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.

A novel detection chain, based on 8 Silicon Photomultipliers (forming a wide-area custom-made detection probe) and on a time-to-digital converter, was developed to improve the signal level in multi-wavelength (635-1060 nm) time domain optical mammography. The performances of individual components and of the overall chain were assessed using established protocols (BIP and MEDPHOT). The photon detection efficiency was improved by up to 3 orders of magnitude, and the maximum count rate level was increased by a factor of 10 when compared to the previous system, based on photomultiplier tubes and conventional time-correlated single-photon counting boards. In the estimate of optical parameters, the novel detection chain provides performances comparable to the previous system, widely validated in clinics, but with higher signal level, higher robustness, and at a lower price per channel, thus targeting important requirements for clinical applications.

Two main bottlenecks prevent time-domain diffuse optics instruments to reach their maximum performances, namely the limited light harvesting capability of the detection chain and the bounded data throughput of the timing electronics. In this work, for the first time to our knowledge, we overcome both those limitations using a probe-hosted large area silicon photomultiplier detector coupled to high-throughput timing electronics. The system performances were assessed based on international protocols for diffuse optical imagers showing better figures with respect to a state-of-the-art device. As a first step towards applications, proof-of-principle in-vivo brain activation measurements demonstrated superior signal-to-noise ratio as compared to current technologies.

A recent upgrade of the time domain multi-wavelength optical mammograph developed by Politecnico di Milano achieved good performance in laboratory tests [ Biomed. Opt. Express 9, 755 (2018).10.1364/BOE.9.000755 ]. However, it proved unsatisfactory when in vivo measurements were finally performed. That led to a further upgrade, including the replacement of the time-to-digital converter with a new model, and the related set-up changes. The new instrument version offers improved laboratory performance (as assessed through established protocols: BIP and MEDPHOT) and good in vivo performance (extension of the scanned breast area, repeatability, consistency of estimated tissue composition with physiology). Besides introducing the new set-up and detailing its laboratory and in vivo performance, we highlight the importance of systematic in vivo testing before entering clinical trials.

Fast time-gated single-photon detectors demonstrated high depth sensitivity in the detection of localized absorption perturbations inside scattering media, but their use for in vivo clinical applications—such as functional imaging of brain activation—was impaired by their small ( < 0.04 m m 2 ) active area. Here, we demonstrate, both on phantoms and in vivo, the performance of a fast-gated digital silicon photomultiplier (SiPM) that features an overall active area of 8.6 m m 2 , overcoming the photon collection capability of established time-gated single-pixel detectors by orders of magnitude, enabling deep investigations within scattering media and high signal-to-noise ratios at late photon arrival times.

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.