Ultrasound treatment studied for neurological disorders

Scientists at the Massachusetts Instutitue of Technology (MIT) and other institutions have been experimenting with low-frequency, low-intensity ultrasound to provide a non-invasive alternative to techniques such as deep-brain stimulation (DBS) and vagus nerve stimulation, used to treat a growing number of neurological disorders.

"Once people have found out what they can do with DBS and vagus nerve stimulation, we think we can unplug those devices and control activity from outside the body," said William J. Tyler, PhD, a neuroscientist at Arizona State University in Tempe. Tyler has started a company called SynSonix to commercialize the technology.

DBS, which is used to treat Parkinson's disease, dystonia, and obsessive-compulsive disorder, delivers an electrical jolt to the brain via an implanted electrode, according to the MIT Technology Review. Due to its invasive nature, however, DBS is only used for severe cases that are untreatable with medication. Transcranial magnetic stimulation (TMS), in which an electric coil placed over the head generates a magnetic field that passes through the skull and excites neurons in the brain below, is less invasive. Yet, TMS, which treats depression, can only target the more superficial parts of the brain.

"With ultrasound, we have a much better spatial focus than [with] DBS," Tyler said. "And unlike TMS, we can get anywhere in the brain."

Better ultrasound transducers enable more-precise focusing of ultrasound energy. And MRI used in conjunction with ultrasound allows surgeons to target specific areas of the body more precisely. "The ability to marry focused ultrasound with MR guidance is exceedingly powerful," said Neal Kassell, MD, a neurosurgeon at the University of Virginia in Charlottesville, and chairman of the Focused Ultrasound Surgery Foundation.

The MIT Technology Review reported that one of the challenges in using ultrasound to target the brain is figuring out how to get the sound waves through the skull in a controlled manner. Researchers at Brigham and Women's Hospital in Boston have found that an ultrasound frequency of less than one megahertz can ease the problem, but with a trade-off: the lower the frequency, the more difficult it is to focus the energy on a particular point in the brain.

In the past year, however, scientists have had some success in solving this trade-off. Detailed images of the skull generated via CT and MRI can help scientists calculate the best way to focus the sound waves, according to Seung-Schik Yoo, PhD, a neuroscientist at Brigham and Harvard Medical School in Boston. In as yet unpublished work, Yoo and colleagues have demonstrated that low-frequency, low-intensity ultrasound can suppress visual activity in rabbits' brains, as well as selectively trigger activity in the motor cortex.

Researchers hope to co-opt instruments developed for high-frequency ultrasound (HIFU) for this new application, according to the MIT Technology Review. Several instrument companies have developed phased arrays of ultrasound transducers, which allow more precise targeting of ultrasound energy, and which are currently being tested for removal of brain tumors.

"Depending on individual anatomy of the skull, you can program the ultrasound equipment to fire individual elements to deliver a well-characterized beam, in terms of location and size, that can be tailor-made to each patient," Yoo said.

Because focused ultrasound is already used extensively, researchers are optimistic that it will not face any major hurdles in moving toward clinical testing. "I think it will actually be easier to get approval [than it was for HIFU] because the pressure of the focused ultrasound is less pressure than the brain gets from transcranial Doppler, a diagnostic device used to look at vessels in the head after stroke and hemorrhage," Kassell said.

Kassell added that the foundation is most interested in using low-intensity, low-frequency ultrasound for surgical planning. In epilepsy patients, surgeons could use the technology to temporarily silence a piece of brain tissue thought to be responsible for triggering seizures, thus confirming the correct localization, and then use HIFU to ablate that piece of tissue.

Tyler is most interested in using focused ultrasound for treating Parkinson's disease. "Since it's not invasive, we might be able to treat patients much earlier in progression," he noted. "Right now, people who get DBS are the worst-case patients."

While initial devices would likely resemble a smaller version of MRI machines, treating Parkinson's patients would require a wearable or implantable device capable of delivering continual stimulation. Tyler's team is working on flexible ultrasound transducers that could be implanted on top of the skull or formulated into a cap.

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