Focused Ultrasound

Before the advent of deep brain stimulation (DBS) some fifteen to twenty years ago, the only way neurosurgeons could mitigate Parkinsonian symptoms like tremor, rigidity, and dyskinesia, was by directly destroying pieces of brain regions such as the thalamus and globus pallidus internus. In these operations, known as thalamotomies and pallidotomies, surgeons drilled a hole in the skull and physically lesioned the target brain region. Not surprisingly, after DBS came along, such procedures were viewed as too invasive and risky.

But imagine being able to perform thalamotomies and pallidotomies without piercing the skull. That’s the idea behind a novel neurosurgical initiative known as guided focused ultrasound. Ultrasound—high frequency acoustic waves––have long been used for medical imaging. But since the 1940s, researchers have investigated acoustic waves as a means of destroying tissue as well. Researchers wondered if there was a way to focus multiple beams of ultrasonic waves on a target deep inside the brain and then deploy the heat of the combined beams to simply ablate the tissue.

Early experiments ran into a big problem—the skull. According to University of Virginia neurosurgeon Jeff Elias “when you try to send acoustic energy through the skull, the boney structure defocuses the ultrasound. So, it's a bit like the astigmatism of a lens, where an irregular lens will diffract the light. The skull isn't smooth and homogeneous like you might think it is, it’s irregular.” It turns out that the skull not only defocuses the ultrasound waves, it also absorbs them; so only about 10% of the ultrasonic energy is transmitted through the skull to the brain.

In the last decade, engineers have found that by using lower frequency acoustic waves they get much better penetration of the skull. They also figured out a way to compensate for skull distortion; they changed “the phase” to correct for the skull’s disruption of the ultrasound beams and shift them all back into focus.

Now they had a minimally invasive means of doing neurosurgery, practitioners needed a precise way of locating the right target in the brain. Fortunately, using magnetic resonance imaging technology (MRI) surgeons can visualize the smallest targets in the brain. Using MRI, so-called image-guided focused ultrasound surgery allows practitioners the ability to hit targets to within a millimeter, sparing the surrounding tissue. And since hotter objects can be distinguished from cooler ones, MRI also offers surgeons a means of thermal monitoring. According to Elias, “you can actually watch the surgery being delivered deep in the brain in real time as it happens!”

Five years ago UV neurosurgeon Jeff Elias used MRI-guided focused ultrasound to treat 15 patients with essential tremor in a pilot trial. In this procedure, Elias focused 1024 ultrasound beams on a single target—the ventral intermediate nucleus of the thalamus. The beams delivered their energy all at once in a 10 second burst called a “sonication.” Then the team monitored the 10 seconds of heating, made sure it had happened in the right location, and immediately afterwards checked on the conscious patient clinically. They continued this process of serial sonications for four hours until the target brain region had been burned away and the patient’s tremor had stopped. All 15 patients in the trial noted a significant reduction (of around 75%) in their tremors and the effect persisted.

The next application of the technology was for the more complicated tremor encountered in Parkinson’s disease. Surgeons at the University of Virginia and Swedish Medical Center in Seattle, Washingtonhave just completed unilateral focused ultrasound thalamotomies on a cohort of 27 patients with tremor-dominant Parkinson’s. The results are being analyzed.

And a study aimed at testing the technique for Parkinson's dyskinesia, where surgeons focus the beams on either the globus pallidus internus or the subthalamic nucleus, has just started at the University of Virginia and the University of Maryland. The first two surgical cases were so dramatic that one of the patients was featured on TV news.

Focused ultrasound is certainly less invasive than both traditional neurosurgery and DBS. If surgeons can demonstrate that focused ultrasound surgery safely mitigates the symptoms of essential tremor and Parkinson’s disease, it may offer an alternative to DBS. But, so far, the jury is out. As Elias says, “we are, after all, burning a hole in the brain.”

But focused ultrasound may transform the treatment of neurological diseases in other ways. In early November, 2015 researchers at Sunnybrook Health Sciences Centre in Toronto announced yet another application of forced ultra sound: the selective opening of the blood-brain-barrier (BBB) to allow the chemotherapy doxorubicin to more effectively reach a brain tumor. Researchers delivered the drug along with tiny gas filled bubbles into the blood stream of patients. Then, when they focused the ultrasound on the brain, the bubbles vibrated loosening the tight weave of cells making up the BBB, and allowing more doxorubicin to reach the tumor. This ability to open the BBB may have many important applications. It may, for example, allow for the better clearance of amyloid plaques in Alzheimer’s and Parkinson’s disease. (There is some evidence for this in mouse models of Alzheimer’s). If that turns out to be true, then this acoustic technology may prove to be a game changer.