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Increased amplitude of peripheral vasomotion is a potential early marker of sepsis‐related microcirculatory impairment; however, previous reports relied on clinically unsuitable invasive techniques. Hyperspectral near‐infrared spectroscopy (hsNIRS) and diffuse correlation spectroscopy (DCS) are non‐invasive, bedside techniques that can be paired to continuously monitor tissue hemoglobin content (HbT), oxygenation (StO2), and perfusion (rBF) to detect vasomotion as low‐frequency microhemodynamic oscillations. While previous studies have primarily focused on the peripheral microcirculation, cerebral injury is also a common occurrence in sepsis and hsNIRS‐DCS could be used to assess cerebral microcirculatory function. This work aimed to use a hybrid hsNIRS‐DCS system to continuously monitor changes in the peripheral and cerebral microcirculation in a rat model of early sepsis. It was hypothesized that the skeletal muscle would be a more sensitive early indicator of sepsis‐related changes in microhemodynamics than the brain. Control animals received saline while the experimental group received fecal slurry to induce sepsis. Subsequently, hsNIRS‐DCS measurements were acquired from the skeletal muscle and brain for 6 h. Peripheral rBF rapidly decreased in septic animals, but there were no significant changes in peripheral HbT or StO2, nor cerebral HbT, rBF, or StO2. The power of low‐frequency peripheral oscillations in all parameters (i.e., HbT, StO2, and rBF) as well as cerebral HbT oscillations were elevated in septic animals during the final 4 h. These findings suggest that in the early stages of sepsis, while vital organs like the brain are partly protected, changes in peripheral perfusion and vasomotor activity can be detected using hsNIRS‐DCS. Future work will apply the technique to ICU patients. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) relies on the interactions between light, photosensitizers, and tissue oxygen to produce cytotoxic reactive oxygen species (ROS), primarily singlet oxygen (1O2) through Type II photochemical reactions, along with superoxide anion radicals (O2•−), hydrogen peroxide (H2O2), and hydroxyl radicals (•OH) through Type I mechanisms. Accurate dosimetry, accounting for all three components, is crucial for predicting and optimizing PDT outcomes. Conventional dosimetry tracks only light fluence rate and photosensitizer concentration, neglecting the role of tissue oxygenation. Reactive oxygen species explicit dosimetry (ROSED) quantifies the reacted oxygen species concentration ([ROS]rx) by explicit measurements of light fluence (rate), photosensitizer concentration, and tissue oxygen concentration. Here we determine tissue oxygenation from non-invasive diffuse correlation spectroscopy (DCS) measurement of tumor blood flow using a conversion factor established preclinically. In this study, we have enrolled 24 pleural PDT patients into the study. Of these patients, we are able to obtain data on 20. Explicit dosimetry of light fluence, Photofrin concentration, and tissue oxygenation concentrations were integrated into the ROSED model to calculate [ROS]rx across multiple sites inside the pleural cavity and among different patients. Large inter- and intra-patient heterogeneities in [ROS]rx were observed, despite identical 60 J/cm2 light doses, with mean [ROS]rx,meas of 0.56 ± 0.26 mM for 13 patients with 21 sites, and [ROS]rx,calc1 of 0.48 ± 0.23 mM for 20 patients with 76 sites. This study presented the first comprehensive analysis of clinical ROSED in pleural mesothelioma patients, providing valuable data on future ROSED based pleural PDT that can potentially produce uniform ROS and thus improve the PDT efficacy for Photofrin-mediated pleural PDT. [ABSTRACT FROM AUTHOR]

We have designed and built an improved system for combined Time-Domain Near-Infrared Spectroscopy (TD NIRS) and Diffuse Correlation Spectroscopy (DCS) measurements. The system features two independent channels, enabling TD NIRS and DCS acquisition at short and long source-detector distances to enhance depth sensitivity in layered tissues. Moreover, the device can operate at fast acquisition rates (up to 50 Hz) to monitor hemodynamic oscillations in biological tissues. An OEM (Original Equipment Manufacturer) TD NIRS device enables stable and robust acquisition of photon distribution of time-of-flight. For the DCS signals, the use of a time tagger and a software correlator allows us flexibility in post-processing. A user-friendly GUI controls TD NIRS data acquisition and online data analysis. We present results for the system characterization on calibrated tissue phantoms according to standardized protocols for performance assessment of TD NIRS and DCS devices. In-vivo measurements during rest and during vascular occlusions are also reported to validate the system in real settings. [ABSTRACT FROM AUTHOR]

Abstract This study aimed to investigate the simultaneous response of the cerebral and skeletal muscle microvasculature to the same phenylephrine (PE) boluses. A hybrid optical system that combines hyperspectral near‐infrared spectroscopy (hs‐NIRS) and diffuse correlation spectroscopy (DCS) was used to monitor changes in tissue oxygenation and perfusion. Data were collected from the head and hind limb of seven male Sprague–Dawley rats while administering intravenous (IV) injections of PE or saline to all animals. The response to saline was used as a control. Skeletal muscle oxygenation decreased significantly after PE injection, while a statistically underpowered decrease in perfusion was observed, followed by an increase beyond baseline. Vascular conductance also decreased in the muscle reflecting the drug's vasoconstrictive effects. Tissue oxygenation and perfusion increased in the brain in response to PE. Initially, there was a sharp increase in cerebral perfusion but no changes in cerebral vascular conductance. Subsequently, cerebral flow and vascular conductance decreased significantly below baseline, likely reflecting autoregulatory mechanisms to manage the excess flow. Further, fitting an exponential function to the secondary decrease in cerebral perfusion and increase in muscular blood flow revealed a quicker kinetic response in the brain to adjust blood flow. In the skeletal muscle, PE caused a transient decrease in blood volume due to vasoconstriction, which resulted in an overall decrease in hemoglobin content and tissue oxygen saturation. Since PE does not directly affect cerebral vessels, this peripheral vasoconstriction shunted blood into the brain, resulting in an initial increase in oxygenated hemoglobin and oxygen saturation.

This study aimed to investigate the simultaneous response of the cerebral and skeletal muscle microvasculature to the same phenylephrine (PE) boluses. A hybrid optical system that combines hyperspectral near‐infrared spectroscopy (hs‐NIRS) and diffuse correlation spectroscopy (DCS) was used to monitor changes in tissue oxygenation and perfusion. Data were collected from the head and hind limb of seven male Sprague–Dawley rats while administering intravenous (IV) injections of PE or saline to all animals. The response to saline was used as a control. Skeletal muscle oxygenation decreased significantly after PE injection, while a statistically underpowered decrease in perfusion was observed, followed by an increase beyond baseline. Vascular conductance also decreased in the muscle reflecting the drug's vasoconstrictive effects. Tissue oxygenation and perfusion increased in the brain in response to PE. Initially, there was a sharp increase in cerebral perfusion but no changes in cerebral vascular conductance. Subsequently, cerebral flow and vascular conductance decreased significantly below baseline, likely reflecting autoregulatory mechanisms to manage the excess flow. Further, fitting an exponential function to the secondary decrease in cerebral perfusion and increase in muscular blood flow revealed a quicker kinetic response in the brain to adjust blood flow. In the skeletal muscle, PE caused a transient decrease in blood volume due to vasoconstriction, which resulted in an overall decrease in hemoglobin content and tissue oxygen saturation. Since PE does not directly affect cerebral vessels, this peripheral vasoconstriction shunted blood into the brain, resulting in an initial increase in oxygenated hemoglobin and oxygen saturation. [ABSTRACT FROM AUTHOR]

