Fast silicon photomultiplier improves signal harvesting and reduces complexity in time-domain diffuse optics

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 mm2. 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

Towards next generation time-domain diffuse optics devices

Diffuse Optics is growing in terms of applications ranging from e.g. oximetry, to mammography, molecular imaging, quality assessment of food and pharmaceuticals, wood optics, physics of random media. Time-domain (TD) approaches, although appealing in terms of quantitation and depth sensibility, are presently limited to large fiber-based systems, with limited number of source-detector pairs. We present a miniaturized TD source-detector probe embedding integrated laser sources and single-photon detectors. Some electronics are still external (e.g. power supply, pulse generators, timing electronics), yet full integration on-board using already proven technologies is feasible. The novel devices were successfully validated on heterogeneous phantoms showing performances comparable to large state-of-the-art TD rack-based systems. With an investigation based on simulations we provide numerical evidence that the possibility to stack many TD compact source-detector pairs in a dense, null source-detector distance arrangement could yield on the brain cortex about 1 decade higher contrast as compared to a continuous wave (CW) approach. Further, a 3-fold increase in the maximum depth (down to 6 cm) is estimated, opening accessibility to new organs such as the lung or the heart. Finally, these new technologies show the way towards compact and wearable TD probes with orders of magnitude reduction in size and cost, for a widespread use of TD devices in real life

Time-domain diffuse optics: Towards next generation devices

Diffuse optics is a powerful tool for clinical applications ranging from oncology to neurology, but also for molecular imaging, and quality assessment of food, wood and pharmaceuticals. We show that ideally time-domain diffuse optics can give higher contrast and a higher penetration depth with respect to standard technology. In order to completely exploit the advantages of a time-domain system a distribution of sources and detectors with fast gating capabilities covering all the sample surface is needed. Here, we present the building block to build up such system. This basic component is made of a miniaturised source-detector pair embedded into the probe based on pulsed Vertical-Cavity Surface-Emitting Lasers (VCSEL) as sources and Single-Photon Avalanche Diodes (SPAD) or Silicon Photomultipliers (SiPM) as detectors. The possibility to miniaturized and dramatically increase the number of source detectors pairs open the way to an advancement of diffuse optics in terms of improvement of performances and exploration of new applications. Furthermore, availability of compact devices with reduction in size and cost can boost the application of this technique

Effects of time-gated detection in diffuse optical imaging at short source-detector separation

The adoption of a short source-detector distance, combined with a time-resolved acquisition, can be advantageous in diffuse optical imaging due to the stricter spatial localization of the probing photons, provided that the strong burst of early photons is suppressed using a time-gated detection scheme. We propose a model for predicting the effect of the time-gated measurement system using a time-variant operator built on the system response acquired at different gate delays. The discrete representation of the system operator, termed Spread Matrix, can be analyzed to identify the bottlenecks of the detection system with respect to the physical problem under study. Measurements performed on tissue phantoms, using a time-gated single-photon avalanche diode and an interfiber distance of 2 mm, demonstrate that inhomogeneities down to 3 cm can be detected only if the decay constant of the detector is lower than 100 ps, while the transient opening of the gate has a less critical impact

Characterization of a time-resolved non-contact scanning diffuse optical imaging system exploiting fast-gated single-photon avalanche diode detection

We present a system for non-contact time-resolved diffuse reflectance imaging, based on small source-detector distance and high dynamic range measurements utilizing a fast-gated single-photon avalanche diode. The system is suitable for imaging of diffusive media without any contact with the sample and with a spatial resolution of about 1 cm at 1 cm depth. In order to objectively assess its performances, we adopted two standardized protocols developed for time-domain brain imagers. The related tests included the recording of the instrument response function of the setup and the responsivity of its detection system. Moreover, by using liquid turbid phantoms with absorbing inclusions, depth-dependent contrast and contrast-to-noise ratio as well as lateral spatial resolution were measured. To illustrate the potentialities of the novel approach, the characteristics of the non-contact system are discussed and compared to those of a fiber-based brain imager

Validation of an Engineered Cell Model for In Vitro and In Vivo HIF-1 alpha Evaluation by Different Imaging Modalities

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Using Commercial Enzymes to Produce Cellulose Nanofibers from Soybean Straw

This study used commercial enzymes to isolate cellulose nanofibrils (CN) and produce sugars from chemically pretreated soybean straw (SS) (stem, leaves, and pods) by alkali (NaOH 5 or 17.5% v/v at 90°C for 1 h or at 30°C for 15 h) and bleaching (NaClO2 3.3% or H2O2 4%) pretreatments. Depending on the pretreatment applied to the soybean straw, the yield of CN varied from 6.3 to 7.5 g of CN/100 g of SS regardless of the concentration of the alkaline solution (5 or 17.5%). The CN had diameter of 15 nm, measured over 300 nm in length, and had high electrical stability (zeta potentials ranged from −20.8 to −24.5). Given the XRD patterns, the crystallinity index (CrI) of CN ranged from 45 to 68%, depending on the chemical pretreatment the starting material was submitted to. CN obtained from SS treated with NaOH 17.5% and H2O2 (CrI = 45%) displayed better thermal stability probably because a lignin-cellulose complex emerged. The soluble fraction obtained in the first step of CN production contained a large amount of reducing sugars (11.2 to 30.4 g/100 g of SS). SS seems to be a new promising industrial source to produce CN via enzymatic-mechanical treatment, leading to large amounts of reducing sugars for use in bioenergy production