Impairment of cerebral autoregulation and haemodynamics is an important cause of morbidity and mortality in neonates, making a continuous monitoring of brain health extremely important in Neonatal Intensive Care Unit. Time Domain NIRS (TD-NIRS) is an advantageous technique for non-invasively continuous monitoring of brain hemoglobin concentration at bed side. However, NIRS measurements are influenced by superficial tissues (i.e., scalp, skull and cerebrospinal fluid) and head geometry, which could affect the estimation of brain haemodynamic parameters. In this work we evaluated the accuracy of TD-NIRS in estimating neonatal cerebral haemodynamics through Monte Carlo simulations. In particular, we simulated photon propagation inside two realistic meshes of preterm (29 weeks post-menstrual age (PMA)), and term (44 weeks PMA) neonates' head. The obtained results were analyzed with semi-infinite and spherical homogeneous model for photon migration, and showed an underestimation of hemoglobin concentration, and good accuracy for brain saturation, empowering the ability of TD-NIRS technique in estimating brain tissue saturation.

The effect of sustained fatigue during an upper limb isometric exercise is presented to investigate a group of healthy subjects with simultaneous time-domain (TD) NIRS and surface electromyography (sEMG) recordings on the deltoid lateralis muscle. The aim of the work was to understand which TD-NIRS parameters can be used as descriptors for sustained muscular fatigue, focusing on the slow phase of this process and using median frequency (MF) computed from sEMG as gold standard measure. It was found that oxygen saturation and deoxy-hemoglobin are slightly better descriptors of sustained fatigue, than oxy-hemoglobin, since they showed a higher correlation with MF, while total-hemoglobin correlation with MF was lower.

Objectives A new device that combines, for the first time, two photonic technologies (time-resolved near-infrared spectroscopy and diffuse correlation spectroscopy) was provided and tested within the BabyLux project. Aim was to validate the expected changes in cerebral oxygenation and blood flow. Methods A pulse oximeter and the BabyLux device were held in place (right hand/wrist and frontoparietal region, respectively) for 10 min after birth in healthy term infants delivered by elective caesarean section. Pulse oximeter saturation (SpO(2)), cerebral tissue oxygen saturation (StO(2)) and blood flow index (BFI) were measured over time. Tissue oxygen extraction (TOE) and cerebral metabolic rate of oxygen index (CMRO2I) were calculated. Results Thirty infants were enrolled in two centres. After validity check of data, 23% of infants were excluded from TOE and CMRO2I calculation due to missing data. As expected, SpO(2) (estimate 3.05 %/min; 95% CI 2.78 to 3.31 %/min) and StO(2) (estimate 3.95 %/ min; 95% CI 3.63 to 4.27 %/min) increased in the first 10 min after birth, whereas BFI (estimate -2.84x10(-9) cm(2)/s/min; 95% CI -2.50x10(-9) to -3.24x10(-9) cm(2)/s/ min) and TOE (estimate -0.78 %/min; 95% CI -1.12 to -0.45 %/min) decreased. Surprisingly, CMRO2I decreased (estimate -7.94x10(-8)/min; 95% CI -6.26x10(-8) to -9.62x10(-8)/min). Conclusions Brain oxygenation and BFI during transition were successfully and simultaneously obtained by the BabyLux device; no adverse effects were recorded, and the BabyLux device did not limit the standard care. The preliminary results from clinical application of the BabyLux device are encouraging in terms of safety and feasibility; they are consistent with previous reports on brain oxygenation during transition, although the interpretation of the decreasing CMRO2I remains open.