Diffuse correlation spectroscopy (DCS) is a non-invasive technology for the evaluation of blood perfusion in deep tissue. However, it requires high computational resources for data analysis, which poses challenges in its implementation for real-time applications. To address the unmet need, we developed a novel device-on-chip solution that fully integrates all the necessary computational components needed for DCS. It takes the output of a photon detector and determines the blood flow index (BFI). It is implemented on a field-programmable gate array (FPGA) chip including a multi-tau correlator for the calculation of the temporal light intensity autocorrelation function and a DCS analyzer to perform the curve fitting operation that derives the BFI at a rate of 6000 BFIs/s. The FPGA DCS system was evaluated against a lab-standard DCS system for both phantom and cuff ischemia studies. The results indicate that the autocorrelation of the light correlation and BFI from both the FPGA DCS and the reference DCS matched well. Furthermore, the FPGA DCS system was able to achieve a measurement rate of 50 Hz and resolve pulsatile blood flow. This can significantly lower the cost and footprint of the computational components of DCS and pave the way for portable, real-time DCS systems. [ABSTRACT FROM AUTHOR]

The physiological effects on blood flow and oxygen utilization in active muscles during and after involuntary contraction triggered by electrical muscle stimulation (EMS) remain unclear, particularly compared with those elicited by voluntary (VOL) contractions. Therefore, we used diffuse correlation and near-infrared spectroscopy (DCS-NIRS) to compare changes in local muscle blood flow and oxygen consumption during and after these two types of muscle contractions in humans. Overall, 24 healthy young adults participated in the study, and data were successfully obtained from 17 of them. Intermittent (2-s contraction, 2-s relaxation) isometric ankle dorsiflexion with a target tension of 20% of maximal VOL contraction was performed by EMS or VOL for 2 min, followed by a 6-min recovery period. DCS-NIRS probes were placed on the tibialis anterior muscle, and relative changes in local tissue blood flow index (rBFI), oxygen extraction fraction (rOEF), and metabolic rate of oxygen (rMRO2) were continuously derived. EMS induced more significant increases in rOEF and rMRO2 than VOL exercise but a comparable increase in rBFI. After EMS, rBFI and rMRO2 decreased more slowly than after VOL and remained significantly higher until the end of the recovery period. We concluded that EMS augments oxygen consumption in contracting muscles by enhancing oxygen extraction while increasing oxygen delivery at a rate similar to the VOL exercise. Under the conditions examined in this study, EMS demonstrated a more pronounced and/or prolonged enhancement in local muscle perfusion and aerobic metabolism compared with VOL exercise in healthy participants. NEW & NOTEWORTHY: This is the first study to visualize continuous changes in blood flow and oxygen utilization within contracted muscles during and after electrical muscle stimulation (EMS) using combined diffuse correlation and near-infrared spectroscopy. We found that initiating EMS increases blood flow at a rate comparable to that during voluntary (VOL) exercise but enhances oxygen extraction, resulting in higher oxygen consumption. Furthermore, EMS increased postexercise muscle perfusion and oxygen consumption compared with that after VOL exercise. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) relies on the interactions between light, photosensitizers, and tissue oxygen to produce cytotoxic reactive oxygen species (ROS), primarily singlet oxygen (1O2) through Type II photochemical reactions, along with superoxide anion radicals (O2•−), hydrogen peroxide (H2O2), and hydroxyl radicals (•OH) through Type I mechanisms. Accurate dosimetry, accounting for all three components, is crucial for predicting and optimizing PDT outcomes. Conventional dosimetry tracks only light fluence rate and photosensitizer concentration, neglecting the role of tissue oxygenation. Reactive oxygen species explicit dosimetry (ROSED) quantifies the reacted oxygen species concentration ([ROS]rx) by explicit measurements of light fluence (rate), photosensitizer concentration, and tissue oxygen concentration. Here we determine tissue oxygenation from non-invasive diffuse correlation spectroscopy (DCS) measurement of tumor blood flow using a conversion factor established preclinically. In this study, we have enrolled 24 pleural PDT patients into the study. Of these patients, we are able to obtain data on 20. Explicit dosimetry of light fluence, Photofrin concentration, and tissue oxygenation concentrations were integrated into the ROSED model to calculate [ROS]rx across multiple sites inside the pleural cavity and among different patients. Large inter- and intra-patient heterogeneities in [ROS]rx were observed, despite identical 60 J/cm2 light doses, with mean [ROS]rx,meas of 0.56 ± 0.26 mM for 13 patients with 21 sites, and [ROS]rx,calc1 of 0.48 ± 0.23 mM for 20 patients with 76 sites. This study presented the first comprehensive analysis of clinical ROSED in pleural mesothelioma patients, providing valuable data on future ROSED based pleural PDT that can potentially produce uniform ROS and thus improve the PDT efficacy for Photofrin-mediated pleural PDT.

We have designed and built an improved system for combined Time-Domain Near-Infrared Spectroscopy (TD NIRS) and Diffuse Correlation Spectroscopy (DCS) measurements. The system features two independent channels, enabling TD NIRS and DCS acquisition at short and long source-detector distances to enhance depth sensitivity in layered tissues. Moreover, the device can operate at fast acquisition rates (up to 50 Hz) to monitor hemodynamic oscillations in biological tissues. An OEM (Original Equipment Manufacturer) TD NIRS device enables stable and robust acquisition of photon distribution of time-of-flight. For the DCS signals, the use of a time tagger and a software correlator allows us flexibility in post-processing. A user-friendly GUI controls TD NIRS data acquisition and online data analysis. We present results for the system characterization on calibrated tissue phantoms according to standardized protocols for performance assessment of TD NIRS and DCS devices. In-vivo measurements during rest and during vascular occlusions are also reported to validate the system in real settings.

Climbing performance is greatly dependent on the endurance of the finger flexors which, in turn, depends on the ability to deliver and use oxygen within the muscle. Near-infrared spectroscopy (NIRS) and diffuse correlation spectroscopy (DCS) have provided new possibilities to explore these phenomena in the microvascular environment. The aim of the present study was to explore climbing-related microvascular adaptations through the comparison of the oxygen concentration and hemodynamics of the forearm between climbers and non-climber active individuals during a vascular occlusion test (VOT). Seventeen climbers and fifteen non-climbers joined the study. Through NIRS and DCS, the oxyhemoglobin (O2Hb) and deoxyhemoglobin (HHb) concentrations, tissue saturation index (TSI), and blood flow index (BFI) were obtained from the flexor digitorum profundus during the VOT. During the reactive hyperemia, climbers presented greater blood flow slopes (p = 0.043, d = 0.573), as well as greater O2Hb maximum values (p = 0.001, d = 1.263) and HHb minimum values (p = 0.009, d = 0.998), than non-climbers. The superior hemodynamics presented by climbers could indicate potential training-induced structural and functional adaptations that could enhance oxygen transportation to the muscle, and thus enhance muscle endurance and climbing performance. [ABSTRACT FROM AUTHOR]

