Diffuse Optical Spectroscopy Research Articles

Diffuse Optical Spectroscopy: Technology and Applications: introduction to the feature issue

Welcome to the 2024 Feature Issue on Diffuse Optical Spectroscopy: Technology and Applications in Biomedical Optics Express! This feature issue provides an exemplary sample of established and emerging DOS technologies as well as their biomedical applications through 27 contributed research papers and 1 invited review article. DOS researchers are inherently multidisciplinary, advancing topics spanning the basic theory of light-tissue interactions, computational modeling, technique and system development and preclinical and clinical applications. You will find this full range of topics represented in this feature issue.

Diffuse optical spectroscopy of lactating and non-lactating human mammary physiology.

Breastfeeding provides widely recognized advantages for infant and maternal health. Unfortunately, many women experience trouble with breastfeeding. Nevertheless, few suitable imaging modalities are available to study human lactation and determine the possible causes of breastfeeding problems. In this study, we apply broadband, quantitative diffuse optical spectroscopy (DOS) for this purpose. We present a study of fourteen lactating and eight similarly aged, premenopausal, non-lactating women to investigate the feasibility of DOS to study the optical and physiological differences between 1) lactating and non-lactating breasts, 2) the areolar and non-areolar region within the breast, and 3) lactating breasts before and after milk extraction. Our study shows that i) the median total hemoglobin concentration [tHb] of the lactating breast is 51% higher than for the non-lactating breast. ii) the median [tHb] of the lactating breast is 37% higher in the areolar region compared to the non-areolar region. iii) lactating breasts exhibit a positive median difference of 8% in [tHb] after milk extraction. Our findings are consistent with the expected physiological changes that occur during the lactation period. Importantly, we show that DOS provides unique insight into breast tissue composition and physiology, serving as a foundation for future application of the technique in lactation research.

In vivo optimization of the experimental conditions for the non-invasive optical assessment of breast density

In this study, time domain diffuse optical spectroscopy is performed in the range 600–1100 nm on 11 healthy volunteers with a portable system for the quantitative characterization of breast tissue in terms of optical properties and optically-derived blood parameters, tissue constituent concentrations, and scattering parameters. A measurement protocol involving different geometries (reflectance and transmittance), subject’s positions (sitting and lying down), probing locations (outer, lower, and inner breast quadrants), and source-detector distances (2 and 3 cm) allowed us to investigate the effect of tissue heterogeneity and different measurement configurations on the results with the aim of identifying the best experimental conditions for the estimate of breast density (i.e., amount of fibro-glandular tissue in the breast) as a strong independent risk factor for breast cancer. Transmittance results, that in previous studies correlated strongly with mammographic density, are used as a reference for the initial test of the simpler and more comfortable reflectance measurement configuration. The higher source-detector distance, which probes deeper tissue, retrieves optical outcomes in agreement with higher average density tissue. Similarly, results on the outer quadrants indicate higher density than internal quadrants. These findings are coherent with breast anatomy since the concentration of dense fibro-glandular stroma is higher in deep tissue and towards the external portion of the breast, where the mammary gland is located. The dataset generated with this laboratory campaign is used to device an optimal measurement protocol for a future clinical trial, where optical results will be correlated with conventional mammographic density, allowing us to identify a subset of wavelengths and measurement configurations for an effective estimate of breast density. The final objective is the design of a simplified, compact and cost-effective optical device for a non-invasive, routine assessment of density-associated breast cancer risk.

Use of bioresorbable fibers for short-wave infrared spectroscopy using time-domain diffuse optics.

