The future of focused ultrasound

 

Imagine that doctors could deliver therapy deep inside the brain where no scalpel or drug can reach.

This changes the course of a teenager’s depression, a parent’s Alzheimer’s disease or a spouse’s stroke.

Now imagine it’s all done painlessly – using waves of sound.

Sunnybrook is a world leader in exploring the potential of focused ultrasound to meet this vision.

 Focused ultrasound is an emerging medical technology with extraordinary potential that will one day become part of everyday language, like X-ray or MRI.

Here’s how a focused ultrasound brain procedure works: After being fitted with a focused ultrasound helmet – originally developed by Dr. Kullervo Hynynen, a medical biophysicist who came to Sunnybrook from Harvard in 2006 – the patient lies down on the bed of an MRI machine. Neurosurgeons then direct ultrasonic waves, guided by real-time MR imaging, safely through the skull to a target in the brain.

As Dr. Hynynen has shown, focused ultrasound can be used at high intensity to heat or destroy diseased cells, or at low intensity to stimulate cells. When used at low intensity and paired with microbubbles, it can be used to open the blood-brain barrier and allow medication into the brain. The barrier consists of tightly packed cells protecting the brain from harmful, as well as helpful, substances: 97 per cent of treatment drugs cannot penetrate this protective sheath.

This is truly groundbreaking science, and Dr. Hynynen is at its forefront.

Over several decades he has pioneered increasingly sophisticated devices designed to allow focused ultrasound to reach places never thought possible.

He has held firm to his belief, which few scientists shared until recently, that focused ultrasound could open the blood-brain barrier.

Dr. Hynynen is not afraid to explore the unknown, to innovate, as he’s done throughout his career.

Dr. Isabelle Aubert,
Senior Scientist
Sunnybrook Research Institute

In 2015, Sunnybrook was the first in the world to demonstrate that focused ultrasound paired with microscopic bubbles can be used to open the blood-brain barrier temporarily and non-invasively to direct medication into the brain of a research participant with brain cancer.

“Dr. Hynynen is not afraid to explore the unknown, to innovate, as he’s done throughout his career,” says Dr. Isabelle Aubert, a senior scientist at Sunnybrook Research Institute who collaborates with Dr. Hynynen. “He makes focused ultrasound seem so simple, but it’s very hard work.”

In order to push the boundaries of what’s possible using focused ultrasound, Dr. Hynynen works with a team of brain sciences experts at Sunnybrook, from neurobiologists, including Dr. Aubert, to engineers, psychiatrists, neurologists and neurosurgeons. They are united in the drive to discover which therapies – stem cells, chemotherapy, genes, growth factors, immunotherapy – can be paired with focused ultrasound for therapeutic effect.

Advances in focused ultrasound are happening quickly.

Sunnybrook neurosurgeon Dr. Michael Schwartz recently led a practice-changing trial of focused ultrasound to treat essential tremor. Sunnybrook will soon undertake the first clinical trial to test the safety and feasibility of focused ultrasound in the treatment of Alzheimer’s disease. This study will be conducted by neurosurgeon Dr. Nir Lipsman, and Dr. Sandra Black, head of Sunnybrook’s Hurvitz Brain Sciences Research Program, who is a world leader in dementia research.

Dr. Lipsman is also planning studies investigating focused ultrasound’s merit in treating obsessive compulsive disorder, major depression and stroke.

Dr. Hynynen, meanwhile, is hard at work completing a next-generation focused ultrasound helmet. It will map the skull and monitor disruption of the blood-brain barrier with extreme precision, enabling exquisite control for therapy delivery and monitoring, no MRI required.

In the more distant future, focused ultrasound devices will become lighter, more portable, more affordable and capable of delivering treatments in less time and deeper into the brain.

The current clinical system consists of multiple-element transducers, called arrays, that can generate energy in phases for greater power and control. Future systems will be steered completely electronically rather than mechanically, so they can touch previously unreachable parts of the body.

“Fully electronically steerable phased arrays will hugely improve focused ultrasound treatments,” says Dr. Hynynen. He predicts this technology will one day be used in doctors’ offices, ambulances and even homes. It might also become a life-saving solution in developing nations because it doesn’t need to be paired with MRI.

“I have difficulty putting boundaries on it,” he says quietly, and returns to solving complex scientific puzzles few would understand, to accomplish goals from which millions can benefit.

A treatment for the entire body

The future of focused ultrasound is not limited to diseases of the brain. Cancers found throughout the body, heart disorders, stroke, uterine fibroids, back pain – they’re all conditions for which Sunnybrook is undertaking game-changing focused ultrasound research, either in the laboratory or with patients.

Case in point is a world-first clinical trial led by Dr. William Chu involving patients whose rectal cancer has returned. In this study, focused ultrasound is being delivered together with radiation and chemotherapy, with an eye to making therapy more effective for this challenging condition. A similar method is being investigated for head and neck cancer.

In another study, Sunnybrook researchers showed that using focused ultrasound to treat cancer that has spread to bone can ease the debilitating pain often associated with the condition. This pilot study has paved the way for larger trials that could shape clinical care.

Focused ultrasound also offers the potential to eliminate abnormalities with the heart. Dr. Kullervo Hynynen is investigating how focused ultrasound may be used to disrupt abnormal electrical conduction paths that cause an abnormally fast heart rate, a condition called tachycardia. The ability to image in real time what is happening in the heart and precisely target the tissue non-invasively would revolutionize treatment of cardiac arrhythmias.