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Near-infrared spectroscopy (NIRS) is an established technique for measuring tissue oxygen saturation (StO 2 ), which is of high clinical value. For tissues that have layered structures, it is challenging but clinically relevant to obtain StO 2 of the different layers, e.g. brain and scalp. For this aim, we present a new method of data analysis for time-domain NIRS (TD-NIRS) and a new two-layered blood-lipid phantom. The new analysis method enables accurate determination of even large changes of the absorption coefficient (Δ µ a ) in multiple layers. By adding Δ µ a to the baseline µ a , this method provides absolute µ a and hence StO 2 in multiple layers. The method utilizes (i) changes in statistical moments of the distributions of times of flight of photons (DTOFs), (ii) an analytical solution of the diffusion equation for an N-layered medium, (iii) and the Levenberg-Marquardt algorithm (LMA) to determine Δ µ a in multiple layers from the changes in moments. The method is suitable for NIRS tissue oximetry (relying on µ a ) as well as functional NIRS (fNIRS) applications (relying on Δ µ a ). Experiments were conducted on a new phantom, which enabled us to simulate dynamic StO 2 changes in two layers for the first time. Two separate compartments, which mimic superficial and deep layers, hold blood-lipid mixtures that can be deoxygenated (using yeast) and oxygenated (by bubbling oxygen) independently. Simultaneous NIRS measurements can be performed on the two-layered medium (variable superficial layer thickness, L ), the deep (homogeneous), and/or the superficial (homogeneous). In two experiments involving ink, we increased the nominal µ a in one of two compartments from 0.05 to 0.25 cm -1 , L set to 14.5 mm. In three experiments involving blood ( L set to 12, 15, or 17 mm), we used a protocol consisting of six deoxygenation cycles. A state-of-the-art multi-wavelength TD-NIRS system measured simultaneously on the two-layered medium, as well as on the deep compartment for a reference. The new method accurately determined µ a (and hence StO 2 ) in both compartments. The method is a significant progress in overcoming the contamination from the superficial layer, which is beneficial for NIRS and fNIRS applications, and may improve the determination of StO 2 in the brain from measurements on the head. The advanced phantom may assist in the ongoing effort towards more realistic standardized performance tests in NIRS tissue oximetry. Data and MATLAB codes used in this study were made publicly available., Competing Interests: The authors declare no conflicts of interest. MW declares that he is president of the board and founder of OxyPrem AG. AL declares that he is shareholder of Brain Optics., (Published by Optica Publishing Group under the terms of the Creative Commons Attribution 4.0 License. Further distribution of this work must maintain attribution to the author(s) and the published article’s title, journal citation, and DOI.)

A novel methodology for solving the inverse problem of diffuse optics for two-layered structures is proposed to retrieve the absolute quantities of optical absorption and reduced scattering coefficients of the layers simultaneously. A liquid phantom with various optical absorption properties in the deep layer is prepared and experimentally investigated using the space-enhanced time-domain method. Monte-Carlo simulations are applied to analyze the different measurements in time domain, space domain, and by the new methodology. The deviations of retrieved values from nominal values of both layers' optical properties are simultaneously reduced to a very low extent compared to the single-domain methods. The reliability and uncertainty of the retrieval performance are also considerably improved by the new methodology. It is observed in time-domain analyses that for the deep layer the retrieval of absorption coefficient is almost not affected by the scattering properties and this kind of "deep scattering neutrality" is investigated and overcome as well., Competing Interests: The authors declare no conflicts of interest., (© 2020 Optical Society of America under the terms of the OSA Open Access Publishing Agreement.)

Time-domain optical brain imaging techniques introduce a number of different measurands for analyzing absorption changes located deep in the tissue, complicated by superficial absorption changes and noise. We implement a method that allows analysis, quantitative comparison and performance ranking of measurands under various conditions - including different values of reduced scattering coefficient, thickness of the superficial layer, and source-detector separation. Liquid phantom measurements and Monte Carlo simulations were carried out in two-layered geometry to acquire distributions of times of flight of photons and to calculate the total photon count, mean time of flight, variance, photon counts in time windows and ratios of photon counts in different time windows. Quantitative comparison of performance was based on objective metrics: relative contrast, contrast-to-noise ratio (CNR) and depth selectivity. Moreover, the product of CNR and depth selectivity was used to rank the overall performance and to determine the optimal source-detector separation for each measurand. Variance ranks the highest under all considered conditions., Competing Interests: The authors declare no conflicts of interest., (© 2020 Optical Society of America under the terms of the OSA Open Access Publishing Agreement.)

