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Digital camera pixels measure image intensities by converting incident light energy into an analog electrical current, and then digitizing it into a fixed-width binary representation. This direct measurement method, while conceptually simple, suffers from limited dynamic range and poor performance under extreme illumination -- electronic noise dominates under low illumination, and pixel full-well capacity results in saturation under bright illumination. We propose a novel intensity cue based on measuring inter-photon timing, defined as the time delay between detection of successive photons. Based on the statistics of inter-photon times measured by a time-resolved single-photon sensor, we develop theory and algorithms for a scene brightness estimator which works over extreme dynamic range; we experimentally demonstrate imaging scenes with a dynamic range of over ten million to one. The proposed techniques, aided by the emergence of single-photon sensors such as single-photon avalanche diodes (SPADs) with picosecond timing resolution, will have implications for a wide range of imaging applications: robotics, consumer photography, astronomy, microscopy and biomedical imaging., Accepted to CVPR 2021 as an oral presentation

The single-photon timing and sensitivity performance and the imaging ability of asynchronous-readout single-photon avalanche diode (SPAD) array detectors have opened up enormous perspectives in fluorescence (lifetime) laser scanning microscopy (FLSM), such as super-resolution image scanning microscopy and high-information content fluorescence fluctuation spectroscopy (FFS). However, the strengths of these FLSM techniques depend on the many different characteristics of the detector, such as dark-noise, photon-detection efficiency, after-pulsing probability, and optical-cross talk, whose overall optimization is typically a trade-off between these characteristics. To mitigate this trade-off, we present a novel SPAD array detector with an active cooling system, which substantially reduces the dark-noise without significantly deteriorating any other detector characteristics. In particular, we show that lowering the temperature of the sensor to −15°C significantly improves the signal-to-noise ratio due to a 10-fold decrease in the dark-count rate compared to room temperature. As a result, for imaging, the laser power can be decreased by more than a factor of three, which is particularly beneficial for live-cell super-resolution imaging, as demonstrated in fixed and living cells expressing GFP-tagged proteins. For FFS, together with the benefit of the reduced laser power, we show that cooling the detector is necessary to remove artifacts in the correlation function, such as spurious negative correlations observed in the hot elements of the detector, i.e., elements whose dark-noise is substantially higher than the median value. Overall, this detector represents a further step towards the integration of SPAD array detectors in any FLSM system.SIGNIFICANCESingle-photon avalanche diode (SPAD) array detectors are revolutionizing fluorescence laser-scanning microscopy (FLSM). Thanks to their single-photon timing and sensitivity ability and their imaging faculty, a SPAD array detector transforms any FLSM into a super-resolution microscope, and opens a whole range of possibilities for the study of sample dynamics by means of fluorescence fluctuation spectroscopy (FFS). However, dark-noise can be a severe problem for both imaging and FFS. For imaging, the signal overcomes noise only for a relatively high illumination intensity, which can be detrimental for live-cell experiments. For FFS, the noise leads to artifacts in the correlation curves, potentially leading to wrong conclusions about the sample. We show that lowering the temperature of the detector to −15°C solves both problems

Successful demonstration of a unique portable CW-TDDOS system for accurate and multiwavelength retrieval of tissue optical properties. Determining these properties has potential to improve the diagnosis and treatment outcomes in clinical and sports settings.

Two-photon excitation (2PE) laser scanning microscopy is the imaging modality of choice when one desires to work with thick biological samples. However, its spatial resolution is poor, below confocal laser scanning microscopy. Here, we propose a straightforward implementation of 2PE image scanning microscopy (2PE-ISM) that, by leveraging our recently introduced single-photon avalanche diode (SPAD) array detector and a novel blind image reconstruction method, is shown to enhance the effective resolution, as well as the overall image quality of 2PE microscopy. With our adaptive pixel reassignment procedure similar to 1.6 times resolution increase is maintained deep into thick semi-transparent samples. The integration of Fourier ring correlation based semi-blind deconvolution is shown to further enhance the effective resolution by a factor of similar to 2 - and automatic background correction is shown to boost the image quality especially in noisy images. Most importantly, our 2PE-ISM implementation requires no calibration measurements or other input from the user, which is an important aspect in terms of day-to-day usability of the technique. (C) 2020 Optical Society of America under the terms of the OSA Open Access Publishing Agreement H2020 Marie Sklodowska-Curie Actions (AdaptiveSTED, No. 794531); FondsWetenschappelijk Onderzoek (G092915, V429717N); European Research Council (Bright Eyes, No. 818699). Vicidomini, G (corresponding author), Ist Italiano Tecnol, Mol Microscopy & Spect, Genoa, Italy giuseppe.vicidomini@iit.it

