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.
Performance assessment and standardization are indispensable for instruments of clinical relevance in general and clinical instrumentation based on photon migration/diffuse optics in particular. In this direction, a multi-laboratory exercise was initiated with the aim of assessing and comparing their performances. 29 diffuse optical instruments belonging to 11 partner institutions of a European level Marie Curie Consortium BitMap1 were considered for this exercise. The enrolled instruments covered different approaches (continuous wave, CW; frequency domain, FD; time domain, TD and spatial frequency domain imaging, SFDI) and applications (e.g. mammography, oximetry, functional imaging, tissue spectroscopy). 10 different tests from 3 well-accepted protocols, namely, the MEDPHOT2 , the BIP3 , and the nEUROPt4 protocols were chosen for the exercise and the necessary phantoms kits were circulated across labs and institutions enrolled in the study. A brief outline of the methodology of the exercise is presented here. Mainly, the design of some of the synthetic descriptors, (single numeric values used to summarize the result of a test and facilitate comparison between instruments) for some of the tests will be discussed.. Future actions of the exercise aim at deploying these measurements onto an open data repository and investigating common analysis tools for the whole dataset.
Time-domain fNIRS facilitates the elimination of the influence of extracerebral, systemic effects on measured signals since it contains time-of-flight information that is related to the penetration depth. Employing perturbation and MonteCarlo simulations, we quantitatively characterized and compared the performance of measurands based on moments and time windows of time-of-flight distributions. We extend our analysis to investigate whether higher moments and MellinLaplace (ML) moments promise improvements in performance. The comparison is based on spatial sensitivity profiles as well as metrics for relative contrast, contrast-to-noise ratio (CNR), depth selectivity, and the product of CNR and depth selectivity for layered absorption changes. The influence of reduced scattering coefficient, thickness of the superficial layer, and source-detector distance was analyzed. The third central moment performs similarly to variance and is worth considering for data analyzes. Higher order ML moments perform similarly to time windows and they likewise provide variable depth selectivity.
We developed refined methods for time-domain measurements of the optical properties of solid homogeneous turbid phantoms. Employing a reliable time-domain reference setup with a stable, narrow, and clean instrument response function and GPU-based Monte-Carlo fitting, 1% accuracy for optical properties seems realistic. An alternative space-enhanced time-domain method that combines spatially resolved amplitude with a time-domain measurement effectively reduced the crosstalk between absorption and scattering. Besides physical phantoms, we explored and characterized a digital phantom that mimics arbitrary time-of-flight distributions via time-dependent attenuation employing a spatial light modulator and a dedicated multi-fiber delay unit. We discuss potential applications in performance tests.
Open Data philosophy is becoming more popular among scientists. Open Data approach aims to transform science by making high-quality and well-documented scientific data open to everybody in order to promote collaboration and transparency. In diffuse optical and near-infrared spectroscopy community, a large measurement dataset collected with state-of-the-art instrumentation applied on well-defined phantoms is still missing. Within that context, several European labs from BitMap network1 have collected diffuse optical data on standard phantoms involving the largest set of diffuse optics instruments published until now. In this work, we present a running project on the open dataset and associated reporting tools.
Performance assessment of instruments is a growing demand in the diffuse optics community and there is a definite need to get together to address this issue. Within the EU Network BITMAP1, we initiated a campaign for the performance evaluation of 10 diffuse optical instrumentation from 7 partner institutions adopting a set of 3 well accepted, standardized protocols. A preliminary analysis of the outcome along with future perspectives will be presented.
A multivariate method integrating time-domain and space-domain techniques of near-infrared spectroscopy is proposed for simultaneously retrieving the absolute quantities of optical scattering and absorption properties in tissues. The concept is theoretically demonstrated by Monte-Carlo simulations in the homogenous case, and then applied on twolayer liquid phantoms. The deviations from nominal values are typically less than 6% for absorption coefficients in both layers
Monte-Carlo (MC) simulations of photon migration are frequently used to build lookup tables modelling experimental results in Near-Infrared Spectroscopy. The optical properties of samples are inferred by minimizing χ²-deviation between MC model and experiment. Even for long MC simulations these lookup tables contain Poisson noise especially at high absorption or large source-detector separation. In these regimes the noise can cause the gradient of χ² to become discontinuous and complex, hindering retrieval of optical properties. Our simulation generates a large histogram of different but strongly correlated signals, differing in remission position, photon arrival time and acceptance angle. We apply singular value decomposition (SVD) to derive a low-rank-approximation of the lookup table. SVD helps us to harness the correlated signals, while rejecting uncorrelated noise. We found this approach to reduce noise and improve smoothness of χ²-planes, while preserving all features of the simulations exceeding noise-level. To enforce the smoothness of the χ²-planes we removed remaining noise in the singular vectors by a Savitzky-Golay-filtering. In contrast to the filtering of the whole high-dimensional lookup table, smoothing of a few singular vectors can be done in a mild, supervised way. As an additional benefit, the low rank approximation dramatically reduces the amount of memory needed to handle the table. This became especially important when treating lookup tables of high dimensionality created in multilayer simulations. Furthermore evaluation of interpolated MC-curves for intermediate optical properties and detector positions is simplified since it can be performed on the few singular vectors instead of the whole table.