Diffuse correlation spectroscopy (DCS) can non-invasively and continuously asses regional cerebral blood flow (rCBF) at the cot-side by measuring a blood flow index (BFI) in non-traditional units of cm(2)/s. We have validated DCS against positron emission tomography using (15) O-labeled water (O-15-water PET) in a piglet model allowing us to derive a conversion formula for BFI to rCBF in conventional units (ml/100g/min). Neonatal piglets were continuously monitored by the BabyLux device integrating DCS and time resolved near infrared spectroscopy (TRS) while acquiring (15) O-water PET scans at baseline, after injection of acetazolamide and during induced hypoxic episodes. BFI by DCS was highly correlated with rCBF (R = 0.94, p < 0.001) by PET. A scaling factor of 0.89 (limits of agreement for individual measurement: 0.56, 1.39)x10(9)x (ml/100g/min)/(cm(2)/s) was used to derive baseline rCBF from baseline BFI measurements of another group of piglets and of healthy newborn infants showing an agreement with expected values. These results pave the way towards non-invasive, cot-side absolute CBF measurements by DCS on neonates.

Simple Summary Anticipatory behaviour to an oncoming food reward can be triggered via classical conditioning, implies the activation of neural networks, and may serve to study the emotional state of animals. This work aimed to investigate how the anticipatory response affects cerebral cortex activity in sheep. Eight ewes were conditioned to associate a neutral auditory stimulus (water bubble) to a food reward (maize grains). Then, sheep were trained to wait 15 s before accessing the food (anticipatory phase). Behavioural reaction and changes in cortical oxy-haemoglobin ([O(2)Hb]) and deoxy-haemoglobin ([HHb]) concentration were recorded by functional near infrared spectroscopy (fNIRS). During the anticipatory phase, sheep increased their active behaviour together with a cortical activation (increase of [O(2)Hb] and a decrease of [HHb]) compared to baseline. Sheep showed a greater response of the right hemisphere compared to the left hemisphere, possibly indicating frustration. Behavioural and cortical changes observed during anticipation of a food reward reflect a learnt association and an increased arousal, but no clear emotional valence of the sheep subjective experience.

The capability of three different tissue oximeters exploiting visible and near-infrared light to determine oxy- A nd deoxyhemoglobin concentrations and the blood oxygen saturation has been tested in a blood-lipid liquid phantom.

Time-domain diffuse correlation spectroscopy (TD-DCS) is an emerging optical technique with the potential to resolve the blood flow (BF) in depth. The first in vivo measurements have been shown recently on humans, however improvements in terms of signal-to-noise ratio (SNR) and depth sensitivity would be beneficial for biological applications. In this contribution, we explore the possibility of in vivo TD-DCS measurements above 1000 nm, and discuss its possible advantages compared to standard wavelengths (i.e. 700-800 nm). In our experimental setup, we exploited a tunable pulsed laser source extended more to the infrared and an InGaAs photomultiplier. Here, we report the results of a cuff occlusion on the forearm of a healthy adult subject at a wavelength of 1000 nm. Compared to the same experiment at standard wavelength (785 nm), the electric-field auto-correlation functions show a slower decay rate during all the experiment (both during and after the occlusion) as expected, suggesting a higher SNR. Even longer wavelengths, for diminishing water absorption, can be obtained through optimization of the laser source and the use of more efficient detectors.

Large vessel occlusion (LVO) stroke might cause different degrees of hemodynamic impairment that affects microcirculation and contributes to metabolic derangement. Time-domain near-infrared spectroscopy (TD-NIRS) estimates the oxygenation of microcirculation of cerebral outer layers. We measure hemoglobin species and tissue oxygen saturation (StO(2)) of anterior circulation stroke patients, classified as LVO or lacunar, and assess the differences compared with controls and according to LVO recanalization status. Fiducial markers categorize the brain region below each TD-NIRS probe as ischemic or nonstroke areas. The study includes 47 consecutive acute ischemic stroke patients and 35 controls. The ischemic area has significantly higher deoxy-hemoglobin (HbR) and total hemoglobin (HbT) compared with controls in both recanalized and nonrecanalized patients but lower StO(2) only in recanalized patients. Recanalized patients have significantly lower mean StO(2) in the ipsilateral hemisphere compared with nonrecanalized patients. This is the first study to report TD-NIRS measurements in acute ischemic stroke patients. TD-NIRS is able to detect significant differences in hemoglobin species in LVO stroke compared with controls and according to recanalization status. This preliminary data might suggest that StO(2) can serve as a surrogate functional marker of the metabolic activity of rescued brain tissue. (C) The Authors. Published by SPIE under a Creative Commons Attribution 4.0 Unported License.

