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Brain surgeons trade scalpel for mouse in breakthrough using focused sound waves

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Tuesday, January 1, 2019 – Page A1

An experimental technique developed in Canada, known as focused ultrasound, is allowing doctors to do brain surgery using precision imaging and sound waves instead of scalpels and surgical saws.

The procedure is slowly wending its way into mainstream medicine for treatment of a variety of conditions, from tremors to brain cancer. Some of the most promising studies have been on patients with severe, intractable cases of mental illness such as depression and obsessive-compulsive disorder.

"We've been doing surgery on the brain for decades, but this technology allows us to do so without going through the skull and healthy brain, which causes a lot of damage along the way," Anthony Levitt, chief of the Hurvitz Brain Sciences Centre at Sunnybrook Health Sciences Centre in Toronto, said in an interview. "It's a new way of doing something old."

The way focused ultrasound (FUS) works is fairly simple.

Ultrasound, a century-old technology, uses sound waves, or echoes, to make an image of what is inside the body.

Those sound waves travel harmlessly through tissue.

Yet, if you focus sounds waves on a particular spot, they generate heat, in the same way using a magnifying glass to focus beams of light does. In this way, doctors can modify faulty brain wiring.

The sound waves can also be used to access virtually inaccessible parts of the brain and allow drugs to be delivered directly.

Worldwide, focused ultrasound has been used to treat more than 200,000 patients, and is being tested to treat dozens of conditions, according to the Focused Ultrasound Foundation.

In the spring of 2018, surgeons at Sunnybrook used FUS to treat Linda Bohnen, who has suffered from debilitating depression and anxiety for more than 30 years.

"I felt that I had nothing to lose," she said. "I had tried everything else, so why not?" The procedure destroys circuits in the brain that were overactive, a type of surgery that has been performed since the 1940s as a last resort for people with treatment-resistant depression.

Instead of going under the knife, Ms. Bohnen was fitted with a helmet that looks a bit like an old-fashioned hair dryer.

The helmet, equipped with 1,000 transducers that emit sound waves, is what has allowed FUS to flourish because it resolved what researchers call the "bone problem." The skull, unlike tissues, absorbs sound waves so, to get around that barrier, 1,000 weaker beams are transmitted and converge at a precise spot to burn away brain tissue.

Ms. Bohnen was placed in a magnetic resonance imaging (MRI) machine, which allowed surgeons to see the brain function in real time and pinpoint a precise spot on which to focus the highfrequency sonic waves used to destroy the faulty circuit.

"It's surgery using a mouse and a computer monitor," Dr. Levitt said.

Since the FUS surgery, Ms. Bohnen said her condition has improved slowly and steadily. She feels better than she has for decades.

Only about 50 people in the world have undergone the procedure for treatment of depression or OCD, but the outcomes look promising so far. "I have patients who are coming and asking for this procedure," Dr. Levitt said.

He stressed that while FUS holds a lot of potential, it's still experimental and will not replace treatment with antidepressants and cognitive behavioural therapy.

Still, Dr. Levitt is excited about the prospects to treat other conditions such as bipolar disorder, eating disorders or substance-use disorder, all of which, at their root, are caused by misfiring circuits.

Nir Lipsman, a neurosurgeon at Sunnybrook, said the embrace of focused ultrasound is part of continuing efforts to make surgery simpler and safer.

"The trend in brain surgery is to do more with less - smaller openings or no openings," he said.

Other non-invasive or mildly invasive treatments, such as electroconvulsive therapy, transcranial magnetic stimulation and deep brain stimulation are also gaining in popularity. Dr. Lipsman said each of these app-roaches has its pros and cons, but they are all part of a positive trend away from the days of very invasive operations to treat mental illnesses.

"I fondly remember the Star Trek sick bay where they scanned and treated patients without incision," Dr. Lipsman said. "That's not just science fiction any more.

It's almost science."

The most common and successful FUS treatment to date is for essential tremor, a condition that causes the hands to shake.

Surgeons use FUS to perform a thalamotomy, destroying a small bit of brain tissue that causes the disorder.

As with the treatment for depression, it uses high-frequency ultrasound to create a lesion.

But low-frequency ultrasound can also be used for other treatments. It does not generate heat, but is used to temporarily disrupt pathways to facilitate the delivery of drugs.

Specifically, focused ultrasound can be used to breach the blood-brain barrier (BBB), a filtering mechanism that prevents certain substances, such as pathogens and drugs, from getting to the brain and spinal cord.

The BBB is essential, but it makes it difficult to get drugs to the brain, which hampers treatment of conditions such as brain cancer, Alzheimer's disease and Parkinson's disease.

"When you open the bloodbrain barrier, you open up a lot of treatment possibilities," said Kullervo Hynynen, the director of physical sciences at Sunnybrook Research Institute. He is widely regarded as the father of FUS.

Dr. Hynynen estimated that about 98 per cent of potentially helpful molecules, such as chemotherapy and antibodies, cannot penetrate the BBB.

The way researchers have gotten around that problem is by injecting gadolinium, a contrast agent that is used to enhance visibility in imaging, and then bombarding the tiny air bubbles it creates with sound waves.

When they do that, the oscillation of the microbubbles creates tiny tears in the blood-brain barrier, allowing drugs to get directly to the brain. The BBB then repairs itself.

Paul Hudsmith, a 52-year-old engineer from King City, Ont., has undergone this process twice for the treatment of glioblastoma, the same type of brain cancer that claimed the life of Tragically Hip singer Gord Downie.

Mr. Hudsmith underwent emergency surgery last summer to remove most of the tumour, followed by 16 weeks of radiation and chemotherapy. Now, Mr.Hudsmith is doing maintenance chemotherapy - with once-amonth treatment for six months delivered using the experimental focused ultrasound approach.

Each treatment requires him to lie in an MRI machine for up to five hours, with a frame mounted with a FUS helmet screwed to his head.

"I'm a bit claustrophobic so the hardest part is lying in the machine for all that time, but they give me a sedative," Mr. Hudsmith said.

The process is time-consuming because researchers watch, in real time, as the chemo drug makes its way into the brain. The next day, the patient goes for another MRI to ensure the BBB has healed.

The next frontier is to use focused ultrasound to stop degeneration and promote regeneration of brain tissues for the treatment of Alzheimer's disease.

In animal models, this is done using drug therapies, immunotherapy and gene and cell therapies.

But, in humans, the challenge is again the blood-brain barrier.

"Imagine a gene therapy for Alzheimer's delivered to the brain using FUS," said Isabelle Aubert, a senior scientist, biological sciences, at Sunnybrook Research Institute.

She stressed that this is a long way off, but underscores how potentially revolutionary the technology could be.

Associated Graphic

Paul Hudsmith shows his surgery scar at his home in King City, Ont., on Dec. 20, 2018. Mr. Hudsmith underwent emergency surgery last summer to remove most of a tumour in his brain. Now, he is doing maintenance chemotherapy and monthly treatments using the FUS approach.


Wednesday, January 09, 2019


In an article about focused ultrasound published Jan. 1, Paul Hudspith was incorrectly identified as Paul Hudsmith.

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