We demonstrate the usability of bioresorbable phosphate glass fibers for time-domain diffuse optical spectroscopy (TD-DOS) in the short-wave infrared (SWIR) region of 950-1600 nm, with the use of an InGaAs detector. Bioresorbable fibers for diffuse optics present an exciting prospect due to their ability to be left implanted while retrieving optical properties from deeper regions (few cm) for monitoring treatments. Extending TD-DOS to the SWIR region could be useful to better identify biomarkers such as water, lipids and collagen, given their increase in absorption in this range. We attempt to use the bioresorbable fibers to spectrally identify these biomarkers by measuring a series of biological samples known to contain them, such as porcine muscle, porcine fat and bone. We further validate our measurements by comparing the optical properties of high-scattering solid silicone phantoms retrieved with these bioresorbable fibers with those by a standard Si fiber.

Cross-wavelength calibrating method for real-time imaging of tissue optical properties using frequency-domain diffuse optical spectroscopy.

Frequency-domain diffuse optical spectroscopy (FD-DOS) is a powerful non-invasive technique for assessing tissue optical properties, with applications ranging from basic research to clinical diagnosis. In this study, we introduce and validate a novel approach termed the cross-wavelength calibrating (CWC) method within the framework of TrackDOSI, a real-time FD-DOS imaging system for tissue characterization. The CWC method aims to mitigate the effects of changing optical coupling and motion artifacts encountered during probe scanning, thus enhancing the accuracy and reliability of optical property measurements. Notably, the CWC method also allows for a simpler geometry with fewer sources than traditional self-calibrating (SC) methods, reducing instrumental complexity and cost while maintaining robustness in estimating optical properties. We first validate the CWC method on solid silicone phantoms, demonstrating strong agreement with the gold standard SC method with an error of -10% and 1% for absorption and reduced scattering coefficients, respectively. Furthermore, experiments on phantom and human tissue reveal the CWC approach's ability to suppress motion artifacts and optical coupling variations, thereby improving measurement repeatability, signal fidelity, and artifact correction in dynamic imaging scenarios. Our findings underscore the potential of the CWC method to enhance the clinical utility of DOSI techniques by enabling real-time artifact correction and improving the accuracy of tissue optical property measurements.

Monitoring of neoadjuvant chemotherapy through time domain diffuse optics: breast tissue composition changes and collagen discriminative potential.

The purpose of this clinical study is to test a broad spectral range (635-1060 nm) time-domain diffuse optical spectroscopy in monitoring the response of breast cancer patients to neoadjuvant chemotherapy (NAC). The broadband operation allows us to fully analyze tissue composition in terms of hemoglobin, water, lipids and collagen concentration, which has never been systematically studied until now during the course of therapy. Patients are subjected to multiple breast optical imaging sessions, each one performed at different stages of NAC, both on tumor-bearing and contralateral healthy breasts. We correlate the optical results with conventional imaging techniques and pathological response. Preliminary outcomes on 10 patients' data show an average significant reduction in the concentrations of oxy-hemoglobin (-53%, p = 0.0020), collagen (-36%, p = 0.0039) and water (-15%, p = 0.0195), and increase in lipids (+39%, p = 0.0137) from baseline to the end of therapy in the tumor-bearing breast of patients who responded to therapy at least partially. With respect to scattering, the scattering amplitude, a, increases slightly (+15%, p = 0.0039) by the end of the therapy compared to the baseline, while the scattering slope, b, shows no significant change (+4%, p = 0.9219). Some change in the constituents' concentrations was also noticed in the contralateral healthy breast, even though it was significant only for oxy-hemoglobin concentration. We observed that collagen seems to be the only component distinguishing between complete and partial responders by the end of 2-3 weeks from the baseline. In the complete responder group, collagen significantly decreased after 2-3 weeks with respect to baseline (p = 0.0423). While the partial responder group also showed a decrease, it did not reach statistical significance (p = 0.1012). This suggests that collagen could serve as a potential biomarker to measure NAC effectiveness early during treatment. Even though obtained on a small group of patients, these initial results are consistent with those of standard medical modalities and highlight the sensitivity of the technique to changes that occur in breast composition during NAC.

Non-Invasive Monitoring of Microvascular Oxygenation and Reactive Hyperemia using Hybrid, Near-Infrared Diffuse Optical Spectroscopy for Critical Care.

