Wavelet-based neurovascular coupling can predict brain abnormalities in neonatal encephalopathy

Abstract

Background: Hypoxic-ischemic encephalopathy (HIE) is a leading cause of morbidity and mortality in neonates, but quantitative methods to predict outcomes early in their course of illness remain elusive. Real-time physiologic biomarkers of neurologic injury are needed in order to predict which neonates will benefit from therapies. Neurovascular coupling (NVC) describes the correlation of neural activity with cerebral blood flow, and the degree of impairment could predict those at risk for poor outcomes.

Objective: To determine if neurovascular coupling (NVC) calculated in the first 24-hours of life based on wavelet transform coherence analysis (WTC) of near-infrared spectroscopy (NIRS) and amplitude-integrated electroencephalography (aEEG) can predict abnormal brain MRI in neonatal HIE.

Methods: WTC analysis was performed between dynamic oscillations of simultaneously recorded aEEG and cerebral tissue oxygen saturation (SctO2) signals for the first 24 h after birth. The squared cross-wavelet coherence, R², of the time-frequency domain described by the WTC, is a localized correlation coefficient (ranging between 0 and 1) between these two signals in the time-frequency domain. Statistical analysis was based on Monte Carlo simulation with a 95% confidence interval to identify the time-frequency areas from the WTC scalograms. Brain MRI was performed on all neonates and classified as normal or abnormal based on an accepted classification system for HIE. Wavelet metrics of % significant SctO2-aEEG coherence was compared between the normal and abnormal MRI groups.

Result: This prospective study recruited a total of 36 neonates with HIE. A total of 10 had an abnormal brain MRI while 26 had normal MRI. The analysis showed that the SctO2-aEEG coherence between the group with normal and abnormal MRI were significantly different (p = 0.0007) in a very low-frequency (VLF) range of 0.06-0.2 mHz. Using receiver operating characteristic (ROC) curves, the use of WTC-analysis of NVC had an area under the curve (AUC) of 0.808, and with a cutoff of 10% NVC. Sensitivity was 69%, specificity was 90%, positive predictive value (PPV) was 94%, and negative predictive value (NPV) was 52% for predicting brain injury on MRI. This was superior to the clinical Total Sarnat score (TSS) where AUC was 0.442 with sensitivity 61.5%, specificity 30%, PPV 75%, and NPV 31%.

Conclusion: NVC is a promising neurophysiological biomarker in neonates with HIE, and in our prospective cohort was superior to the clinical Total Sarnat score for prediction of abnormal brain MRI.

Keywords: Amplitude-integrated EEG; Hypoxic-ischemic encephalopathy; Near infrared spectroscopy; Neonatal EEG analysis; Neurovascular coupling; Wavelet coherence analysis.