Cerebral and systemic physiological effects of wearing face masks in young adults.

The COVID-19 pandemic led to widespread mandates requiring the wearing of face masks, which led to debates on their benefits and possible adverse effects. To that end, the physiological effects at the systemic and at the brain level are of interest. We have investigated the effect of commonly available face masks (FFP2 and surgical) on cerebral hemodynamics and oxygenation, particularly microvascular cerebral blood flow (CBF) and blood/tissue oxygen saturation (StO2), measured by transcranial hybrid near-infrared spectroscopies and on systemic physiology in 13 healthy adults (ages: 23 to 33 y). The results indicate small but significant changes in cerebral hemodynamics while wearing a mask. However, these changes are comparable to those of daily life activities. This platform and the protocol provides the basis for large or targeted studies of the effects of mask wearing in different populations and while performing critical tasks.

Multi-mode fiber-based speckle contrast optical spectroscopy: analysis of speckle statistics.

Speckle contrast optical spectroscopy/tomography (SCOS/T) provides a real-time, non-invasive, and cost-efficient optical imaging approach to mapping of cerebral blood flow. By measuring many speckles (n>>10), SCOS/T has an increased signal-to-noise ratio relative to diffuse correlation spectroscopy, which measures one or a few speckles. However, the current free-space SCOS/T designs are not ideal for large field-of-view imaging in humans because the curved head contour cannot be readily imaged with a single flat sensor and hair obstructs optical access. Herein, we evaluate the feasibility of using cost-efficient multi-mode fiber (MMF) bundles for use in SCOS/T systems. One challenge with speckle contrast measurements is the potential for confounding noise sources (e.g., shot noise, readout noise) which contribute to the standard deviation measure and corrupt the speckle contrast measure that is central to the SCOS/T systems. However, for true speckle measurements, the histogram of pixel intensities from light interference follows a non-Gaussian distribution, specifically a gamma distribution with non-zero skew, whereas most noise sources have pixel intensity distributions that are Gaussian. By evaluating speckle data from static and dynamic targets imaged through an MMF, we use histograms and statistical analysis of pixel histograms to evaluate whether the statistical properties of the speckles are retained. We show that flow-based speckle can be distinguished from static speckle and from sources of system noise through measures of skew in the pixel intensity histograms. Finally, we illustrate in humans that MMF bundles relay blood flow information.

Early assessment of injury with optical markers in a piglet model of neonatal encephalopathy.

BACKGROUND: Opportunities for adjunct therapies with cooling in neonatal encephalopathy are imminent; however, robust biomarkers of early assessment are lacking. Using an optical platform of broadband near-infrared spectroscopy and diffuse correlation spectroscopy to directly measure mitochondrial metabolism (oxCCO), oxygenation (HbD), cerebral blood flow (CBF), we hypothesised optical indices early (1-h post insult) after hypoxia-ischaemia (HI) predicts insult severity and outcome. METHODS: Nineteen newborn large white piglets underwent continuous neuromonitoring as controls or following moderate or severe HI. Optical indices were expressed as mean semblance (phase difference) and coherence (spectral similarity) between signals using wavelet analysis. Outcome markers included the lactate/N-acetyl aspartate (Lac/NAA) ratio at 6 h on proton MRS and TUNEL cell count. RESULTS: CBF-HbD semblance (cerebrovascular dysfunction) correlated with BGT and white matter (WM) Lac/NAA (r2 = 0.46, p = 0.004, r2 = 0.45, p = 0.004, respectively), TUNEL cell count (r2 = 0.34, p = 0.02) and predicted both initial insult (r2 = 0.62, p = 0.002) and outcome group (r2 = 0.65 p = 0.003). oxCCO-HbD semblance (cerebral metabolic dysfunction) correlated with BGT and WM Lac/NAA (r2 = 0.34, p = 0.01 and r2 = 0.46, p = 0.002, respectively) and differentiated between outcome groups (r2 = 0.43, p = 0.01). CONCLUSION: Optical markers of both cerebral metabolic and vascular dysfunction 1 h after HI predicted injury severity and subsequent outcome in a pre-clinical model. IMPACT: This study highlights the possibility of using non-invasive optical biomarkers for early assessment of injury severity following neonatal encephalopathy, relating to the outcome. Continuous cot-side monitoring of these optical markers can be useful for disease stratification in the clinical population and for identifying infants who might benefit from future adjunct neuroprotective therapies beyond cooling.

Blood flow response to orthostatic challenge identifies signatures of the failure of static cerebral autoregulation in patients with cerebrovascular disease.

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 < 0.001) or ICA stenosis (8.6% [3.1,14.0], p = 0.003)). MAP in AIS patients did not return to baseline values (2.6 mmHg [0.5, 4.7], p = 0.018), but in ICA stenosis patients and controls did. Instead ipsilesional but not contralesional CBF was correlated with MAP (AIS 6.0%/mmHg [- 2.4,14.3], p = 0.038; ICA stenosis 11.0%/mmHg [2.4,19.5], p < 0.001). CONCLUSIONS: The observed associations between ipsilateral CBF and MAP suggest that short HOB position changes may elicit deficits in cerebral autoregulation in cerebrovascular disorders. Additional research is required to further characterize this phenomenon.