In this paper we present a Time Resolved Near Infrared device for bed-side neuromonitoring of ischemic stroke patients. This system features three wavelengths allowing a better and robust retrieval of the absolute values of oxy and deoxyhaemoglobin. The device has been fully characterized following the guidelines of the MEDPHOT and BIP protocols, developed under NEUROPt project. Time Resolved spectroscopy is a promising technology that can provide reproducible results in terms of absorption and scattering coefficients. This portable and non-invasive system has been proven suitable for operation in clinical settings. Data were collected from a cohort of 47 ischemic stroke patients and, according to their cerebral impairment, compared with normal values obtained from a group of 35 healthy subjects. Significant differences in haemoglobin species concentration and saturation were found between healthy and ischemic stroke patients. In the ischemic area of both recanalized and non-recanalized ischemic stroke patients, deoxy-haemoglobin and total haemoglobin values are higher than in controls, while tissue oxygen saturation values are lower only in recanalized patients. © 2019 SPIE.

Functional near infrared spectroscopy (NIRS) is a widespread non-invasive technique to monitor skeletal muscle metabolism. However, only variation of oxygenated (HHb), deoxygenated (O2Hb), total (tHb) hemoglobin and saturation (SO2) are usually reported. In this study, Time Domain (TD) NIRS approach was exploited to perform a preliminary quantitative characterization of vastus lateralis muscle during incremental exercise. A population of 11 healthy young male subjects performed on a mechanical cycle ergometer an incremental exercise (initial work rate range = 60-96 W, increment = 12-18 W/min) until exhaustion. TD NIRS, heart rate, pulmonary ventilation (VE), O2 uptake (VO2), CO2 output (VCO2), blood lactate concentration ([La]b) and Borg scale were measured during the exercise. From TD NIRS, muscles absolute values of absorption and scattering coefficients were obtained with a homogeneous approach and hemoglobin concentrations and saturation levels were calculated. The time courses of HHb, O2Hb, tHb and SO2 were consistent with previous literature results. A high inter-subject variability was found for both optical properties and hemodynamic concentrations. Further statistical group analysis will be required in order to highlight significant behavior within the population and correlation with physiological parameters.

Glaucoma is a multifactorial optic neuropathy characterized by progressive loss of retinal ganglion cells, changes in optic disk morphology and visual field defects; its pathophysiology is still unclear. Recently it was demonstrated that glaucoma can be associated with a degenerative effect at the level of the optic nerve and the primary visual cortex. Functional near infrared spectroscopy (fNIRS) is a non-invasive optical technique, which allows the brain hemodynamic monitoring. In particular, the Time Domain fNIRS (TD-fNIRS) allows to remove from the detected signal the contribution coming from the surface (scalp, skull and cerebral fluid) in order to obtain the brain hemodynamic activation. The aim of this preliminary study is to understand if in the glaucomatous patients, the visual cortex activation during a visual stimulus is different from the one of a control group. A total of 20 subjects took part to the study. We divided them into three groups: 7 controls, 5 ocular hypertension (HYPER), and 8 glaucoma. The hemodynamic time courses of oxy- (OHB) and deoxy- (HHB) hemoglobin were compared with a hemodynamic response function (HRF) with the adaptive HRF approach. Finally, an inference test was applied (t-student) to statistically determine the visual cortex activation (simultaneous increase in OHB and decrease in HHB). The p-value threshold was set at 0.05. The 86% of the controls and the 80% of the HYPER combinations are activated; while the 81% of the glaucoma ones are not, outlining a well-defined trend. Also the OHB and HHB show drastic differences between controls and patients.