Significance: Mechanical ventilation (MV) is a cornerstone technology in the intensive care unit as it assists with the delivery of oxygen in critically ill patients. The process of weaning patients from MV can be long and arduous and can lead to serious complications for many patients. Despite the known importance of inspiratory muscle function in the success of weaning, current clinical standards do not include direct monitoring of these muscles. Aim: The goal of this project was to develop and validate a combined frequency domain near-infrared spectroscopy (FD-NIRS) and diffuse correlation spectroscopy (DCS) system for the noninvasive characterization of inspiratory muscle response to a load. Approach: The system was fabricated by combining a custom digital FD-NIRS and DCS system. It was validated via liquid phantom titrations and a healthy volunteer study. The sternocleidomastoid (SCM), an accessory muscle of inspiration, was monitored during a short loading period in fourteen young, healthy volunteers. Volunteers performed two different respiratory exercises, a moderate load and a high load, which consisted of a one-minute baseline, a one-minute load, and a six-minute recovery period. Results: The system has low crosstalk between absorption, reduced scattering, and flow when tested in a set of liquid titrations. Faster dynamics were observed for changes in blood flow index (BF,), and metabolic rate of oxygen (MRO2) compared with hemoglobin + myoglobin (Hb+Mb) based parameters after the onset of loads in males. Additionally, larger percent changes in BF,, and MRO2 were observed compared with Hb+Mb parameters in both males and females. There were also sex differences in baseline values of oxygenated Hb+Mb, total Hb+Mb, and tissue saturation. Conclusions: The dynamic characteristics of Hb+Mb concentration and blood flow were distinct during loading of the SCM, suggesting that the combination of FD-NIRS and DCS may provide a more complete picture of inspiratory muscle dynamics. [ABSTRACT FROM AUTHOR]

Diffuse optical measurement is an evolving optical modality providing a fast and portable solution for microcirculation assessment. Diffuse optics in static and dynamic modalities are combined here in a system to assess hemodynamics in skin tissues of control and diabetic subjects. The in‐house developed system consists of a laser source, fiber optic probe, a low‐cost avalanche photodiode, a finite element model (FEM) derived static optical property estimator, and a software correlator for continuous flow monitoring through microvasculature. The studies demonstrated that the system quantifies the changes in blood flow rate in the immediate skin subsurface. The system is calibrated with in vitro flow models and a proof‐of‐concept was demonstrated on a limited number of subjects in a clinical environment. The flow changes in response to vasoconstrictive and vasodilative stimuli were analyzed and used to classify different stages of diabetes, including diabetic neuropathy. [ABSTRACT FROM AUTHOR]

Significance: Diffuse correlation spectroscopy (DCS) permits non-invasive assessment of skeletal muscle blood flow but may misestimate changes in muscle perfusion. Aim: We aimed to highlight recent evidence that DCS blood flow index (BFI) misestimates changes in muscle blood flow during physiological perturbation and to introduce a novel approach that adjusts BFI for estimated changes in vasodilation. Approach: We measured changes in muscle BFI during quadriceps and forearm exercises using DCS, the latter of which were adjusted for estimated changes in microvascular flow area and then compared to Doppler ultrasound in the brachial artery. Then, we compared adjusted BFI- and arterial spin labeling (ASL) MRI measures of gastrocnemius blood flow during reactive hyperemia and plantar flexion exercise. Results: We observed little-to-no change in quadriceps BFI during maximal-effort exercise. Similarly, forearm BFI was modestly increased during handgrip exercise, but the magnitude was significantly lower than measured by Doppler ultrasound in the brachial artery. However, this difference was ameliorated after adjusting BFI for estimated changes in microvascular flow area. Similar observations were also observed in the gastrocnemius when directly comparing the adjusted BFI values to ASL-MRI. Conclusions: Adjusting BFI for estimated changes in microvascular flow area may improve DCS estimates of muscle blood flow, but further study is needed to validate these methods moving forward. [ABSTRACT FROM AUTHOR]

Diffuse correlation spectroscopy (DCS) is a non-invasive technology for the evaluation of blood perfusion in deep tissue. However, it requires high computational resources for data analysis, which poses challenges in its implementation for real-time applications. To address the unmet need, we developed a novel device-on-chip solution that fully integrates all the necessary computational components needed for DCS. It takes the output of a photon detector and determines the blood flow index (BFI). It is implemented on a field-programmable gate array (FPGA) chip including a multi-tau correlator for the calculation of the temporal light intensity autocorrelation function and a DCS analyzer to perform the curve fitting operation that derives the BFI at a rate of 6000 BFIs/s. The FPGA DCS system was evaluated against a lab-standard DCS system for both phantom and cuff ischemia studies. The results indicate that the autocorrelation of the light correlation and BFI from both the FPGA DCS and the reference DCS matched well. Furthermore, the FPGA DCS system was able to achieve a measurement rate of 50 Hz and resolve pulsatile blood flow. This can significantly lower the cost and footprint of the computational components of DCS and pave the way for portable, real-time DCS systems.

Significance: Diffuse correlation spectroscopy (DCS) is a powerful, noninvasive optical technique for measuring blood flow. Traditionally the blood flow index (BFi) is derived through nonlinear least-square fitting the measured intensity autocorrelation function (ACF). However, the fitting process is computationally intensive, susceptible to measurement noise, and easily influenced by optical properties (absorption coefficient µa and reduced scattering coefficient µ's) and scalp and skull thicknesses. Aim: We aim to develop a data-driven method that enables rapid and robust analysis of multiple-scattered light's temporal ACFs. Moreover, the proposed method can be applied to a range of source-detector distances instead of being limited to a specific source-detector distance. Approach: We present a deep learning architecture with one-dimensional convolution neural networks, called DCS neural network (DCS-NET), for BFi and coherent factor (ß) estimation. This DCS-NET was performed using simulated DCS data based on a three-layer brain model. We quantified the impact from physiologically relevant optical property variations, layer thicknesses, realistic noise levels, and multiple source-detector distances (5, 10, 15, 20, 25, and 30 mm) on BFi and ß estimations among DCS-NET, semi-infinite, and three-layer fitting models. Results: DCS-NET shows a much faster analysis speed, around 17,000-fold and 32-fold faster than the traditional three-layer and semi-infinite models, respectively. It offers higher intrinsic sensitivity to deep tissues compared with fitting methods. DCSNET shows excellent anti-noise features and is less sensitive to variations of µa and µ's at a source-detector separation of 30 mm. Also, we have demonstrated that relative BFi (rBFi) can be extracted by DCS-NET with a much lower error of 8.35%. By contrast, the semi-infinite and three-layer fitting models result in significant errors in rBFi of 43.76% and 19.66%, respectively. Conclusions: DCS-NET can robustly quantify blood flow measurements at considerable source-detector distances, corresponding to much deeper biological tissues. It has excellent potential for hardware implementation, promising continuous realtime blood flow measurements. [ABSTRACT FROM AUTHOR]

This document is a list of references cited in an article that compares the performance potential of different techniques for measuring blood flow in the brain. The article discusses various spectroscopy methods, imaging systems, and mathematical models used in the field of diffuse correlation spectroscopy. The references include studies on different types of spectroscopy, as well as specific products and equipment used in these studies. [Extracted from the article]

