The best ideas are often simple in nature, though complex in detail, and great in potential. The stentrode is a perfect example, combining the familiar off-the-shelf technologies of a stent and an electrode. When situated in the brain, a stentrode could open the door to direct communication between thought and machine.
Transforming the Stent into the Strentrode
A team partly funded by the U.S. Defense Advanced Research Projects Agency (DARPA) has taken the stent—a small mesh tube used to treat narrow or weak arteries—and turned it into a recording device for neural signals that can be introduced to the brain through blood vessels. This approach removes the need for invasive surgery that has, until now, been a risk associated with similar technologies. The stentrode, which is the size of a matchstick, is the world’s first endovascular neural interface, and it could have profound implications for users of prosthetic limbs, wheelchairs, and other devices designed for assisted living.
“We have developed a technology that can record neural signals from within a blood vessel,” says Nick Opie, Ph.D. (right), a biomedical engineer at the University of Melbourne, Australia, who is one of the driving forces behind the technology. “By translating these signals, the stentrode could enable people to control switches and, therefore, any appropriate piece of equipment just by thinking about it.”
The initial idea came from neurologist Tom Oxley, M.D., the now New York-based chief executive officer and founder of the neural interface company Synchron, Inc., which is developing the stentrode technology. Ultimately, the device could be used to diagnose and treat a range of brain pathologies, such as paralysis, epilepsy, and movement disorders, although its initial use will be the control of external devices such as prosthetic limbs. In many different use cases, it could bring about a fundamental change in the quality of life for many patients with neurological conditions.
The Path to Human Trials
Oxley is a vascular neurologist and world expert in endovascular bionics. He is also an academic at the University of Melbourne, where the team behind the stentrode came together. Opie, cofounder and chief technology officer of Synchron, and biomedical engineer Sam John (right), a specialist in neural prosthetics, were part of a team working on a bionic eye project under the aegis of Prof. David Grayden (lower right) in the university’s Department of Electrical and Electronic Engineering.
According to Grayden, “Tom approached me very early on, when it was just an idea that had interest from DARPA. He and I put our heads together with Prof. Terry O’Brien from the Royal Melbourne Hospital and the University of Melbourne’s Medicine, Dentistry, and Health Sciences faculty, along with Professor of Engineering Tony Burkitt. I have more of a supervisory role and concentrate on the analysis of signals from the brain.”
Funding for the Project
DARPA’s interest in the stentrode came through its Reliable Neural-Interface Technology (RE-NET) program, which focuses on technology for a broad range of applications in military uniforms, body armor, and life-saving equipment for soldiers injured on the battlefield. Many battle survivors sustain serious injuries, including the loss of limbs and damage to the brain, so RE-NET places particular emphasis on developing high-performance neural interfaces to control advanced prosthetic limbs.
After an initial meeting, DARPA pledged US$1 million to Oxley’s project to support the development and testing of the stentrode. Further funding came in the form of US$2.2 million from the Australian National Health and Medical Research Council. So far, the project has raised US$10 million to complete its series A funding, which will help to propel the project toward a first human clinical trial in 2018.
The Testing Phase
To reach the stage where such trials are possible, the team had to overcome many challenges, not only in terms of the technology, but also in regard to successfully placing the device within the body.
“The first question to answer was how to access the motor cortex, the part of the brain responsible for motor control,” says Opie. “We developed an angiographic method to assess the motor cortex using blood vessels as the conduit. We had to look at how to map the areas and get a stent in there.” As Opie explains, “We developed a technique to compress the stentrode to less than 1 mm in size and to expand it to 4 mm in size once it was in place. The delivery of the stentrode uses common techniques for stent delivery as would be used to remove a blood clot. Then we had to look at how to record and decode the signals, for which we looked at many different options.”
The stentrode has to be both flexible enough to pass through the complex structure of blood vessels and rigid enough to fix itself in position when it reaches the correct place in the brain. The device is steered into place using catheter angiography, which poses far less risk to patients than the surgical techniques most commonly used to implant electrode arrays into the brain. With a catheter inserted into a blood vessel in the neck, the stentrode can be guided with real-time imaging and then precisely fixed into place. Once in situ, the electrode can detect signals from neurons in the motor cortex.
There is a series of sequential challenges, notes Grayden. “When we try the technology in humans, the priority is safety. After that, it is an ongoing challenge to develop the right algorithms. We are now developing rudimentary control algorithms, and we are building on a body of work that has developed algorithms that can, for example, control a mouse cursor on a screen.”
Previous projects run by DARPA have shown that the neural control of a prosthesis is possible through electrode arrays implanted surgically. The results of trials suggest that stentrodes could achieve similar results without the invasive procedure.
Tests of the stentrode in sheep have been encouraging. The device was guided into the sheep’s brain and remained there for six months, transmitting signals that were in line with what would be expected from a surgical implant. This proof-of-concept trial showed that the technology is both responsive and reliable, having operated successfully over an extended period in the sheep’s body.
From Prosthetics to Therapeutic Use: Human Trials
Synchron has a firm platform from which to prepare for a pilot clinical trial of the stentrode in humans to assess the technology’s feasibility and safety and enable patient-directed control of mobility-assist devices.
“The neural recordings we acquired compare to techniques that require an invasive surgical procedure, removing a portion of the skull, to access the brain,” Opie remarks. Grayden continues, “There are many devices that can be placed in the brain, but the stentrode is similar in performance to putting electrodes on the surface of the brain. BrainGate technology uses needle electrodes pushed into the brain, which is highly invasive and, although it performs better than stentrodes, does not last very long.” As Grayden explains, “That brings risks and limitations on lifespan, but with an electrode in the blood vessels, the brain may not even know that it is there. Furthermore, stents in the cardiac area last for the life of the patient.”
Human trials will come in the not-too-distant future, but the main challenge to overcome before then is one of manufacturing to ensure the stentrode can be placed in the human body without risk to the patient. After that comes the real challenge of developing the language and communication protocols to translate the signals into meaningful messages.
“We need to develop control algorithms that are more advanced than cursor control,” says John, who was involved in getting the software working and integrating it with the hardware to extract usable information. “The first trial will record signals from the brain to see what we can and cannot achieve,” he explains. “Hopefully, we will be able to improve the control of a wheelchair. For that, we have to create the right language. The stent is in a different position to previous electrodes, so we can’t know the limits of what is possible in terms of maximizing people’s control over external devices.”
From there, the next steps in development could be equally revolutionary. Potential future applications of the technology go beyond the control of external devices to encompass actual therapeutic uses. The stentrode could, for example, be employed to provide electrical stimulation and be useful for the bionic eye project, during which the key team members met.
“While our initial device was suitable to demonstrate the feasibility of endovascular recording, the manufacture of a device suitable for human implantation must be done in a certified cleanroom,” Opie elaborates. “We are currently investigating neural recording for paralysis. But, in the future, we will be looking at neural stimulation, which has the potential to treat numerous other neurological conditions, such as the suppression of seizures in people with Parkinson’s disease, [using] a device that is safer to implant than previous technologies because it requires no removal of a part of the skull.”
The rapid progress of the technology from concept to clinical trials is a testament to the great potential the team and its backers see in stentrodes. Funders and engineers are eagerly awaiting next year’s clinical trials, which could set into motion something truly revolutionary.