We propose a straightforward implementation of two-photon image scanning microscopy (2PE-ISM) that, by leveraging our recently introduced single-photon avalanche diode (SPAD) array detector and a novel blind image reconstruction algorithm is shown to dramatically improve the optical resolution of two-photon imaging, in various test samples. We show how our computational ISM approach is able to adapt to changing imaging conditions, thus ensuring optimal image quality. We also show how our recently introduced blind deconvolution approaches can be integrated into the image reconstruction workflow to further improve the image quality.

Fluorescence microscopy and derived techniques are continuously looking for photodetectors able to guarantee increased sensitivity, high spatial and temporal resolution and ease of integration into modern microscopy architectures. Recent advances in single photon avalanche diodes (SPADs) fabricated with industry-standard microelectronic processes allow the development of new detection systems tailored to address the requirements of advanced imaging techniques (such as image-scanning microscopy). To this aim, we present the complete design and characterization of two bidimensional SPAD arrays composed of 25 fully independent and asynchronously-operated pixels, both having fill-factor of about 50% and specifically designed for being integrated into existing laser scanning microscopes. We used two different microelectronics technologies to fabricate our detectors: the first technology exhibiting very low noise (roughly 200 dark counts per second at room temperature), and the second one showing enhanced detection efficiency (more than 60% at a wavelength of 500 nm). Starting from the silicon-level device structures and moving towards the in pixel and readout electronics description, we present performance assessments and comparisons between the two detectors. Images of a biological sample acquired after their integration into our custom image-scanning microscope finally demonstrate their exquisite on-field performance in terms of spatial resolution and contrast enhancement. We envisage that this work can trigger the development of a new class of SPAD-based detector arrays able to substitute the typical single-element sensor used in fluorescence laser scanning microscopy., 15 pages, 7 figures, 3 tables

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 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.

The autocorrelation of laser speckles from coherent near infrared light is used for noninvasive estimates of relative changes in blood perfusion in techniques such as laser Doppler flowmetry (LDF) and diffuse correlation spectroscopy (DCS). In this study, a 2D array of single photon avalanche diodes (SPADs) was used to combine the strengths of multiple detectors in LDF with high light sensitivity in DCS. The system was tested on milk phantoms with varying detector fiber diameter (200 and 600 μm), source-detector fiber separation (4.6-10.2 mm), fiber-SPAD distance (2.5-36.5 mm), contiguous measurement time per repetition for the autocorrelation (1-33 ms) and temperature (15.6-46.7°C). An in vivo blood occlusion test was also performed. The multipixel approach improved signal-to-noise ratio (SNR) and, in our setup, the use of a multimode detector fiber was beneficial for SNR. In conclusion, the multipixel system works, but improvements and further studies regarding, for example, the data acquisition and optimal settings are still needed.

Two-photon excitation (2PE) laser scanning microscopy is the imaging modality of choice when one desires to work with thick biological samples. However, its spatial resolution is poor, below confocal laser scanning microscopy. Here, we propose a straightforward implementation of 2PE image scanning microscopy (2PE-ISM) that, by leveraging our recently introduced ISM platform – based on a new single-photon avalanche diode (SPAD) array detector – coupled with a novel blind image reconstruction method, is shown to improve the effective resolution, as well as the overall image quality of 2PE microscopy. Indeed, in stark contrast to conventional single-point detectors, SPAD array detectors give access to the images of any excited scanning region, from which it is possible to decode information about the aberrations/distortions – occurring during imaging – able to substantially improve the reconstruction. Most importantly, our 2PE-ISM implementation requires no calibration or other input from the user; it works like any familiar two-photon system, but produces higher resolution images deep into thick samples. In our view, this novel implementation is the key for making 2PE-ISM mainstream.

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.

