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Thyroid vascularization and hemodynamics become altered in thyroid pathologies and could thus inform diagnostics, therapy planning, and follow-up. However, the current non-invasive monitoring methods available in clinics lack the necessary sensitivity and/or are impractical for large-scale deployment. As a step towards proposing a new modality, we applied the first platform, to our knowledge, designed to do simultaneous measurements of neck anatomy and thyroid microvascular hemodynamics and metabolism in a single probe placement, integrating state-of-the-art near-infrared spectroscopy techniques and clinical ultrasound. A rich dataset was formed with sixty-five subjects (forty-eight females), including eighteen healthy volunteers and forty-seven patients with thyroid nodules, characterizing thyroid tissue and the effects of demographic and anatomical variables while preserving the standard clinical workflow. We have found marked reductions with age and body mass index in thyroid total hemoglobin concentration ( THC ), tissue oxygen saturation ( StO 2 ), and blood flow index ( BFi ), among others. Patients showed lower THC and BFi than healthy subjects, and the limited sample of malignant nodules showed a higher StO 2 than the benign. These findings support the need for personalized clinical approaches., Competing Interests: The role of all the companies (HemoPhotonics S.L., Vermon SA, IMV Imaging) and their employees involved has been defined by the project objectives, tasks, and work packages and has been reviewed by the European Commission (European Union’s Horizon 2020 research and innovation programme, LUCA project, grant agreement No. 688303). ICFO has equity ownership in the spin-off company HemoPhotonics S.L. and UMW is the CEO. TD and UMW are inventors of relevant patents. MB, DC, ADM and AT are co-founders of PIONIRS s.r.l., a spin-off company from Politecnico di Milano (Italy), and MB is the CEO of the company. Their involvement in the study primarily preceded the company’s foundation. All potential financial conflicts of interest and research objectivity were monitored by ICFO’s Knowledge & Technology Transfer Department., (© 2024 Optica Publishing Group.)

Significance: Anemia is a common problem in preterm neonates, and red blood cell transfusion (RBCT) is used to improve oxygen delivery. However, RBCT is associated with complications, although an increase in cerebral oxygenation has been documented, and no universally accepted biomarker for the need for transfusion (i.e., the concentration of hemoglobin in the blood) has been defined., Aim: We used a hybrid optical device (BabyLux device) that merges time-domain near-infrared spectroscopy (TD-NIRS) and diffuse correlation spectroscopy (DCS) to potentially obtain a better assessment of the cerebral effects of RBCT compared with previous studies using continuous wave (CW) spatially resolved NIRS., Approach: Eighteen clinically stable preterm neonates were assessed before and after RBCT by the BabyLux device as five repetitions of 60 s measurement (with 1 s acquisition time), estimating the cerebral blood flow (CBF) as a blood flow index (BFI), the total hemoglobin concentration (tHb), and the cerebral tissue oxygen saturation ( S t O 2 ). S t O 2 was also continuously monitored by a commercial CW-NIRS device, as well as peripheral saturation, S p O 2 . Tissue oxygen extraction (TOE) and cerebral metabolic rate of oxygen consumption ( tCMRO 2 ) were computed, and the Wilcoxon signed-rank test for paired data was performed, comparing the data acquired before and after RBCT., Results: The BabyLux data from four neonates did not meet quality criteria and were discarded. After the transfusion, tHb and S t O 2 (measured both with TD-NIRS and CW-NIRS devices) significantly increased, causing a significant decrease in TOE. CW-NIRS showed a wider dispersion of S t O 2 data compared with TD-NIRS. However, CBF did not decrease proportionally but the variation was high, as well as for tCMRO 2 ., Conclusions: The results confirm previous CW-NIRS studies, but the wide variability of BFI makes the effects of RBCT on cerebral metabolism uncertain., Competing Interests: A.T. and D.C. are co-founders of PIONIRS S.r.l., Italy (I). U.M.W. is the CEO and co-founder of HemoPhotonics S.L. Other authors declare that there are no conflicts of interest related to this article., (© 2024 The Authors.)

