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.
KEYWORDS: Monte Carlo methods, Diffuse optical tomography, Sensors, Near infrared spectroscopy, Spectroscopy, Oxygen, Injuries, Hybrid optics, Heart, Head
We present a simulation study on the design of a multi-modal high-density hybrid diffuse optical tomographic probe for monitoring infants with congenital heart disease (CHD) before, during, and after surgery. Different probe designs are evaluated based on the signal distribution and sensitivity profile generated using a Monte Carlo-based simulation toolbox. An optimal design was chosen after several iterations starting from the initial design. To cover a wide region of interest, this unit design was extended in a modular fashion, while respecting mechanical restrictions as well as the need for dense distribution of sources and detectors.
Time domain diffuse optics (TD-DO) relies on the injection of ps laser pulses and on the collection of the arrival times of scattered photons. To reach the ultimate limits of the technique (allowing to investigate even structures at depth <5 cm), a large area detector is needed. To this extent, we realized and present a new silicon photomultiplier featuring a 1 cm2 area. To the best of our knowledge, it represents the largest detector ever proposed for TD-DO and shows a light harvesting capability which is more than 1 decade larger than the state-of-the-art technology system. To assess its suitability for TDDO measurements, we tested the detector with several procedures from shared protocols (BIP, nEUROPt and MEDPHOT). However, the light harvesting capability of a detector with large area can be proficiently exploited only if coupled to timing electronics working in sustained count-rate CR (i.e., well above the single photon statistics). For this reason, we study the possibility to work in a regime where (even more than) one photon per laser pulse is detected (i.e., more than 100% laser repetition rate) exploiting in-silico technology. The results show that the possibility to use sustained count-rate represents a dramatic improvement in the number of photons detected with respect to current approaches (where count-rate of 1-5% of the laser repetition rate are used) without significant losses in the measurement accuracy. This represents a new horizon for TD-DO measurements, opening the way to new applications (e.g., optical investigation of the lung or monitoring of fast dynamics never studied before).
Large-area detectors for time-domain diffuse optics are increasingly available, with enormous gain in collected light intensity. Pile-up distortion is nowadays the main limit, here studied to anticipate the possibility of a new working modality.
KEYWORDS: Sensors, Optical properties, In vivo imaging, Diffuse optical imaging, Signal detection, Light harvesting, Absorption, Silicon, Radiography, Radio optics
We present the largest detectors for time-domain diffuse optics, showing superior performances in depth penetration and light-harvesting capability. In-vivo measurements demonstrate their potentialities for futuristic disruptive applications such as optical radiography.
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.
In this paper we present the ex-vivo characterization of a full-custom made multi-wavelength, two channel Time-Resolved Spectroscopy (TRS) module developed with the aim of being integrated in to a multi-modal spectroscopic device. This module overcomes all the main drawbacks of systems based on time-domain techniques such as high complexity and bulkiness while guaranteeing performances comparable to expensive state-of-the-art available devices. Each subcomponent of the module has been tailored and optimized to meet all the above-mentioned requirements. In order to assess and translate the performances of these tools for effective clinical use, we characterized the system following the guidelines of common standardization protocols. By following MEDPHOT guidelines, the linearity and accuracy in retrieving absolute values of absorption and scattering coefficients were determined by means of measurements on homogeneous phantoms. Finally, by means of a mechanically switchable solid inhomogeneous phantom (developed under the nEUROPT project) we simulated the clinical problem of detecting and localizing an absorption perturbation in a homogeneous background with broad applications such as detection of cancer lesions, thyroid, etc.
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.
We present here a novel time-domain diffuse optical detection chain consisting of a large area Silicon PhotoMultipliers (SiPM) coupled to a high count-rate timing electronics (TimeHarp 260 PICO) to achieve sustainable count-rates up to 10 Mcps without significant distortions to the distribution of time-of-flight (DTOF). Thanks to the large area of the detector (9 mm2) and the possibility to directly place it in contact with the sample (thus achieving a numerical aperture close to unity), the photon collection efficiency of the proposed detection chain is almost two orders of magnitude higher than traditional fiber-mounted PMT-based systems. This allows the detection also of the few late photons coming from deeper layers at short acquisition times, thus improving the robustness of the detection of localized inhomogeneities. We then demonstrate that, despite the high dark count rate of the detector, it is possible to reliably extract the optical properties of calibrated phantoms, with proper linearity and accuracy. We also explore the capability of the new detection chain for detecting brain activations. This work opens up the possibility of ultimate performance in terms of high signal and photon throughput, with compact, low cost, relatively simple front-end electronics detector coupled to innovative timing electronics, with exciting opportunities to expand it to tomographic applications.
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.
We present a new full-custom instrument for time-domain diffuse optical spectroscopy developed within Horizon 2020 LUCA (Laser and Ultrasound Co-Analyzer for thyroid nodules) project. It features eight different picosecond diode lasers (in the 635 - 1050 nm range), two 1.3 × 1.3 mm2 active-area SiPMs (Silicon PhotoMultipliers) working in single-photon mode and two 10 ps resolution time-to-digital converters. A custom FPGA-based control board manages the instrument and communicates with an external computer via USB connection. The instrument proved state-of-the-art performance: an instrument response function narrower than 160 ps (fullwidth at half-maximum), a long-term measurement stability better than 1%, and an output average optical power higher than 1 mW at 40 MHz. The instrument has been validated with phantom measurements.
Light is a powerful non-invasive tool that can be exploited to probe highly scattering media like biological tissues for different purposes, from the detection of brain activity to the characterization of cancer lesions. In the last decade, timedomain diffuse optics (TDDO) systems demonstrated improved sensitivity when using time-gated acquisition chains and short source-detector separations (ρ), both theoretically and experimentally. However, the sensitivity to localized absorption changes buried inside a diffusive medium strongly depends on many parameters such as: SDS, laser power, delay and width of the gating window, absorption and scattering properties of the medium, instrument response function (IRF) shape, etc. In particular, relevant effects due to slow tails in the IRF were noticed, with detrimental effects on performances. We present simulated experimental results based on the diffusion approximation of the Radiative Transfer Equation and the perturbation theory subjected to the Born approximation. To quantify the system sensitivity to deep (few cm) and localized absorption perturbations, we exploited contrast and contrast-to-noise ratio (CNR), which are internationally agreed on standardized figures of merit. The purpose of this study is to determine which parameters have the greatest impact on these figures of merit, thus also providing a range of best operative conditions. The study is composed by two main stages: the former is a comparison between simulations and measurements on tissue-mimicking phantom, while the latter is a broad simulation study in which all relevant parameters are tuned to determine optimal measurement conditions. This study essentially demonstrates that under the influence of the slow tails in the IRF, the use of a small SDS no longer corresponds to optimal contrast and CNR. This work sets the ground for future studies with next-generation of TDDO components, presently under development, providing useful hints on relevant features to which one should take care when designing TDDO components.
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