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.
Time-domain diffuse correlation spectroscopy (TD-DCS) is a non-invasive optical technique, which measures tissue blood flow with path-length resolution. Ideally, this technique requires a pulsed laser with an adequate illumination power, a long coherence length, and a narrow instrument response function (IRF), while available laser modules cannot satisfy all these conditions. We systematically characterized three pulsed laser sources and compared their performances using phantom and in vivo measurements. We found that each laser has the potential to be used in TD-DCS applications. Also, the effects caused by the IRF are more significant than the effect of the limited coherence length.
KEYWORDS: In vivo imaging, Single photon detectors, Superconductors, Nanowires, Spectroscopy, Signal to noise ratio, Sensors, Picosecond phenomena, Liquids, Tissues
Diffuse correlations spectroscopy (DCS) is a non-invasive optical technique that, studying the speckle intensity fluctuations of light diffused through a biological tissue, measures its microvascular blood flow. Typically, a long coherence length continuous wave source is used, which limits the possibility to resolve the photon path lengths. Recently, time-domain (TD) DCS was proposed, where a pulsed yet coherent light source is used to resolve the speckle fluctuations at different time-of-flights. Due to the constraint of single-speckle detection and time-resolved acquisition, the technique has a limited throughput which limits depth sensitivity. Here, we demonstrate TD DCS with a superconducting nanowire single-photon detector (SNSPD). The SNSPD has a high quantum efficiency and temporal resolution, while maintaining a very low background and no after-pulsing.We report results on phantom and in vivo experiments, which show the potentiality of the proposed detection system for highly accurate TD DCS experiments.
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.
Diffuse correlation spectroscopy (DCS) is an optical technique which, by studying the speckle intensity fluctuations of coherent light diffused in a turbid medium, retrieves information regarding the scatterers motion. In the case of biological tissues, the particles of interest are the red blood cells, from which is possible to measure non-invasively microvascular blood flow (BF). However, being based on a continuous-wave light source, depth discrimination is achievable only by using multiple source-detector separations. On the other hand, time-domain (TD) DCS is a novel approach which exploits a pulsed yet coherent light source to discriminate the intensity fluctuations at different photon time-of-flights. This additional information is beneficial for in vivo applications, due to the physical relationship between photon time-of-flight and mean depth penetration. TD-DCS is typically performed in the spectral range between 700 and 800 nm. Here, we explore TD-DCS in a new spectral range compared to the typical one, moving to the spectral region beyond the water absorption peak (i.e., >970 nm). We performed liquid phantom and in vivo experiments on the human muscle at a wavelength of 1000 nm. Also, the possible advantages in terms of depth sensitivity and signal-to-noise ratio are discussed.
Time-domain diffuse optics exploits near infrared light pulses diffused in turbid samples to retrieve their optical properties e.g., absorption and reduced scattering coefficients. Typically, interference effect are discarded, but speckle effects are exploited in other techniques e.g., diffuse correlation spectroscopy (DCS) to retrieve information regarding the tissue dynamics. Here, using a highly coherent Ti:Sapphire mode-locked laser and a single-mode detection fiber, we report the direct observation of temporal fluctuations in the measured distribution of time-of-flights (DTOF) curve. We study the dependence of these fluctuations on the sample dynamical properties (moving from fluid to rigid tissue-mimicking phantoms) and on the area of the detection fiber, which is directly linked to the number of collected coherence areas. Our observation agree with a time-resolved speckle pattern, and may enable the simultaneous monitoring of the tissue optical and dynamical properties.
Time-domain diffuse correlation spectroscopy (TD-DCS) is an emerging noninvasive optical technique with the potential to resolve blood flow (BF) and optical coefficients (reduced scattering and absorption) in depth. Here, we study the effects of finite temporal resolution and gate width in a realistic TD-DCS experiment. We provide a model for retrieving the BF from gated intensity autocorrelations based on the instrument response function, which allows for the use of broad time gates. This, in turn, enables a higher signal-to-noise ratio that is critical for in vivo applications. In numerical simulations, the use of the proposed model reduces the error in the estimated late gate BF from 34% to 3%. Simulations are also performed for a wide set of optical properties and source–detector separations. In a homogeneous phantom experiment, the discrepancy between later gates BF index and ungated BF index is reduced from 37% to 2%. This work not only provides a tool for data analysis but also physical insights, which can be useful for studying and optimizing the system performance.
We propose a time domain speckle contrast optical spectroscopy (SCOS) system that makes use of a gated detector and pulsed light source to measure the blood flow variations at very short, quasi-null (<3mm) source-detector separation. We present the results of a human arm cuff occlusion and a comparison with standard SCOS, highlighting that we can probe deeper into tissue, reduce probe footprint, make efficient use of the signal and decrease cost.3
Time-domain diffuse correlation spectroscopy (TD-DCS) is an emerging optical technique with the potential to resolve the blood flow (BF) in depth. The first in vivo measurements have been shown recently on humans, however improvements in terms of signal-to-noise ratio (SNR) and depth sensitivity would be beneficial for biological applications. In this contribution, we explore the possibility of in vivo TD-DCS measurements above 1000 nm, and discuss its possible advantages compared to standard wavelengths (i.e. 700-800 nm). In our experimental setup, we exploited a tunable pulsed laser source extended more to the infrared and an InGaAs photomultiplier. Here, we report the results of a cuff occlusion on the forearm of a healthy adult subject at a wavelength of 1000 nm. Compared to the same experiment at standard wavelength (785 nm), the electric-field auto-correlation functions show a slower decay rate during all the experiment (both during and after the occlusion) as expected, suggesting a higher SNR. Even longer wavelengths, for diminishing water absorption, can be obtained through optimization of the laser source and the use of more efficient detectors.
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