Investigation of the quantification of hemoglobin and cytochrome-c-oxidase in the exposed cortex with near-infrared hyperspectral imaging: a simulation study

Abstract

Significance: We present a Monte Carlo (MC) computational framework that simulates nearinfrared (NIR) hyperspectral imaging (HSI) aimed at assisting quantification of the in vivo hemodynamic and metabolic states of the exposed cerebral cortex in small animal experiments. This can be done by targeting the NIR spectral signatures of oxygenated (HbO 2) and deoxygenated (HHb) hemoglobin for hemodynamics as well as the oxidative state of cytochrome-c-oxidase (oxCCO) for measuring tissue metabolism. Aim: The aim of this work is to investigate the performances of HSI for this specific application as well as to assess key factors for the future design and operation of a benchtop system. Approach: The MC framework, based on Mesh-based Monte Carlo (MMC), reproduces a section of the exposed cortex of a mouse from an in vivo image and replicates hyperspectral illumination and detection at multiple NIR wavelengths (up to 121). Results: The results demonstrate: (1) the fitness of the MC framework to correctly simulate hyperspectral data acquisition; (2) the capability of HSI to reconstruct spatial changes in the concentrations of HbO 2 , HHb, and oxCCO during a simulated hypoxic condition; (3) that eight optimally selected wavelengths between 780 and 900 nm provide minimal differences in the accuracy of the hyperspectral results, compared to the "gold standard" of 121 wavelengths; and (4) the possibility to mitigate partial pathlength effects in the reconstructed data and to enhance quantification of the hemodynamic and metabolic responses. Conclusions: The MC framework is proved to be a flexible and useful tool for simulating HSI also for different applications and targets.

Light transport modeling in highly complex tissues using implicit mesh-based Monte Carlo algorithm

“…6 represent a highly sophisticated microvascular network in comparison to the benchmarks in Fig. 4 or other tissue models explored in earlier research [32]. In Figs.…”

“…On the microscopic scales, multi-photon microscopy continues pushing limits in high spatial resolution and researchers have been using MC for improving the penetration depth [30,31]. Aside from numerous studies using MC for processing functional near-infrared spectroscopy (fNIRS) data [18] -a macroscopic imaging technique for neural imaging, a recent study has attempted to build connections between fNIRS hemodynamic signals using MC simulations with a simplified mesh-based vessel network [32]. From these recent studies, it is strongly evident that an accurate, fast and versatile MC model could offer widespread impact towards pushing frontiers in biophotonics research.…”

A Hyperspectral Imaging System for Mapping Haemoglobin and Cytochrome-c-Oxidase Concentration Changes in the Exposed Cerebral Cortex

“…Afterwards, MBLL is applied pixel-wise (for each pixel k, l) on the attenuation values in (1) to calculate the corresponding haemodynamic and metabolic maps of Δ[HbO2], Δ[HHb] and Δ[oxCCO], for each time window Δt of all the experimental phases. Thus, for each pixel k, l of the pre-processed hypercubes the following systems of algebraic equations are set: The reference spectra for the molar extinction coefficients ε HbO2 and ε HHb of haemoglobin are taken from Matcher et al [14], [18], while the oxidised-reduced differential molar extinction coefficients ε diffCCO for CCO are calculated from data measured in vivo at UCL by J. Moody [9], [14].…”

“…The maps (for each wavelength λ) of the spatial distributions of the average total pathlength PLk,l (λ) of the detected photons on the FOV in (2) are estimated by running MC simulations using the methodology we developed and presented in Giannoni et al [14]. A high-contrast picture of the FOV, that is obtained with the imaging side of the hNIR system using broadband illumination, is used to replicate the meshed domain of the targeted region of the exposed cortex.…”

“…We previously demonstrated computationally the fitness of HSI in mapping and quantifying changes in the concentration of HbO2, HHb and oxCCO on the exposed cortex during hypoxia, using Monte Carlo (MC) simulations [14]. In the same MC studies we also proved that the use of only 8 optimallyselected NIR wavelengths in the range 780-900 nm (784, 800, 818, 835, 851, 868, 881 and 894 nm) provides minimal differences (less than 2%) in the accuracy at simultaneously resolving haemoglobin and CCO signals, compared to the 'gold standard' of 121 wavelengths used in bNIRS [14]. We now present in this work the first in vivo application of HSI to image and monitor HbO2, HHb and oxCCO in the exposed cortex of mice, using the same 8 NIR spectral bands, plus the addition of 3 visible wavelengths (600, 630 and 665 nm).…”