Image scanning microscopy (ISM) can improve the effective spatial resolution of confocal microscopy to its theoretical limit. However, current implementations are not robust or versatile, and are incompatible with fluorescence lifetime imaging (FLIM). We describe an implementation of ISM based on a single-photon detector array that enables super-resolution FLIM and improves multicolor, live-cell and in-depth imaging, thereby paving the way for a massive transition from confocal microscopy to ISM. A single-photon detector array enables robust and versatile image scanning microscopy (ISM) on any confocal microscope. This implementation makes super-resolution FLIM possible and eases a transition from confocal microscopy to ISM.

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.

The spatial resolution of a stimulated emission depletion (STED) microscope is theoretically unlimited and practically determined by the signal-to-noise ratio. Typically, an increase of the STED beam's power leads to an improvement of the effective resolution. However, this improvement may vanish because an increased STED beam's power is often accompanied by an increased photobleaching, which worsen the effective resolution by reducing the signal strength. A way to lower the photobleaching in pulsed STED (P-STED) implementations is to reduce the peak intensity lengthening the pulses duration (for a given average STED beam's power). This also leads to a reduction of the fluorophores quenching, thus a reduction of the effective resolution, but the time-gated detection was proved to be successful in recovering these reductions. Here we demonstrated that a subnanosecond fiber laser beam (pulse width ∼600 ps) reduces the photobleaching with respect to a traditional stretched hundreds picosecond (∼200 ps) beam provided by a Ti:Sapphire laser, without any effective spatial resolution lost.

We present a handheld, low-power, time-resolved single-photon detection system, consisting of a time measurement platform, able to record optical waveforms with 10 ps resolution and a detection board, which can host both CMOS and custom-made single-photon avalanche diodes (SPADs). It has been validated using up to 200 $\mu \text{m}$ diameter CMOS SPADs, reaching 40% photon detection efficiency at 450 nm and less than 100 HZ dark count rate at room temperature (with a 50 $\mu \text{m}$ device). The system provides 50 ps full-width at half-maximum single-shot timing precision, with 1.2% of least significant bit (LSB) (RMS) differential non-linearity (DNL) and 160 $\mu \text{s}$ full-scale range. Both data communication and power supply are provided by a USB 2.0 link. The module comes in a very compact ( $1 \,\, \times \,\, 2$ in2) handheld housing and consumes less than 1.3 W (even at the maximum rate of 5 Mconversion/s). Because of the field programmable gate array (FPGA) data processing, this complete time-correlated single-photon counting system enables customized and cost-effective new applications, which require high portability and configurability, with no compromises on performance.

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.

Ranging and imaging in low light level conditions are a key application of active imaging systems. Typically, intensified cameras (ICCD, EBCMOS) are used to sense the intensity of reflected laser light pulses used for illumination. Recent developments in single photon avalanche diodes (SPAD) show, that sensors having single photon counting capabilities are about to revolutionize low light level imaging and laser ranging. These sensors have the ability to count detection events caused by single photons with very high timing precision. By application of statistical measurement means, the sensitivity of such devices can be increased far beyond classical sensing devices and the needed photon flux has significant lower intensities. New SPAD devices enable the development of novel sensing methods and technologies, and open laser ranging and imaging to new fields of application. Here, we focus on novel hardware structures which are under development as well as the application of avalanche photo diode detectors for light-in-flight detection and non-line-of-sight imaging.

Image scanning microscopy (ISM) improves the spatial resolution of conventional confocal laser-scanning microscopy (CLSM), but current implementations reduce versatility and restrict its combination with fluorescence spectroscopy techniques, such as fluorescence lifetime. Here, we describe a natural design of ISM based on a fast single-photon detector array, which allows straightforward upgrade of an existing confocal microscope, without compromising any of its functionalities. In contrast to all-optical ISM implementations, our approach provides access to the raw scanned images, opening the way to adaptive reconstruction methods, capable of considering different imaging conditions and distortions. We demonstrate its utility in the context of fluorescence lifetime, deep, multicolor and live-cell imaging. This implementation will pave the way for a transparent and massive transition from conventional CLSM to ISM.confocal microscopy | time-resolved spectroscopy | image scanning microscopy | single-photon detector array

If a scanning illumination spot is combined with a detector array, we acquire a 4 dimensional signal. Unlike confocal microscopy with a small pinhole, we detect all the light from the object, which is particularly important for fluorescence microscopy, when the signal is weak. The image signal is basically a cross-correlation, and is highly redundant. It has more than sufficient information to reconstruct an improved resolution image. A 2D image can be generated from the measured signal by pixel reassignment. The result is improved resolution and signal strength, the system being called image scanning microscopy. A variety of different signal processing techniques can be used to predict the reassignment and deconvolve the partial images. We use an innovative single-photon avalanche diode (SPAD) array detector of 25 detectors (arranged into a 5× 5 matrix). We can simultaneously acquire 25 partial images and process to calculate the final reconstruction online.

