Simultaneous monitoring of cerebral perfusion and cytochrome c oxidase by combining broadband near-infrared spectroscopy and diffuse correlation spectroscopy

Ajay Rajaram, Gemma Bale, Matthew Kewin, Laura B Morrison, Ilias Tachtsidis, Keith St Lawrence, Mamadou Diop, Ajay Rajaram, Gemma Bale, Matthew Kewin, Laura B Morrison, Ilias Tachtsidis, Keith St Lawrence, Mamadou Diop

Abstract

Preterm infants born with very low birth weights are at a high risk of brain injury, in part because the premature brain is believed to be prone to periods of low cerebral blood flow (CBF). Tissue damage is likely to occur if reduction in CBF is sufficient to impair cerebral energy metabolism for extended periods. Therefore, a neuromonitoring method that can detect reductions in CBF, large enough to affect metabolism, could alert the neonatal intensive care team before injury occurs. In this report, we present the development of an optical system that combines diffuse correlation spectroscopy (DCS) for monitoring CBF and broadband near-infrared spectroscopy (B-NIRS) for monitoring the oxidation state of cytochrome c oxidase (oxCCO) - a key biomarker of oxidative metabolism. The hybrid instrument includes a multiplexing system to enable concomitant DCS and B-NIRS measurements while avoiding crosstalk between the two subsystems. The ability of the instrument to monitor dynamic changes in CBF and oxCCO was demonstrated in a piglet model of neonatal hypoxia-ischemia (HI). Experiments conducted in eight animals, including two controls, showed that oxCCO exhibited a delayed response to ischemia while CBF and tissue oxygenation (StO2) responses were instantaneous. These findings suggest that simultaneous neuromonitoring of perfusion and metabolism could provide critical information regarding clinically significant hemodynamic events prior to the onset of brain injury.

Keywords: (170.3660) Light propagation in tissues; (170.3880) Medical and biological imaging; (170.3890) Medical optics instrumentation; (170.6510) Spectroscopy, tissue diagnostics.

Conflict of interest statement

The authors declare that there are no conflicts of interest related to this article.

Figures

Fig. 1
Fig. 1
Simplified schematic of B-NIRS/DCS system with the shutter-based multiplexer. Red dots: B-NIRS emission and detection probes; blue dots: DCS emission and detection fibers.
Fig. 2
Fig. 2
Autocorrelation functions (blue symbols) acquired with (a) DCS alone, and (b) DCS in the presence of light from the B-NIRS source (10 mm). The red lines in both figures are the best fit to the diffusion approximation.
Fig. 3
Fig. 3
(A) DCS autocorrelation curves with B-NIRS light (30 mm from DCS detection) at varying intensities, (B) diffusion coefficient values without (blue) and with (red) the B-NIRS light; data were averaged over 10 acquisitions, error bars represent standard deviation.
Fig. 4
Fig. 4
Estimation of StO2 from simulated spectra of varying SNR (obtained by varying the number of averaged spectra). The circles represent the mean and the error bars are the standard deviation over 500 repetitions for each set of averaged spectra.
Fig. 5
Fig. 5
Broadband NIRS analysis showing (A) raw intensity measurements at baseline and during HI insult, (B) attenuation and best fit of the 2- (Hb and HbO2) and 3-component models (Hb, HbO2, and oxCCO), and (C) and residuals between measured and modelled attenuation, with CCO difference spectrum (ox-redCCO) for comparison.
Fig. 6
Fig. 6
DCS autocorrelation curves measured in one piglet during (A) baseline (CBF = 35.2 ± 0.8 ml/100g/min), (B) HI insult (CBF = 2.6 ± 0.1 ml/100g/min), and (C) following insult recovery (CBF = 32.5 ± 0.8 ml/100g/min). The red lines represent best fit to the diffusion approximation.
Fig. 7
Fig. 7
Simultaneous monitoring of StO2, absolute CBF, and oxCCO in 3 hypoxia-ischemia (HI) animals (A, B, C) and a control piglet (D). The HI insult began with clamping the carotid arteries (region (i)), followed by inducing hypoxia by reducing the inspired oxygen fraction to 8% (region (ii)).
Fig. 8
Fig. 8
Correlation plots of a) oxCCO vs CBF, and b) StO2 vs CBF; * indicates a significant change in either oxCCO or StO2 from baseline (p<0.05). Error bars represent the standard error of the mean. CBF intervals with mean values of 0.62 and 0.76 show only data from two and one animals, respectively.

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