Light is a powerful tool to non-invasively probe highly scattering media for clinical applications ranging from oncology to neurology, but also for molecular imaging, and quality assessment of food, wood and pharmaceuticals. Here we show that, for a paradigmatic case of diffuse optical imaging, ideal yet realistic time-domain systems yield more than 2-fold higher depth penetration and many decades higher contrast as compared to ideal continuous-wave systems, by adopting a dense source-detector distribution with picosecond time-gating. Towards this aim, we demonstrate the first building block made of a source-detector pair directly embedded into the probe based on a pulsed Vertical-Cavity Surface-Emitting Laser (VCSEL) to allow parallelization for dense coverage, a Silicon Photomultiplier (SiPM) to maximize light harvesting, and a Single-Photon Avalanche Diode (SPAD) to demonstrate the time-gating capability on the basic SiPM element. This paves the way to a dramatic advancement in terms of increased performances, new high impact applications, and availability of devices with orders of magnitude reduction in size and cost for widespread use, including quantitative wearable imaging. Opt. 19, 086012 (2014). 26. S. Carraresi, T. S. Shatir, F. Martelli, and G. Zaccanti, "Accuracy of a perturbation model to predict the effect of scattering and absorbing inhomogeneities on photon migration," Appl. Opt. 40, 4622-4632 (2001). 27. D. Contini, F. Martelli, and G. Zaccanti, "Photon migration through a turbid slab described by a model based on diffusion approximation. I. Theory," Appl. Opt. 36, 4587-4599 (1997). #230929Received 23

We report on the design, development, and performance assessment of a portable time resolved system measuring absorption and scattering spectra of highly diffusive media over the 600-1350 nm range. In view of clinical use, two strategies were implemented; the first one equips the system with high responsivity in key tissue absorbing regions, whereas the second one makes the system immune to time drift. The MEDPHOT protocol was used for the performance assessment of the instrument. Finally, the system was enrolled into its first in vivo trial phase, measuring the broadband absorption and scattering spectra of human manubrium, abdomen fat tissues, and forehead for the in vivo quantification of key tissue constituents.

Diffuse correlation spectroscopy (DCS), combined with time-resolved reflectance spectroscopy (TRS) or frequency domain spectroscopy, aims at path length (i.e. depth) resolved, non-invasive and simultaneous assessment of tissue composition and blood flow. However, while TRS provides a path length resolved data, the standard DCS does not. Recently, a time domain DCS experiment showed path length resolved measurements for improved quantification with respect to classical DCS, but was limited to phantoms and small animal studies. Here, we demonstrate time domain DCS for studies on the adult forehead and the arm. We achieve path length resolved DCS by means of an actively mode-locked Ti:Sapphire laser that allows high coherence pulses, thus enabling adequate signal-to-noise ratio in relatively fast (~1 s) temporal resolution. This work paves the way to the translation of this approach to practical use.

Abstract:We present a proof of concept prototype of a time-domain diffuse optics probe exploiting a fast Silicon PhotoMultiplier (SiPM), featuring a timing resolution better than 80 ps, a fast tail with just 90 ps decay time-constant and a wide active area of 1 mm 2 . The detector is hosted into the probe and used in direct contact with the sample under investigation, thus providing high harvesting efficiency by exploiting the whole SiPM numerical aperture and also reducing complexity by avoiding the use of cumbersome fiber bundles. Our tests also demonstrate high accuracy and linearity in retrieving the optical properties and suitable contrast and depth sensitivity for detecting localized inhomogeneities. In addition to a strong improvement in both instrumentation cost and size with respect to legacy solutions, the setup performances are comparable to those of state-of-the-art time-domain instrumentation, thus opening a new way to compact, low-cost and high-performance time-resolved devices for diffuse optical imaging and spectroscopy.

We present the design and preliminary characterization of the first detection module based on Silicon Photomultiplier (SiPM) tailored for single-photon timing applications. The aim of this work is to demonstrate, thanks to the design of a suitable module, the possibility to easily exploit SiPM in many applications as an interesting detector featuring large active area, similarly to photomultipliers tubes, but keeping the advantages of solid state detectors (high quantum efficiency, low cost, compactness, robustness, low bias voltage, and insensitiveness to magnetic field). The module integrates a cooled SiPM with a total photosensitive area of 1 mm(2) together with the suitable avalanche signal read-out circuit, the signal conditioning, the biasing electronics, and a Peltier cooler driver for thermal stabilization. It is able to extract the single-photon timing information with resolution better than 100 ps full-width at half maximum. We verified the effective stabilization in response to external thermal perturbations, thus proving the complete insensitivity of the module to environment temperature variations, which represents a fundamental parameter to profitably use the instrument for real-field applications. We also characterized the single-photon timing resolution, the background noise due to both primary dark count generation and afterpulsing, the single-photon detection efficiency, and the instrument response function shape. The proposed module can become a reliable and cost-effective building block for time-correlated single-photon counting instruments in applications requiring high collection capability of isotropic light and detection efficiency (e.g., fluorescence decay measurements or time-domain diffuse optics 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 Ã\u97 160 Ã\u97 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

Abstract. We report the development of a compact probe for time-domain (TD) functional near-infrared spectroscopy (fNIRS) based on a fast silicon photomultiplier (SiPM) that can be put directly in contact with the sample without the need of optical fibers for light collection. We directly integrated an avalanche signal amplification stage close to the SiPM, thus reducing the size of the detection channel and optimizing the signal immunity to electromagnetic interferences. The whole detection electronics was placed in a plastic screw holder compatible with the electroencephalography standard cap for measurement on brain or with custom probe holders. The SiPM is inserted into a transparent and insulating resin to avoid the direct contact of the scalp with the 100-V bias voltage. The probe was integrated in an instrument for TD fNIRS spectroscopy. The system was characterized on tissue phantoms in terms of temporal resolution, responsivity, linearity, and capability to detect deep absorption changes. Preliminary in vivo tests on adult volunteers were performed to monitor hemodynamic changes in the arm during a cuff occlusion and in the brain cortex during a motor task.

We characterized the single-photon timing response function of various silicon photomultipliers (SiPMs) over a broad (500-1100 nm) spectral range. We selected two SiPM manufacturers, and we investigated two active areas, i.e., a small (1-1.69 mm2 and a large (9 mm2) one, for each of them. We demonstrate that selected SiPMs are suitable for time-resolved diffuse optics (DO) applications where a very large detection area and sensitivity down to single photons are crucial to detecting the very faint return signal from biological tissues, like the brain, thus allowing replacement of photomultiplier tubes and opening the way to a novel generation of DO multichannel instrumentation. Due to our custom front-end electronics, we show the world's best single-photon timing resolution for SiPMs, namely, 57-ps full-width at half maximum for Hamamatsu 1.69 mm2 and 115 ps for Excelitas 9 mm2. Even further, we provide a thorough spectral investigation of the full single-photon timing response function, also detailing diffusion tails' time constants and dynamic range. The achieved insight and the reported performance open the way to a widespread diffusion of SiPMs not just in many-photon regimes (e.g., PET) but at single-photon counting regimes like DO as well