We present a novel device and a method based on speckle contrast optical spectroscopy (SCOS) for measuring absolute blood flow in deep tissue. The device was validated on healthy adult subjects.

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 compact instrument for time-resolved diffuse optical spectroscopy based on two pulsed diode lasers, a Silicon PhotoMultiplier working in single-photon regime and a custom-made Time-to-Digital Converter. The temporal width of the Instrument Response Function is narrower than 300 ps (Full-Width at Half Maximum) and the time measurement unit exhibits 10 ps temporal resolution with a Full Scale Range of 80 ns. The laser pulses are injected into the sample through two 400 μm core optical fibers and re-emitted light is collected by 1 mm core plastic optical fiber aligned with detector active area. The instrument is housed in a compact 200 × 160 × 50 mm3 metal case, weighs less than 2 kg and requires a single 15 V DC voltage power supply, with a power consumption lower than 10 W, thus being suitable for battery operation. The long-time measurement stability makes the system ideal for monitoring applications on the field, where state-of-the-art bulky time-resolved systems cannot be exploited.

Can we reconstruct the entire internal shape of a room if all we can directly observe is a small portion of one internal wall, presumably through a window in the room? While conventional wisdom may indicate that this is not possible, motivated by recent work on ‘looking around corners’, we show that one can exploit light echoes to reconstruct the internal shape of hidden rooms. Existing techniques for looking around the corner using transient images model the hidden volume using voxels and try to explain the captured transient response as the sum of the transient responses obtained from individual voxels. Such a technique inherently suffers from challenges with regards to low signal to background ratios (SBR) and has difficulty scaling to larger volumes. In contrast, in this paper, we argue for using a plane-based model for the hidden surfaces. We demonstrate that such a plane-based model results in much higher SBR while simultaneously being amenable to larger spatial scales. We build an experimental prototype composed of a pulsed laser source and a single-photon avalanche detector (SPAD) that can achieve a time resolution of about 30ps and demonstrate high-fidelity reconstructions both of individual planes in a hidden volume and for reconstructing entire polygonal rooms composed of multiple planar walls.

The use of an array of detectors can help overcoming the traditional limitation of confocal microscopy: the compromise between signal and theoretical resolution. Each element independently records a view of the sample and the final image can be reconstructed by pixel reassignment or by inverse filtering (e.g. deconvolution). In this work, we used a SPAD array of 25 detectors specifically designed for this goal and our scanning microscopy control system (Carma) to acquire the partial images and to perform online image processing. Further work will be devoted to optimize the image reconstruction step and to improve the fill-factor of the detector.

We present a portable 64-channel photon-counting system employing a monolithic array of Single-Photon Avalanche Diodes (SPADs) and a custom-designed Time-to-Digital Converter (TDC), for single-photon counting and timing applications. The system provides state-of-art singlephoton detection performance and time-resolved measurement capability, with timing precision down to 100 ps FWHM and linearity better than 2% LSB (RMS). The compact form factor (1″ diameter by 2″ length), extensive customization capabilities, and low power consumption enable its use in applications requiring both high-end single-photon performance and system portability, such as wearable health monitoring, hand-held equipment, and automotive time-of-flight 3D ranging measurement.

