Systematic investigation of changes in oxidized cerebral cytochrome c oxidase concentration during frontal lobe activation in healthy adults

Abstract

Using transcranial near-infrared spectroscopy (NIRS) to measure changes in the redox state of cerebral cytochrome c oxidase (Δ[oxCCO]) during functional activation in healthy adults is hampered by instrumentation and algorithm issues. This study reports the Δ[oxCCO] response measured in such a setting and investigates possible confounders of this measurement. Continuous frontal lobe NIRS measurements were collected from 11 healthy volunteers during a 6-minute anagram-solving task, using a hybrid optical spectrometer (pHOS) that combines multi-distance frequency and broadband components. Only data sets showing a hemodynamic response consistent with functional activation were interrogated for a Δ[oxCCO] response. Simultaneous systemic monitoring data were also available. Possible influences on the Δ[oxCCO] response were systematically investigated and there was no effect of: 1) wavelength range chosen for fitting the measured attenuation spectra; 2) constant or measured, with the pHOS in real-time, differential pathlength factor; 3) systemic hemodynamic changes during functional activation; 4) changes in optical scattering during functional activation. The Δ[oxCCO] response measured in the presence of functional activation was heterogeneous, with the majority of subjects showing significant increase in oxidation, but others having a decrease. We conclude that the heterogeneity in the Δ[oxCCO] response is physiological and not induced by confounding factors in the measurements.

Event-related changes of the prefrontal cortex oxygen delivery and metabolism during driving measured by hyperspectral fNIRS

“…However, due to recent progress in both light detection and spectral analysis algorithms, in a series of recent papers, the feasibility of CCO measurements has been conclusively established [17][18][19]. To resolve all three chromophores, HbO 2 , HHb, and CCO the best spectral resolution provided by the hyperspectral method, which measures light absorbance at a quasi-continuum of wavelengths was required in combination with advanced data processing methods.…”

Optimal wavelength combinations for near-infrared spectroscopic monitoring of changes in brain tissue hemoglobin and cytochrome c oxidase concentrations

“…It has been claimed that chromophore cross-talk, insufficient separability due to physical noise, and any concurrent changes in scattering can all give rise to spurious ∆[oxCCO] traces [12,22]. Yet, recent studies disprove these claims and establish ∆[oxCCO] as a NIRS-derived indicator of the redox state of mitochondrial cytochrome c oxidase and hence as a brain-specific optical biomarker of cerebral metabolic status [5,[8][9][10][11]14,15,32,33]. Also note that our study employs a restrictive wavelength range of 780-900 nm; exclusion of shorter wavelengths helps to enhance the contribution of cytochrome c oxidase to attenuation signals [14].…”

“…Also note that our study employs a restrictive wavelength range of 780-900 nm; exclusion of shorter wavelengths helps to enhance the contribution of cytochrome c oxidase to attenuation signals [14]. Further, this chromophore is expressed predominantly in deeper brain regions [5,10] that are thoroughly probed with our transmission mode measurements.…”

“…Numerous experimental and clinical studies have been carried out to delineate the biological basis of optical signals obtained from healthy and injured brain. These studies present sound evidence that NIRS-derived changes in chromophore concentrations can act as markers of cerebral physiology and pathology; the results offer significant insights into the feasibility of NIRS for observation of functional activation [5,6], detection of autoregulation or metabolic failure during routine surgery or after brain injury [7,8], and assessment of impending neurological damage due to hypoxia-ischemia (HI) in adults or neonates [9][10][11].…”

“…Since the total concentration of cytochrome c oxidase remains constant over the time course of our experiments [5,10,15], this law can be formulated as…”