A new approach to detecting concussion utilizes a laser to deliver infrared (IR) light pulses to the brain, where the light interacts with cytochrome C oxidase (CCO), a mitochondrial enzyme important to brain metabolism. CCO is known to decrease when cells are in distress. Measuring CCO “can tell us if the tissue is healthy and is metabolizing or ‘eating’ properly,” Ioulia Kovelman, associate professor at the University of Michigan, said. To noninvasively measure changes in CCO as well as blood oxygenation, researchers at the University of Michigan developed the Super-Continuum Infrared Spectroscopy of Cytochrome-C-Oxidase (SCISCCO) system, a device that uses an all-fiber integrated, supercontinuum light source to simultaneously measure both the CCO and the traditional blood oxygenation markers of neural metabolism. Beyond providing real-time information on whether the brain is getting oxygen, the new device can provide information about whether the brain cells are able to use that oxygen. By reliably measuring brain metabolism, the SCISCCO system could potentially result in faster and more certain diagnoses for concussion. The SCISCCO device enables researchers to look at tissue oxygen and cell metabolism at the same time. This could lead to a fast and noninvasive way for doctors to monitor the health of brain cells. Courtesy of Joseph Xu/Michigan Engineering, Communications & Marketing. The researchers used wavelengths between 750 nm and 900 nm to excite the CCO. Previous experiments have used IR lamps to excite CCO molecules, but with these experiments, the signal from the CCO was not very distinct. “Hemoglobin, which tells us about the blood oxygen levels, also responds to the range of wavelengths we use to probe CCO, and it is 10 to 20 times more plentiful in human tissue,” professor Mohammed Islam said. “We needed a stronger signal from the CCO to distinguish it from the hemoglobin and other molecules in the body, and we got that stronger response by using a laser that is nearly 10 times brighter than the lamps.” The increased brightness, along with measurement techniques to suppress noise during the measurements, allowed reliable measurement of CCO during cognitive attention tests with a portable device. Such attention tests are often used with concussion patients. The researchers conducted a pilot study of 25 people using a cognitive attention test in combination with principled physiological validations of the technology such as blood pressure and breath-holding approaches. The SCISCCO system was validated by confirming the near-infrared (NIR) spectrum of CCO in vitro. To demonstrate in vivo feasibility, the measured responses of oxygenation and CCO responses to acute ischemia (e.g., blood pressure tests) in human participants were compared to data from the literature. The researchers further demonstrated that the new device’s measurements of oxygenated (HbO) and deoxygenated (HbR) hemoglobin in response to breath-hold challenges were consistent with previously reported findings. Professor Mohammed Islam and doctoral student Allyssa Memmini at the University of Michigan led an experiment testing a laser designed to detect concussions at the Center for Human Growth and Development at the University of Michigan. Courtesy of Joseph Xu/Michigan Engineering, Communications & Marketing. As individuals were completing the attention task, the researchers observed an increase in oxygenated blood flow to their frontal lobes, a part of the brain that is essential to being able to attend. “Along with the increase in oxygenated blood flow, we also saw a change in the brain’s CCO redox state — in other words, as oxygen supply increased, so did the consumption of the oxygen by the neurons of the frontal lobe that were busy attending to the task,” Kovelman said. This means that our new method can effectively measure brain metabolism, an index of brain function.” Using the all-fiber-integrated supercontinuum light source as a key enabling technology, the SCISCCO system has the potential of being a practical, cost-effective, portable, noninvasive means of monitoring brain and organ oxygenation and metabolism in medical facilities. Applications of the SCISCCO system could range from a new tool for screening concussion patients to use in an intensive care unit to gauge patient’s organ response to treatments. The University of Michigan is pursuing patent protection and seeking partners to bring the technology to market. The research was presented at an invited talk at SPIE Photonics West BiOS on Feb. 2 in San Francisco. The paper on this work is titled “Brain Metabolism Monitoring through CCO Measurements Using All-Fiber-Integrated Super-Continuum Source.”