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.

Over the recent years, a typical implementation of diffuse correlation spectroscopy (DCS) instrumentation has been adapted widely. However, there are no detailed and accepted recipes for designing such instrumentation to meet pre-defined signal-to-noise ratio (SNR) and precision targets. These require specific attention due to the subtleties of the DCS signals. Here, DCS experiments have been performed using liquid tissue simulating phantoms to study the effect of the detected photon count-rate, the number of parallel detection channels and the measurement duration on the precision and SNR to suggest scaling relations to be utilized for device design.

Despite the wide range of clinical and research applications, the reliability of the absolute oxygenation measurements of continuous wave near-infrared spectroscopy sensors is often questioned, partially due to issues of standardization. In this study, we have compared the performances of 13 units of a continuous wave near-infrared spectroscopy device (PortaMon, Artinis Medical Systems, NL) to test their suitability for being used in the HEMOCOVID-19 clinical trial in 10 medical centers around the world. Detailed phantom and in vivo tests were employed to measure the precision and reproducibility of measurements of local blood oxygen saturation and total hemoglobin concentration under different conditions: for different devices used, different operators, for probe repositioning over the same location, and over time (hours/days/months). We have detected systematic differences between devices when measuring phantoms (inter-device variability, <4%), which were larger than the intra-device variability (<1%). This intrinsic variability is in addition to the variability during in vivo measurements on the forearm muscle resulting from errors in probe positioning and intrinsic physiological noise (<9%), which was also larger than the inter-device differences (<3%) during the same test. Lastly, we have tested the reproducibility of the protocol of the HEMOCOVID-19 clinical trial; that is, forearm muscle oxygenation monitoring during vascular occlusion tests over days. Overall, our conclusion is that these devices can be used in multi-center trials but care must be taken to characterize, follow-up, and statistically account for inter-device variability.

In this review, we present an overview of the applications and computed parameters of electromyography (EMG) and near-infrared spectroscopy (NIRS) methods on patients in clinical practice. The eligible studies were those where both techniques were combined in order to assess muscle characteristics from the electrical and hemodynamic points of view. With this aim, a comprehensive screening of the literature based on related keywords in the most-used scientific data bases allowed us to identify 17 papers which met the research criteria. We also present a brief overview of the devices designed specifically for muscular applications with EMG and NIRS sensors (a total of eight papers). A critical analysis of the results of the review suggests that the combined use of EMG and NIRS on muscle has been only partially exploited for assessment and evaluation in clinical practice and, thus, this field shows promises for future developments.

Acute ischemic stroke is a highly dynamic condition. Indeed, large vessels occlusion (LVO) might cause different degrees of hemodynamic impairment that result in complex interplay between LVO, collateral status, and clinical symptomatology. The study of microcirculation, which is the site of cerebral autoregulation and neurovascular coupling, might be a valuable strategy to improve our insight in this field. The concept of the neurovascular unit is one of the key elements of stroke pathophysiology. It has been shown that capillary flow patterns undergo profound changes in cerebral ischemia and affect local oxygen delivery.¹ Modifications in the capillary bed contribute to the neurovascular dysfunction and to the metabolic derangement in the ischemic tissue, where tissue survival depends on oxygen extraction to compensate for the reduced perfusion. Other factors such as involvement of small cerebral veins and the role of the rete vasorum remain undefined.² In addition, secondary changes may develop in ipsilateral hemisphere outside the ischemic area and in the contralateral hemisphere as well. The alteration of regional cerebral blood flow and metabolism in the contralateral hemisphere has been reported.³ 4. ^{– 5} Near-infrared spectroscopy (NIRS) is an optical technique that provides information about oxygenation in the microcirculation of cerebral outer layers.^6,7 Furthermore, it is a noninvasive, safe, and portable methodology that enables real-time monitoring at the bedside of the patient.^6,7 Technical advances have overcome some limitations of the previous NIRS systems. Indeed, the contamination from the extra-cerebral layers and the possibility to retrieve only relative changes with respect to a baseline were the most limiting drawbacks of the continuous-wave NIRS (CW-NIRS) technique.⁸ Advanced optical techniques, such as time-domain NIRS (TD-NIRS) and frequency-domain (FD)-NIRS, allow to recover the absolute concentrations of hemoglobin species and to better separate the contribution of the extra-cerebral layers from the brain cortical ones.⁶ In particular, in TD-NIRS with single source–detector pair, the effect of extra-cerebral layers can be marginal even if fitting with homogeneous model is used.⁹ Therefore, the estimation of brain optical properties is less dependent on the superficial layers. Of course, the use of a multidistance approach and of a priori information on the head anatomy could further improve the accuracy of the estimate, at the cost of increased complexity of the approach. A recent study reported TD-NIRS measurements of cerebral deoxyhemoglobin (HbR), oxyhemoglobin (HbO), total hemoglobin (HbT = HbR + HbO), and tissue oxygen saturation (${\mathrm{StO}}_2=\mathrm{HbO}/\mathrm{HbT}$) values of healthy subjects, demonstrating the reproducibility of results.¹⁰ The study of the cerebral microcirculation by means of cerebral time-domain near infrared spectroscopy (TD-NIRS) could inform about the effect of LVO. The vast majority of studies in ischemic stroke patients have used CW-NIRS,¹¹ 12. 13. 14. 15. 16. ^{– 17} whereas only few were performed with FD-NIRS.^18,19 In addition, in all but one previous studies,¹⁸ recordings were limited to the forehead of the subjects,¹¹ 12. 13. 14. 15. ^{– 16,19} irrespective of the site of ischemic area.

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.