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OBJECTIVE: Diffuse correlation spectroscopy (DCS) is an optical technique that allows for the non-invasive measurement of blood flow. Recent work has shown that utilizing longer wavelengths beyond the traditional NIR range provides a significant improvement to signal-to-noise ratio (SNR). However, current detectors both sensitive to longer wavelengths and suitable for clinical applications (InGaAs/InP SPADs) suffer from suboptimal afterpulsing and dark noise characteristics. To overcome these barriers, we introduce a cross correlation method to more accurately recover blood flow information using InGaAs/InP SPADs. METHODS: Two InGaAs/InP SPAD detectors were used for during in vitro and in vivo DCS measurements. Cross correlation of the photon streams from each detector was performed to calculate the correlation function. Detector operating parameters were varied to determine parameters which maximized measurement SNR. State-space modeling was performed to determine the detector characteristics at each operating point. RESULTS: Evaluation of detector characteristics was performed across the range of operating conditions. Modeling the effects of the detector noise on the correlation function provided a method to correct the distortion of the correlation curve, yielding accurate recovery of flow information as confirmed by a reference detector. CONCLUSION: Through a combination of cross-correlation of the signals from two detectors, model-based characterization of detector response, and optimization of detector operating parameters, the method allows for the accurate estimation of the true blood flow index. Significance: This work presents a method by which DCS can be performed at longer NIR wavelengths with existing detector technology, taking advantage of the increased SNR.

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

Non-Line-Of-Sight (NLOS) imaging aims at recovering the 3D geometry of objects that are hidden from the direct line of sight. One major challenge with this technique is the weak available multibounce signal limiting scene size, capture speed, and reconstruction quality. To overcome this obstacle, we introduce a multipixel time-of-flight non-line-of-sight imaging method combining specifically designed Single Photon Avalanche Diode (SPAD) array detectors with a fast reconstruction algorithm that captures and reconstructs live low-latency videos of non-line-of-sight scenes with natural non-retroreflective objects. We develop a model of the signal-to-noise-ratio of non-line-of-sight imaging and use it to devise a method that reconstructs the scene such that signal-to-noise-ratio, motion blur, angular resolution, and depth resolution are all independent of scene depth suggesting that reconstruction of very large scenes may be possible., Non-line-of-sight imaging can recover the 3D geometry of hidden objects, but is limited by weak multibounce signals. Here, the authors introduce a multipixel time-of-flight NLOS imaging approach, combining array detectors and a fast algorithm, for live reconstruction of natural nonretroreflective objects.

We present a novel instrument for fast-gated operation of a 50 μm CMOS SPAD (Complementary Metal-Oxide-Semiconductor Single-Photon Avalanche Diode), driven by an integrated fast-gated active quenching circuit with transition times faster than 300 ps (20-80%). The instrument is based on a custom system-in-package where the SPAD and its driving electronics are housed in a TO-8 package. The detector can be operated at repetition rates up to 160 MHz, with gate on-times as short as 500 ps, always guaranteeing a temporal response with 60 ps (FWHM) timing jitter and short exponential decay (53 ps time-constant). A dark-count rate as low as 1 cps is achieved operating the CMOS SPAD at 5 V above breakdown at a temperature of 263 K, still keeping the afterpulsing probability lower than 2%, with only 50 ns hold-off time, thanks to the fast-gating driving electronics. The instrument is housed in a compact 5 × 4 × 8 cm3 case and can be triggered by either an external or internal source. A USB link allows to adjust measurement parameters, SPAD bias voltage and operating temperature. The high re-configurability of the instrument and its state-of-the-art performance make it suitable for applications where high detection rates and low timing jitter are required.

The paper reports the mechanical properties of 4H-SiC die with different thicknesses, that have been determined through a 3-point bend (3-PB) test. In particular, it reports 1) the measurement of the failure strength of thin 4H-SiC rectangular die; 2) the Weibull analysis of the failure strength of 4H-SiC die, exploited to determine the maximal load that can be applied to the die, without any breakage; 3) the measure of 244±15 GPa for the effective Young modulus E of SiC die, gained from the 3-PB test elaborations.

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.

We present the LUCA device, a multi-modal platform combining eight-wavelength near infrared time resolved spectroscopy, sixteen-channel diffuse correlation spectroscopy and a clinical ultrasound in a single device. By simultaneously measuring the tissue hemodynamics and performing ultrasound imaging, this platform aims to tackle the low specificity and sensitivity of the current thyroid cancer diagnosis techniques, improving the screening of thyroid nodules. Here, we show a detailed description of the device, components and modules. Furthermore, we show the device tests performed through well established protocols for phantom validation, and the performance assessment for in vivo. The characterization tests demonstrate that LUCA device is capable of performing high quality measurements, with a precision in determining in vivo tissue optical and dynamic properties of better than 3%, and a reproducibility of better than 10% after ultrasound-guided probe repositioning, even with low photon count-rates, making it suitable for a wide variety of clinical applications.

The paper reports the mechanical properties of 4H-SiC die with different thicknesses, that have been determined through a 3-point bending (3-PB) test. In particular, it reports 1) the measurement of the failure strength of thin 4H-SiC rectangular die; 2) the Weibull analysis of the failure strength of 4H-SiC die, exploited to determine the maximal load that can be applied to the die, without any breakage; 3) the measure of 244±15 GPa for the flexural Young modulus E of SiC die, gained from the 3-PB test elaborations.