Time-resolved (TR) techniques are exploited in many biomedical applications in order to find absolute values of absorption (?a) and reduced scattering (?s') coefficients that characterize biological tissues chemical and microstructure properties. However, the concomitant acquisition of tissue distribution time-of-flight (DTOF) and instrument response function (IRF) is necessary to perform quantitative measurements. This can be a non-trivial time consuming operation which typically requires to detach the optical fibers from the measurement probe (usually put in a reflectance configuration for in-vivo applications) in order to face them one to each other ("reference" geometry). To overcome these difficulties, a new IRF measurement method that exploit the "reflectance" geometry is here proposed. A practical 3D printed implementation has been carried out for a specific device to test the feasibility of this approach and if the IRF acquired in the "reflectance" geometry is equivalent to the "reference" one. A particular problem addressed is the determination of the temporal shift T0 that can occur between IRF and sample DTOF. Two different approaches, based respectively on the curves barycenters difference and on a calibration phantom, are proposed. Both methods are valid and indifferently applicable according to specific measurement requirements. This allows "reflectance" IRF acquisition to be eligible as standard methodology for TR measurements.

The BabyLux device is a hybrid diffuse optical neuromonitor that has been developed and built to be employed in neonatal intensive care unit for the noninvasive, cot-side monitoring of microvascular cerebral blood flow and blood oxygenation. It integrates time-resolved near-infrared and diffuse correlation spectroscopies in a user-friendly device as a prototype for a future medical grade device. We present a thorough characterization of the device performance using test measurements in laboratory settings. Tests on solid phantoms report an accuracy of optical property estimation of about 10%, which is expected when using the photon diffusion equation as the model. The measurement of the optical and dynamic properties is stable during several hours of measurements within 3% of the average value. In addition, these measurements are repeatable between different days of measurement, showing a maximal variation of 5% in the optical properties and 8% for the particle diffusion coefficient on a liquid phantom. The variability over test/retest evaluation is <3%. The integration of the two modalities is robust and without any cross talk between the two. We also perform in vivo measurements on the adult forearm during arterial cuff occlusion to show that the device can measure a wide range of tissue hemodynamic parameters. We suggest that this platform can form the basis of the next-generation neonatal neuromonitors to be developed for extensive, multicenter clinical testing. (C) The Authors. Published by SPIE under a Creative Commons Attribution 4.0 Unported License.

We have investigated the accuracy and precision of "the BabyLux device", a hybrid time-resolved near-infrared (TRS) and diffuse correlation spectroscopy (DCS) neuro-monitor for the pre-term infant. Numerical data with realistic noise were simulated and analyzed using the BabyLux device as a reference system and different experimental and analysis parameters. The results describe the limits for the precision and the accuracy to be expected. The dependence of these limits on different experimental conditions and choices of the analysis method is also described. Experiments demonstrate comparable values for precision with respect to the simulation results. (C) 2019 Optical Society of America under the terms of the OSA Open Access Publishing Agreement

In this paper, a time-domain fast gated near-infrared spectroscopy system is presented. The system is composed of a fiber-based laser providing two pulsed sources and two fast gated detectors. The system is characterized on phantoms and was tested in vivo, showing how the gating approach can improve the contrast and contrast-to-noise-ratio for detection of absorption perturbation inside a diffusive medium, regardless of source-detector separation.

