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Treating chronic pain with ultrasound

U researchers demonstrate potential of new technology that stimulates regions of the deep brain.

Those struggling with chronic pain or depression often report feeling “hopeless” or “despairing” when multiple therapies and interventions have not led to relief. Such people, however, described their experience in more hopeful terms after participating in a recent study of a new biomedical technology developed at the University of Utah.

“This is the first time in three years I’ve felt like myself. It feels like my brain has been woken up,” one patient said. Others said, “That trauma is no longer with me. It is finally gone,” and “I was walking around the grocery store and just felt so clear. I was wondering, is this what normal people feel like?”

Tom Riis, left, and Jan Kubanek of the Department of Biomedical Engineering

The device at the center of these human clinical trials, called Diadem, promises to change how certain neurological disorders are treated. Resembling a pair of oversized headphones, it stimulates regions of the deep brain underlying chronic pain and depression—all with the power and precision of focused ultrasound.

Diadem’s creators are now seeking volunteers to participate in its final phase of clinical trials needed to obtain regulatory approval and provide these treatments at a large scale.

“We’ve been blown away by the positive results so far,” said the paper’s lead author, Tom Riis, a postdoctoral researcher in the Department of Biomedical Engineering. “After just a single 40-minute stimulation session, patients are showing immediate, clinically substantial improvements in symptoms.”

To participate in Diadem’s next round of clinical trials, contact

The cover story

Featured on the February cover of the journal IEEE Transactions on Biomedical Engineering, their study, “Device for multifocal delivery of ultrasound into deep brain regions in humans,” is a collaboration between the university’s John and Marcia Price College of Engineering and the Huntsman Mental Health Institute.

Riis conducted the research in the lab of engineering professor Jan Kubanek, the paper’s senior author. They collaborated with Huntsman researchers Brian Mickey, a professor of psychiatry, graduate student Daniel Feldman and laboratory technician Adam Losser.

“The potential for this technique to change, even save, people’s lives is becoming increasingly clear,” Kubanek said. “We encourage those who are dealing with these conditions to join our upcoming study. It’s very important to us to get this potential treatment to those who need it as soon as possible.”

Big results

In both the initial paper and two subsequent trials awaiting publication, the majority of patients saw improvement.

Of the 20 subjects who completed the chronic pain trial, 15 saw clinically meaningful reduction (more than 33%) in pain immediately following treatment. Of the 19 patients who completed the depression trial, 10 met the criteria for remission one week following just one stimulation session. There were no adverse events or worsening of pain.

In the depression trial, 14 patients experienced a durable improvement, while two experienced a temporary worsening of depression.

“Overall, the treatments were well tolerated,” Riis said. “Regarding safety, we saw no evidence of safety issues or long-term side effects.”

The researchers, however, stressed the results are preliminary.

“We’ve still got a lot to learn,” Kubanek said. “More research is needed to back up the initial data and establish things like how long the improvements last.”

Phase 3 clinical trials are rigorous, lasting up to two years, and only a small portion of them result in an FDA-approved drug or treatment. That kind of progress requires a deeper understanding of the underlying technology and physiology.  To reach this point, the researchers had to confront complex challenges, both on the inside and outside of the human head.

Circuits, interrupted

“The neural circuits underlying chronic pain and depression involve deep brain regions, which have been characterized by decades of careful imaging and interventional studies,” Riis said.

Targeting these sites is now possible thanks to decades of major advances in decoding and mapping the brain’s intricate tangle of 86 billion neurons. Researchers know where the neural circuits underlying chronic pain and depression are usually located.

Yet even with these spots deep inside the brain identified, there’s still the question of how to access and treat them. The body protects its most powerful organ with a quarter-inch layer of bone.

“You can cut open the skull and then physically manipulate the delicate brain matter inside, as with brain surgery or deep brain stimulation with electrodes, but this comes with significant risks and financial cost,” Riis said. “Traditional pharmacological approaches, on the other hand, offer a less invasive option, but at the cost of precision—acting on the brain, and body, as a whole.”

Enter neuromodulation, a new set of techniques that the multifocal ultrasound treatment builds upon. These therapeutic interventions direct electrical, magnetic or acoustic energy through the skull, which then target and stimulate specific regions of the brain.

Ultrasonic benefits

“Ultrasound-based approaches can reach millimeter-level precision,” Riis said. “The same way you can focus light through a magnifying glass, you can focus sound waves into a small, intense volume. So we can stimulate a region about the volume of a peanut anywhere we want within the brain.”

But the skull’s variable thickness and irregular shape scatters and distorts sound waves, hindering attempts to precisely target small regions of the deep brain.

The team’s technical breakthrough was in enabling the Diadem device to take into account the many “acoustical distortions” caused by the skull. Understanding how those distortions change the shape and trajectory of sound waves enables Diadem to correctly target those “peanut-sized” areas, even if they are deep inside the brain, without the need to move the device or the subject.

For all the complex science behind the device, patients’ clinical experience with Diadem is relatively straightforward.

In a preliminary visit, the apparatus is fitted to the patient’s head and an MRI scan records an image of the brain. In the next session outside the scanner, the researchers set the device to target the correct spot that underlies a patient’s condition. Ultrasonic stimulation is then delivered to that area for about 40 minutes, with the aim of modulating the neural activity that was causing the patient’s symptoms.

“While it should be kept in mind that not every participant saw drastic improvement, in the ones that did the change could be quite remarkable,” Riis said. “For several, you could just see it in their eyes—coming out of the session, their mood and behavior were a total 180 from when they had walked in. They were noticeably at ease, less burdened, more present.”


  • Evan Lerner Director of communications, John and Marcia Price College of Engineering