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.

Mass Spectrometric Analysis of Purine Intermediary Metabolism Indicates Cyanide Induces Purine Catabolism in Rabbits.

Purines are the building blocks of DNA/RNA, energy substrates, and cofactors. Purine metabolites, including ATP, GTP, NADH, and coenzyme A, are essential molecules in diverse biological processes such as energy metabolism, signal transduction, and enzyme activity. When purine levels increase, excess purines are either recycled to synthesize purine metabolites or catabolized to the end product uric acid. Purine catabolism increases during states of low oxygen tension (hypoxia and ischemia), but this metabolic pathway is incompletely understood in the context of histotoxic hypoxia (i.e., inhibition of oxygen utilization despite normal oxygen tension). In rabbits exposed to cyanide-a classical histotoxic hypoxia agent-we demonstrated significant increases in several concordant metabolites in the purine catabolic pathway (including plasma levels of uric acid, xanthosine, xanthine, hypoxanthine, and inosine) via mass spectrometry-based metabolite profiling. Pharmacological inhibition of the purine catabolic pathway with oxypurinol mitigated the deleterious effects of cyanide on skeletal muscle cytochrome c oxidase redox state, measured by non-invasive diffuse optical spectroscopy. Finally, plasma uric acid levels correlated strongly with those of lactic acid, an established clinical biomarker of cyanide exposure, in addition to a tissue biomarker of cyanide exposure (skeletal muscle cytochrome c oxidase redox state). Cumulatively, these findings not only shed light on the in vivo role(s) of cyanide but also have implications in the field of medical countermeasure (MCM) development.

Assessment of power spectral density of microvascular hemodynamics in skeletal muscles at very low and low-frequency via near-infrared diffuse optical spectroscopies: erratum

This publisher’s note contains a correction to Biomed. Opt. Express 14(11), 5994 (2023)10.1364/BOE.502618.

Initial non-invasive in vivo sensing of the lung using time domain diffuse optics

The in vivo diagnosis and monitoring of pulmonary disorders (caused for example by emphysema, Covid-19, immature lung tissue in infants) could be effectively supported by the non-invasive sensing of the lung through light. With this purpose, we investigated the feasibility of probing the lung by means of time-resolved diffuse optics, leveraging the increased depth (a few centimeters) attained by photons collected after prolonged propagation time (a few nanoseconds). We present an initial study that includes measurements performed on 5 healthy volunteers during a breathing protocol, using a time-resolved broadband diffuse optical spectroscopy system. Those measurements were carried out across the spectral range of 600–1100 nm at a source-detector distance of 3 cm, and at 820 nm over a longer distance (7–9 cm). The preliminary analysis of the in vivo data with a simplified homogeneous model revealed a maximum probing depth of 2.6–3.9 cm, suitable for reaching the lung. Furthermore, we observed variations in signal associated with respiration, particularly evident at long photon propagation times. However, challenges stemming from both intra- and inter-subject variability, along with inconsistencies potentially arising from conflicting scattering and absorption effects on the collected signal, hindered a clear interpretation. Aspects that require further investigation for a more comprehensive understanding are outlined.

Real-Time Tissue Classification Using a Novel Optical Needle Probe for Biopsy.

Core needle biopsy is a part of the histopathological process, which is required for cancerous tissue examination. The most common method to guide the needle inside of the body is ultrasound screening, which in greater part is also the only guidance method. Ultrasound screening requires user experience. Furthermore, patient involuntary movements such as breathing might introduce artifacts and blur the screen. Optically enhanced core needle biopsy probe could potentially aid interventional radiologists during this procedure, providing real-time information on tissue properties close to the needle tip, while it is advancing inside of the body. In this study, we used diffuse optical spectroscopy in a custom-made core needle probe for real-time tissue classification. Our aim was to provide initial characteristics of the smart needle probe in the differentiation of tissues and validate the basic purpose of the probe of informing about breaking into a desired organ. We collected optical spectra from rat blood, fat, heart, kidney, liver, lungs, and muscle tissues. Gathered data were analyzed for feature extraction and evaluation of two machine learning-based classifiers: support vector machine and k-nearest neighbors. Their performances on training data were compared using subject-independent k-fold cross-validation. The best classifier model was chosen and its feasibility for real-time automated tissue recognition and classification was then evaluated. The final model reached nearly 80% of correct real-time classification of rat organs when using the needle probe during real-time classification.

