Using Ultrasound to Boost Brain Implant Biocompatibility

Kozai headshot

A collaboration between University of Pittsburgh bioengineers and a medical technology company may bring us one step closer to measuring human brain activity more efficiently - and potentially benefit people with nervous system injuries as well as improve artificial intelligence. 

Takashi D.Y. (TK) Kozai, Associate Professor of Bioengineering and Ernest E. Roth Faculty Fellow, works to improve the long-term performance of implanted electrodes and integrate technology with the human brain to study nervous systems in vivo at the cellular level. For the past five years at Pitt’s Swanson School of Engineering, he’s worked with Actuated Medical to enhance the biocompatibility of implanted devices in the brain. Their findings, "Low-intensity pulsed ultrasound stimulation (LIPUS) modulates microglial activation following intracortical microelectrode implantation,” were recently published in Nature Communications.

“When you implant devices in the brain, the brain recognizes them as a foreign body and tries to wall it off with glial scars, which prevent brain signals from reaching the electrode itself,” Kozai said. “Reducing glial scars would improve the electrodes’ effectiveness and provide clearer scans of brain activity.”

During the project, Kozai’s team investigated the effects of using low-intensity pulsed ultrasound stimulation (LIPUS) on microglial activity to measure its impact on the performance of chronically implanted microelectrode arrays. After testing this technology on mice and rats, Kozai’s project was a success — by using the ultrasound technology to gently massage the tissue around the electrodes, glial scar tissue didn’t build up around the implant, which vastly improved the signals that the team was able to receive from the electrodes. 

“These findings give us a new lever to push and pull in terms of understanding the brain,” Kozai said. “We want to implant these devices to be able to record the brain activity, and by recording the brain activity, we can eventually learn how to treat motor function in people who have spinal cord injury or work to treat vision in patients who are blind.” 

Actuated Medical developed the SonoShield Defender, the ultrasound transducer used by Kozai's team, and performed their own longitudinal electrophysiology experiments in parallel with the Kozai lab’s imaging experiments. According to Actuated Medical President and CEO Maureen L. Mulvihill, the success of this project is a significant breakthrough that will enable other neuroscience researchers to use SonoShield Defender in preclinical models. 

“We developed this prototype, TK tested it in his work, and it performed well, so now we're going to commercialize it so that other researchers have the ability to use this technology,” Mulvihill said. “We’re now looking at multiple applications for non-invasive ultrasound to help reduce cell damage in the brain and elsewhere in the body.”

For Grace Hwang, program officer at the National Institutes of Health (NIH) Brain Research Through Advancing Innovative Neurotechnologies® Initiative (The BRAIN Initiative®), Kozai’s project supports their goal to enable researchers to improve how we treat, prevent, and cure brain disorders through a detailed understanding of the brain. 

“These results highlight the versatility of ultrasound as a non-invasive tool, with potential to enhance the efficacy of other, more invasive interventions,” Hwang said. “The present study aligns well with the mission of The BRAIN Initiative to revolutionize our understanding of the human brain.”

Looking ahead, Kozai also hopes that this technology will enable further research modulating different types of brain cells that can prove useful for cell therapy or for building more energy efficient artificial intelligence. 

“These findings open the door for looking at non-neuronal cell activity with our two-photon microscope using ultrasound. If we can modulate those, likely we can modulate many of the other types of non-neuronal cells in the brain,” Kozai said. “These cells all play an important role in neural network activity that has been underappreciated both from a cell therapy perspective as well as with bio-inspired artificial intelligence.”