We present a wearable time-domain near infrared spectroscopy (TD-NIRS) system (two wavelengths, one detection channel), which fits in a backpack and performs real-time hemodynamic measurements on the brain and muscle tissues of freely moving subjects. It can provide concentration values of oxygenated hemoglobin (O2Hb), deoxygenated hemoglobin (HHb), total hemoglobin (tHb = O2Hb + HHb) and tissue oxygen saturation (StO2). The system is battery-operated and can be wirelessly controlled. By following established characterization protocols for performance assessment of diffuse optics instruments, we achieved results comparable with state-of-the-art research-grade TD-NIRS systems. We also performed in-vivo measurements such as finger tapping (motor cortex monitoring), breath holding (prefrontal cortex monitoring and forearm muscle monitoring), and outdoor bike riding (vastus lateralis muscle monitoring), in order to test the system capabilities in evaluating both muscle and brain hemodynamics.

In this work the warpage of a power modules ceramic substrates due to temperature variation has been numerically calculated. It has been used a not linear finite element model, which account the experimentally characterized material properties, including the copper elastoplasticity. Model results have been compared with dedicated interferometric measurements to validate the model. As application example, it has been calculated the benefit in terms of temperature warpage realized with a different substrate design option.

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.

We present a lightweight TD-NIRS system, two-wavelength, one detection channel that can be battery operated and worn as a backpack for freely-moving cerebral and muscle hemodynamic monitoring. Oxy- and deoxy-genated hemoglobin absolute concentration can be retrieved in real time even in outdoor measurements thanks to the rugged feature of the device.

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 sub-component 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.

We present a wearable TD-NIRS system (two wavelengths, one channel). The system is battery operated, can be remotely controlled and is able to perform measurements on brain and muscle on freely-moving subjects.

In this paper we present a novel single-photon detector specifically designed for Non-Line-Of-Sight (NLOS) imaging applications within the framework of the DARPA REVEAL program. The instrument is based on a linear 16 &times, 1 Complementary Metal-Oxide-Semiconductor (CMOS) Single-Photon Avalanche Diode (SPAD) array operated in fast-gated mode by a novel fast-gating Active Quenching Circuit (AQC) array, which enables the detectors with sub-ns transitions thanks to a SPAD-dummy approach. The detector exhibits a timing resolution better than 50 ps (Full Width at Half Maximum - FWHM) at a measurement repetition rate up to 40 MHz, and provides 16 independent outputs compatible with commercial Time-Correlated Single-Photon Counting (TCSPC) instrumentation. The instrument has been experimentally characterized and operated in preliminary NLOS imaging acquisitions where a 40 &times, 60 cm hidden object is successfully reconstructed by scanning over a grid of 150 &times, 150 positions.

We present the current status of the LUCA project whose aim is to develop an innovative device combining ultrasound and diffuse optics for an improved screening of the thyroid cancer.

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.

We present the current status of the LUCA-project whose aim is to develop an innovative device combining ultrasound and diffuse optics for an improved screening of the thyroid cancer.

Wet chemical and electrochemical etching of doped Si samples is a promising technique with a variety of applications ranging from micro-mechanical manufacturing to profiles delineation in electronic devices. We have developed simulation tools specifically designed to support the optimization phase and the control of these processes. The morphologic evolution of sub-micrometric portions of the material is simulated at atomic level by means of a stochastic approach, in which the single atom detachment probability depends on its coordination status. Etching profile evolution is simulated using a level-set technique for propagating interfaces. The nano-structural features (e.g. surface status) of the etched material are accessible using an atomic level stochastic approach. The simulation results show a general agreement with the experimental finding on etched material characterization, capturing also many peculiar characteristics of the real profiles and nano-structures of the etched material.

This paper presents a complete, compact, and low power consumption instrument designed for time-domain near-infrared spectroscopy. It employs two custom-designed pulsed diode lasers (operating at 830 and 670 nm, with average optical power higher than 2 mW at 40 MHz repetition frequency), a single-photon detection module (based on a 1 mm2 active area silicon photomultiplier), and a custom time-to-digital converter with 10 ps time resolution. The system experimental characterization shows an instrument response function narrower than 300 ps (full-width at half maximum), with measurement stability better than ±1% over several hours of operation. The instrument, which is housed into a compact aluminum case (size 200 × 160 × 50 mm3), is specifically tailored for portability and ease of operation, hence fostering the diffusion of time-domain diffuse optics techniques. Thanks to a total power consumption lower than 10 W, this system is suitable for battery operation, thus enabling on-field measurements.

In this paper, we present an innovative instrument for near-infrared time-resolved spectroscopy. The system is based on eight custom-designed pulsed diode lasers emitting at different wavelengths in the near-infrared region (635–1050 nm), all exhibiting an average optical power higher than 1 mW at 40 MHz pulse repetition rate, two custom-made single-photon detectors based on wide-area silicon photomultipliers and two time-measurement units based on a custom time-to-digital converter with 10 ps timing resolution. The system instrument response function has a width narrower than 160 ps (fullwidth at half-maximum) and stability better than ±1% for several hours for all the wavelengths. All the components of the instrument were designed in order to be compact. The entire system will be hosted in a standard 19 inches, 5U rack case (size 48 × 38 × 20 cm3 ). The system communicates with the external computer through a USB 2.0 link and is designed to be employed in a clinical environment. The proposed instrument, thanks to the reduction of its cost and dimensions, paves the way to a wider diffusion of multiwavelengths near-infrared time-resolved spectroscopy systems.