Speckle contrast optical spectroscopy (SCOS) measures absolute blood flow in deep tissue, by taking advantage of multi-distance (previously reported in the literature) or multi-exposure (reported here) approach. This method promises to use inexpensive detectors to obtain good signal-to-noise ratio, but it has not yet been implemented in a suitable manner for a mass production. Here we present a new, compact, low power consumption, 32 by 2 single photon avalanche diode (SPAD) array that has no readout noise, low dead time and has high sensitivity in low light conditions, such as in vivo measurements. To demonstrate the capability to measure blood flow in deep tissue, healthy volunteers were measured, showing no significant differences from the diffuse correlation spectroscopy. In the future, this array can be miniaturized to a low-cost, robust, battery operated wireless device paving the way for measuring blood flow in a wide-range of applications from sport injury recovery and training to, on-field concussion detection to wearables. Fundació CELLEX Barcelona, Ministerio de Economía y Competitividad (PHOTODEMEN-TIA (DPI2015-64358-c1 and c2 (MINECO/FEDER)), Instituto de Salud Carlos III/FEDER(MEDPHOTAGE DTS16/00087), the “Severo Ochoa” Programme for Centres of Excellence inR&D (SEV-2015-0522), the Obra social “la Caixa” Foundation (LlumMedBcn), LASERLAB-EUROPE IV. J.L.Hollmann acknowledges the Marie Curie COFUND (FP7-PEOPLE-2013-COFUND) fellowship.

We present a new InGaAs/InP Single-Photon Avalanche Diode (SPAD) with high detection efficiency and low noise, which has been employed in a sinusoidal-gated setup to achieve very low afterpulsing probability and high count rate. The new InGaAs/InP SPAD has lower noise compared to previous generations thanks to the improvement of Zinc diffusion conditions and the optimization of the vertical structure. A detector with 25 μm active-area diameter, operated in gated-mode with ON time of tens of nanoseconds, has a dark count rate of few kilo-counts per second at 225 K and 5 V of excess bias, 30% photon detection efficiency at 1550 nm and a timing jitter of less than 90 ps (FWHM) at 7 V of excess bias. In order to reduce significantly the afterpulsing probability, these detectors were operated with a sinusoidal gate at 1.3 GHz. The extremely short gate ON time (less than 200 ps) reduces the charge flowing through the junction, thus reducing the number of trapped carriers and, eventually, lowering the afterpulsing probability. The resulting detection system achieves a maximum count rate higher than 650 Mcount/s with an afterpulsing probability of about 1.5%, a photon detection efficiency greater than 30% at 1550 nm and a temporal resolution of less than 90 ps (FWHM).

By using time-of-flight information encoded in multiply scattered light, it is possible to reconstruct images of objects hidden from the camera's direct line of sight. Here, we present a non-line-of-sight imaging system that uses a single-pixel, single-photon avalanche diode (SPAD) to collect time-of-flight information. Compared to earlier systems, this modification provides significant improvements in terms of power requirements, form factor, cost, and reconstruction time, while maintaining a comparable time resolution. The potential for further size and cost reduction of this technology make this system a good base for developing a practical system that can be used in real world applications.

We present a single-photon counter based on a silicon single-photon avalanche diode (SPAD) fabricated in a 0.35-μm CMOS technology. The detector is monolithically integrated with a front-end circuit and a digital pulse output driver. External components are kept to a minimum, and the resulting instrument is low-cost, low-power, and compact, being housed into an industry-standard 1-in aluminum optical mounting tube. It features a maximum power consumption of just 250 mW from a USB link. The embedded 50-μm-diameter SPAD has high photon detection efficiency in the visible range (55% at 420 nm), low noise (

Stimulated emission depletion (STED) microscopy provides fluorescence imaging with sub-diffraction resolution. Experimentally demonstrated at the end of the 90s, STED microscopy has gained substantial momentum and impact only in the last few years. Indeed, advances in many fields improved its compatibility with everyday biological research. Among them, a fundamental step was represented by the introduction in a STED architecture of the time-gated detection, which greatly reduced the complexity of the implementation and the illumination intensity needed. However, the benefits of the time-gated detection came along with a reduction of the fluorescence signal forming the STED microscopy images. The maximization of the useful (within the time gate) photon flux is then an important aspect to obtain super-resolved images. Here we show that by using a fast-gated single-photon avalanche diode (SPAD), i.e. a detector able to rapidly (hundreds picoseconds) switch-on and -off can improve significantly the signal-to-noise ratio (SNR) of the gated STED image. In addition to an enhancement of the image SNR, the use of the fast-gated SPAD reduces also the system complexity. We demonstrate these abilities both on calibration and biological sample. The experiments were carried on a gated STED microscope based on a STED beam operating in continuous-wave (CW), although the fast-gated SPAD is fully compatible with gated STED implementations based on pulsed STED beams.

