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Significance: Multi-laboratory initiatives are essential in performance assessment and standardization-crucial for bringing biophotonics to mature clinical use-to establish protocols and develop reference tissue phantoms that all will allow universal instrument comparison., Aim: The largest multi-laboratory comparison of performance assessment in near-infrared diffuse optics is presented, involving 28 instruments and 12 institutions on a total of eight experiments based on three consolidated protocols (BIP, MEDPHOT, and NEUROPT) as implemented on three kits of tissue phantoms. A total of 20 synthetic indicators were extracted from the dataset, some of them defined here anew., Approach: The exercise stems from the Innovative Training Network BitMap funded by the European Commission and expanded to include other European laboratories. A large variety of diffuse optics instruments were considered, based on different approaches (time domain/frequency domain/continuous wave), at various stages of maturity and designed for different applications (e.g., oximetry, spectroscopy, and imaging)., Results: This study highlights a substantial difference in hardware performances (e.g., nine decades in responsivity, four decades in dark count rate, and one decade in temporal resolution). Agreement in the estimates of homogeneous optical properties was within 12% of the median value for half of the systems, with a temporal stability of <5  %   over 1 h, and day-to-day reproducibility of <3  %  . Other tests encompassed linearity, crosstalk, uncertainty, and detection of optical inhomogeneities., Conclusions: This extensive multi-laboratory exercise provides a detailed assessment of near-infrared Diffuse optical instruments and can be used for reference grading. The dataset-available soon in an open data repository-can be evaluated in multiple ways, for instance, to compare different analysis tools or study the impact of hardware implementations.

A mechanically switchable solid inhomogeneous phantom simulating localized absorption changes was developed and characterized. The homogeneous host phantom was made of epoxy resin with black toner and titanium dioxide particles added as absorbing and scattering components, respectively. A cylindrical rod, movable along a hole in the block and made of the same material, has a black polyvinyl chloride cylinder embedded in its center. By varying the volume and position of the black inclusion, absorption perturbations can be generated over a large range of magnitudes. The phantom has been characterized by various time-domain diffuse optics instruments in terms of absorption and scattering spectra, transmittance images, and reflectance contrast. Addressing a major application of the phantom for performance characterization for functional near-infrared spectroscopy of the brain, the contrast was measured in reflectance mode while black cylinders of volumes from ≈20  mm3 to ≈270  mm3 were moved in lateral and depth directions, respectively. The new type of solid inhomogeneous phantom is expected to become a useful tool for routine quality check of clinical instruments or implementation of industrial standards provided an experimental characterization of the phantom is performed in advance.

In this work, we have tested the optimal estimation (OE) algorithm for the reconstruction of the optical properties of a two-layered liquid tissue phantom from time-resolved single-distance measurements. The OE allows a priori information, in particular on the range of variation of fit parameters, to be included. The purpose of the present investigations was to compare the performance of OE with the Levenberg–Marquardt method for a geometry and real experimental conditions typically used to reconstruct the optical properties of biological tissues such as muscle and brain. The absorption coefficient of the layers was varied in a range of values typical for biological tissues. The reconstructions performed demonstrate the substantial improvements achievable with the OE provided a priori information is available. We note the extreme reliability, robustness, and accuracy of the retrieved absorption coefficient of the second layer obtained with the OE that was found for up to six fit parameters, with an error in the retrieved values of less than 10%. A priori information on fit parameters and fixed forward model parameters clearly improves robustness and accuracy of the inversion procedure.

Performance assessment of instruments devised for clinical applications is of key importance for validation and quality assurance. Two new protocols were developed and applied to facilitate the design and optimization of instruments for time-domain optical brain imaging within the European project nEUROPt. Here, we present the "Basic Instrumental Performance" protocol for direct measurement of relevant characteristics. Two tests are discussed in detail. First, the responsivity of the detection system is a measure of the overall efficiency to detect light emerging from tissue. For the related test, dedicated solid slab phantoms were developed and quantitatively spectrally characterized to provide sources of known radiance with nearly Lambertian angular characteristics. The responsivity of four time-domain optical brain imagers was found to be of the order of 0.1 m² sr. The relevance of the responsivity measure is demonstrated by simulations of diffuse reflectance as a function of source-detector separation and optical properties. Second, the temporal instrument response function (IRF) is a critically important factor in determining the performance of time-domain systems. Measurements of the IRF for various instruments were combined with simulations to illustrate the impact of the width and shape of the IRF on contrast for a deep absorption change mimicking brain activation.

