Depth-resolved assessment of changes in concentration of chromophores using time-resolved near-infrared spectroscopy: estimation of cytochrome-c-oxidase uncertainty by Monte Carlo simulations.

Time-resolved near-infrared spectroscopy (TR-NIRS) measurements can be used to recover changes in concentrations of tissue constituents ( Δ C ) by applying the moments method and the Beer-Lambert law. In this work we carried out the error propagation analysis allowing to calculate the standard deviations of uncertainty in estimation of the Δ C . Here, we show the process of choosing wavelengths for the evaluation of hemodynamic (oxy-, deoxyhemoglobin) and metabolic (cytochrome-c-oxidase (CCO)) responses within the brain tissue as measured with an in-house developed TR-NIRS multi-wavelength system, which measures at 16 consecutive wavelengths separated by 12.5 nm and placed between 650 and 950 nm. Data generated with Monte Carlo simulations on three-layered model (scalp, skull, brain) for wavelengths range from 650 to 950 nm were used to carry out the error propagation analysis for varying choices of wavelengths. For a detector with a spectrally uniform responsivity, the minimal standard deviation of the estimated changes in CCO within the brain layer, σ Δ C CCO brain  = 0.40 µM, was observed for the 16 consecutive wavelengths from 725 to 912.5 nm. For realistic a detector model, i.e. the spectral responsivity characteristic is considered, the minimum, σ Δ C CCO brain  = 0.47 µM, was observed at the 16 consecutive wavelengths from 688 to 875 nm. We introduce the method of applying the error propagation analysis to data as measured with spectral TR-NIRS systems to calculate uncertainty of recovery of tissue constituents concentrations.