The detection of levels of impairment in microvascular oxygen consumption and reactive hyperemia is vital in critical care. However, there are no practical means for a robust and quantitative evaluation. This paper describes a protocol to evaluate these impairments using a hybrid near-infrared diffuse optical device. The device contains modules for near-infrared time-resolved and diffuse correlation spectroscopies and pulse-oximetry. These modules allow the non-invasive, continuous, and real-time measurement of the absolute, microvascular blood/tissue oxygen saturation (StO2) and the blood flow index (BFI) along with the peripheral arterial oxygen saturation (SpO2). This device uses an integrated, computer-controlled tourniquet system to execute a standardized protocol with optical data acquisition from the brachioradialis muscle. The standardized vascular occlusion test (VOT) takes care of the variations in the occlusion duration and pressure reported in the literature, while the automation minimizes inter-operator differences. The protocol we describe focuses on a 3-min occlusion period but the details described in this paper can readily be adapted to other durations and cuff pressures, as well as other muscles. The inclusion of an extended baseline and post-occlusion recovery period measurement allows the quantification of the baseline values for all the parameters and the blood/tissue deoxygenation rate that corresponds to the metabolic rate of oxygen consumption. Once the cuff is released, we characterize the tissue reoxygenation rate, magnitude, and duration of the hyperemic response in BFI and StO2. These latter parameters correspond to the quantification of the reactive hyperemia, which provides information about the endothelial function. Furthermore, the above-mentioned measurements of the absolute concentration of oxygenated and deoxygenated hemoglobin, BFI, the derived metabolic rate of oxygen consumption, StO2, and SpO2 provide a yet-to-be-explored rich data set that can exhibit disease severity, personalized therapeutics, and management interventions.

Objective. In this paper, we present a detailed in vivo characterization of the optical and hemodynamic properties of the human sternocleidomastoid muscle (SCM), obtained through ultrasound-guided near-infrared time-domain and diffuse correlation spectroscopies. Approach. A total of sixty-five subjects (forty-nine females, sixteen males) among healthy volunteers and thyroid nodule patients have been recruited for the study. Their SCM hemodynamic (oxy-, deoxy- and total hemoglobin concentrations, blood flow, blood oxygen saturation and metabolic rate of oxygen extraction) and optical properties (wavelength dependent absorption and reduced scattering coefficients) have been measured by the use of a novel hybrid device combining in a single unit time-domain near-infrared spectroscopy, diffuse correlation spectroscopy and simultaneous ultrasound imaging. Main results. We provide detailed tables of the results related to SCM baseline (i.e. muscle at rest) properties, and reveal significant differences on the measured parameters due to variables such as side of the neck, sex, age, body mass index, depth and thickness of the muscle, allowing future clinical studies to take into account such dependencies. Significance. The non-invasive monitoring of the hemodynamics and metabolism of the sternocleidomastoid muscle during respiration became a topic of increased interest partially due to the increased use of mechanical ventilation during the COVID-19 pandemic. Near-infrared diffuse optical spectroscopies were proposed as potential practical monitors of increased recruitment of SCM during respiratory distress. They can provide clinically relevant information on the degree of the patient's respiratory effort that is needed to maintain an optimal minute ventilation, with potential clinical application ranging from evaluating chronic pulmonary diseases to more acute settings, such as acute respiratory failure, or to determine the readiness to wean from invasive mechanical ventilation., (Creative Commons Attribution license.)

