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In the past year, however, scientists have had some success in solving this trade-off. Detailed images of the skull generated via CT scan and MRI can help scientists calculate the best way to focus the sound waves, says Seung-Schik Yoo, a neuroscientist at Brigham and Women’s and Harvard Medical School. In as yet unpublished work, Yoo and his colleagues have demonstrated that low-frequency, low-intensity ultrasound can successfully suppress visual activity in rabbits’ brains, as well as selectively trigger activity in the motor cortex. “We are also looking at the ability to modulate hormones or neurotransmitters, which may have application for psychiatric disorders, obesity, and addiction,” says Yoo.

In a paper published last year in the journal PLoS ONE, Tyler demonstrated that low-frequency, low-intensity ultrasound can activate channels that sit in the membrane of nerve cells in a slice of brain tissue, triggering the cells to send an electrical message through the neural circuit. He has since been able to use ultrasound to stimulate the motor cortex and trigger movement in live mice. This work has not yet been published.

Researchers hope to co-opt instruments developed for HIFU for this new application. Several instrument companies have developed phased arrays of ultrasound transducers, which allow 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,” says Yoo.

Because focused ultrasound is already used extensively, researchers are optimistic that it will not face any major hurdles in moving toward clinical testing. “For neurologists and neurosurgeons, it’s a well-established technique,” says Tyler. “The safety margins are well known.” Adds Kassell, “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 says 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 says. “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.

It’s not yet clear how ultrasound triggers electrical activity in neurons, but some believe that it is through thermal energy generated by sound waves. Tyler, however, says he has evidence that the neurons are activated through mechanical energy. Previous research has indeed shown that the neuron channels that control electrical activity in the brain can be activated with mechanical pressure. “What we think is happening is some kind of microcavitational effect, such as radiation or sheer strain, which affect the channels that control neural activity,” he says.

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Credit: William Tyler, Arizona State University
Video by William Tyler, Arizona State University

Tagged: Biomedicine, brain, neuroscience, implant, ultrasound, deep brain stimulation

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