The influence of voxelotor on cerebral blood flow and oxygen extraction in pediatric sickle cell disease

AbstractVoxelotor is an inhibitor of sickle hemoglobin polymerization that is used to treat sickle cell disease. Although voxelotor has been shown to improve anemia, the clinical benefit on the brain remains to be determined. This study quantified the cerebral hemodynamic effects of voxelotor in children with sickle cell anemia (SCA) using noninvasive diffuse optical spectroscopies. Specifically, frequency-domain near-infrared spectroscopy combined with diffuse correlation spectroscopy were used to noninvasively assess regional oxygen extraction fraction (OEF), cerebral blood volume, and an index of cerebral blood flow (CBFi). Estimates of CBFi were first validated against arterial spin–labeled magnetic resonance imaging (ASL-MRI) in 8 children with SCA aged 8 to 18 years. CBFi was significantly positively correlated with ASL-MRI–measured blood flow (R2 = 0.651; P = .015). Next, a single-center, open-label pilot study was completed in 8 children with SCA aged 4 to 17 years on voxelotor, monitored before treatment initiation and at 4, 8, and 12 weeks (NCT05018728). By 4 weeks, both OEF and CBFi significantly decreased, and these decreases persisted to 12 weeks (both P < .05). Decreases in CBFi were significantly correlated with increases in blood hemoglobin (Hb) concentration (P = .025), whereas the correlation between decreases in OEF and increases in Hb trended toward significance (P = .12). Given that previous work has shown that oxygen extraction and blood flow are elevated in pediatric SCA compared with controls, these results suggest that voxelotor may reduce cerebral hemodynamic impairments. This trial was registered at www.ClinicalTrials.gov as #NCT05018728.

Chassis-based fiber-coupled opticalprobe design for reproducible quantitative diffuse optical spectroscopy measurements.

Advanced optical neuromonitoring of cerebral hemodynamics with hybrid diffuse optical spectroscopy (DOS) and diffuse correlation spectroscopy (DCS) methods holds promise for non-invasive characterization of brain health in critically ill patients. However, the methods' fiber-coupled patient interfaces (probes) are challenging to apply in emergent clinical scenarios that require rapid and reproducible attachment to the head. To address this challenge, we developed a novel chassis-based optical probe design for DOS/DCS measurements and validated its measurement accuracy and reproducibility against conventional, manually held measurements of cerebral hemodynamics in pediatric swine (n = 20). The chassis-based probe design comprises a detachable fiber housing which snaps into a 3D-printed, circumferential chassis piece that is secured to the skin. To validate its reproducibility, eight measurement repetitions of cerebral tissue blood flow index (BFI), oxygen saturation (StO2), and oxy-, deoxy- and total hemoglobin concentration were acquired at the same demarcated measurement location for each pig. The probe was detached after each measurement. Of the eight measurements, four were acquired by placing the probe into a secured chassis, and four were visually aligned and manually held. We compared the absolute value and intra-subject coefficient of variation (CV) of chassis versus manual measurements. No significant differences were observed in either absolute value or CV between chassis and manual measurements (p > 0.05). However, the CV for BFI (mean ± SD: manual, 19.5% ± 9.6; chassis, 19.0% ± 10.8) was significantly higher than StO2 (manual, 5.8% ± 6.7; chassis, 6.6% ± 7.1) regardless of measurement methodology (p<0.001). The chassis-based DOS/DCS probe design facilitated rapid probe attachment/re-attachment and demonstrated comparable accuracy and reproducibility to conventional, manual alignment. In the future, this design may be adapted for clinical applications to allow for non-invasive monitoring of cerebral health during pediatric critical care.