Diffuse correlation spectroscopy is a non-invasive optical modality used to measure cerebral blood flow in real time, and it has important potential applications in clinical monitoring and neuroscience. As such, many research groups have recently been investigating methods to improve the signal-to-noise ratio, imaging depth, and spatial resolution of diffuse correlation spectroscopy. Such methods have included multispeckle, long wavelength, interferometric, depth discrimination, time-of-flight resolution, and acousto-optic detection strategies. In this review, we exhaustively appraise this plethora of recent advances, which can be used to assess limitations and guide innovation for future implementations of diffuse correlation spectroscopy that will harness technological improvements in the years to come. [ABSTRACT FROM AUTHOR]

Hemodynamic models provide a mathematical representation and computational framework that describe the changes in blood flow, blood volume, and oxygenation levels that occur in response to neural activity and systemic changes, while near-infrared spectroscopy (NIRS) measures deoxyhemoglobin, oxyhemoglobin, and other chromophores to analyze cerebral hemodynamics and metabolism. In this study, we apply a dynamic hemometabolic model to NIRS data acquired during cardiac arrest and cardiopulmonary resuscitation (CPR) in pigs. Our goals were to test the model's ability to accurately describe the observed phenomena, to gain an understanding of the intricate behavior of cerebral microvasculature, and to compare the obtained parameters with known values. By employing the inverse of the hemometabolic model, we measured a range of significant physiological parameters, such as the rate of oxygen diffusion from blood to tissue, the arteriole and venule volume fractions, and the Fåhraeus factor. Statistical analysis uncovered significant differences in the baseline and post-cardiac arrest values of some of the parameters. [ABSTRACT FROM AUTHOR]

Hyperventilation (HV) therapy uses vasoconstriction to reduce intracranial pressure (ICP) by reducing cerebral blood volume. However, as HV also lowers cerebral blood flow (CBF), it may provoke misery perfusion (MP), in which the decrease in CBF is coupled with increased oxygen extraction fraction (OEF). MP may rapidly lead to the exhaustion of brain energy metabolites, making the brain vulnerable to ischemia. MP is difficult to detect at the bedside, which is where transcranial hybrid, near-infrared spectroscopies are promising because they non-invasively measure OEF and CBF. We have tested this technology during HV (∼30 min) with bilateral, frontal lobe monitoring to assess MP in 27 sessions in 18 patients with traumatic brain injury. In this study, HV did not lead to MP at a group level (p > 0.05). However, a statistical approach yielded 89 events with a high probability of MP in 19 sessions. We have characterized each statistically significant event in detail and its possible relationship to clinical and radiological status (decompressive craniectomy and presence of a cerebral lesion), without detecting any statistically significant difference (p > 0.05). However, MP detection stresses the need for personalized, real-time assessment in future clinical trials with HV, in order to provide an optimal evaluation of the risk–benefit balance of HV. Our study provides pilot data demonstrating that bedside transcranial hybrid near-infrared spectroscopies could be utilized to assess potential MP. [ABSTRACT FROM AUTHOR]

The aim of the current study was to establish the interplay between blood flow patterns within a large cerebral artery and a downstream microvascular segment under conditions of transiently reduced mean arterial pressure (MAP). We report data from nine young, healthy participants (5 women; 26 ± 4 yr) acquired during a 15-s bout of sudden-onset lower body negative pressure (LBNP; -80 mmHg). Simultaneous changes in microvascular cerebral blood flow (CBF) and middle cerebral artery blood velocity (MCAvmean) were captured using diffuse correlation spectroscopy (DCS) and transcranial Doppler ultrasound (TCD), respectively. Brachial blood pressure (finger photoplethysmography) and TCD waveforms were extracted at baseline and during the nadir blood pressure (BP) response to LBNP and analyzed using a modified Windkessel model to calculate indices of cerebrovascular resistance (Ri) and compliance (Ci). Compared with baseline, rapid-onset LBNP decreased MAP by 22 ± 16% and Ri by 14 ± 10% (both P ≤ 0.03). Ci increased (322 ± 298%; P < 0.01) but MCAvmean (-8 ± 16%; P = 0.09) and CBF (-2 ± 3%; P = 0.29) were preserved. The results provide evidence that changes in both vascular resistance and compliance preserve CBF, as indexed by no significant changes in MCAvmean or DCS microvascular flow, during transient hypotension. [ABSTRACT FROM AUTHOR]

Dynamic cerebral autoregulation (dCA) can be derived from spontaneous oscillations in arterial blood pressure (ABP) and cerebral blood flow (CBF). Transcranial Doppler (TCD) measures CBF-velocity and is commonly used to assess dCA. Diffuse correlation spectroscopy (DCS) is a promising optical technique for non-invasive CBF monitoring, so here we aimed to validate DCS as a tool for quantifying dCA. In 33 healthy adults and 17 acute ischemic stroke patients, resting-state hemodynamic were monitored simultaneously with high-speed (20 Hz) DCS and TCD. dCA parameters were calcaulated by a transfer function analysis using a Fourier decomposition of ABP and CBF (or CBF-velocity). Strong correlation was found between DCS and TCD measured gain (magnitude of regulation) in healthy volunteers (r = 0.73, p < 0.001) and stroke patients (r = 0.76, p = 0.003). DCS-gain retained strong test-retest reliability in both groups (ICC 0.87 and 0.82, respectively). DCS and TCD-derived phase (latency of regulation) did not significantly correlate in healthy volunteers (r = 0.12, p = 0.50) but moderately correlated in stroke patients (r = 0.65, p = 0.006). DCS-derived phase was reproducible in both groups (ICC 0.88 and 0.90, respectively). High-frequency DCS is a promising non-invasive bedside technique that can be leveraged to quantify dCA from resting-state data, but the discrepancy between TCD and DCS-derived phase requires further investigation. [ABSTRACT FROM AUTHOR]

Goal: Cerebrovascular impedance is modulated by a vasoactive autoregulative mechanism in response to changes in cerebral perfusion pressure. Characterization of impedance and the limits of autoregulation are important biomarkers of cerebral health. We developed a method to quantify impedance based on the spectral content of cerebral blood flow and volume at the cardiac frequency, measured with diffuse optical methods. Methods: In three non-human primates, we modulated cerebral perfusion pressure beyond the limits of autoregulation. Cerebral blood flow and volume were measured with diffuse correlation spectroscopy and near-infrared spectroscopy, respectively. Results: We show that impedance can be used to identify the lower and upper limits of autoregulation. Conclusions: This impedance method may be an alternative method to measure autoregulation and a way of assessing cerebral health non-invasively at the clinical bedside.

Climbing performance is greatly dependent on the endurance of the finger flexors which, in turn, depends on the ability to deliver and use oxygen within the muscle. Near-infrared spectroscopy (NIRS) and diffuse correlation spectroscopy (DCS) have provided new possibilities to explore these phenomena in the microvascular environment. The aim of the present study was to explore climbing-related microvascular adaptations through the comparison of the oxygen concentration and hemodynamics of the forearm between climbers and non-climber active individuals during a vascular occlusion test (VOT). Seventeen climbers and fifteen non-climbers joined the study. Through NIRS and DCS, the oxyhemoglobin (O2Hb) and deoxyhemoglobin (HHb) concentrations, tissue saturation index (TSI), and blood flow index (BFI) were obtained from the flexor digitorum profundus during the VOT. During the reactive hyperemia, climbers presented greater blood flow slopes (p = 0.043, d = 0.573), as well as greater O2Hb maximum values (p = 0.001, d = 1.263) and HHb minimum values (p = 0.009, d = 0.998), than non-climbers. The superior hemodynamics presented by climbers could indicate potential training-induced structural and functional adaptations that could enhance oxygen transportation to the muscle, and thus enhance muscle endurance and climbing performance.

