Biomedical Optical Devices to Monitor Cerebral Health

Drs. Baker, Kilbaugh, and Licht (left to right), co-leaders of the Biomedical Optical Devices to Monitor Cerebral Health Frontier Program.

By Nancy McCann

Editor’s note: Frontier Programs represent a critical element of CHOP’s strategy to differentiate itself on the basis of combining extraordinary clinical care with breakthrough discoveries. In July 2019, six new Frontier Programs joined this prestigious group that is redefining pediatric care. Read on to meet the leaders of the Biomedical Optical Devices to Monitor Cerebral Health Program.

You’ve been trained in cardiopulmonary resuscitation (CPR) and practiced where to place your hands on the chest, how deep to push, and at the correct pace (think Bee Gee’s song “Stayin’ Alive”). A person’s chance of surviving cardiac arrest can double, or even triple, by performing CPR immediately, according to the American Heart Association. But how can you be sure you’re actually doing it correctly when someone’s life is literally in your hands?

“When we deliver CPR, we have no way of knowing if the patient’s brain is getting enough blood and oxygen,” said Daniel Licht, MD, pediatric neurologist and director of the Neurovascular Imaging Lab at Children’s Hospital of Philadelphia.

The mortality rate for pediatric cardiac arrest is about 50 percent. Among the survivors, it’s the minority who escape significant neurologic injury because of the oxygen loss to the brain.

“It’s so much more than just surviving,” said Dr. Licht, a professor of Neurology and Pediatrics in the Perelman School of Medicine at the University of Pennsylvania. “It’s the quality of survival that’s important.”

A newly named Frontier Program called Biomedical Optical Devices to Monitor Cerebral Health co-led by Dr. Licht, Todd Kilbaugh, MD, and Wesley Baker, PhD, has the goal of developing an optical device that could revolutionize cardiac resuscitation by providing real-time feedback to the person performing CPR. In theory, the instrument, via a small rubber pad that sticks to the patient’s forehead, will be able to sense oxygen demand and oxygen delivery to the brain using near infrared light, and then relay that information back to the care provider.

“We envision it would provide a green light/red light to rescuers on whether their chest compressions adequately perfuse the brain,” said Dr. Baker, a physicist in the Wolfson Laboratory for Clinical and Biomedical Optics. “If it’s good, the device will tell them so. If not, then it will offer instructions on what they need to do differently like press faster, deeper, or move the location of their hands. These instructions will be based on what our device is measuring in the brain.”

The Center for Resuscitation Science in the Perelman School of Medicine at the University of Penn has worked diligently to develop CPR that is directed to the individual patient’s needs over the last several years, said Dr. Kilbaugh, anesthesiologist and medical director of the Extracorporeal Membrane Oxygenation (ECMO) Center at CHOP.

“The next frontier, in many ways, is no longer survival, but giving children a life worth living,” said Dr. Kilbaugh, who is also on the faculty of the Perelman School of Medicine at Penn. “Our devices will give us a window into each child’s brain during their critical illness, allowing us to tailor the therapy. Ultimately, our goal is to limit neurologic injury and return them home — to their families and lives — the same children before they were entrusted into our care.”

Improving Extracorporeal Membrane Oxygenation

The Frontier team is also developing this technology to be used with ECMO — a mechanical pump that provides life-sustaining oxygenation to the body via a modified cardiopulmonary bypass machine to critically ill patients who do not respond to conventional management. ECMO takes the venous blood out of the body, sends it through an oxygenator, and then pushes the blood back into the body and brain to maintain sufficient oxygen delivery while resting injured lungs and/or heart. It’s most commonly used in the cardiac ICU, Dr. Licht said, but “you could land on ECMO because of sepsis, or a congenital diaphragmatic hernia, or because of a bad asthmatic attack. It’s a heroic, last ditch effort to save the patient.”

Physicians set the ECMO flow rate initially according to patient weight, and then adjust it based on systemic vital signs.

“Systemic vital signs, however, provide no information about cerebral flow, which leads to risks of hyperemia (too much flow) or ischemia (not enough flow), both of which can cause strokes,” Dr. Baker said.

To lower these risks, Drs. Licht, Kilbaugh, and Baker aim to develop an algorithm that continually adjusts the ECMO pump flow rate based on feedback from optical monitoring of cerebral blood flow and oxygenation. Through ensuring optimal brain perfusion on an ongoing basis, the biomedical optical device would individualize the ECMO treatment and could improve neurologic outcomes, Dr. Licht said. The accuracy of the device could also increase the likelihood that ECMO could become a preferred, first line strategy. Unlike high pressure ventilation, oxygenating the blood outside of the body doesn’t injure any tissues.

“We want to develop a clinically, user-friendly interface that gives a green light if the person is administering the CPR correctly, or if ECMO is adequately perfusing the brain,” Dr. Baker said. “Ultimately, we hope to see CPR and ECMO improved by our device.”

The ECMO Center at CHOP is one of the few Platinum ECMO Centers in the world, as awarded by the Extracorporeal Life Support Organization (ELSO). Leading the field for many years, CHOP’s Center develops clinical strategies and devices for extracorporeal support.

“The Frontier program will fund the development of a transformative symbiosis between these life-saving machines and children who are clinging to life, altering ECMO support to the individual patient’s needs as they rapidly change during critical illness often unseen by clinicians with current technology,” Dr. Kilbaugh said.

Pioneering Precision Medicine

The Frontier Program’s primary investigators’ first order of business is to prove that the technology works with animal models of cardiac arrest and ECMO. Specifically, they’ll conduct pre-clinical trials on whether using the device to guide CPR and ECMO therapy improves brain outcomes.

“Thresholding (one-size-fits-all treatment for a population) blood flow or oxygen saturations doesn’t really work,” Dr. Licht said. “It doesn’t address the individual’s needs. Creating thresholds for a population may help 60 percent of the kids that you care for, but if you can measure these things exactly and know what a patient’s oxygen demand is — and be able to match that with oxygen delivery — then 100 percent of your patients will benefit from the technology.”

This is the first Frontier Program that is oriented toward device development. The research team is starting with a “proof of concept” instrument for in-hospital use, and by the end of the three-year program, they hope to have successfully tested it in humans. After that, they’ll look for further investment to package and manufacture it. Eventually, these devices could be available anywhere to improve CPR administration, but that will take several generations of improvements.

“This Frontier Program will provide the funding for a transformative leap by allowing us to alter CPR based on noninvasive devices that direct resuscitation to the brain, our most vital organ,” Dr. Kilbaugh said.