Time-domain diffuse correlation spectroscopy (TD-DCS) is an emerging noninvasive optical technique with the potential to resolve blood flow (BF) and optical coefficients (reduced scattering and absorption) in depth. Here, we study the effects of finite temporal resolution and gate width in a realistic TD-DCS experiment. We provide a model for retrieving the BF from gated intensity autocorrelations based on the instrument response function, which allows for the use of broad time gates. This, in turn, enables a higher signal-to-noise ratio that is critical for in vivo applications. In numerical simulations, the use of the proposed model reduces the error in the estimated late gate BF from 34% to 3%. Simulations are also performed for a wide set of optical properties and source-detector separations. In a homogeneous phantom experiment, the discrepancy between later gates BF index and ungated BF index is reduced from 37% to 2%. This work not only provides a tool for data analysis but also physical insights, which can be useful for studying and optimizing the system performance. (C) The Authors. Published by SPIE under a Creative Commons Attribution 4.0 Unported License.

BACKGROUND: The BabyLux device is a prototype optical neuro-monitor of cerebral oxygenation and blood flow for neonatology integrating time-resolved reflectance spectroscopy and diffuse correlation spectroscopy.

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.

The content and composition of the main antioxidants in the pulp of mangoes depend also on cultivar and maturity degree, the latter being non-destructively evaluated by the absorption coefficient measured by Time-resolved Reflectance Spectroscopy (TRS) at 540 nm (µ540). Aiming at evaluating the levels of antioxidants [carotenoids (CAR), phenols (TPC), ascorbic acid (AA)] and antioxidant capacity (TAC) in relation to µ540 maturity class, selected 'Haden' and 'Palmer' mangoes were measured for µ540 by TRS, classified based on µ540 value as less (LeM), medium (MeM) and more (MoM) mature and analyzed for pulp firmness, pulp color (a*, h°, Yellowness Index), CAR (total and composition by HPLC-DAD), TPC, AA and TAC. 'Palmer' fruit had higher TPC, AA and TAC than 'Haden' mangoes. On average MoM fruit showed higher TPC, total CAR, total all-trans-violaxanthin esters and all-trans-?-carotene than MeM and LeM fruit. LeM fruit did not have compounds belonging to the 9-cis-violaxanthin group, while cis-?-cryptoxanthin was approx. 19% of total carotenoids. In MoM mangoes the main carotenoid was all-trans-?-carotene (53%), followed by total all-trans-violaxanthin esters (30%), 9-cis-violaxanthin group (8%) and cis-?-cryptoxanthin (6%). The µ540 significantly correlated (r=0.78-0.94) with total CAR, all-trans-?-carotene, all-trans-violaxanthin no.3 (both cultivars), TPC, all-trans-violaxanthin no.1, no.2, no.6 ('Haden'), and 9-cis-violaxanthin no.2, no.3 ('Palmer'). Our results indicate that TRS is suitable to non-destructively measure the pulp color of mangoes and to sort fruit with different ripening degree and nutraceutical properties.

Dementia disorders are increasingly becoming sources of a broad range of problems, strongly interfering with the normal daily tasks of a growing number of individuals. Such neurodegenerative diseases are often accompanied with progressive brain atrophy that, at late stages, leads to drastically reduced brain dimensions. Currently, this structural change could be followed with X-ray computed tomography (XCT) or magnetic resonance imaging (MRI), but they share numerous disadvantages in terms of usability, invasiveness and costs. In this work, we aim to retrieve information concerning the brain-atrophy stage and its evolution, proposing a novel approach based on non-invasive time-resolved near infra-red (tr-NIR) measurements. For this purpose, we created a set of virtual human-head atlases in which we eroded the brain as it would happen in a clinical brain-atrophy progression. These realistic meshes were used to simulate a longitudinal tr-NIR study, investigating the effects of an increased amount of cerebral spinal fluid (CSF) in the photon diffusion. The analysis of late photons in the time-resolved reflectance curve-obtained via accurate Monte Carlo simulations-exhibited peculiar slope-changes upon CSF layer increase. The visibility of the effect under several measurement conditions suggested good sensitivity to CSF variation, even in the case of real measurement and under different geometrical models. The robustness of the results might promote the technique as a potential indicator of the dementia progression, relying only on fast and non-invasive optical observations.