Hypoxic-ischemic (HI) studies in preterms lack reliable prognostic biomarkers for diagnostic tests of HI encephalopathy (HIE). Our group’s observations from in utero fetal sheep models suggest that potential biomarkers of HIE in the form of developing HI micro-scale epileptiform transients emerge along suppressed EEG/ECoG background during a latent phase of 6–7[Formula: see text]h post-insult. However, having to observe for the whole of the latent phase disqualifies any chance of clinical intervention. A precise automatic identification of these transients can help for a well-timed diagnosis of the HIE and to stop the spread of the injury before it becomes irreversible. This paper reports fusion of Reverse-Biorthogonal Wavelets with Type-1 Fuzzy classifiers, for the accurate real-time automatic identification and quantification of high-frequency HI spike transients in the latent phase, tested over seven in utero preterm sheep. Considerable high performance of 99.78 ± 0.10% was obtained from the Rbio-Wavelet Type-1 Fuzzy classifier for automatic identification of HI spikes tested over 42[Formula: see text]h of high-resolution recordings (sampling-freq:1024[Formula: see text]Hz). Data from post-insult automatic time-localization of high-frequency HI spikes reveals a promising trend in the average rate of the HI spikes, even in the animals with shorter occlusion periods, which highlights considerable higher number of transients within the first 2[Formula: see text]h post-insult.

The timing of hypoxia-ischemia (HI) in preterm infants is often uncertain and there are few biomarkers to determine whether infants are in a treatable stage of injury. We evaluated whether epileptiform sharp waves recorded from the parietal cortex could provide early prediction of neuronal loss after HI. Preterm fetal sheep (0.7 gestation) underwent acute HI induced by complete umbilical cord occlusion for 25 minutes (n = 6) or sham occlusion (control, n = 6). Neuronal survival was assessed 7 days after HI by immunohistochemistry. Sharp waves were quantified manually and using a wavelet-type-2-fuzzy-logic-system during the first 4 hours of recovery. HI resulted in significant subcortical neuronal loss. Sharp waves counted by the automated classifier in the first 30 minutes after HI were associated with greater neuronal survival in the caudate nucleus (r = 0.80), whereas sharp waves between 2–4 hours after HI were associated with reduced neuronal survival (r = −0.83). Manual and automated counts were closely correlated. This study suggests that automated quantification of sharp waves may be useful for early assessment of HI injury in preterm infants. However, the pattern of evolution of sharp waves after HI was markedly affected by the severity of neuronal loss, and therefore early, continuous monitoring is essential.

Currently, there are no developed methods to detect sharp wave transients that exist in the latent phase after hypoxia-ischemia (HI) in the electroencephalogram (EEG) in order to determine if these micro-scale transients are potential biomarkers of HI. A major issue with sharp waves in the HI-EEG is that they possess a large variability in their sharp wave profile making it difficult to build a compact 'footprint of uncertainty' (FOU) required for ideal performance of a Type-2 fuzzy logic system (FLS) classifier. In this paper, we develop a novel computational EEG analysis method to robustly detect sharp waves using over 30[Formula: see text]h of post occlusion HI-EEG from an equivalent, in utero, preterm fetal sheep model cohort. We demonstrate that initial wavelet transform (WT) of the sharp waves stabilizes the variation in their profile and thus permits a highly compact FOU to be built, hence, optimizing the performance of a Type-2 FLS. We demonstrate that this method leads to higher overall performance of [Formula: see text] for the clinical [Formula: see text] sampled EEG and [Formula: see text] for the high resolution [Formula: see text] sampled EEG that is improved upon over conventional standard wavelet [Formula: see text] and [Formula: see text], respectively, and fuzzy approaches [Formula: see text] and [Formula: see text], respectively, when performed in isolation.

Hypoxic-ischemic (HI) insults before and during birth, secondary to events such as placental abruption or umbilical cord occlusion, are a significant contributor to neonatal brain injury (hypoxic-ischemic encephalopathy; HIE). [1,2] The preterm newborn is at greater risk of HIE. [1] In contrast to an overall incidence of 1-3/1000 live births at term in high-income countries, preterm babies born before 37 weeks have an HIE incidence of around 37.3/1000 babies born before 37 weeks of gestation, rising to an overall rate of HIE of 120/ 1000 in infants born before 28 weeks of gestation. [1,3] Survivors face lifelong neurodevelopmental problems, including learning and cognitive impairments, behavioral problems, cerebral palsy, and epilepsy. [4] The burden for individuals and their families and health and education economic costs are substantial. [4,5] To develop effective treatments or to appropriately utilize existing treatments requires that we fully understand how brain injury evolves and to identify biological markers (biomarkers) that allow us to determine phases of injury. Key to effective therapy is the knowledge that injury evolves in different phases over time-a latent phase of recovery of oxidative metabolism, which is followed by a secondary loss of cerebral energy metabolism during which time most brain cell injury occurs, followed by a tertiary phase of both repair and ongoing injury. [1,3,6] Therapeutic hypothermia (TH) is currently the only established treatment for HIE in babies born >36 weeks of gestation with moderate-severe HIE, and this treatment is now being cautiously explored for use in preterm babies. [1,2] The current clinical protocol for TH was based on our preclinical studies in term and preterm fetal sheep, which established that this therapy is only effective if started within 6 h after the end of an HI insult and continued for %3 days. [1-3] However, current clinical data show that many babies do not benefit from TH. [2] This in part reflects late recruitment of babies (typically 4-5 h) into treatment. However, it also reflects the fact that birth cannot always be taken as time zero. Many babies may also have experienced HI insults before birth, so that injury may have already evolved beyond the 6 h window of opportunity for TH efficacy.

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