Diffuse optics (DO) encompasses a range of photonics tools based on the study of random photon migration in highly scattering media—biological tissues in particular. Due to its unique features, DO is emerging as a powerful means for clinical or homecare diagnostics.¹ The basic physics of DO is related to the detection of temporal or spatial alteration in photon distribution re-emitted on the tissue surface.² Due to the low power (typically few mW) of injected near-infrared light (600- to 1100-nm range), DO is inherently noninvasive. The photon temporal (or spatial) distribution carries information on the absorption—ultimately related to tissue chemical composition, such as water, lipid, collagen content, oxy- and deoxy-hemoglobin concentration, cytochrome c-oxidase³—and scattering properties—linked to tissue microstructure. Further, DO is one of the few noninvasive modalities capable of providing functional information, e.g., brain or muscle activation.⁴ It can be operated noncontact through remote light illumination and collection.⁵ It explores the tissue well below the skin at depths of up to 2 to 4 cm. It can provide quantitative operator-independent assessment of the tissue status, such as hemoglobin oxygenation level in the brain. Finally, it is highly scalable, sharing the same technology from large clinical tomographic systems down to wearable devices or homecare appliances.⁶ For all these aspects, DO is attracting more and more interest in many fields, such as monitoring vital signs like brain oxygenation in critical care or during interventions,⁷ tumor diagnostics as for breast cancer,⁸ investigating the impact of lifestyle and nutrition on our body,⁹ or other fields such as neuroscience and psychology,¹⁰ sports, and leisure.¹¹ Even further, the operator independence, the depth sensitivity, and the scalability in addition to noninvasiveness make this option attractive for telemedicine and homecare of patients remotely.

In this paper, we present an innovative instrument for near-infrared time-resolved spectroscopy. The system is based on eight custom-designed pulsed diode lasers emitting at different wavelengths in the near-infrared region (635-1050 nm), all exhibiting an average optical power higher than 1 mW at 40 MHz pulse repetition rate, two custom-made single-photon detectors based on wide-area silicon photomultipliers and two time-measurement units based on a custom time-to-digital converter with 10 ps timing resolution. The system instrument response function has a width narrower than 160 ps (fullwidth at half-maximum) and stability better than ±1% for several hours for all the wavelengths. All the components of the instrument were designed in order to be compact. The entire system will be hosted in a standard 19 inches, 5U rack case (size 48 × 38 × 20 cm ³ ). The system communicates with the external computer through a USB 2.0 link and is designed to be employed in a clinical environment. The proposed instrument, thanks to the reduction of its cost and dimensions, paves the way to a wider diffusion of multiwavelengths near-infrared time-resolved spectroscopy systems.

Near-infrared diffuse optical tomography is a non-invasive photonics-based imaging technology suited to functional brain imaging applications. Recent developments have proved that it is possible to build a compact time-domain diffuse optical tomography system based on silicon photomultipliers (SiPM) detectors. The system presented in this paper was equipped with the same eight SiPM probe-hosted detectors, but was upgraded with six injection fibers to shine the sample at several points. Moreover, an automatic switch was included enabling a complete measurement to be performed in less than one second. Further, the system was provided with a dual-wavelength (670 $\mathrm{n}$ $\mathrm{m}$ and 820 $\mathrm{n}$ $\mathrm{m}$ ) light source to quantify the oxy- and deoxy-hemoglobin concentration evolution in the tissue. This novel system was challenged against a solid phantom experiment, and two in-vivo tests, namely arm occlusion and motor cortex brain activation. The results show that the tomographic system makes it possible to follow the evolution of brain activation over time with a 1 $\mathrm{s}$ -resolution.

Silicon photomultipliers (SiPM) are pixelated single-photon detectors combining high sensitivity, good time resolution and high dynamic range. They are emerging in many fields, such as time-domain diffuse optics (TD-DO). This is a promising technique in neurology, oncology, and quality assessment of food, wood, and pharmaceuticals. SiPMs can have very large areas and can significantly increase the sensitivity of TD-DO in tissue investigation. However, such improvement is currently limited by the high detector noise and the worsening of SiPM single-photon time resolution due to the large parasitic capacitances. To overcome such limitation, in this paper, we present two single-photon detection modules, based on 6 × 6 mm² and 10 × 10 mm² SiPMs, housed in vacuum-sealed TO packages, cooled to −15 °C and −36 °C, respectively. They integrate front-end amplifiers and temperature controllers, being very useful instruments for TD-DO and other biological and physical applications. The signal extraction from the SiPM was improved. The noise is reduced by more than two orders of magnitude compared to the room temperature level. The full suitability of the proposed detectors for TD-DO measurements is outside the scope of this work, but preliminary tests were performed analyzing the shape and the stability of the Instrument Response Function. The proposed modules are thus fundamental building blocks to push the TD-DO towards deeper investigations inside the body.

In this work we present a detector module based on large-area silicon photomultiplier, whose design has been optimized for time-domain diffuse optics measurements. In this application, to the best of our knowledge, it represents the largest area detector ever demonstrated, with expected breakthrough performance in terms of scattered light harvesting efficiency. It has been characterized using widely adopted protocols for performance assessment of instruments. We demonstrate the superior light harvesting capability and improved depth sensitivity, which can reach 4 cm. Moreover, the retrieval of optical properties has been demonstrated to be linear and with sufficient accuracy in the range corresponding to the human tissues. As a first step toward clinical application, we first performed in-vivo measurement at very large source-detector distances to show the suitability of the realized detector to tackle new challenges like lung or heart optical monitoring as well as imaging of deep cerebral function.