Study of optimal measurement conditions for time-domain diffuse optics systems

Light is a powerful non-invasive tool that can be exploited to probe highly scattering media like biological tissues for different purposes, from the detection of brain activity to the characterization of cancer lesions. In the last decade, timedomain diffuse optics (TDDO) systems demonstrated improved sensitivity when using time-gated acquisition chains and short source-detector separations (ρ), both theoretically and experimentally. However, the sensitivity to localized absorption changes buried inside a diffusive medium strongly depends on many parameters such as: SDS, laser power, delay and width of the gating window, absorption and scattering properties of the medium, instrument response function (IRF) shape, etc. In particular, relevant effects due to slow tails in the IRF were noticed, with detrimental effects on performances. We present simulated experimental results based on the diffusion approximation of the Radiative Transfer Equation and the perturbation theory subjected to the Born approximation. To quantify the system sensitivity to deep (few cm) and localized absorption perturbations, we exploited contrast and contrast-to-noise ratio (CNR), which are internationally agreed on standardized figures of merit. The purpose of this study is to determine which parameters have the greatest impact on these figures of merit, thus also providing a range of best operative conditions. The study is composed by two main stages: the former is a comparison between simulations and measurements on tissue-mimicking phantom, while the latter is a broad simulation study in which all relevant parameters are tuned to determine optimal measurement conditions. This study essentially demonstrates that under the influence of the slow tails in the IRF, the use of a small SDS no longer corresponds to optimal contrast and CNR. This work sets the ground for future studies with next-generation of TDDO components, presently under development, providing useful hints on relevant features to which one should take care when designing TDDO components

Instrumental, optical and geometrical parameters affecting time-gated diffuse optical measurements: a systematic study

In time-domain diffuse optics the sensitivity to localized absorption changes buried inside a diffusive medium depends strongly on the interplay between instrumental, optical and geometrical parameters, which can hinder the theoretical advantages of novel measurement strategies like the short source-detector distance approach. Here, we present a study based on experimental measurements and simulations to comprehensively evaluate the effect of all different parameters. Results are evaluated exploiting standardized figures of merit, like contrast and contrast-to-noise ratio, to quantify the system sensitivity to deep localized absorption perturbations. Key findings show that the most critical hardware parameter is the memory effect which ultimately limits the dynamic range. Further, a choice of the source-detector distance around 10 mm seems to be a good compromise to compensate non-idealities in practical systems still preserving the advantages of short distances. This work provides both indications for users about the best measurement conditions and strategies, and for technology developers to identify the most crucial hardware features in view of next generation diffuse optics systems

An innovative 8 channels system for time-resolved diffuse optical tomography based on SiPMs

We present the design of a novel 8 channels system for time resolved optical tomography based on Silicon Photomultipliers (SiPMs), therefore knocking down cost and complexity of this technique and paving the way to a widespread diffusion. We validated the system performances on phantoms

Time-resolved optical spectrometer based on a monolithic array of high-precision TDCs and SPADs

We present a compact time-resolved spectrometer suitable for optical spectroscopy from 400 nm to 1 μm wavelengths. The detector consists of a monolithic array of 16 high-precision Time-to-Digital Converters (TDC) and Single-Photon Avalanche Diodes (SPAD). The instrument has 10 ps resolution and reaches 70 ps (FWHM) timing precision over a 160 ns full-scale range with a Differential Non-Linearity (DNL) better than 1.5 % LSB. The core of the spectrometer is the application-specific integrated chip composed of 16 pixels with 250 μm pitch, containing a 20 μm diameter SPAD and an independent TDC each, fabricated in a 0.35 μm CMOS technology. In front of this array a monochromator is used to focus different wavelengths into different pixels. The spectrometer has been used for fluorescence lifetime spectroscopy: 5 nm spectral resolution over an 80 nm bandwidth is achieved. Lifetime spectroscopy of Nile blue is demonstrated

Breaking the rules of time-domain diffuse optics: working with 1 cm2 SiPM and well-beyond the single-photon statistics

Time domain diffuse optics (TD-DO) relies on the injection of ps laser pulses and on the collection of the arrival times of scattered photons. To reach the ultimate limits of the technique (allowing to investigate even structures at depth >5 cm), a large area detector is needed. To this extent, we realized and present a new silicon photomultiplier featuring a 1 cm2 area. To the best of our knowledge, it represents the largest detector ever proposed for TD-DO and shows a light harvesting capability which is more than 1 decade larger than the state-of-the-art technology system. To assess its suitability for TDDO measurements, we tested the detector with several procedures from shared protocols (BIP, nEUROPt and MEDPHOT). However, the light harvesting capability of a detector with large area can be proficiently exploited only if coupled to timing electronics working in sustained count-rate CR (i.e., well above the single photon statistics). For this reason, we study the possibility to work in a regime where (even more than) one photon per laser pulse is detected (i.e., more than 100% laser repetition rate) exploiting in-silico technology. The results show that the possibility to use sustained count-rate represents a dramatic improvement in the number of photons detected with respect to current approaches (where count-rate of 1-5% of the laser repetition rate are used) without significant losses in the measurement accuracy. This represents a new horizon for TD-DO measurements, opening the way to new applications (e.g., optical investigation of the lung or monitoring of fast dynamics never studied before)

Quantification in time-domain diffuse optical tomography using mellin-laplace transforms

Simulations and phantom measurements are used to evaluate the ability of time-domain diffuse optical tomography using Mellin-Laplace transforms to quantify the absorption perturbation of centimetric objects immersed at depth 1-2 cm in turbid media. We find that the estimated absorption coefficient varies almost linearly with the absorption change in the range of 0-0.15 cm-1 but is underestimated by a factor that depends on the inclusion depth (~2, 3 and 6 for depths of 1.0, 1.5 and 2.0 cm respectively). For larger absorption changes, the variation is sublinear with ~20% decrease for δμa = 0.37 cm-1. By contrast, constraining the absorption change to the actual volume of the inclusion may considerably improve the accuracy and linearity of the reconstructed absorption

Use of bioresorbable fibers for interstitial time-domain diffuse optical spectroscopy using fast-gating

Bioresorbable materials have gained interest for implantable optical components such as fibers for medical devices and have been demonstrated as suitable to perform diffuse optical measurements. In this work, we demonstrate interstitial, broadband, time-domain diffuse optical spectroscopy measurements using bioresorbable fibers, by employing a single-photon avalanche diode operated in an ultrafast time-gate mode for photon detection. Using tissue equivalent liquid phantoms, we test the system absorption linearity as per the MEDPHOT protocol and demonstrate the scattering independent absorption retrieval of the water spectrum in the 600-920 nm range. Consequently, we also attempt to distinguish the spectral changes due to the presence of optically denser speck inclusion in a tissue equivalent liquid phantom

Time-domain functional diffuse optical tomography system based on fiber-free silicon photomultipliers

Based on recent developments in both single-photon detectors and timing electronic circuits, we designed a compact and cost effective time-domain diffuse optical tomography system operated at 1 Hz acquisition rate, based on eight silicon photomultipliers and an 8-channel time-to-digital converter. The compact detectors are directly hosted on the probe in a circular arrangement around a single light injection fiber, so to maximize light harvesting. Tomography is achieved exploiting the depth sensitivity that is encoded in the arrival time of detected photons. The system performances were evaluated on simulations to assess possible the limitations arising from the use of a single injection point, and then on phantoms and in vivo to prove the eligibility of these technologies for diffuse optical tomography

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