Comparison of Broadband and Discrete Wavelength Near-Infrared Spectroscopy Algorithms for the Detection of Cytochrome aa3 Reduction.

BACKGROUND Cytochrome aa3, the terminal component of the electron transport chain, absorbs near-infrared radiation (NIR) differentially depending on its oxidation state (Cytox), which can in theory be measured using near-infrared spectroscopy (NIRS) by relating light absorption at specific wavelengths to chromophore concentrations. Some NIRS algorithms use discrete wavelengths, while others analyze a band of NIR (broadband NIRS). The purpose of this study was to test the ability of discrete wavelength and broadband algorithms to measure changes in Cytox (primary outcome), and to determine whether or not a discreet wavelength NIRS algorithm could perform similarly to a broadband NIRS algorithm for the measurement of Cytox in a staged hypoxia-cyanide model (hypoxia and cyanide have oppositional effects on tissue saturation, but both cause cytochrome reduction). METHODS Twenty Sprague-Dawley rats were anesthetized with isoflurane, intubated, and instrumented. Blood pressure, end-tidal carbon dioxide, and arterial oxygen saturation were measured. A halogen light source transmitted NIR transcranially. NIR from the light source and the skull was transmitted to 2 cooled charge-coupled device spectrometers. Rats were subjected to anoxia (fraction of inspired oxygen, 0.0) until arterial oxygen saturation decreased to 70%. After recovery, 5 mg/kg sodium cyanide was injected intravenously. The cycle was repeated until cardiac arrest occurred. Relative concentrations of hemoglobin and cytochrome aa3 were calculated using discreet wavelength and broadband NIRS algorithms. RESULTS Hypoxia led to an increase in calculated deoxyhemoglobin (0.20 arbitrary units [AUs]; 95% confidence interval [CI], 0.17-0.22; P < .0001), a decrease in calculated oxyhemoglobin (-0.16 AUs; 95% CI, -0.19 to -0.14; P < .0001), and a decrease in calculated Cytox (-0.057 AUs; 95% CI, -0.073 to 0.0040; P < .001). Cyanide led to a decrease in calculated deoxyhemoglobin (-0.037 AUs; 95% CI, 0.046 to -0.029; P < .001), an increase in calculated oxyhemoglobin (0.053 AUs; 95% CI, 0.040-0.065; P < .001), and a decrease in calculated Cytox (-0.056 AUs; 95% CI, -0.064 to -0.048; P < .001). The correlations between "discreet" wavelength algorithms (using 4, 6, 8, and 10 wavelengths) and the broadband algorithm for the measurement of calculated Cytox were 0.54 (95% CI, 0.52-0.56), 0.87 (0.87-0.88), 0.88 (0.88-0.89), and 0.95 (0.95-0.95), respectively. CONCLUSIONS The broadband and 10 wavelength algorithm were able to accurately track changes in Cytox for all experiments.

[1]  S. D. De Hert,et al.  Evaluation of different near-infrared spectroscopy technologies for assessment of tissue oxygen saturation during a vascular occlusion test , 2017, Journal of Clinical Monitoring and Computing.

[2]  D. Altman,et al.  Statistics notes: Calculating correlation coefficients with repeated observations: Part 1—correlation within subjects , 1995 .

[3]  D. Delpy,et al.  Quantification in tissue near–infrared spectroscopy , 1997 .

[4]  R. Ordidge,et al.  Use of Mitochondrial Inhibitors to Demonstrate That Cytochrome Oxidase Near-Infrared Spectroscopy Can Measure Mitochondrial Dysfunction Noninvasively in the Brain , 1999, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[5]  Torin D. Shear,et al.  Extracranial contamination in the INVOS 5100C versus the FORE-SIGHT ELITE cerebral oximeter: a prospective observational crossover study in volunteers , 2016, Canadian Journal of Anesthesia/Journal canadien d'anesthésie.

[6]  R. Thiele,et al.  Broadband near-infrared spectroscopy can detect cyanide-induced cytochrome aa3 inhibition in rats: a proof of concept study , 2017, Canadian Journal of Anesthesia/Journal canadien d'anesthésie.

[7]  Marco Ferrari,et al.  Near Infrared Brain and Muscle Oximetry: From the Discovery to Current Applications , 2012 .

[8]  F. Jöbsis Noninvasive, infrared monitoring of cerebral and myocardial oxygen sufficiency and circulatory parameters. , 1977, Science.

[9]  Matthew Brenner,et al.  Non-invasive in vivo diffuse optical spectroscopy monitoring of cyanide poisoning in a rabbit model , 2007, Physiological measurement.

[10]  D. Delpy,et al.  Characterization of the near infrared absorption spectra of cytochrome aa3 and haemoglobin for the non-invasive monitoring of cerebral oxygenation. , 1988, Biochimica et biophysica acta.

[11]  D. Delpy,et al.  Performance comparison of several published tissue near-infrared spectroscopy algorithms. , 1995, Analytical biochemistry.

[12]  Solomon G Diamond,et al.  Continuous correction of differential path length factor in near-infrared spectroscopy , 2013, Journal of biomedical optics.

[13]  J. Volpe,et al.  Cerebral Oxygenation Measured by Near Infrared Spectroscopy during Cardiopulmonary Bypass and Deep Hypothermic Circulatory Arrest in Piglets , 1996, Pediatric Research.

[14]  J. Tepperman,et al.  A spectrophotometric study of the competition of methemoglobin and cytochrome oxidase for cyanide in vitro. , 1946, The Journal of biological chemistry.

[15]  Martin Wolf,et al.  General equation for the differential pathlength factor of the frontal human head depending on wavelength and age , 2013, Journal of biomedical optics.

[16]  H. Grocott,et al.  Impact of Extracranial Contamination on Regional Cerebral Oxygen Saturation: A Comparison of Three Cerebral Oximetry Technologies , 2012, Anesthesiology.

[17]  J. Tepperman,et al.  The in vivo inactivation by cyanide of brain cytochrome oxidase and its effect on glycolysis and on the high energy phosphorus compounds in brain. , 1946, The Journal of biological chemistry.

[18]  A. Villringer,et al.  Determination of the wavelength dependence of the differential pathlength factor from near-infrared pulse signals , 1998, Physics in medicine and biology.

[19]  Non-invasive measurements of mitochondrial damage during neonatal hypoxia-ischaemia--a role for nitric oxide? , 1997, Biochemical Society transactions.