Assessing cerebral blood flow, oxygenation and cytochrome c oxidase stability in preterm infants during the first 3 days after birth

Abstract

A major concern with preterm birth is the risk of neurodevelopmental disability. Poor cerebral circulation leading to periods of hypoxia is believed to play a significant role in the etiology of preterm brain injury, with the first three days of life considered the period when the brain is most vulnerable. This study focused on monitoring cerebral perfusion and metabolism during the first 72 h after birth in preterm infants weighing less than 1500 g. Brain monitoring was performed by combining hyperspectral near-infrared spectroscopy to assess oxygen saturation and the oxidation state of cytochrome c oxidase (oxCCO), with diffuse correlation spectroscopy to monitor cerebral blood flow (CBF). In seven of eight patients, oxCCO remained independent of CBF, indicating adequate oxygen delivery despite any fluctuations in cerebral hemodynamics. In the remaining infant, a significant correlation between CBF and oxCCO was found during the monitoring periods on days 1 and 3. This infant also had the lowest baseline CBF, suggesting the impact of CBF instabilities on metabolism depends on the level of blood supply to the brain. In summary, this study demonstrated for the first time how continuous perfusion and metabolic monitoring can be achieved, opening the possibility to investigate if CBF/oxCCO monitoring could help identify preterm infants at risk of brain injury.

Conflict of interest statement

The authors declare no competing interests.

© 2022. The Author(s).

Figures

Figure 1

(a) Time courses of relative cerebral blood flow (rCBF), tissue saturation (StO2), and change in the oxidation state of cytochrome c oxidase (ΔoxCCO) for one patient on the first day of life. (b) Corresponding frequency-time plots generated by wavelet transform of rCBF, StO2, and ΔoxCCO. The red box highlights the frequency band of notable CBF oscillation (0.001 to 0.005 Hz). The dotted white lines indicate the cone of influence. Wavelet values outside this region were considered distorted due to edge artefacts.

Figure 2

(a) Coherence between relative cerebral blood flow (rCBF) and tissue saturation (StO2), rCBF and oxidation state of cytochrome c oxidase (oxCCO), and StO2 and oxCCO for one patient on the first day of life. (b) Average coherence value in the frequency range 0.001 − 0.005 Hz [indicated by the red box in column (a)]. The red dashed line indicates the statistical threshold.

Figure 3

(a) Coherence between rCBF and StO2, rCBF and oxCCO, and StO2 and oxCCO for one patient on the first day of life. (b) Average coherence value in the frequency range 0.001−0.005 Hz. The red dashed line indicates the statistical threshold.

Figure 4

Boxplots of the fraction of time that coherence between two optical parameters reached the statistical threshold of 0.57. Data are presented separately for the two monitoring periods and for the three combinations of coherence estimates: rCBF/StO2, rCBF/ΔoxCCO and StO2/ΔoxCCO. Statistical outliers are indicated by + , and the bars indicate significant differences in coherence duration between rCBF/StO2 on day 1 and rCBF/ΔoxCCO on days 1 (p = 0.025) and 3 (p = 0.004). Details of each boxplot are as follows: rCBF/StO2 (day 1): median: 26.9, 75th percentile: 42.1, 25th percentile: 9.8; rCBF/StO2 (day 3): median: 16.6, 75th percentile: 27.5, 25th percentile: 11.5; rCBF/oxCCO (day 1): median: 11.0, 75th percentile: 17.0, 25th percentile: 5.5; rCBF/oxCCO (day 3): median: 8.3, 75th percentile: 10.4, 25th percentile: 4.0; StO2/oxCCO (day 1): median: 8.2; 75th percentile: 14.0; 25-th percentile: 4.9; and StO2/oxCCO (day 3): median: 10.3, 75th percentile: 14.1, 25th percentile: 5.6.

Figure 5

(a) Premature infant with optical probes secured to the forehead and a phototherapy eye shield, (b) schematic of probe holder showing the position of the NIRS (3-cm SDD) and DCS (2-cm SDD) sources and the common detection location (shaded circle). Probe holder was 5 × 2 × 1 cm.