Time-domain measurements facilitate the elimination of the influence of extracerebral, systemic effects, a key problem in functional near-infrared spectroscopy (fNIRS) of the adult human brain. The analysis of measured time-of-flight distributions of photons often relies on moments or time windows. However, a systematic and quantitative characterization of the performance of these measurands is still lacking. Based on perturbation simulations for small localized absorption changes, we compared spatial sensitivity profiles and depth selectivity for moments (integral, mean time of flight and variance), photon counts in time windows and their ratios for different time windows. The influence of the instrument response function (IRF) was investigated for all measurands and for various source-detector separations. Variance exhibits the highest depth selectivity among the moments. Ratios of photon counts in different late time windows can achieve even higher selectivity. An advantage of moments is their robustness against the shape of the IRF and instrumental drifts., Competing Interests: The authors declare no conflicts of interest., (© 2020 Optical Society of America under the terms of the OSA Open Access Publishing Agreement.)

In this article we propose an implementation of the extended Kalman filter (EKF) for the retrieval of optical and geometrical properties in two-layered turbid media assuming a dynamic setting, where absorption of each layer was changed in different steps. Prior works implemented the EKF in frequency-domain with several pairs of light sources and detectors and for static parameters estimation problems. Here we explore the use of the EKF in single distance, time-domain measurements, together with a corresponding forward model. Results show good agreement between retrieved and nominal values, with rather narrow analytical credibility intervals, indicating that the recovery process has low uncertainty, especially for the absorption coefficients., Competing Interests: The authors declare that there are no conflicts of interest related to this article., (© 2019 Optical Society of America under the terms of the OSA Open Access Publishing Agreement.)

We present broadband measurements of the optical properties of tissue-mimicking solid phantoms using a single integrating sphere to measure the hemispherical reflectance and transmittance under a direct illumination at the normal incident angle. These measurements are traceable to reflectance and transmittance scales. An inversion routine using the output of the adding-doubling algorithm restricted to the reflectance and transmittance under a direct illumination was developed to produce the optical parameters of the sample along with an uncertainty budget at each wavelength. The results for two types of phantoms are compared to measurements by time-resolved approaches. The results between our method and these independent measurements agree within the estimated measurement uncertainties., Competing Interests: The authors declare that there are no conflicts of interest related to this article.

We hypothesize that combining quantitative near-infrared spectroscopy (NIRS) with established invasive techniques will enable advanced insights into renal hemodynamics and oxygenation in small animal models. We developed a NIRS technique to monitor absolute values of oxygenated and deoxygenated hemoglobin and of oxygen saturation of hemoglobin within the renal cortex of rats. This NIRS technique was combined with invasive methods to simultaneously record renal tissue oxygen tension and perfusion. The results of test procedures including occlusions of the aorta or the renal vein, hyperoxia, hypoxia, and hypercapnia demonstrated that the combined approach, by providing different but complementary information, enables a more comprehensive characterization of renal hemodynamics and oxygenation.

A multi-center study has been set up to accurately characterize the optical properties of diffusive liquid phantoms based on Intralipid and India ink at near-infrared (NIR) wavelengths. Nine research laboratories from six countries adopting different measurement techniques, instrumental set-ups, and data analysis methods determined at their best the optical properties and relative uncertainties of diffusive dilutions prepared with common samples of the two compounds. By exploiting a suitable statistical model, comprehensive reference values at three NIR wavelengths for the intrinsic absorption coefficient of India ink and the intrinsic reduced scattering coefficient of Intralipid-20% were determined with an uncertainty of about 2% or better, depending on the wavelength considered, and 1%, respectively. Even if in this study we focused on particular batches of India ink and Intralipid, the reference values determined here represent a solid and useful starting point for preparing diffusive liquid phantoms with accurately defined optical properties. Furthermore, due to the ready availability, low cost, long-term stability and batch-to-batch reproducibility of these compounds, they provide a unique fundamental tool for the calibration and performance assessment of diffuse optical spectroscopy instrumentation intended to be used in laboratory or clinical environment. Finally, the collaborative work presented here demonstrates that the accuracy level attained in this work for optical properties of diffusive phantoms is reliable.

In functional near-infrared spectroscopy (fNIRS) superficial hemodynamics can mask optical signals related to brain activity. We present a method to separate superficial and cerebral absorption changes based on the analysis of changes in moments of time-of-flight distributions and a two-layered model. The related sensitivity factors were calculated from individual optical properties. The method was validated on a two-layer liquid phantom. Absorption changes in the lower layer were retrieved with an accuracy better than 20%. The method was successfully applied to in vivo data and compared to the reconstruction of homogeneous absorption changes.

We report on the design and first in vivo tests of a novel non-contact scanning imaging system for time-domain near-infrared spectroscopy. Our system is based on a null source-detector separation approach and utilizes polarization-selective detection and a fast-gated single-photon avalanche diode to record late photons only. The in-vivo tests included the recording of hemodynamics during arm occlusion and two brain activation tasks. Localized and non-localized changes in oxy- and deoxyhemoglobin concentration were detected for motor and cognitive tasks, respectively. The tests demonstrate the feasibility of non-contact imaging of absorption changes in deeper tissues.