In this work, we used a hybrid time domain near-infrared spectroscopy (TD-NIRS) and diffuse correlation spectroscopy (DCS) device to retrieve hemoglobin and blood flow oscillations of skeletal muscle microvasculature. We focused on very low (VLF) and low-frequency (LF) oscillations ( i.e., frequency lower than 0.145 Hz), that are related to myogenic, neurogenic and endothelial activities. We measured power spectral density (PSD) of blood flow and hemoglobin concentration in four muscles (thenar eminence, plantar fascia, sternocleidomastoid and forearm) of 14 healthy volunteers to highlight possible differences in microvascular hemodynamic oscillations. We observed larger PSDs for blood flow compared to hemoglobin concentration, in particular in case of distal muscles ( i.e., thenar eminence and plantar fascia). Finally, we compared the PSDs measured on the thenar eminence of healthy subjects with the ones measured on a septic patient in the intensive care unit: lower power in the endothelial-dependent frequency band, and larger power in the myogenic ones were observed in the septic patient, in accordance with previous works based on laser doppler flowmetry., Competing Interests: The role in the project of all the companies and their employees involved (pioNIRS s.r.l., ASPHALION S.L, BioPixs Ltd, HemoPhotonics S.L.) has been defined by the project objectives, tasks, and work packages and has been reviewed by the European Commission (European Union's Horizon 2020 research and innovation programme, VASCOVID project, grant agreement No. 101016087). ICFO has equity ownership in the spin-off company HemoPhotonics S.L. and UMW is the CEO. TD and UMW are inventors on relevant patents. All the potential financial conflicts of interest and objectivity of research have been monitored by ICFO’s Knowledge & Technology Transfer Department. No financial conflicts of interest were identified. M.B., M.L. A.T., A.T., and D.C. are cofounders of pioNIRS S.r.l., (Italy)., (© 2023 Optica Publishing Group under the terms of the Optica Open Access Publishing Agreement.)

Significance: Critically ill newborns are at risk of brain damage from cerebrovascular disturbances. A cerebral hemodynamic monitoring system would have the potential role to guide targeted intervention., Aim: To obtain, in a population of newborn infants, simultaneous near-infrared spectroscopy (NIRS)-based estimates of cerebral tissue oxygen saturation ( StO 2 ) and blood flow during variations of carbon dioxide tension ( pCO 2 ) levels within physiologic values up to moderate permissive hypercapnia, and to examine if the derived estimate of metabolic rate of oxygen would stay constant, during the same variations., Approach: We enrolled clinically stable mechanically ventilated newborns at postnatal age > 24    h without brain abnormalities at ultrasound. StO 2 and blood flow index were measured using a non-invasive device (BabyLux), which combine time-resolved NIRS and diffuse-correlation spectroscopy. The effect of changes in transcutaneous pCO 2 on StO 2 , cerebral blood flow (CBF), and cerebral metabolic rate of oxygen index ( tCMRO 2 i ) were estimated., Results: Ten babies were enrolled and three were excluded. Median GA at enrollment was 39 weeks and median weight 2720 g. StO 2 increased 0.58% (95% CI 0.55; 0.61, p < 0.001 ), CBF 2% (1.9; 2.3, p < 0.001 ), and tCMRO 2 0.3% (0.05; 0.46, p = 0.017 ) per mmHg increase in pCO 2 ., Conclusions: BabyLux device detected pCO 2 -induced changes in cerebral StO 2 and CBF, as expected. The small statistically significant positive relationship between pCO 2 and tCMRO 2 i variation is not considered clinically relevant and we are inclined to consider it as an artifact., (© 2023 The Authors.)

Significance: The optical measurement of cerebral oxygen metabolism was evaluated., Aim: Compare optically derived cerebral signals to the electroencephalographic bispectral index (BIS) sensors to monitor propofol-induced anesthesia during surgery., Approach: Relative cerebral metabolic rate of oxygen ( rCMRO 2 ) and blood flow (rCBF) were measured by time-resolved and diffuse correlation spectroscopies. Changes were tested against the relative BIS (rBIS) ones. The synchronism in the changes was also assessed by the R-Pearson correlation., Results: In 23 measurements, optically derived signals showed significant changes in agreement with rBIS: during propofol induction, rBIS decreased by 67% [interquartile ranges (IQR) 62% to 71%], rCMRO 2 by 33% (IQR 18% to 46%), and rCBF by 28% (IQR 10% to 37%). During recovery, a significant increase was observed for rBIS (48%, IQR 38% to 55%), rCMRO 2 (29%, IQR 17% to 39%), and rCBF (30%, IQR 10% to 44%). The significance and direction of the changes subject-by-subject were tested: the coupling between the rBIS, rCMRO 2 , and rCBF was witnessed in the majority of the cases (14/18 and 12/18 for rCBF and 19/21 and 13/18 for rCMRO 2 in the initial and final part, respectively). These changes were also correlated in time ( R > 0.69 to R = 1 , p - values < 0.05 )., Conclusions: Optics can reliably monitor rCMRO 2 in such conditions., (© 2023 The Authors.)