Rapid screening for ischemic strokes in prehospital settings may improve patient outcomes by allowing early deployment of vascular recanalization therapies. However, there are no low‐cost and convenient methods that can assess ischemic strokes in such a setting. Diffuse correlation spectroscopy (DCS) is a promising method for continuous, noninvasive transcranial monitoring of cerebral blood flow. In this study, we used a DCS system to detect cerebral hemodynamics before and after acute ischemic stroke in pigs. Seven adult porcines were chosen to establish ischemic stroke models via bilateral common carotid artery ligation (n = 5) or air emboli (n = 2). The results showed a significant difference in blood flow index (BFI) between the normal and ischemic groups. Relative blood flow index (rBFI) exhibited excellent results. Therefore, the diffuse optical method can assess the hemodynamic changes in acute cerebral ischemic stroke onset in pigs, and rBFI may be a promising biomarker for identifying cerebral ischemic stroke. [ABSTRACT FROM AUTHOR]

One of the common complications of non-traumatic subarachnoid hemorrhage (SAH) is delayed cerebral ischemia (DCI). Intrathecal (IT) administration of nicardipine, a calcium channel blocker (CCB), upon detection of large-artery cerebral vasospasm holds promise as a treatment that reduces the incidence of DCI. In this observational study, we prospectively employed a non-invasive optical modality called diffuse correlation spectroscopy (DCS) to quantify the acute microvascular cerebral blood flow (CBF) response to IT nicardipine (up to 90min) in 20 patients with medium-high grade non-traumatic SAH. On average, CBF increased significantly with time post-administration. However, the CBF response was heterogeneous across subjects. A latent class mixture model was able to classify 19 out of 20 patients into two distinct classes of CBF response: patients in Class 1 (n = 6) showed no significant change in CBF, while patients in Class 2 (n = 13) showed a pronounced increase in CBF in response to nicardipine. The incidence of DCI was 5 out of 6 in Class 1 and 1 out of 13 in Class 2 (p < 0.001). These results suggest that the acute (<90min) DCS-measured CBF response to IT nicardipine is associated with intermediate-term (up to 3 weeks) development of DCI. [ABSTRACT FROM AUTHOR]

Objectives: Hemodynamic abnormalities and brain development disorders have been reported previously in fetuses and infants with transposition of the great arteries and intact ventricular septum (TGA‐IVS). A ventricular septal defect (VSD) is thought to be an additional risk factor for adverse neurodevelopment, but literature describing this population is sparse. The objectives of this study were to assess fetal cardiac hemodynamics throughout pregnancy, to monitor cerebral hemodynamics and oxygen metabolism in neonates, and to compare these data between patients with TGA‐IVS, those with TGA‐VSD and age‐matched controls. Methods: Cardiac hemodynamics were assessed in TGA‐IVS and TGA‐VSD fetuses and compared with healthy controls matched for gestational age (GA) during three periods: ≤ 22 + 5 weeks (GA1), 27 + 0 to 32 + 5 weeks (GA2) and ≥ 34 + 5 weeks (GA3). Left (LVO), right (RVO) and combined (CVO) ventricular outputs, ductus arteriosus flow (DAF, sum of ante‐ and retrograde flow in systole and diastole), diastolic DAF, transpulmonary flow (TPF) and foramen ovale diameter were measured. Aortic (AoF) and main pulmonary artery (MPAF) flows were derived as a percentage of CVO. Fetal middle cerebral artery and umbilical artery (UA) pulsatility indices (PI) were measured and the cerebroplacental ratio (CPR) was derived. Bedside optical brain monitoring was used to measure cerebral hemoglobin oxygen saturation (SO2) and an index of microvascular cerebral blood flow (CBFi), along with peripheral arterial oxygen saturation (SpO2), in TGA‐IVS and TGA‐VSD neonates. Using hemoglobin (Hb) concentration measurements, these parameters were used to derive cerebral oxygen delivery and extraction fraction (OEF), as well as an index of cerebral oxygen metabolism (CMRO2i). These data were acquired in the early preoperative period (within 3 days after birth and following balloon atrial septostomy) and compared with those of age‐matched healthy controls, and repeat measurements were collected before discharge when vital signs were stable. Results: LVO was increased in both TGA groups compared with controls throughout pregnancy. Compared with controls, TPF was increased and diastolic DAF was decreased in TGA‐IVS fetuses throughout pregnancy, but only during GA1 and GA2 in TGA‐VSD fetuses. Compared with controls, DAF was decreased in TGA‐IVS fetuses throughout pregnancy and in TGA‐VSD fetuses at GA2 and GA3. At GA2, AoF was higher in TGA‐IVS and TGA‐VSD fetuses than in controls, while MPAF was lower. At GA3, RVO and CVO were higher in the TGA‐IVS group than in the TGA‐VSD group. In addition, UA‐PI was lower at GA2 and CPR higher at GA3 in TGA‐VSD fetuses compared with TGA‐IVS fetuses. Within 3 days after birth, SpO2 and SO2 were lower in both TGA groups than in controls, while Hb, cerebral OEF and CMRO2i were higher. Preoperative SpO2 was also lower in TGA‐VSD neonates than in those with TGA‐IVS. From preoperative to predischarge periods, SpO2 and OEF increased in both TGA groups, but CBFi and CMRO2i increased only in the TGA‐VSD group. During the predischarge period, SO2 was higher in TGA‐IVS than in TGA‐VSD neonates, while CBFi was lower. Conclusions: Fetal cardiac and neonatal cerebral hemodynamic/metabolic differences were observed in both TGA groups compared with controls. Compared to those with TGA‐IVS, fetuses with TGA‐VSD had lower RVO and CVO in late gestation. A higher level of preoperative hypoxemia was observed in the TGA‐VSD group. Postsurgical cerebral adaptive mechanisms probably differ between TGA groups. Patients with TGA‐VSD have a specific physiology that warrants further study to improve neonatal care and neurodevelopmental outcome. © 2022 International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]

Background: Infants born at 29-36 weeks gestational age (GA) are at risk of experiencing neurodevelopmental challenges. We hypothesize that cerebral hemodynamics and oxygen metabolism measured by bedside optical brain monitoring are potential biomarkers of brain development and are associated with neurological examination at term-equivalent age (TEA). Methods: Preterm infants (N D 133) born 29-36 weeks GA and admitted in the neonatal intensive care unit were enrolled in this prospective cohort study. Combined frequency-domain near infrared spectroscopy (FDNIRS) and diffuse correlation spectroscopy (DCS) were used from birth to TEA to measure cerebral hemoglobin oxygen saturation and an index of microvascular cerebral blood flow (CBFi) along with peripheral arterial oxygen saturation (SpO2). In combination with hemoglobin concentration in the blood, these parameters were used to derive cerebral oxygen extraction fraction (OEF) and an index of cerebral oxygen metabolism (CMRO2i). The Amiel-Tison and Gosselin Neurological Assessment was performed at TEA. Linear regression models were used to assess the associations between changes in FDNIRS-DCS parameters from birth to TEA and GA at birth. Logistic regression models were used to assess the associations between changes in FDNIRS-DCS parameters from birth to TEA and neurological examination at TEA. Results: Steeper increases in CBFi (p < 0.0001) and CMRO2i (p D 0.0003) were associated with higher GA at birth. Changes in OEF, CBFi, and CMRO2i from birth to TEA were not associated with neurological examination at TEA. Conclusion: In this population, cerebral FDNIRS-DCS parameters were not associated with neurological examination at TEA. Larger increases in CBFi and CMRO2i from birth to TEA were associated with higher GA. Non-invasive bedside FDNIRS-DCS monitoring provides cerebral hemodynamic and metabolic parameters that may complement neurological examination to assess brain development in preterm infants. [ABSTRACT FROM AUTHOR]