Estimation of Photon Path Length and Penetration Depth in Articular Cartilage Zonal Architecture Over the Therapeutic Window.

The key characteristics of light propagation are the average penetration depth, average maximum penetration depth, average maximum lateral spread, and average path length of photons. These parameters depend on tissue optical properties and, thus, on the pathological state of the tissue. Hence, they could provide diagnostic information on tissue integrity. This study investigates these parameters for articular cartilage which has a complex structure. We utilize Monte Carlo simulation to simulate photon trajectories in articular cartilage and estimate the average values of the light propagation parameters (penetration depth, maximum penetration depth, maximum lateral spread, and path length) in the spectral band of 400-1400 nm based on the optical properties of articular cartilage zonal layers and bulk tissue. Our findings suggest that photons in the visible band probe a localized small volume of articular cartilage superficial and middle zones, while those in the NIR band penetrate deeper into the tissue and have larger lateral spread. In addition, we demonstrate that a simple model of articular cartilage tissue, based on the optical properties of the bulk tissue, is capable to provide an accurate description of the light-tissue interaction in articular cartilage. The results indicate that as the photons in the spectral band of 400-1400 nm can reach the full depth of articular cartilage matrix, they can provide viable information on its pathological state. Therefore, diffuse optical spectroscopy holds significant importance for objectively assessing articular cartilage health. In this study, for the first time, we estimate the light propagation parameters in articular cartilage.

Continuous monitoring of tissue oxygen metabolism based on multi-wavelength diffuse correlation spectroscopy using LSTM-based RNN model

Growing incidences of cardiovascular diseases have driven demand for continuous tissue oxygen metabolism monitoring. Diffuse optical spectroscopy (DOS) or near-infrared spectroscopy (NIRS) is typically employed to measure oxygenated and de-oxygenated hemoglobin, while diffuse correlation spectroscopy (DCS) provides a direct measure of tissue blood flow noninvasively. Traditionally, combined DCS and DOS/NIRS approaches are utilized for monitoring oxygen metabolism, which needs two different numerical models to calculate blood flow and oxygen saturation. In this paper, we evaluate the utility of multi-wavelength diffuse correlation spectroscopy (mwDCS) using a proposed deep learning approach, i.e., long short-term memory (LSTM) based recurrent neural network (RNN). Arterial occlusion experiments were performed in vivo to generate the data from 6 healthy individuals. Further, based on the dataset acquired by mwDCS, a LSTM-based RNN model was developed to directly assess changes of blood flow and oxygen saturation. Compared to conventional methods, the in vivo experiments in this study demonstrated a more portable system with promising results. Pearsons correlation coefficients of the proposed model reached 0.82 and 0.64 for the changes of blood flow and oxygen saturation, respectively. Our results shows that mwDCS using LSTM-based RNN model provides an alternative method for continuous tissue oxygen metabolism monitoring.

In vivo characterization of the optical and hemodynamic properties of the human sternocleidomastoid muscle through ultrasound-guided hybrid near-infrared spectroscopies

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.

Hybrid Bladder Phantom to Validate Next-Generation Optical Wearables for Neurogenic Bladder Volume Monitoring.

The development of optics-based wearables for bladder volume monitoring has emerged as a significant topic in recent years. Given the innovative nature of this technology, there is currently no bladder phantom available to effectively validate these devices against more established gold standards, such as ultrasound. In this study, we showcase and demonstrate the performance of our hybrid bladder phantom by using an optical device and making comparisons with ultrasound. A series of validation tests, including phantom repeatability, ultrasound scanning, and an optical test, were performed. A near-infrared optical device was utilized to conduct diffuse optical spectroscopy (DOS). Machine learning models were employed to construct predictive models of volume using optical signals. The size and position of an embedded balloon, serving as an analog for the bladder, were shown to be consistent when infused with 100 mL to 350 mL of water during repeatability testing. For DOS data, we present 7 types of machine learningbased models based on different optical signals. The 2 best-performing models demonstrated an average absolute volume error ranging from 12.7 mL to 19.0 mL. In this study, we introduced a hybrid bladder phantom designed for the validation of near-infrared spectroscopy-based bladder monitoring devices in comparison with ultrasound techniques. By offering a reproducible and robust validation tool, we aim to support the advancement of next-generation optical wearables for bladder volume monitoring.

