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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

The use of technologies still under development (Silicon PhotoMultipliers and Time-to-Digital Converter) for the upgrade of our time-resolved optical mammograph highlighted the crucial need for a thorough and progressive instrument characterization (from extensive laboratory tests on phantoms to in vivo measurements), potentially of general interest. Despite satisfying results on phantoms, in vivo tests urged an instrumental change, with the adoption of a just released high-throughput TDC to obtain high-quality breast scans (much wider scan area, better day-by-day reproducibility, improved signal quality, simpler set-up). A clinical study on monitoring of neoadjuvant chemotherapy is now ongoing at the San Raffaele Hospital, Milan.

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.

To improve non-invasively the specificity in the diagnosis of breast cancer after a positive screening mammography or doubt/suspicious ultrasound examination, the SOLUS project developed a multimodal imaging system that combines: Bmode ultrasound (US) scans (to assess morphology), Color Doppler (to visualize vascularization), shear-wave elastography (to measure stiffness), and time domain multi-wavelength diffuse optical tomography (to estimate tissue composition in terms of oxy- and deoxy-hemoglobin, lipid, water, and collagen concentrations). The multimodal probe arranges 8 innovative photonic modules (optodes) around the US transducer, providing capability for optical tomographic reconstruction. For more accurate estimate of lesion composition, US-assessed morphological priors can be used to guide the optical reconstructions. Each optode comprises: i) 8 picosecond pulsed laser diodes with different wavelengths, covering a wide spectral range (635-1064 nm) for good probing of the different tissue constituents; ii) a large-area (variable, up to 8.6 mm2 ) fast-gated digital Silicon Photomultiplier; iii) the acquisition electronics to record the distribution of time-of-flight of the re-emitted photons. The optode is the basic element of the optical part of the system, but is also a stand-alone, ultra-compact (about 4 cm3 ) device for time domain multi-wavelength diffuse optics, with potential application in various fields.

To improve the specificity of breast cancer diagnosis SOLUS combines ultrasound, shear-wave elastography and time-domain diffuse optical tomography in a multimodal imaging system. An innovative compact device for time-domain multi-wavelength diffuse optics was also developed.

A time-domain functional near-infrared spectroscopy system with probe-hosted large-area detector capable of a throughput of 30 million of counts per second is presented and validated on phantoms and in vivo.

Two main bottlenecks prevent time-domain diffuse optics instruments to reach their maximum performances, namely the limited light harvesting capability of the detection chain and the bounded data throughput of the timing electronics. In this work, for the first time to our knowledge, we overcome both those limitations using a probe-hosted large area silicon photomultiplier detector coupled to high-throughput timing electronics. The system performances were assessed based on international protocols for diffuse optical imagers showing better figures with respect to a state-of-the-art device. As a first step towards applications, proof-of-principle in-vivo brain activation measurements demonstrated superior signal-to-noise ratio as compared to current technologies.

A multi-laboratory exercise, involving 29 diffuse optical instruments, aimed at performance assessment of diffuse optics instruments on standardized protocols is presented. The overarching methodology and future actions will also be discussed.

Time domain Diffuse Optical Tomography (TD-DOT) non-invasively probes the optical proprieties of biological tissue. These can be related to changes in tissue composition, thus making TD-DOT potentially valuable for cancer imaging. In particular, an application of interest is therapy monitoring for breast cancer. Thus, we developed a software tool for multiwavelength TD-DOT in reflectance geometry. While the use of multiple wavelengths probes the main components of the breast, the chosen geometry offers the advantage of linking the photon flight time to the investigated depth. We validated the tool on silicon phantoms embedding an absorbing inclusion to simulate a malignant lesion in breast tissue. Also, we exploited the a priori information on position and geometry of the inclusion by using a morphological prior constraint. The results show a good localization of the depth of inclusion but a reduced quantification. When the morphological constraint is used, though, the localization improves dramatically, also reducing surface artifacts and improving quantification as well. Still, there is room for improvement in the quantification of the “lesion” properties.

Time Domain Diffuse Optical Tomography (TD-DOT) performed at multiple wavelengths can be used to non-invasively probe tissue composition. Then, tissue composition can be related to breast tissue and lesion type. Thus, TD-DOT could be used for therapy monitoring for breast cancer. We developed a software tool for multi-wavelength TD-DOT and performed a validation on meat phantoms to mimic tissue heterogeneity. An inclusion of different meat was exploited to mimic the presence of a lesion in the breast. Results show good localization of the inclusion, but poor quantification of the reconstructed breast composition. The use of a morphological prior constraint, providing information on inclusion geometry and position, significantly improves both localization and composition estimate.

Time Domain Diffuse Optical Tomography (TD-DOT) at different wavelengths can be used to retrieve tissue reconstructing the components of a two-region system starting from self-normalized time-dependent measurements performed in reflectivity geometry over multiple wavelengths. The proposed method performs a fit of a limited number of tissues parameters providing a good quantification of the components’ concentrations by applying a FEM-based Diffusion approximation of the TD-DOT direct model.

