X-ray of spinal cord

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Cross-disciplinary team will design, develop devices to better treat spinal cord injuries

Funded through the Defense Advanced Research Projects Agency, the project will bring together experts from across Johns Hopkins to create solutions that work on the battlefield and on the frontlines of health care

A team of Johns Hopkins biomedical engineers and neurosurgeons has received $13.48 million from the Defense Advanced Research Projects Agency to develop implantable ultrasound and other devices that could revolutionize care for people suffering from spinal cord injuries. The results could benefit thousands of U.S. service members and civilians who sustain spinal cord injuries every year.

The electronic device will be the size and flexibility of a small Band-Aid and will use high-resolution ultrasound technology, as well as miniaturized electrodes, to help doctors monitor and treat the changes in blood flow and prevent tissue death that occur immediately after a traumatic injury to the spinal cord.

The research program, supported by DARPA's Bridging the Gap program, will draw from the clinical expertise and ingenuity of its co-leaders, Nicholas Theodore, professor of neurosurgery and biomedical engineering, and Amir Manbachi, assistant professor of neurosurgery and biomedical engineering, to bring the devices from concept to human use within an ambitious five-year timeline.

The team also includes external collaborators, such as the Johns Hopkins University Applied Physics Laboratory, Columbia University, and Sonic Concepts, Inc., as well as various departments within Johns Hopkins University, including the departments of Neurosurgery, Neurology, Biomedical Engineering, Radiology, Anesthesiology, and Critical Care. Experts at the Berman Institute for Bioethics at the Johns Hopkins' Bloomberg School of Public Health also are involved.

"The main factors that make a device useable in a war theatre are size and ease of application in low-resource settings—both of which can only improve our clinical approaches as well."
Nicholas Theodore
Professor of neurosurgery and biomedical engineering

Joshua Doloff, assistant professor of biomedical engineering, and Nitish Thakor, professor of biomedical engineering, are two Hopkins co-investigators supporting Manbachi's engineering deliverables on this award. Assistant professors Jennifer Son and Javad Azadi are collaborating with biomedical engineers and neurosurgeons to push the boundaries of what is currently detectable with ultrasound.

"There are few places taking a close look at how engineering approaches could improve the treatment of spinal cord injuries. I think there are tremendous opportunities here," says Theodore, who worked for more than 10 years as a neurosurgeon in the U.S. Navy, treating soldiers and sailors with spinal cord injuries. "Johns Hopkins' world-class biomedical engineers work closely with physicians and surgeons to solve problems that have traditionally been thought of as impossible."

Though the primary mission of the team is to develop devices that can be deployed to service members on military fronts, the researchers aim to make the technology available to benefit the approximately 17,000 civilians who experience spinal cord injuries in the U.S. every year.

"The main factors that make a device useable in a war theatre are size and ease of application in low-resource settings—both of which can only improve our clinical approaches as well," says Theodore.

The project's strategy is to target the disruption in blood flow that occurs alongside injury to the spinal cord. By utilizing ultrasound and electrical technology to image and stimulate the blood vessels and tissue at the site of spinal cord injury, as well as controlling spinal fluid dynamics, the delivery of oxygen and nutrients can be optimized. This approach could prevent additional damage to the spinal cord, which can lead to increased inflammation, pain, and worsening paralysis.

"There are very few treatment options available to minimize the damage initially—for example, increasing the patient's blood pressure; however, we still need to understand, in real-time, how the body reacts to these treatments," says Manbachi. "When Dr. Theodore described this challenge to me for the first time four years ago, as an acoustic engineer, I immediately thought to use ultrasound as a tool to monitor and stimulate these damaged tissues."

To accomplish this, the electronic devices will use ultrasound "pulse echoes"—similar to the radar submarines use to navigate—as well as electrical stimulation, to monitor and treat the previously unobservable tiny blood vessels and surrounding tissue at and around the spinal cord injury site.

"This will be a real engineering feat."
Amir Manbachi
Assistant professor of neurosurgery and biomedical engineering

"This will be a real engineering feat," says Manbachi. "Typical ultrasound transducers are bulky and designed to gather images of larger structures. We want to take this technology and shrink it for use on structures the size of a pinky finger, while still capturing clear ultrasound images of the spinal cord microvasculature."

Doloff, who specializes in immunoengineering and regenerative medicine, will assist in developing the packaging of the implantable ultrasound device system, taking into account tissue and immune biocompatibility. His team will also aid in assessing wound healing and tissue response after implantation. Thakor, who specializes in neuroengineering and imaging and medical devices, will assist in setting up the animal model, and will work to stimulate the neural tissue and enhance blood flow to the injured areas.

Images derived from the team's devices will allow clinicians to observe how blood is flowing to the injury site. This can give them valuable information on how much oxygen, nutrients, and medication are reaching the area. The data will allow physicians to respond to their patient's condition in real-time by administering medications or possibly electrical or ultrasound stimulation to improve blood flow, stop inflammation, offer pain relief, and neuroprotective therapies to stop damage to the injured tissue.

The sound waves generated by these implantable devices can also be used to stimulate healing in the area. "Similar to how the sun's rays can be focused by a magnifying glass, therapeutic sound waves from the device can, in theory, be focused to promote blood flow at the injury site to promote healing," says Manbachi.

The five-year timeline to bring a completely new technology to animal studies, FDA regulatory approvals, and human trials will push the limits of the typical pace of innovation that may otherwise take decades.

"It is an extraordinary team effort to bring together the smartest engineers and neurosurgeons to solve this problem," says Theodore. "There are very few places in the world that are able to pull together the resources we have for this project."

The team expects the initial technologies to be used experimentally and clinically to treat acute spinal cord injury. The researchers' ultimate goal, however, is to develop more advanced versions applicable for patients suffering from chronic spinal cord injury.

"This research will lead to further advancements in the field of implantable systems for therapeutic diagnosis and intervention," said Doloff. "It is our hope that such platform technology might, in the future, be adapted to aid other medical applications as well."

Larry Nagahara, associate dean for research at Johns Hopkins Whiting School of Engineering, says the project came out of initial discussions of patient need and institutional capabilities as early as 2018.

"Johns Hopkins' world-class research and technologies have provided immense opportunities to contribute to public health through collaborative research efforts with academic, industry, and government partners," Nagahara says. "Building a strong relationship with DARPA is of utmost importance to WSE and to Johns Hopkins."