Wearable NIRS Device for Continuous Monitoring of Cytochrome C Oxidase in Hypoxic Ischemic Encephalopathy - Project Summary/Abstract Hypoxic ischemic encephalopathy (HIE) remains one of the leading causes of neonatal morbidity and mortality, affecting 1-8 per 1000 live births in the developed world and even more in the developing world. Randomized controlled trials have demonstrated a reduction in death or disability in newborns with moderate or severe HIE treated with therapeutic hypothermia (TH). The gold standard for assessment of brain injury after HI is brain magnetic resonance imaging with spectroscopy (MRI-MRS). However, this study is not obtained until the 72-hour TH treatment is complete. Therefore, there is a need for informative and real-time bedside tools and biomarkers to continuously monitor cerebral hemodynamics and metabolism and guide intervention, to prevent further brain injury, provide prognostic information to families, and potentially improve neurodevelopmental outcome. Building on our extensive history of success monitoring infants with non-invasive bedside optical methods, we propose to design and build a novel, 8-wavelength, low-cost, wearable, wireless oxCCO near-infrared spectroscopy (NIRS) device. This device will quantify the oxidation state of cytochrome c (oxCCO) providing a measurement of cerebral metabolism, in addition to hemoglobin concentration (Hb) and hemoglobin oxygenation (SO2). Prior work by other groups has demonstrated a relationship between oxCCO and brain injury severity. We will extend this work by continuous monitoring throughout TH, rewarming, and after rewarming. This oxCCO-NIRS technology is an extension of our LED-based wearable device, called FlexNIRS, which has been used and tested by the Massachusetts General Hospital (MGH) team in phantoms and humans to verify performance and demonstrate accuracy in measurements. The device will be tested initially in term neonates with transient respiratory distress in the MGH NICU to demonstrate changes in oxCCO during periods of mild oxygen desaturation. Finally, the device will be used to continuously monitor 20 neonates being treated with 72 hours of TH, during rewarming, and 1-2 days after rewarming to test our hypothesis that an increased frequency of dynamic changes in cerebral metabolism during each epoch of time will correlate with brain injury presence and severity. Our goal is to provide a non-invasive bedside monitor of cerebral metabolism to guide early prognostication and to provide an opportunity for individualized intervention in real-time to reduce brain injury and improve neurodevelopmental outcome. This “proof of principle” pilot study will set the stage for a larger trial using this device in the future.
