Novel Wavelet Real Time Analysis of Neurovascular Coupling in Neonatal Encephalopathy

Abstract

Birth asphyxia constitutes a major global public health burden for millions of infants, despite hypothermia therapy. There is a critical need for real time surrogate markers of therapeutic success, to aid in patient selection and/or modification of interventions in neonatal encephalopathy (NE). This is a proof of concept study aiming to quantify neurovascular coupling (NVC) using wavelet analysis of the dynamic coherence between amplitude-integrated electroencephalography (aEEG) and near-infrared spectroscopy in NE. NVC coupling is assessed by a wavelet metric estimation of percent time of coherence between NIRS S_ctO₂ and aEEG for 78 hours after birth. An abnormal outcome was predefined by a Bayley III score <85 by 18-24 m. We observed high coherence, intact NVC, between the oscillations of S_ctO₂ and aEEG in the frequency range of 0.00025-0.001 Hz in the non-encephalopathic newborns. NVC coherence was significantly decreased in encephalopathic newborns who were cooled vs. non-encephalopathic controls (median IQR 3[2-9] vs.36 [33-39]; p < 0.01), and was significantly lower in those with abnormal 24 months outcomes relative to those with normal outcomes (median IQR 2[1-3] vs 28[19-26], p = 0.04). Wavelet coherence analysis of neurovascular coupling in NE may identify infants at risk for abnormal outcomes.

Figure 1. Wavelet-based S_ctO₂-aEEG coherence showing intact neurovascular coupling (NVC).

This extract is from a cooled neonate with normal outcome (MRI showed no injury and Bayley III >85. (A) An enlarged segment of the real-time S_ctO₂ and aEEG data. (B) Squared wavelet coherence, , where the x-axis represents time, the y-axis represents scale in minute representing the range of frequencies, and the color scale represents the magnitude of R². Significant coherence between the S_ctO₂ and aEEG is seen in a very low-frequency (VLF) range of 0.00025–0.001 Hz.

Figure 2. Wavelet-based S_ctO₂-aEEG coherence showing low neurovascular coupling.

This infant had white matter injury on MRI. The Bayley III scores at 18 months are: cognitive 71, language 70, and motor 85. (A) An enlarged segment of the real-time S_ctO₂ and aEEG data. (B) Squared wavelet coherence, , where the x-axis represents time, the y-axis represents scale of frequencies. No significant areas of coherence are seen through the range of time and frequencies studied.

Figure 3

Individual data of significant S_ctO₂→aEEG in-phase coherence from newborns quantified in: (A) normal outcome group (n = 4), and (B) abnormal outcome group (n = 6). The two non-cooled are labeled by + and • in the left panel. Significant differences between normal vs. abnormal groups (p < 0.05) was observed in the frequency range of 0.00025–0.001 Hz, highlighted by gray shade.

Figure 4. Area under the curve (AUC) of significant SctO2-aEEG coherence in infants categorized by the 18–24 developmental outcomes.

X axis shows infants divided into two groups: normal (n = 4) and abnormal outcomes (n = 6) based on Bayley <85 at 18–24 months. Y axis is AUC for significant NVC coherences. Boxplot (median, 25% and 75% percentiles) for the % NVC coherence AUC over the frequency range of 0.00025–0.001 Hz, p = 0.01 by Exact Wilcoxon Rank Sum test.