Large area silicon photomultipliers allow extreme depth penetration in time-domain diffuse optics

We present the design of a novel single-photon timing module, based on a Silicon Photomultiplier (SiPM) featuring a collection area of 9 mm2. The module performs Single-Photon Timing Resolution of about 140 ps, thus being suitable for diffuse optics application. The small size of the instrument (5 cm × 4 cm × 10 cm) allows placing it directly in contact with the sample under investigation, maximizing that way the signal harvesting. Thanks to that, it is possible to increase the source detector distance up to 6 cm or more, therefore enhancing the penetration depth up to an impressive value of 4 cm and paving the way to the exploration of the deepest human body structures in a completely non-invasive approach

Optical characterization of porcine tissues from various organs in the 650-1100 nm range using time-domain diffuse spectroscopy

We present a systematic characterization of the optical properties (µa and µs') of nine representative ex vivo porcine tissues over a broadband spectrum (650-1100 nm). We applied time-resolved diffuse optical spectroscopy measurements for recovering the optical properties of porcine tissues depicting a realistic representation of the tissue heterogeneity and morphology likely to be found in different ex vivo tissues. The results demonstrate a large spectral and inter-tissue variation of optical properties. The data can be exploited for planning or simulating ex vivo experiments with various biophotonics techniques, or even to construct artificial structures mimicking specific pathologies exploiting the wide assortment in optical properties.This article is freely available via Open Access. Click on the Publisher URL to access it via the publisher's site.Horizon 2020 Framework Programme10.13039/100010661 (654148;, 675332); Engineering and Physical Sciences Research Council10.13039/501100000266 (EP/R020965/1).published version, accepted versio

Non-invasive investigation of adipose tissue by time domain diffuse optical spectroscopy

The human abdominal region is very heterogeneous and stratified with subcutaneous adipose tissue (SAT) being one of the primary layers. Monitoring this tissue is crucial for diagnostic purposes and to estimate the effects of interventions like caloric restriction or bariatric surgery. However, the layered nature of the abdomen poses a major problem in monitoring the SAT in a non-invasive way by diffuse optics. In this work, we examine the possibility of using multi-distance broadband time domain diffuse optical spectroscopy to assess the human abdomen non-invasively. Broadband absorption and reduced scattering spectra from 600 to 1100 nm were acquired at 1, 2 and 3 cm source-detector distances on ten healthy adult male volunteers, and then analyzed using a homogeneous model as an initial step to understand the origin of the detected signal and how tissue should be modeled to derive quantitative information. The results exhibit a clear influence of the layered nature on the estimated optical properties. Clearly, the underlying muscle makes a relevant contribution in the spectra measured at the largest source-detector distance for thinner subjects related to blood and water absorption. More unexpectedly, also the thin superficial skin layer yields a direct contamination, leading to higher water content and steeper reduced scattering spectra at the shortest distance, as confirmed also by simulations. In conclusion, provided that data analysis properly accounts for the complex tissue structure, diffuse optics may offer great potential for the continuous non-invasive monitoring of abdominal fat

Evaluation of Haemoglobin and Cytochrome Responses During Forearm Ischaemia Using Multi-wavelength Time Domain NIRS

We demonstrate the ability of a 16-wavelength time domain near-infrared spectroscopy system to monitor changes in oxy- and deoxy haemoglobin ([HbO2] [HHb]) and the oxidation of cytochrome-c-oxidase ([oxCCO]), during forearm ischaemia. We tested two methods to retrieve the concentration changes. The first uses the measured changes in light attenuation and the modified Beer-Lambert law, and the second uses the absorption and scattering estimated by the measured time-point spread function. The system is able to retrieve the concentration changes with both methods, giving similar results. At the end of forearm ischaemia (t = 5 min), we measured an increase in [HHb] of 16.77 ± 2.52 and 16.37 ± 2.33 μMol, and a decrease in [HbO2] of -6.12 ± 1.62 and -5.57 ± 2.02 μMol for method 1 and 2, respectively. At that same time, the changes in [oxCCO] were -0.36 ± 0.33 and -1.40 ± 1.20 μMol, for method 1 and 2, respectively. These small changes in [oxCCO], despite a huge change in haemoglobin, demonstrate the absence of crosstalk and are comparable to previous measurements using broadband NIRS

In vivo time-domain diffuse correlation spectroscopy above the water absorption peak

Time-domain diffuse correlation spectroscopy (TD-DCS) is a newly emerging optical technique that exploits pulsed, yet coherent light to non-invasively resolve the blood flow in depth. In this work, we have explored TD-DCS at longer wavelengths compared to those previously used in literature (i.e., 750-850 nm). The measurements were performed using a custom-made titanium-sapphire mode-locked laser, operating at 1000 nm, and an InGaAs photomultiplier as a detector. Tissue-mimicking phantoms and in vivo measurements during arterial arm cuff occlusion in n=4 adult volunteers were performed to demonstrate the proof of concept. We obtained a good signal-to-noise ratio, following the hemodynamics continuously with a relatively fast (1 Hz) sampling rate. In all the experiments, the auto-correlation functions show a decay rate approximately five-fold slower compared to shorter wavelengths. This work demonstrates the feasibility of in vivo TD-DCS in this spectral region and its potentiality for biomedical applications

In vivo time-domain diffuse correlation spectroscopy beyond the water absorption peak

Time-domain diffuse correlation spectroscopy is an emerging method for depth resolved blood flow measurements. To improve depth sensitivity and SNR, we explore this technique at wavelengths beyond water peak, with phantoms and in vivo experiments

Functional monitoring of lung tissue using a hybrid hyperspectral Time-Resolved GASMAS system: A systematic study on ex vivo sample

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

Multi-variable compensated quantum yield measurements of upconverting nanoparticles with high dynamic range : a systematic approach

Non-linear materials such as upconverting nanoparticles (UCNPs) are emerging technology with fast-growing applications in various fields. The power density dependence of the emission quantum yield (QY) of these non-linear materials makes them challenging to characterize using currently available commercial QY systems. We propose a multimodal system to measure QY over a wide dynamic range (1:104), which takes into account and compensates for various distorting parameters (scattering, beam profile, inner filter effect and bandwidth of emission lines). For this, a beam shaping approach enabling speckle free beam profiles of two different sizes (530 µm or 106 µm) was employed. This provides low noise high-resolution QY curves. In particular, at low power densities, a signal-to-noise ratio of >50 was found. A Tm-based core-shell UCNP with excitation at 976 nm and emission at 804 nm was investigated with the system

Broadband time domain diffuse optical reflectance spectroscopy: a review of systems, methods, and applications

This review presents recent developments and a wide overview of broadband time domain diffuse optical spectroscopy (TD-DOS). Various topics including physics of photon migration, advanced instrumentation, methods of analysis, applications covering multiple domains (tissue chromophore, in vivo studies, food, wood, pharmaceutical industry) are elaborated. The key role of standardization and recent studies in that direction are discussed. Towards the end, a brief outlook is presented on the current status and future trends in broadband TD-DO