Automatically Identified Micro-scale Sharp-wave Transients in the Early-Latent Phase of Hypoxic-Ischemic EEG from Preterm Fetal Sheep Reveal Timing Relationship to Subcortical Neuronal Survival.

Abstract

Perinatal Hypoxic-Ischemia Encephalopathy (HIE) in newborn infants, due to birth-related circumstances such as oxygen deprivation in brain cells, is caused by the disruption in blood flow through the umbilical cord. Subcortical neuronal loss due to the HIE can lead to cerebral palsy and other chronic neurological conditions. Pre-clinical EEG studies using in utero sheep have demonstrated that particular micro-scale HI transients emerge along a suppressed EEG background during a latent phase of 3-6 hours, after a severe HI insult. Whilst the nature of these micro-scale transients is not well understood, it has been hypothesized that such transients may be signatures of the evolving hypoxic-ischemic brain injury, possessing the potential to be served as the diagnosis biomarkers for the injury. Cerebral hypothermia is optimally neuroprotective only if administered within the first 2-3 hours post HI insult. Using data from a cohort of in utero preterm fetal sheep (n=5, at 0.7 of gestational age), this paper indicates how the number of automatically quantified micro-scale sharp wave transients from asphyxiated preterm fetal sheep, statistically correlate to the amount of NeuN-positive neurons measured in caudate nucleus of striatum. Different temporal window sizes of 2hrs, 1hr, ½hr and 10mins within the early phase of the latent phase are examined using our developed Wavelet Type-2 Fuzzy classifier for sharp detection. Analyses were narrowed down to 10min intervals to assess where exactly in time the occurrence of the HI micro-scale sharp waves demonstrate a significant correlation. Signal processing wise, results from the sub-windows indicate a timing trend that highlights a positive correlation, between the number of automatic quantifications and the amount of surviving neurons in the preterm brain, permitting the possibility of a point of care (POC) intervention to stop the spread of injury before it becomes irreversible.