. At the University of Utah, researchers are testing a headphone-style device, called DIADEM, that uses non-invasive deep brain therapies with ultrasound waves to treat depression.

“It resets the deep regions of the brain,” focusing on the insular cortex, said Jan Kubanek, PhD, a professor of biomedical engineering at the University of Utah, Salt Lake City, Utah, who is leading the research.

They will soon begin their Phase 3 trials, hoping to get FDA approval within the next 1-2 years. And depression is just the beginning.

“We’ve also started clinical studies for PTSD, Alzheimer’s disease and weight loss,” Kubanek said.

There has also been promising research into how focused ultrasound could play a role in addiction treatment.

“It’s a method we call neuromodulation,” Kassell said, “where ultrasound is used to stimulate or block neural activity in areas of the brain related to addiction, to drugs, alcohol, tobacco , food, etc. stage research, but it’s very encouraging.”

At West Virginia University’s Rockefeller Neuroscience Institute, focused ultrasound is being explored as a possible treatment option for opioid use disorder, but could also be expanded to include cannabis addictions , alcohol, methamphetamines and more. The outpatient procedure involves MRI-guided focused ultrasound waves that target the nucleus accumbens, the brain’s “pleasure center” that plays an important role in reward and addiction.

At the neighboring University of Virginia campus, researchers at the UVA Center for Cutting Edge Addiction Research are recruiting participants for a new clinical trial exploring how focused sound waves can target the insular cortex dorsal anterior cingulate, a different brain lobe involved in compulsive cocaine use in rats, which could reduce cocaine cravings. Although his study is still in its infancy, it has already generated enough hopeful optimism that the National Institute on Drug Abuse has pledged $5 million in support.

The future of biopsies

Of course, treating diseases and disorders is only half the battle. What if focused ultrasound offered an alternative to traditional biopsies and was not only less uncomfortable for the patient, but could provide even more accurate and faster results? John Lewis, PhD, professor of oncology at the University of Alberta, Edmonton, Alberta, Canada, has been studying the early detection and stratification of prostate cancer for several decades, and said focused ultrasound can offer exactly that.

“A physical biopsy, especially in a bone where metastatic prostate cancer might reside, is an extremely invasive procedure,” Lewis said. “But using high-intensity focused ultrasound to release extracellular vesicles is a completely non-invasive method of capturing the same information, which would be painless and have much less chance of side effects.”

Lewis and his research team at the University of Alberta, which includes electrical engineering professor Roger Zemp, MSc, PhD, began developing a new ultrasound technology called micro-histotripsy, which involves liquefying vols. tissue to release tiny biomarkers “that are present in the circulation.” tumor cells and released by ultrasound, but which are absent in blood cells,” said Zemp. “We have shown that this approach can release even more biomarkers than previous methods and that our approach is much more reliable than a fine needle aspiration. We can even detect individual tumor cells in several milliliters of blood.”

It has the potential to save the lives of cancer patients. “We can detect clinically significant prostate cancer with much better detection performance compared to more conventional PSA tests,” Zemp said.

While he believes large core needle biopsies will remain the standard of care, at least for now, Zemp and his colleagues are confident that focused ultrasound could be the future of biopsies. “With further work, we hope to show that we could confidently detect clinically significant prostate cancer with a blood test and avoid 30% to 50% of biopsies,” Zemp said.

Challenges and what’s next

Focused ultrasound has a few hurdles to overcome before it becomes a medical standard. “We need more evidence of safety, effectiveness, costs, etc.,” Kassell said. “It has to be developed through clinical trials, and then you have to get regulatory approval, which takes a long time because clinical trials are complicated and expensive. Then there’s the issue of reimbursement, the companies of insurance and what they will do and earn.” cover, which can be an agonizing process.”

As with any new technology, he said, there will be people within the medical field who will cling to the old ways of doing things, who will push back against doctors and researchers who seek to innovate.

“There are some pretty vicious turf wars going on between different medical specialists because this is a highly disruptive technology that is disrupting referral patterns and practice patterns,” Kassell said.

But despite the obstacles, Kassell believes the future is bright. Kassell estimated that approximately 100,000 patients were treated with focused ultrasound by 2022. And in the next 5 years, that number could grow substantially, as costs come down and more hospitals and medical centers begin to offer it for a range of wider range of conditions, with potentially up to a million patients treated with focused ultrasound, around 10,000 commercial. treatment locations worldwide, every year, Kassell said.

The arguments for focused ultrasound far outweigh the arguments against it, Kassell said. “It improves the safety, increases the effectiveness and decreases the side effects of the therapy because it is completely non-invasive,” he said. “There are no incisions, so there are no blood clots, and there are no infections. It’s shorter and more comfortable. It’s an outpatient procedure.”

For Hynynen, convenience may be the highlight of focused ultrasound and the reason he believes patients will embrace it. “You can have a biopsy or fibroid treatment in the morning and then go sailing and biking in the afternoon instead of staying in bed for 10 days,” Hynynen said. “What’s not to love about that?”