A practical assessment of the general health and microvascular function of the palm muscle, abductor pollicis brevis (APB), is important for the diagnosis of different conditions. In this study, we have developed a protocol and a probe to study microvascular blood flow using near-infrared diffuse correlation spectroscopy (DCS) in APB during and after thumb abduction at 55% of maximum voluntary contraction (MVC). Near-infrared time resolved spectroscopy (TRS) was also used to characterize the baseline optical and hemodynamic properties. Thirteen (n=13) subjects were enrolled and subdivided in low MVC (N=6, MVC<2.3 kg) and high MVC (N=7, MVC≥2.3 kg) groups. After ruling out significant changes in the systemic physiology that influence the muscle hemodynamics, we have observed that the high MVC group showed a 56% and 36% decrease in the blood flow during exercise, with respect to baseline, in the long and short source-detector (SD) separations (p=0.031 for both). No statistical differences were shown for the low MVC group (p=1 for short and p=0.15 for long SD). These results suggest that the mechanical occlusion, due to increased intramuscular pressure, exceeded the vasodilation elicited by the higher metabolic demand. Also, blood flow changes during thumb contraction negatively correlated (R=-0.7, p<0.01) with the absolute force applied by each subject. Furthermore, after the exercise, muscular blood flow increased significantly immediately after thumb contractions in both high and low MVC groups, with respect to the recorded values during the exercise (p=0.031). An increase of 251% (200%) was found for the long (short) SD in the low MVC group. The high MVC groups showed a significant 90% increase in blood flow only after 80 s from the start of the protocol. For both low and high MVC groups, blood flow recovered to baseline values within 160 s from starting the exercise. In conclusion, DCS allows the study of the response of a small muscle to static exercise and can be potentially used in multiple clinical conditions scenarios for assessing microvascular health., Competing Interests: Turgut Durduran is an inventor on relevant patents (Patent US8082015B2, "Optical measurement of tissue blood flow, hemodynamics and oxygenation”). ICFO has equity ownership in the spin-off company HemoPhotonics S.L. Potential financial conflicts of interest and objectivity of research have been monitored by ICFO’s Knowledge & Technology Transfer Department. No financial conflicts of interest were identified. Udo Weigel is the CEO, has equity ownership in HemoPhotonics S.L. and is an employee in the company., (© 2021 Optical Society of America under the terms of the OSA Open Access Publishing Agreement.)

We present the LUCA device, a multi-modal platform combining eight-wavelength near infrared time resolved spectroscopy, sixteen-channel diffuse correlation spectroscopy and a clinical ultrasound in a single device. By simultaneously measuring the tissue hemodynamics and performing ultrasound imaging, this platform aims to tackle the low specificity and sensitivity of the current thyroid cancer diagnosis techniques, improving the screening of thyroid nodules. Here, we show a detailed description of the device, components and modules. Furthermore, we show the device tests performed through well established protocols for phantom validation, and the performance assessment for in vivo . The characterization tests demonstrate that LUCA device is capable of performing high quality measurements, with a precision in determining in vivo tissue optical and dynamic properties of better than 3%, and a reproducibility of better than 10% after ultrasound-guided probe repositioning, even with low photon count-rates, making it suitable for a wide variety of clinical applications., Competing Interests: The role in the project of all the companies and their employees involved has been defined by the project objectives, tasks, and work packages and has been reviewed by the European Commission. MB, DC, ADM, AT are co-founders of pioNIRS s.r.l., spin off company from Politecnico di Milano (Italy). Potential financial conflicts of interest and objectivity of research have been monitored by ICFO’s Knowledge & Technology Transfer Department., (© 2021 Optical Society of America under the terms of the OSA Open Access Publishing Agreement.)

