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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

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

Thanks to recent developments in time-domain near-infrared spectroscopy (TD-NIRS), it is now possible to monitor brain activity during freely moving exercises. A wearable single-channel TD-NIRS instrument has been exploited to retrieve oxy- and deoxygenated hemoglobin absolute concentrations during gaiting experiments. It was possible to retrieve quantitative results concerning functional brain activation in the motor cortex areas, with high rejection of motion artifacts.

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.

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

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.

Bulkiness and complexity of current Time-Domain (TD) NIRS systems have strongly limited the spread of this technique in biomedical research and clinical applications. We present an instrument developed to overcome those limitations, making TD-NIRS more accessible to non-experts and adaptable to any measurement condition, paving the way to muscle and brain oximetry in healthcare and sport environments.

In this work, we present a new multi-distance diffuse correlation spectroscopy (DCS) device integrated with a compact state-of-the-art time domain near infrared spectroscopy (TD-NIRS) device. The hybrid DCS and TD-NIRS system allows to retrieve information on blood flow, tissue oxygenation, and oxygen metabolic rate. The DCS device performances were estimated in terms of stability, repeatability, ability in retrieving variations of diffusion coefficient, influence of the tissue optical properties, effect of varying count rates and depth sensitivity. Crosstalk between DCS and TD-NIRS optical signals was also evaluated. Finally, in vivo experiments (venous and arterial cuff occlusions on the arm) were conducted to test the ability of the hybrid system in measuring blood flow variations.

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.

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 portable hybrid system of three optical techniques GASMAS (Gas in scattering media absorption spectroscopy), TR-NIRS (time-resolved near-infrared spectroscopy) and CWBS (continuous wave broadband spectroscopy) have been proposed to monitor optical properties and gas concentration during the gas exchange in an ex vivo bovine lung. Increasing levels of lung inflation at different pressures showed significant changes in optical properties and gas dynamics, providing valuable insights for non-invasive monitoring of lung function.

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.

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.

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.

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.

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.