Diffuse correlation spectroscopy is a non-invasive optical modality used to measure cerebral blood flow in real time, and it has important potential applications in clinical monitoring and neuroscience. As such, many research groups have recently been investigating methods to improve the signal-to-noise ratio, imaging depth, and spatial resolution of diffuse correlation spectroscopy. Such methods have included multispeckle, long wavelength, interferometric, depth discrimination, time-of-flight resolution, and acousto-optic detection strategies. In this review, we exhaustively appraise this plethora of recent advances, which can be used to assess limitations and guide innovation for future implementations of diffuse correlation spectroscopy that will harness technological improvements in the years to come.

BackgroundInfants born at 29–36 weeks gestational age (GA) are at risk of experiencing neurodevelopmental challenges. We hypothesize that cerebral hemodynamics and oxygen metabolism measured by bedside optical brain monitoring are potential biomarkers of brain development and are associated with neurological examination at term-equivalent age (TEA).MethodsPreterm infants (N = 133) born 29–36 weeks GA and admitted in the neonatal intensive care unit were enrolled in this prospective cohort study. Combined frequency-domain near infrared spectroscopy (FDNIRS) and diffuse correlation spectroscopy (DCS) were used from birth to TEA to measure cerebral hemoglobin oxygen saturation and an index of microvascular cerebral blood flow (CBFi) along with peripheral arterial oxygen saturation (SpO2). In combination with hemoglobin concentration in the blood, these parameters were used to derive cerebral oxygen extraction fraction (OEF) and an index of cerebral oxygen metabolism (CMRO2i). The Amiel-Tison and Gosselin Neurological Assessment was performed at TEA. Linear regression models were used to assess the associations between changes in FDNIRS-DCS parameters from birth to TEA and GA at birth. Logistic regression models were used to assess the associations between changes in FDNIRS-DCS parameters from birth to TEA and neurological examination at TEA.ResultsSteeper increases in CBFi (p < 0.0001) and CMRO2i (p = 0.0003) were associated with higher GA at birth. Changes in OEF, CBFi, and CMRO2i from birth to TEA were not associated with neurological examination at TEA.ConclusionIn this population, cerebral FDNIRS-DCS parameters were not associated with neurological examination at TEA. Larger increases in CBFi and CMRO2i from birth to TEA were associated with higher GA. Non-invasive bedside FDNIRS-DCS monitoring provides cerebral hemodynamic and metabolic parameters that may complement neurological examination to assess brain development in preterm infants.

One of the common complications of non-traumatic subarachnoid hemorrhage (SAH) is delayed cerebral ischemia (DCI). Intrathecal (IT) administration of nicardipine, a calcium channel blocker (CCB), upon detection of large-artery cerebral vasospasm holds promise as a treatment that reduces the incidence of DCI. In this observational study, we prospectively employed a non-invasive optical modality called diffuse correlation spectroscopy (DCS) to quantify the acute microvascular cerebral blood flow (CBF) response to IT nicardipine (up to 90 min) in 20 patients with medium-high grade non-traumatic SAH. On average, CBF increased significantly with time post-administration. However, the CBF response was heterogeneous across subjects. A latent class mixture model was able to classify 19 out of 20 patients into two distinct classes of CBF response: patients in Class 1 (n = 6) showed no significant change in CBF, while patients in Class 2 (n = 13) showed a pronounced increase in CBF in response to nicardipine. The incidence of DCI was 5 out of 6 in Class 1 and 1 out of 13 in Class 2 (p < 0.001). These results suggest that the acute (

Diffuse Correlation Spectroscopy (DCS), a noninvasive optical technique, measures deep tissue blood flow using avalanche photon counting modules and data acquisition devices such as FPGAs or correlator boards. Conventional DCS instruments use in-processor counter modules that consume 32 bits/channel which is inefficient for low-photon budget situations prevalent in diffuse optics. Scaling these photon counters for large-scale imaging applications is difficult due to bandwidth and processing time considerations. Here, we introduce a new, lossless compressed sensing approach for fast and efficient detection of photon counts. The compressed DCS method uses an array of binary-coded-decimal counters to record photon counts from 8 channels simultaneously as a single 32-bit number. We validate the compressed DCS approach by comparisons with conventional DCS in experiments on tissue simulating phantoms and in-vivo arm cuff occlusion. Lossless compressed DCS was implemented with 87.5% compression efficiency. In tissue simulating phantoms, it was able to accurately estimate a tissue blood flow index, with no statistically significant difference compared to conventional DCS. Compressed DCS also recorded blood flow in vivo, in human forearm, with signal-to-noise ratio and dynamic range comparable to conventional DCS. Lossless 87.5% efficient compressed sensing counting of photon counts meets and exceeds benchmarks set by conventional DCS systems, offering a low-cost alternative for fast (~100 Hz) deep tissue blood flow measurement with optics.

Aim: Cardiac arrest often results in severe neurologic injury. Improving care for these patients is difficult as few noninvasive biomarkers exist that allow physicians to monitor neurologic health. The amount of low-frequency power (LFP, 0.01-0.1 Hz) in cerebral haemodynamics has been used in functional magnetic resonance imaging as a marker of neuronal activity. Our hypothesis was that increased LFP in cerebral blood flow (CBF) would be correlated with improvements in invasive measures of neurologic health.Methods: We adapted the use of LFP for to monitoring of CBF with diffuse correlation spectroscopy. We asked whether LFP (or other optical biomarkers) correlated with invasive microdialysis biomarkers (lactate-pyruvate ratio - LPR - and glycerol concentration) of neuronal injury in the 4 h after return of spontaneous circulation in a swine model of paediatric cardiac arrest (Sus scrofa domestica, 8-11 kg, 51% female). Associations were tested using a mixed linear effects model.Results: We found that higher LFP was associated with higher LPR and higher glycerol concentration. No other biomarkers were associated with LPR; cerebral haemoglobin concentration, oxygen extraction fraction, and one EEG metric were associated with glycerol concentration.Conclusion: Contrary to expectations, higher LFP in CBF was correlated with worse invasive biomarkers. Higher LFP may represent higher neurologic activity, or disruptions in neurovascular coupling. Either effect may be harmful in the acute period after cardiac arrest. Thus, these results suggest our methodology holds promise for development of new, clinically relevant biomarkers than can guide resuscitation and post-resuscitation care. Institutional protocol number: 19-001327. [ABSTRACT FROM AUTHOR]