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., Competing Interests: The role in the project of all the companies and their employees involved has been defined by the project objectives, tasks, and work packages and has been reviewed by the European Commission (grant agreement No. 688303, LUCA-project). Turgut Durduran is an inventor of a relevant patent (Patent US8082015B2). ICFO has equity ownership in the spin-off company HemoPhotonics S.L.. Udo Weigel is the CEO, has equity ownership and is an employee of the company. The potential financial conflicts of interest and objectivity of research have been monitored by ICFO’s Knowledge & Technology Transfer Department and none were identified. Davide Contini and Alberto Dalla Mora are co-founders of pioNIRS s.r.l., spin-off company from Politecnico di Milano (POLIMI, Italy). Their potential financial conflicts of interest and the objectivity of research has been monitored by POLIMI and none were identified., (© 2021 Optical Society of America under the terms of the OSA Open Access Publishing Agreement.)

Intracranial pressure (ICP) is an important parameter to monitor in several neuropathologies. However, because current clinically accepted methods are invasive, its monitoring is limited to patients in critical conditions. On the other hand, there are other less critical conditions for which ICP monitoring could still be useful; therefore, there is a need to develop non-invasive methods. We propose a new method to estimate ICP based on the analysis of the non-invasive measurement of pulsatile, microvascular cerebral blood flow with diffuse correlation spectroscopy. This is achieved by training a recurrent neural network using only the cerebral blood flow as the input. The method is validated using a 50% split sample method using the data from a proof-of-concept study. The study involved a population of infants ( n  = 6) with external hydrocephalus (initially diagnosed as benign enlargement of subarachnoid spaces) as well as a population of adults ( n  = 6) with traumatic brain injury. The algorithm was applied to each cohort individually to obtain a model and an ICP estimate. In both diverse cohorts, the non-invasive estimation of ICP was achieved with an accuracy of <4 mm Hg and a negligible small bias. Further, we have achieved a good correlation (Pearson's correlation coefficient >0.9) and good concordance (Lin's concordance correlation coefficient >0.9) in comparison with standard clinical, invasive ICP monitoring. This preliminary work paves the way for further investigations of this tool for the non-invasive, bedside assessment of ICP.

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 ( 15 O-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)×10 9 × (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.

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 (CMRO 2 I) were calculated., Results: Thirty infants were enrolled in two centres. After validity check of data, 23% of infants were excluded from TOE and CMRO 2 I 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 -2.84×10 -9 cm 2 /s/min; 95% CI -2.50×10 -9 to -3.24×10 -9 cm 2 /s/min) and TOE (estimate -0.78 %/min; 95% CI -1.12 to -0.45 %/min) decreased. Surprisingly, CMRO 2 I decreased (estimate -7.94×10 -8 /min; 95% CI -6.26×10 -8 to -9.62×10 -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 CMRO 2 I remains open., Trial Registration Number: NCT02815618., Competing Interests: Competing interests: UMW is the CEO, has equity ownership in HemoPhotonics S.L. and is an employee in the company. His role in the project has been defined by the project objectives, tasks and work-packages and was reviewed by the European Commission., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

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., Competing Interests: Turgut Durduran is an inventor on a relevant patent (Patent US8082015B2, “Optical measurement of tissue blood flow, hemodynamics and oxygenation”). ICFO has equity ownership in the spin-off company HemoPhotonics S.L. Potential financial conflicts of interest and objectivity of research have been monitored by ICFO’s Knowledge & Technology Transfer Department. No financial conflicts of interest were identified. Udo Weigel is the CEO, has equity ownership in HemoPhotonics S.L. and is an employee in the company. His role in the project has been defined by the project objectives, tasks and work-packages and was reviewed by the European Commission.