Time Domain Diffuse Optical Tomography (TD-DOT) enables a full 3D reconstruction of the optical properties of tissue, and could be used for non-invasive and cost-effective in-depth body exploration (e.g., thyroid and breast imaging). Performance quantification is crucial for comparing results coming from different implementations of this technique. A general-purpose simulation platform for TD-DOT clinical systems was developed with a focus on performance assessment through meaningful figures of merit. The platform was employed for assessing the feasibility and characterizing a compact hand-held probe for breast imaging and characterization in reflectance geometry. Important parameters such as hardware gating of the detector, photon count rate and inclusion position were investigated. Results indicate a reduced error (&lt, 10%) on the absorption coefficient quantification of a simulated inclusion up to 2-cm depth if a photon count rate &ge, 106 counts per second is used along with a good localization (error &lt, 1 mm down to 25 mm-depth).

A recent upgrade of the time domain multi-wavelength optical mammograph developed by Politecnico di Milano achieved good performance in laboratory tests [Biomed. Opt. Express 9, 755 (2018).10.1364/BOE.9.000755]. However, it proved unsatisfactory when in vivo measurements were finally performed. That led to a further upgrade, including the replacement of the time-to-digital converter with a new model, and the related set-up changes. The new instrument version offers improved laboratory performance (as assessed through established protocols: BIP and MEDPHOT) and good in vivo performance (extension of the scanned breast area, repeatability, consistency of estimated tissue composition with physiology). Besides introducing the new set-up and detailing its laboratory and in vivo performance, we highlight the importance of systematic in vivo testing before entering clinical trials.

Fast time-gated single-photon detectors demonstrated high depth sensitivity in the detection of localized absorption perturbations inside scattering media, but their use for in vivo clinical applications—such as functional imaging of brain activation—was impaired by their small ( < 0.04 m m 2 ) active area. Here, we demonstrate, both on phantoms and in vivo, the performance of a fast-gated digital silicon photomultiplier (SiPM) that features an overall active area of 8.6 m m 2 , overcoming the photon collection capability of established time-gated single-pixel detectors by orders of magnitude, enabling deep investigations within scattering media and high signal-to-noise ratios at late photon arrival times.

A novel detection chain, based on 8 Silicon Photomultipliers (forming a wide-area custom-made detection probe) and on a time-to-digital converter, was developed to improve the signal level in multi-wavelength (635-1060 nm) time domain optical mammography. The performances of individual components and of the overall chain were assessed using established protocols (BIP and MEDPHOT). The photon detection efficiency was improved by up to 3 orders of magnitude, and the maximum count rate level was increased by a factor of 10 when compared to the previous system, based on photomultiplier tubes and conventional time-correlated single-photon counting boards. In the estimate of optical parameters, the novel detection chain provides performances comparable to the previous system, widely validated in clinics, but with higher signal level, higher robustness, and at a lower price per channel, thus targeting important requirements for clinical applications. (C) 2018 Optical Society of America under the terms of the OSA Open Access Publishing Agreement

Quantitative Time-Domain Diffuse Optical Tomography simulations are systematically performed through a developed tool. Reflectance geometry and fixed sources and detectors provide 4 mm localization error and 80% accuracy on reconstructed absorption in depth (2 cm).

To enhance photon harvesting and improve data quality, an 8-channel compact SiPM probe and TDC acquisition replace PMTs and TCSPC boards in a time-resolved optical mammograph still providing similar performances for optical properties estimation.

An 8-channel Silicon PhotoMultiplier (SiPM) probe and Time-to-Digital-Converter (TDC) realize a higher-throughput, cheaper and compact detection chain for time-resolved optical mammography than photomultiplier tubes (PMTs) and Time Correlated Single Photon Counting (TCSPC) boards, providing comparable estimate of optical properties with increased optical responsivity.

An 8-channel Silicon Photomultiplier probe and a Time-toDigital Converter are used to build a higher-throughput, cheaper and compact detection chain for time-resolved optical mammography as compared with conventional PhotoMultiplier Tubes and Time-Correlated Single-Photon Counting boards, still providing comparable performance in the estimation of optical properties, but with higher optical responsivity.

In the last decade, multimodal imaging raised increasing interest to overcome the limits of single techniques and improve the diagnostic potential during the same examination. This gives rise to the need for phantoms and procedures for standardizing performance assessment of the multimodal instrument. The SOLUS1 project adopts this methodology with the aim to build a multimodal instrument (based on diffuse optics -DO-, shear wave elastography -SWE-, and ultrasound imaging -US-) to increase the specificity of breast cancer diagnosis. Here we propose a long-lasting phantom based on silicone material (easier to manipulate with respect to other material for bimodal phantom such as polyvinyl alcohol, PVA) and suitable for both diffuse optical imaging/tomography and ultrasound acquisitions, designed within the SOLUS project. To achieve this goal, we explored a new silicone material for diffuse optics and ultrasound (Ecoflex 00-30), creating a new fabrication recipe and demonstrating its suitability for multimodal imaging if coupled to another silicone elastomer (Sylgard 184), featuring similar optical and acoustical performances except for the echogenicity. The main advantage of the proposed phantom is the capability of tuning independently optical and acoustical performances, thus allowing one to mimic a wide range of clinical scenarios.