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.