In the clinically relevant field of tissue oximetry, there is an urgent need to develop phantom-based methods for validation. Physical phantom approaches based on solid or liquid turbid media containing hemoglobin with variable oxygenation have limited capabilities to represent real tissues regarding optical properties, structure and variability. Digital phantoms are an alternative with high flexibility. Rather than physically simulating the process of light propagation, they provide the detector with light signals mimicking the signals detected in vivo. We present a technique to produce digital phantoms for time-domain diffuse optical spectroscopy that mimic arbitrary photon time-of-flight distributions (DTOFs) by creating a time-dependent attenuation. The setup contains a spatial light modulator (SLM) and a set of optical fibers of different lengths corresponding to a stepwise delay. The light pulse entering the arrangement is spatially dispersed and illuminates the SLM which controls the intensity at each pixel. The SLM array is imaged onto the entrance faces of the delay fibers. The amount of photons received by each individual fiber can be adjusted. Finally, the light transmitted through all fibers are combined and fed to the detector of the timedomain instrument under test. In this way, DTOFs of any desired shape can be obtained. For first proof-of-principle experiments to demonstrate the general feasibility of the concept we used a liquid-crystal SLM and a set of four graded-index fibers differing in length by about 100 mm. The tests were performed with a timedomain instrument based on time-correlated single photon counting, with picosecond diode and supercontinuum laser sources and a single-photon avalanche diode as well as a hybrid photomultiplier as detectors. This large separation in fiber lengths allowed the performance regarding amplitude and temporal shape to be assessed for each delay independently. The generation of arbitrary DTOFs was simulated by realizing various patterns of target amplitudes. Temporal position and width of the measured pulse profiles for all fibers were in agreement with the expectations. Amplitude linearity was reasonable while the contrast between highest and lowest amplitude values was not yet satisfactory. Steps of further development are discussed.
Diffuse materials that approximate the optical properties of human tissue are commonly used as phantoms. In order to use the phantoms in a manner that provides consistent results relative to independent measurements, the optical properties need to be tied to a physics based scale. Such a scale is needed for volume scattering of diffuse materials and this is currently being addressed by the development of a sphere based optical scattering reference instrument at the National Institute of Standards and Technology (NIST). Previous work towards that goal was constrained to the use of several laser lines at discrete wavelengths. Current work has expanded the spectral range for contiguous coverage. Here we report measurement results of the optical properties of solid phantoms, using two different base materials, acquired using NISTs diffuse optical properties reference instrument with visible or near infrared broadband illumination. The measurements of diffuse hemispherical reflectance and transmittance are analyzed using a custom inversion algorithm of the adding-doubling routine, and the expanded uncertainties on the results are provided. The broadband diffuse optical properties measured with the improved system agree to within the estimated uncertainty of the discrete measurements from two other institutes using alternative methods. This work expands the capabilities of the facility and can provide services for a wider range of applications.
We report on a procedure to build and characterize solid tissue-mimicking phantoms of polydimethylsiloxane (PDMS) polymers. Controlled inclusion of light scattering titanium dioxide (TiO2) nanoparticles enables the creation of phantoms having tunable light scattering properties with reduced scattering coefficients consistent across different measurement platforms including an integrating sphere and a time-resolved diffuse optical spectroscopic system. Backscatter confocal microscopy is also used to characterize the shape and distribution of included TiO2 particles. The double integrating sphere and time-resolved diffuse spectroscopy were used to measure the reduced scattering coefficients of the phantoms. The results across different systems are in good agreement, suggesting that the PDMS/TiO2 composite is a promising tissue-mimicking material for developing standards useful to validate measurements by different devices for multiplatform and multi-laboratory tests.
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