The road less travelled

Teams at Sunnybrook Research Institute (SRI) are at the vanguard of testing the use of focused ultrasound to treat the most intractable brain disorders, including psychiatric illnesses. These diseases are especially difficult to treat because many patients do not get better with drugs or psychotherapy. For example, a Canadian study of people with depression who were treated in primary care settings showed that about 22% failed to respond to antidepressants. Other studies have shown that in obsessive-compulsive disorder (OCD), 25% to 60% of patients do not respond adequately to serotonin reuptake inhibitors, a first-line treatment.

High-intensity focused ultrasound, which uses image guidance to direct ultrasound energy that ablates symptom-causing targets in the brain, could one day be another option. Dr. Kullervo Hynynen, director of Physical Sciences at SRI, has pioneered the technology. For more than 30 years, he has engineered focused ultrasound devices, taking them from ideas all the way to testing in patients.

“We’ve known for some time which regions of the brain are under- or over-active in mood and anxiety circuits. In neurosurgery, if you knock out some of the major ‘highways’ between those structures, you have a chance at helping mood and anxiety symptoms. Focused ultrasound allows us to interact directly with the circuits in the brain driving those abnormal, faulty connections,” says Dr. Nir Lipsman, a neurosurgeon and scientist at SRI. He is leading the first North American clinical trial of focused ultrasound for treatment-resistant OCD, and is poised to launch one for treatment-resistant depression.

To provide guidance on studies of how the technology may be used to treat psychiatric disorders, Lipsman organized a workshop in partnership with the Focused Ultrasound Foundation. It was held Oct. 18 to 20, 2017 at the Estates of Sunnybrook. The goal was to establish a framework for research in this domain. “We wanted to take the temperature of where the field is right now, and predict where it’s going in the next five to 10 years,” says Lipsman, who specializes in functional neurosurgery, which uses different techniques to address problems with brain function.

Holding the workshop at Sunnybrook was a logical step, says Dr. Tim Meakem, chief medical officer of the Focused Ultrasound Foundation, which sponsored the event. “[Sunnybrook’s] facilities are outstanding, not only in clinical care that’s given, but there’s also a lot of preclinical and technical development that is occurring there that really makes it a leader­­ in this area,” he says. In 2016, the foundation designated Sunnybrook a Centre of Excellence in Focused Ultrasound, the first in Canada and one of only seven in the world.

The organizers invited a “wish list” of experts in psychiatry and in focused ultrasound research from Europe, North America and Asia. Guests included neurosurgeons, psychiatrists, engineers, psychologists, physicists and biologists. The workshop was capped at 30 to foster dialogue and partnerships. They examined the state of the technology and challenges in using it, past studies and future research directions.

Dr. Jin Woo Chang, a neurosurgeon and director of the Brain Research Institute at Yonsei University College of Medicine in South Korea, was one of the event’s nine speakers. Chang, who led the world’s first clinical trials of MRI-guided focused ultrasound for treatment-resistant OCD and for treatment-resistant depression, discussed technical and clinical challenges. These include finding optimal candidates for the procedure and delivering ultrasound energy to patients with thicker skulls.

“I don’t think I had appreciated the limitations of what can be done,” says Dr. Anthony Levitt, a psychiatrist and neuroscientist at SRI, and chief of the Hurvitz Brain Sciences Program at Sunnybrook. He describes the workshop as “eye-opening.” “There were lots of opportunities for communication between the disciplines, and not just to find out the data. Dr. Chang’s data is fascinating, but to hear the real-world experiences of people [like him] who’ve been doing this kind of work—ablative neurosurgery for psychiatric conditions—was just invaluable.”

Dr. Clement Hamani, a clinician-scientist newly recruited to SRI, spoke on using preclinical models that mimic psychiatric disease, and how they can guide neuromodulation. This type of treatment, which includes focused ultrasound, changes nerve activity by delivering electrical stimulation or drugs to a target. Lipsman says that having a talk on translational research allowed the group to look ahead. “We didn’t want it to be only about what we’re doing now. We wanted to look at 10 or 20 years from now—what’s [focused ultrasound] technology going to look like, and how can preclinical research today help inform that?”

The Focused Ultrasound Foundation has produced a white paper based on discussions from the workshop that is available on its website. Meakem says the meeting will help prioritize which areas of research to support. “We always look at applications for funding based on what’s being done, and we’re going to be focusing on the conclusions of this [meeting] because we’ve gotten the best people in the world to talk about what should be done next,” he says.

Lipsman says feedback on the workshop has been positive. “I think everybody felt it was an important discussion to take part in,” he says, noting the outlook is one of cautious optimism. “We see this as a potentially powerful tool, but one that requires a lot more investigation to determine where it fits into the treatment of psychiatric patients. That was the general consensus: it’s tremendously promising, but requires a lot more study.”