The nEUROPt protocol is one of two new protocols developed within the European project nEUROPt to characterize the performances of time-domain systems for optical imaging of the brain. It was applied in joint measurement campaigns to compare the various instruments and to assess the impact of technical improvements. This protocol addresses the characteristic of optical brain imaging to detect, localize, and quantify absorption changes in the brain. It was implemented with two types of inhomogeneous liquid phantoms based on Intralipid and India ink with well-defined optical properties. First, small black inclusions were used to mimic localized changes of the absorption coefficient. The position of the inclusions was varied in depth and lateral direction to investigate contrast and spatial resolution. Second, two-layered liquid phantoms with variable absorption coefficients were employed to study the quantification of layer-wide changes and, in particular, to determine depth selectivity, i.e., the ratio of sensitivities for deep and superficial absorption changes. We introduce the tests of the nEUROPt protocol and present examples of results obtained with different instruments and methods of data analysis. This protocol could be a useful step toward performance tests for future standards in diffuse optical imaging.

We present the experimental implementation and validation of a phantom for diffuse optical imaging based on totally absorbing objects for which, in the previous paper [J. Biomed. Opt.18(6), 066014, (2013)], we have provided the basic theory. Totally absorbing objects have been manufactured as black polyvinyl chloride (PVC) cylinders and the phantom is a water dilution of intralipid-20% as the diffusive medium and India ink as the absorber, filled into a black scattering cell made of PVC. By means of time-domain measurements and of Monte Carlo simulations, we have shown the reliability, the accuracy, and the robustness of such a phantom in mimicking typical absorbing perturbations of diffuse optical imaging. In particular, we show that such a phantom can be used to generate any absorption perturbation by changing the volume and position of the totally absorbing inclusion.

The design of inhomogeneous phantoms for diffuse optical imaging purposes using totally absorbing objects embedded in a diffusive medium is proposed and validated. From time-resolved and continuous-wave Monte Carlo simulations, it is shown that a given or desired perturbation strength caused by a realistic absorbing inhomogeneity of a certain absorption and volume can be approximately mimicked by a small totally absorbing object of a so-called equivalent black volume (equivalence relation). This concept can be useful in two ways. First, it can be exploited to design realistic inhomogeneous phantoms with different perturbation strengths simply using a set of black objects with different volumes. Further, it permits one to grade physiological or pathological changes on a reproducible scale of perturbation strengths given as equivalent black volumes, thus facilitating the performance assessment of clinical instruments. A set of plots and interpolating functions to derive the equivalent black volume corresponding to a given absorption change is provided. The application of the equivalent black volume concept for grading different optical perturbations is demonstrated for some examples.

Non-invasive detection of fluorescence from the optical tracer indocyanine green is feasible in the adult human brain when employing a time-domain technique with picosecond resolution. A fluorescence-based assessment may offer higher signal-to-noise ratio when compared to bolus tracking relying on changes in time-resolved diffuse reflectance. The essential challenge is to discriminate the fluorescence originating from the brain from contamination by extracerebral fluorescence and hence to reconstruct the bolus kinetics; however, a method to reliably perform the necessary separation is missing. We present a novel approach for the decomposition of the fluorescence contributions from the two tissue compartments. The corresponding sensitivity functions pertaining to the brain and to the extracerebral compartment are directly derived from the in-vivo measurement. This is achieved by assuming that during the initial and the late phase of bolus transit the fluorescence signal originates largely from one of the compartments. Solving the system of linear equations allows one to approximate time courses of a bolus for each compartment. We applied this method to repetitive measurements on two healthy subjects with an overall 34 boluses. A reconstruction of the bolus kinetics was possible in 62% of all cases.