Self-calibrated pulse oximetry algorithm based on photon pathlength change and the application in human freedivers.

Pulse oximetry estimates the arterial oxygen saturation of hemoglobin () based on relative changes in light intensity at the cardiac frequency. Commercial pulse oximeters require empirical calibration on healthy volunteers, resulting in limited accuracy at low oxygen levels. An accurate, self-calibrated method for estimating is needed to improve patient monitoring and diagnosis. Given the challenges of calibration at low levels, we pursued the creation of a self-calibrated algorithm that can effectively estimate across its full range. Our primary objective was to design and validate our calibration-free method using data collected from human subjects. We developed an algorithm based on diffuse optical spectroscopy measurements of cardiac pulses and the modified Beer-Lambert law (mBLL). Recognizing that the photon mean pathlength () varies with related absorption changes, our algorithm aligns/fits the normalized (across wavelengths) obtained from optical measurements with its analytical representation. We tested the algorithm with human freedivers performing breath-hold dives. A continuous-wave near-infrared spectroscopy probe was attached to their foreheads, and an arterial cannula was inserted in the radial artery to collect arterial blood samples at different stages of the dive. These samples provided ground-truth via a blood gas analyzer, enabling us to evaluate the accuracy of estimation derived from the NIRS measurement using our self-calibrated algorithm. The self-calibrated algorithm significantly outperformed the conventional method (mBLL with a constant ratio) for estimation through the diving period. Analyzing 23 ground-truth data points ranging from 41% to 100%, the average absolute difference between the estimated and the ground truth is for our algorithm, significantly lower than the observed with the conventional approach. By factoring in the variations in the spectral shape of relative to , our self-calibrated algorithm enables accurate estimation, even in subjects with low levels.

Diffuse Optical Monitoring of Cerebral Hemodynamics and Oxygen Metabolism during and after Cardiopulmonary Bypass: Hematocrit Correction and Neurological Vulnerability.

Cardiopulmonary bypass (CPB) provides cerebral oxygenation and blood flow (CBF) during neonatal congenital heart surgery, but the impacts of CPB on brain oxygen supply and metabolic demands are generally unknown. To elucidate this physiology, we used diffuse correlation spectroscopy and frequency-domain diffuse optical spectroscopy to continuously measure CBF, oxygen extraction fraction (OEF), and oxygen metabolism (CMRO2) in 27 neonatal swine before, during, and up to 24 h after CPB. Concurrently, we sampled cerebral microdialysis biomarkers of metabolic distress (lactate-pyruvate ratio) and injury (glycerol). We applied a novel theoretical approach to correct for hematocrit variation during optical quantification of CBF in vivo. Without correction, a mean (95% CI) +53% (42, 63) increase in hematocrit resulted in a physiologically improbable +58% (27, 90) increase in CMRO2 relative to baseline at CPB initiation; following correction, CMRO2 did not differ from baseline at this timepoint. After CPB initiation, OEF increased but CBF and CMRO2 decreased with CPB time; these temporal trends persisted for 0-8 h following CPB and coincided with a 48% (7, 90) elevation of glycerol. The temporal trends and glycerol elevation resolved by 8-24 h. The hematocrit correction improved quantification of cerebral physiologic trends that precede and coincide with neurological injury following CPB.

Assessment of power spectral density of microvascular hemodynamics in skeletal muscles at very low and low-frequency via near-infrared diffuse optical spectroscopies.

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.