Near-infrared spectroscopy (NIRS) measurements of tissue oxygen saturation (StO2) are frequently used during vascular and cardiac surgeries as a non-invasive means of assessing brain health; however, signal contamination from extracerebral tissues remains a concern. As an alternative, hyperspectral (hs)NIRS can be used to measure changes in the oxidation state of cytochrome c oxidase (ΔoxCCO), which provides greater sensitivity to the brain given its higher mitochondrial concentration versus the scalp. The purpose of this study was to evaluate the depth sensitivity of the oxCCO signal to changes occurring in the brain and extracerebral tissue components. The oxCCO assessment was conducted using multi-distance hsNIRS (source-detector separations = 1 and 3 cm), and metabolic changes were compared to changes in StO2. Ten participants were monitored using an in-house system combining hsNIRS and diffuse correlation spectroscopy (DCS). Data were acquired during carotid compression (CC) to reduce blood flow and hypercapnia to increase flow. Reducing blood flow by CC resulted in a significant decrease in oxCCO measured at rSD = 3 cm but not at 1 cm. In contrast, significant changes in StO2 were found at both distances. Hypercapnia caused significant increases in StO2 and oxCCO at rSD = 3 cm, but not at 1 cm. Extracerebral contamination resulted in elevated StO2 but not oxCCO after hypercapnia, which was significantly reduced by applying regression analysis. This study demonstrated that oxCCO was less sensitive to extracerebral signals than StO2. [ABSTRACT FROM AUTHOR]

Objective: This pilot study aims to show the feasibility of noninvasive and real-time cerebral hemodynamic monitoring during carotid endarterectomy (CEA) via diffuse correlation spectroscopy (DCS) and near-infrared spectroscopy (NIRS). Methods: Cerebral blood flow index (CBFi) was measured unilaterally in seven patients and bilaterally in seventeen patients via DCS. In fourteen patients, hemoglobin oxygenation changes were measured bilaterally and simultaneously via NIRS. Cerebral autoregulation (CAR) and cerebrovascular resistance (CVR) were estimated using CBFi and arterial blood pressure data. Further, compensatory responses to the ipsilateral hemisphere were investigated at different contralateral stenosis levels. Results: Clamping of carotid arteries caused a sharp increase of CVR (~70%) and a marked decrease of ipsilateral CBFi (57%). From the initial drop, we observed partial recovery in CBFi, an increase of blood volume, and a reduction in CVR in the ipsilateral hemisphere. There were no significant changes in compensatory responses between different contralateral stenosis levels as CAR was intact in both hemispheres throughout the CEA phase. A comparison between hemispheric CBFi showed lower ipsilateral levels during the CEA and post-CEA phases (p < 0.001, 0.03). Conclusion: DCS alone or combined with NIRS is a useful monitoring technique for real-time assessment of cerebral hemodynamic changes and allows individualized strategies to improve cerebral perfusion during CEA by identifying different hemodynamic metrics. [ABSTRACT FROM AUTHOR]

We measure tissue blood flow markers in breast tumors during neoadjuvant chemotherapy and investigate their correlation to pathologic complete response in a pilot longitudinal patient study (n  =  4). Tumor blood flow is quantified optically by diffuse correlation spectroscopy (DCS), and tissue optical properties, blood oxygen saturation, and total hemoglobin concentration are derived from concurrent diffuse optical spectroscopic imaging (DOSI). The study represents the first longitudinal DCS measurement of neoadjuvant chemotherapy in humans over the entire course of treatment; it therefore offers a first correlation between DCS flow indices and pathologic complete response. The use of absolute optical properties measured by DOSI facilitates significant improvement of DCS blood flow calculation, which typically assumes optical properties based on literature values. Additionally, the combination of the DCS blood flow index and the tissue oxygen saturation from DOSI permits investigation of tissue oxygen metabolism. Pilot results from four patients suggest that lower blood flow in the lesion-bearing breast is correlated with pathologic complete response. Both absolute lesion blood flow and lesion flow relative to the contralateral breast exhibit potential for characterization of pathological response. This initial demonstration of the combined optical approach for chemotherapy monitoring provides incentive for more comprehensive studies in the future and can help power those investigations.

Diffuse optical spectroscopic imaging (DOSI) and diffuse correlation spectroscopy (DCS) are model-based near-infrared (NIR) methods that measure tissue optical properties (broadband absorption, ? a , and reduced scattering, ? s ? ) and blood flow (blood flow index, BFI), respectively. DOSI-derived ? a values are used to determine composition by calculating the tissue concentration of oxy- and deoxyhemoglobin ( HbO 2 , HbR), water, and lipid. We developed and evaluated a combined, coregistered DOSI/DCS handheld probe for mapping and imaging these parameters. We show that uncertainties of 0.3 ?? mm ? 1 (37%) in ? s ? and 0.003 ?? mm ? 1 (33%) in ? a lead to ? 53 % and 9% errors in BFI, respectively. DOSI/DCS imaging of a solid tissue-simulating flow phantom and

Abstract Background The cortical microvascular cerebral blood flow response (CBF) to different changes in head-of-bed (HOB) position has been shown to be altered in acute ischemic stroke (AIS) by diffuse correlation spectroscopy (DCS) technique. However, the relationship between these relative ΔCBF changes and associated systemic blood pressure changes has not been studied, even though blood pressure is a major driver of cerebral blood flow. Methods Transcranial DCS data from four studies measuring bilateral frontal microvascular cerebral blood flow in healthy controls (n = 15), patients with asymptomatic severe internal carotid artery stenosis (ICA, n = 27), and patients with acute ischemic stroke (AIS, n = 72) were aggregated. DCS-measured CBF was measured in response to a short head-of-bed (HOB) position manipulation protocol (supine/elevated/supine, 5 min at each position). In a sub-group (AIS, n = 26; ICA, n = 14; control, n = 15), mean arterial pressure (MAP) was measured dynamically during the protocol. Results After elevated positioning, DCS CBF returned to baseline supine values in controls (p = 0.890) but not in patients with AIS (9.6% [6.0,13.3], mean 95% CI, p

Peripheral veno-arterial extracorporeal membrane oxygenation (ECMO) artificially oxygenates and circulates blood retrograde from the femoral artery, potentially exposing the brain to asymmetric perfusion. Though ECMO patients frequently experience brain injury, neurologic exams and imaging are difficult to obtain. Diffuse correlation spectroscopy (DCS) non-invasively measures relative cerebral blood flow (rBF) at the bedside using an optical probe on each side of the forehead. In this study we observed interhemispheric rBF differences in response to mean arterial pressure (MAP) changes in adult ECMO recipients. We recruited 13 subjects aged 21–78 years (7 with cardiac arrest, 4 with acute heart failure, and 2 with acute respiratory distress syndrome). They were dichotomized via Glasgow Coma Scale Motor score (GCS-M) into comatose (GCS-M ≤ 4; n = 4) and non-comatose (GCS-M > 4; n = 9) groups. Comatose patients had greater interhemispheric rBF asymmetry (ASYMrBF) vs. non-comatose patients over a range of MAP values (29 vs. 11%, p = 0.009). ASYMrBF in comatose patients resolved near a MAP range of 70–80 mmHg, while rBF remained symmetric through a wider MAP range in non-comatose patients. Correlations between post-oxygenator pCO2 or pH vs. ASYMrBF were significantly different between comatose and non-comatose groups. Our findings indicate that comatose patients are more likely to have asymmetric cerebral perfusion. [ABSTRACT FROM AUTHOR]