Time-resolved near-infrared spectroscopy allows for depth-selective determination of absorption changes in the adult human head that facilitates separation between cerebral and extra-cerebral responses to brain activation. The aim of the present work is to analyze which combinations of moments of measured distributions of times of flight (DTOF) of photons and source-detector separations are optimal for the reconstruction of absorption changes in a two-layered tissue model corresponding to extra- and intra-cerebral compartments. To this end we calculated the standard deviations of the derived absorption changes in both layers by considering photon noise and a linear relation between the absorption changes and the DTOF moments. The results show that the standard deviation of the absorption change in the deeper (superficial) layer increases (decreases) with the thickness of the superficial layer. It is confirmed that for the deeper layer the use of higher moments, in particular the variance of the DTOF, leads to an improvement. For example, when measurements at four different source-detector separations between 8 and 35 mm are available and a realistic thickness of the upper layer of 12 mm is assumed, the inclusion of the change in mean time of flight, in addition to the change in attenuation, leads to a reduction of the standard deviation of the absorption change in the deeper tissue layer by a factor of 2.5. A reduction by another 4% can be achieved by additionally including the change in variance.

We present results of a clinical study on bedside perfusion monitoring of the human brain by optical bolus tracking. We measure the kinetics of the contrast agent indocyanine green using time-domain near-IR spectroscopy (tdNIRS) in 10 patients suffering from acute unilateral ischemic stroke. In all patients, a delay of the bolus over the affected when compared to the unaffected hemisphere is found (mean: 1.5 s, range: 0.2 s to 5.2 s). A portable time-domain near-IR reflectometer is optimized and approved for clinical studies. Data analysis based on statistical moments of time-of-flight distributions of diffusely reflected photons enables high sensitivity to intracerebral changes in bolus kinetics. Since the second centralized moment, variance, is preferentially sensitive to deep absorption changes, it provides a suitable representation of the cerebral signals relevant for perfusion monitoring in stroke. We show that variance-based bolus tracking is also less susceptible to motion artifacts, which often occur in severely affected patients. We present data that clearly manifest the applicability of the tdNIRS approach to assess cerebral perfusion in acute stroke patients at the bedside. This may be of high relevance to its introduction as a monitoring tool on stroke units.

Limitations in the accuracy of measurements of optical properties (absorption and scattering coefficients) of strongly scattering media that are due to temporal dispersion inside the detection fibers of a time-of-flight setup were investigated for a tissue-like phantom. It is shown that the absorption and reduced scattering coefficients may be overestimated by up to 90% (depending on length and numerical aperture of the fibers) if the instrumental response measurements for the setup are performed by direct illumination of the tip of the detection fibers with collimated short laser pulses. However, the accuracy can be improved significantly if a thin layer of scattering media is used in front of the detection fibers during the response measurements. The relevance of the investigated dispersion effects is discussed with respect to frequency-domain measurements as well., ((c) 2003 Society of Photo-Optical Instrumentation Engineers.)

For the first time we use a random walk methodology based on time-dependent contrast functions to quantify the optical properties of breast tumors (invasive ductal carcinoma) of two patients. Previously this theoretical approach was successfully applied for analysis of embedded objects in several phantoms. Data analysis was performed on distributions of times of flight for photons transmitted through the breast which were recorded in vivo using a time-domain scanning mammograph at 670 and 785 nm. The size of the tumors, their optical properties, and those of the surrounding tissue were reconstructed at both wavelengths. The tumors showed increased absorption and scattering. From the absorption coefficients at both wavelengths blood oxygen saturation was estimated for the tumors and the surrounding tissue.

Optical mammography with near-infrared (NIR) light using time-domain, frequency-domain, or continuous-wave techniques is a novel imaging modality to locate human breast tumors. By investigating excised specimens of normal and diseased mamma tissue we were able to demonstrate that differences in their scattering properties are a poor predictive parameter for normal and diseased mamma tissue. This paper describes the application of a NIR dye to improve the differentiation between breast tumors and normal tissue in a rat model. The NIR dye furnished a high tumor-to-tissue contrast ratio (6:1) in fluorescence images. Furthermore, this dye was used to develop liquid scattering phantoms with absorbing and fluorescent inhomogeneities. Using frequency-domain and time-domain instrumentation these inhomogeneities were localized at sufficient contrast by their increased absorption and fluorescence. Contrast between inhomogeneities and surrounding medium could be improved by combining fluorescence and transmittance images.