For monitoring of concussion, brain function, organ condition and other medical applications, what is needed isa non-invasive method of monitoring tissue metabolism. MRI-based functional imaging technology detects changes inblood oxygenation, a correlate of neural activity, and thus may offer a prediction of prognosis in cases of concussion andother cerebral traumas. Yet, potential relationships between perturbations to cerebral metabolism and patient outcomescannot be effectively exploited clinically because we lack a practical, low-cost, non-invasive means to monitor cerebraloxygenation and metabolism in the emergency department, operating room, or medical facilities.We have developed a device to optically assay the redox state of Cytochrome-C-Oxidase (CCO), themitochondrial enzyme responsible for the last step of the electron transport chain. Changes in CCO redox reflect changesin respiratory flux, and thus changes in the rate of oxidative adenosine triphosphate (ATP) synthesis. In other words,changes in CCO reflect brain cell’s metabolic activity more directly than the traditional blood oxygenation measurementmethods. To non-invasively measure changes in CCO as well as blood oxygenation, we have developed a Super-Continuum Infrared Spectroscopy of Cytochrome-C-Oxidase (SCISCCO) system that uses an all-fiber integrated, supercontinuumlight source to simultaneously measure both of the new (CCO) and the traditional (blood oxygenation) markersof neural metabolism. The SCISCCO system is validated by confirming the near-infrared spectrum of CCO in vitro. Todemonstrate in vivo feasibility, the measured responses of oxygenation and CCO responses to acute ischemia (e.g., bloodpressure tests) in human participants are compared to data from the literature. Furthermore, we show that the new device’smeasurements of oxygenated (HbO) and deoxygenated (HbR) hemoglobin in response to breath hold challenges areprincipled and consistent with previously reported findings.The validated SCISCCO system is finally applied to measure cerebral oxygenation and the redox state of CCO inparticipants during an attention test protocol. Twenty-five healthy adults completed an attention task that included nine60-second periods of attention task, interleaved with 60-s periods of resting baseline. It has been well established that thefrontal lobe of the human brain is active during tasks of attention. We therefore predicted that attention task should elicitan increase in HbO concentration accompanied by a decrease in redox state of CCO (e.g., ratio of oxidized CCO to reducedCCO) in frontal lobe brain regions as measured with the SCISCCO system. Our findings are consistent with ourpredictions: HbO concentration increases while CCO concentration decreases during the attention blocks relative to theresting baseline, thereby indicating an increase in oxidative metabolism of the frontal lobe brain regions of interest. Oursystematic, multi-method approach thus validates the new device as well as the validity of the metabolic biomarkers thatit measures. The SCISCCO system could be a new tool for monitoring brain and organ metabolism, which could beinvaluable for screening concussion patients or use in an operating or emergency room to gauge patient’s organ responseto treatments.
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