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.

We present the recipe and characterization for preparing liquid phantoms that are suitable for both near-infrared spectroscopy and diffuse correlation spectroscopy. The phantoms have well-defined and tunable optical and dynamic properties, and consist of a solution of water and glycerol with fat emulsion as the scattering element. The recipe takes into account the effect of bulk refractive index changes due to the addition of glycerol, which is commonly used to alter the sample viscosity., Competing Interests: ICFO has equity ownership in the spin-off company HemoPhotonics S.L.. Udo Weigel is the CEO, has equity ownership and is an employee of the company. Potential financial conflicts of interest and objectivity of research have been monitored by ICFO’s Knowledge & Technology Transfer Department. No financial conflicts of interest were identified.

The in vivo optical and hemodynamic properties of the healthy (n = 22) and pathological (n = 2) human thyroid tissue were measured non-invasively using a custom time-resolved spectroscopy (TRS) and diffuse correlation spectroscopy (DCS) system. Medical ultrasound was used to guide the placement of the hand-held hybrid optical probe. TRS measured the absorption and reduced scattering coefficients (μa, μs') at three wavelengths (690, 785 and 830 nm) to derive total hemoglobin concentration (THC) and oxygen saturation (StO2). DCS measured the microvascular blood flow index (BFI). Their dependencies on physiological and clinical parameters and positions along the thyroid were investigated and compared to the surrounding sternocleidomastoid muscle. The THC in the thyroid ranged from 131.9 μM to 144.8 μM, showing a 25-44% increase compared to the surrounding sternocleidomastoid muscle tissue. The blood flow was significantly higher in the thyroid (BFIthyroid = 16.0 × 10-9 cm2/s) compared to the muscle (BFImuscle = 7.8 × 10-9 cm2/s), while StO2 showed a small (StO2, muscle = 63.8% to StO2, thyroid = 68.4%), yet significant difference. Two case studies with thyroid nodules underwent the same measurement protocol prior to thyroidectomy. Their THC and BFI reached values around 226.5 μM and 62.8 × 10-9 cm2/s respectively showing a clear contrast to the nodule-free thyroid tissue as well as the general population. The initial characterization of the healthy and pathologic human thyroid tissue lays the ground work for the future investigation on the use of diffuse optics in thyroid cancer screening.

We present a new hardware simulator (HS) for characterization, testing and benchmarking of digital correlators used in various optical correlation spectroscopy experiments where the photon statistics is Gaussian and the corresponding time correlation function can have any arbitrary shape. Starting from the HS developed in [Rev. Sci. Instrum. 74, 4273 (2003)], and using the same I/O board (PCI-6534 National Instrument) mounted on a modern PC (Intel Core i7-CPU, 3.07GHz, 12GB RAM), we have realized an instrument capable of delivering continuous streams of TTL pulses over two channels, with a time resolution of Δt = 50ns, up to a maximum count rate of 〈I〉 ∼ 5MHz. Pulse streams, typically detected in dynamic light scattering and diffuse correlation spectroscopy experiments were generated and measured with a commercial hardware correlator obtaining measured correlation functions that match accurately the expected ones.

The abnormal, uncontrolled production of blood cells in the bone marrow causes hematological malignancies which are common and tend to have a poor prognosis. These types of cancers may alter the hemodynamics of bone marrow. Therefore, noninvasive methods that measure the hemodynamics in the bone marrow have a potential impact on the earlier diagnosis, more accurate prognosis, and in treatment monitoring. In adults, the manubrium is one of the few sites of bone marrow that is rich in hematopoietic tissue and is also relatively superficial and accessible. To this end we have combined time resolved spectroscopy and diffuse correlation spectroscopy to evaluate the feasibility of the noninvasive measurement of the hemodynamics properties of the healthy manubrium in 32 subjects. The distribution of the optical properties (absorption and scattering) and physiological properties (hemoglobin concentration, oxygen saturation and blood flow index) of this tissue are presented as the first step toward investigating its pathology.