We present the design and characterization of a complete single-photon counting module capable of time-gating a silicon single-photon avalanche diode with ON and OFF transition times down to 110 ps, at repetition rates up to 80 MHz. Thanks to this sharp temporal filtering of incoming photons, it is possible to reject undesired strong light pulses preceding (or following) the signal of interest, allowing to increase the dynamic range of optical acquisitions up to 7 decades. A complete experimental characterization of the module highlights its very flat temporal response, with a time resolution of the order of 30 ps. The instrument is fully user-configurable via a PC interface and can be easily integrated in any optical setup, thanks to its small and compact form factor.

We present the design and characterization of a large-area, fast-gated, all-digital single-photon detector with programmable active area, internal gate generator, and time-to-digital converter (TDC) with a built-in histogram builder circuit, suitable for performing high-sensitivity time-domain near-infrared spectroscopy (TD-NIRS) measurements when coupled with pulsed laser sources. We used a novel low-power differential sensing technique that optimizes area occupation. The photodetector is a time-gated digital silicon photomultiplier (dSiPM) with an 8.6-mm2 photosensitive area, 37% fill-factor, and ~300 ps (20%–80%) gate rising edge, based on low-noise single-photon avalanche diodes (SPADs) and fabricated in 0.35- $\mu \text{m}$ CMOS technology. The built-in TDC with a histogram builder has a least-significant-bit (LSB) of 78 ps and 128 time-bins, and the integrated circuit can be interfaced directly with a low-cost microcontroller with a serial interface for programming and readout. Experimental characterization demonstrated a temporal response as good as 300-ps full-width at half-maximum (FWHM) and a dynamic range >100 dB (thanks to the programmable active area size). This microelectronic detector paves the way for a miniaturized, stand-alone, multi-wavelength TD-NIRS system with an unprecedented level of integration and responsivity, suitable for portable and wearable systems.

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.

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.

This work shows that InGaAs/InP Single-Photon Avalanche Diodes (SPADs) can achieve high count rate (> 500 Mcps) and high detection efficiency (> 30 % at 1550 nm) when operated with sub-nanosecond gates.

The combination of confocal laser-scanning microscopy (CLSM) and fluorescence fluctuation spectroscopy (FFS) is a powerful tool in studying fast, sub-resolution biomolecular processes in living cells. A detector array can further enhance CLSM-based FFS techniques, as it allows the simultaneous acquisition of several samples–essentially images—of the CLSM detection volume. However, the detector arrays that have previously been proposed for this purpose require tedious data corrections and preclude the combination of FFS with single-photon techniques, such as fluorescence lifetime imaging. Here, we solve these limitations by integrating a novel single-photon-avalanche-diode (SPAD) array detector in a CLSM system. We validate this new implementation on a series of FFS analyses: spot-variation fluorescence correlation spectroscopy, pair-correlation function analysis, and image-derived mean squared displacement analysis. We predict that the unique combination of spatial and temporal information provided by our detector will make the proposed architecture the method of choice for CLSM-based FFS.

Significance: This study is a preliminary step toward the identification of a noninvasive and reliable tool for monitoring the presence and progress of gaiting dysfunctions. Aim: We present the results of a pilot study for monitoring the motor cortex hemodynamic response function (HRF) in freely walking subjects, with time-domain functional near-infrared spectroscopy (TD fNIRS). Approach: A compact and wearable single-channel TD fNIRS oximeter was employed. The lower limb motor cortex area of three healthy subjects was monitored while performing two different freely moving gaiting tasks: forward and backward walking. Results: The time course of oxygenated and deoxygenated hemoglobin was measured during the different walking tasks. Brain motor cortex hemodynamic activations have been analyzed throughout an adaptive HRF fitting procedure, showing a greater involvement of motor area in the backward walking task. By comparison with the HRF obtained in a finger-tapping task performed in a still condition, we excluded any effect of motion artifacts in the gaiting tasks. Conclusions: For the first time to our knowledge, the hemodynamic motor cortex response was measured by TD fNIRS during natural, freely walking exercises. The cortical response during forward and backward walking shows differences, possibly related to the diverse involvement of the motor cortex in the two types of gaiting.