Correlation has a variety of applications that require signal processing. However, it is computationally intensive, and software correlators require high-performance processors for real-time data analysis. This is a challenge for embedded devices because of the limitation of computing resources. Hardware correlators that use Field Programmable Gate Array (FPGA) technology can significantly boost computational power and bridge the gap between the need for high-performance computing and the limited processing power available in embedded devices. This paper presents a detailed FPGA-based correlator design at the register level along with the open-source Very High-Speed Integrated Circuit Hardware Description Language (VHDL) code. It includes base modules for linear and multi-tau correlators of varying sizes. Every module implements a simple and unified data interface for easy integration with standard and publicly available FPGA modules. Eighty-lag linear and multi-tau correlators were built for validation of the design. Three input data sets—constant signal, pulse signal, and sine signal—were used to test the accuracy of the correlators. The results from the FPGA correlators were compared against the outputs of equivalent software correlators and validated with the corresponding theoretical values. The FPGA correlators returned results identical to those from the software references for all tested data sets and were proven to be equivalent to their software counterparts. Their computation speed is at least 85,000 times faster than the software correlators running on a Xilinx MicroBlaze processor. The FPGA correlator can be easily implemented, especially on System on a Chip (SoC) integrated circuits that have processor cores and FPGA fabric. It is the ideal component for device-on-chip solutions in biosensing. [ABSTRACT FROM AUTHOR]

Abstract Background Despite controversies, epinephrine remains a mainstay of cardiopulmonary resuscitation (CPR). Recent animal studies have suggested that epinephrine may decrease cerebral blood flow (CBF) and cerebral oxygenation, possibly potentiating neurological injury during CPR. We investigated the cerebrovascular effects of intravenous epinephrine in a swine model of pediatric in-hospital cardiac arrest. The primary objectives of this study were to determine if (1) epinephrine doses have a significant acute effect on CBF and cerebral tissue oxygenation during CPR and (2) if the effect of each subsequent dose of epinephrine differs significantly from that of the first. Methods One-month-old piglets (n = 20) underwent asphyxia for 7 min, ventricular fibrillation, and CPR for 10–20 min. Epinephrine (20 mcg/kg) was administered at 2, 6, 10, 14, and 18 min of CPR. Invasive (laser Doppler, brain tissue oxygen tension [PbtO2]) and noninvasive (diffuse correlation spectroscopy and diffuse optical spectroscopy) measurements of CBF and cerebral tissue oxygenation were simultaneously recorded. Effects of subsequent epinephrine doses were compared to the first. Results With the first epinephrine dose during CPR, CBF and cerebral tissue oxygenation increased by > 10%, as measured by each of the invasive and noninvasive measures (p

Peripheral veno-arterial extracorporeal membrane oxygenation (ECMO) artificially oxygenates and circulates blood retrograde from the femoral artery, potentially exposing the brain to asymmetric perfusion. Though ECMO patients frequently experience brain injury, neurologic exams and imaging are difficult to obtain. Diffuse correlation spectroscopy (DCS) non-invasively measures relative cerebral blood flow (rBF) at the bedside using an optical probe on each side of the forehead. In this study we observed interhemispheric rBF differences in response to mean arterial pressure (MAP) changes in adult ECMO recipients. We recruited 13 subjects aged 21–78 years (7 with cardiac arrest, 4 with acute heart failure, and 2 with acute respiratory distress syndrome). They were dichotomized via Glasgow Coma Scale Motor score (GCS-M) into comatose (GCS-M ≤ 4; n = 4) and non-comatose (GCS-M > 4; n = 9) groups. Comatose patients had greater interhemispheric rBF asymmetry (ASYMrBF) vs. non-comatose patients over a range of MAP values (29 vs. 11%, p = 0.009). ASYMrBF in comatose patients resolved near a MAP range of 70–80 mmHg, while rBF remained symmetric through a wider MAP range in non-comatose patients. Correlations between post-oxygenator pCO2 or pH vs. ASYMrBF were significantly different between comatose and non-comatose groups. Our findings indicate that comatose patients are more likely to have asymmetric cerebral perfusion.

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.)

Significance: The ability to monitor cerebral blood flow (CBF) at the bedside is essential to managing critical-care patients with neurological emergencies. Diffuse correlation spectroscopy (DCS) is ideal because it is non-invasive, portable, and inexpensive. We investigated a near-infrared spectroscopy (NIRS) approach for converting DCS measurements into physiological units of blood flow., Aim: Using magnetic resonance imaging perfusion as a reference, we investigated the accuracy of absolute CBF measurements from a bolus-tracking NIRS method that used transient hypoxia as a flow tracer and hypercapnia-induced increases in CBF measured by DCS., Approach: Twelve participants (7 female, 28 ± 6 years) completed a hypercapnia protocol with simultaneous CBF recordings from DCS and arterial spin labeling (ASL). Nine participants completed the transient hypoxia protocol while instrumented with time-resolved NIRS. The estimate of baseline CBF was subsequently used to calibrate hypercapnic DCS data., Results: Moderately strong correlations at baseline ( slope = 0.79 and R 2 = 0.59 ) and during hypercapnia ( slope = 0.90 and R 2 = 0.58 ) were found between CBF values from calibrated DCS and ASL (range 34 to 85    mL / 100    g / min )., Conclusions: Results demonstrated the feasibility of an all-optics approach that can both quantify CBF and perform continuous perfusion monitoring., (© 2024 The Authors.)

Manipulative therapy (MT) is applied to motor organs through a therapist’s hands. Although MT has been utilized in various medical treatments based on its potential role for increasing the blood flow to the local muscle, a quantitative validation of local muscle blood flow in MT remains challenging due to the lack of appropriate bedside evaluation techniques. Therefore, we investigated changes in the local blood flow to the muscle undergoing MT by employing diffuse correlation spectroscopy, a portable and emerging optical measurement technology that non-invasively measures blood flow in deep tissues. This study investigated the changes in blood flow, heart rate, blood pressure, and autonomic nervous activity in the trapezius muscle through MT application in 30 volunteers without neck and shoulder injury. Five minutes of MT significantly increased the median local blood flow relative to that of the pre-MT period (p < 0.05). The post-MT local blood flow increase was significantly higher in the MT condition than in the control condition, where participants remained still without receiving MT for the same time (p < 0.05). However, MT did not affect the heart rate, blood pressure, or cardiac autonomic nervous activity. The post-MT increase in muscle blood flow was significantly higher in the participants with muscle stiffness in the neck and shoulder regions than in those without (p < 0.05). These results suggest that MT could increase the local blood flow to the target skeletal muscle, with minimal effects on systemic circulatory function.

There is a need for quantitative biomarkers for early diagnosis of autism. Cerebral blood flow and oxidative metabolism parameters may show superior contrasts for improved characterization. Diffuse correlation spectroscopy (DCS) has been shown to be reliable method to obtain cerebral blood flow contrast in animals and humans. Thus, in this study, we evaluated the combination of DCS and fNIRS in an established autism mouse model. Our results indicate that autistic group had significantly (P =.001) lower (~40%) blood flow (1.16 ± 0.26) × 10−8 cm2/s), and significantly (P =.015) lower (~70%) oxidative metabolism (52.4 ± 16.6 μmol/100 g/min) compared to control group ([1.93 ± 0.74] × 10−8 cm2/s, 177.2 ± 45.8 μmol/100 g/min, respectively). These results suggest that the combination of DCS and fNIRS can provide hemodynamic and metabolic contrasts for in vivo assessment of autism pathological conditions noninvasively. [ABSTRACT FROM AUTHOR]