Neurodevelopmental profile in children with benign external hydrocephalus syndrome. A pilot cohort study.

PURPOSE: The management of children with benign external hydrocephalus (BEH) remains controversial. Most BEH children do well in the long-term, but a substantial number have temporary or permanent psychomotor delays. The study aims to assess the prevalence and pattern of neurodevelopmental delay in a cohort of children with BEH. METHODS: We conducted a cohort study of 42 BEH children (30 boys and 12 girls, aged 6 to 38 months). A pediatric neurosurgeon performed a first clinical evaluation to confirm/reject the diagnosis according to the clinical features and neuroimaging studies. Two trained evaluators assessed the child's psychomotor development using the third edition of the Bayley Scales of Infant and Toddler Development (Bayley-III). Developmental delay was defined as a scaled score < 7 according to the simple scale and/or a composite score < 85. RESULTS: Eighteen children (43%) presented statistically lower scores in the gross motor and composite motor of the Bayley-III scales compared to their healthy peers. CONCLUSION: In BEH, it is important to establish a diagnostic algorithm that helps to discriminate BEH patients that have self-limiting delays from those at risk of a persistent delay that should be referred for additional studies and/or interventions that might improve the natural evolution of a disease with high impact on the children and adult's quality of life.

Performance Assessment of a Commercial Continuous-Wave Near-Infrared Spectroscopy Tissue Oximeter for Suitability for Use in an International, Multi-Center Clinical Trial.

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

High-resolution mapping of infraslow cortical brain activity enabled by graphene microtransistors.

Recording infraslow brain signals (<0.1 Hz) with microelectrodes is severely hampered by current microelectrode materials, primarily due to limitations resulting from voltage drift and high electrode impedance. Hence, most recording systems include high-pass filters that solve saturation issues but come hand in hand with loss of physiological and pathological information. In this work, we use flexible epicortical and intracortical arrays of graphene solution-gated field-effect transistors (gSGFETs) to map cortical spreading depression in rats and demonstrate that gSGFETs are able to record, with high fidelity, infraslow signals together with signals in the typical local field potential bandwidth. The wide recording bandwidth results from the direct field-effect coupling of the active transistor, in contrast to standard passive electrodes, as well as from the electrochemical inertness of graphene. Taking advantage of such functionality, we envision broad applications of gSGFET technology for monitoring infraslow brain activity both in research and in the clinic.

Cerebral oxygenation and blood flow in normal term infants at rest measured by a hybrid near-infrared device (BabyLux).

BACKGROUND: The BabyLux device is a prototype optical neuro-monitor of cerebral oxygenation and blood flow for neonatology integrating time-resolved reflectance spectroscopy and diffuse correlation spectroscopy. METHODS: Here we report the variability of six consecutive 30 s measurements performed in 27 healthy term infants at rest. Poor data quality excluded four infants. RESULTS: Mean cerebral oxygenation was 59.6 ± 8.0%, with intra-subject standard deviation of 3.4%, that is, coefficient of variation (CV) of 5.7%. The inter-subject CV was 13.5%. Mean blood flow index was 2.7 × 10-8 ± 1.56 × 10-8 (cm2/s), with intra-subject CV of 27% and inter-subject CV of 56%. The variability in blood flow index was not reduced by the use of individual measures of tissue scattering, nor accompanied by a parallel variability in cerebral oxygenation. CONCLUSION: The intra-subject variability for cerebral oxygenation variability was improved compared to spatially resolved spectroscopy devices, while for the blood flow index it was comparable to that of other modalities for estimating cerebral blood flow in newborn infants. Most importantly, the simultaneous measurement of oxygenation and flow allows for interpretation of the high inter-subject variability of cerebral blood flow as being due to error of measurement rather than to physiological instability.

High-density speckle contrast optical tomography (SCOT) for three dimensional tomographic imaging of the small animal brain.

High-density speckle contrast optical tomography (SCOT) utilizing tens of thousands of source-detector pairs, was developed for in vivo imaging of blood flow in small animals. The reduction in cerebral blood flow (CBF) due to local ischemic stroke in a mouse brain was transcanially imaged and reconstructed in three dimensions. The reconstructed volume was then compared with corresponding magnetic resonance images demonstrating that the volume of reduced CBF agrees with the infarct zone at twenty-four hours.

Fast silicon photomultiplier improves signal harvesting and reduces complexity in time-domain diffuse optics.

We present a proof of concept prototype of a time-domain diffuse optics probe exploiting a fast Silicon PhotoMultiplier (SiPM), featuring a timing resolution better than 80 ps, a fast tail with just 90 ps decay time-constant and a wide active area of 1 mm2. The detector is hosted into the probe and used in direct contact with the sample under investigation, thus providing high harvesting efficiency by exploiting the whole SiPM numerical aperture and also reducing complexity by avoiding the use of cumbersome fiber bundles. Our tests also demonstrate high accuracy and linearity in retrieving the optical properties and suitable contrast and depth sensitivity for detecting localized inhomogeneities. In addition to a strong improvement in both instrumentation cost and size with respect to legacy solutions, the setup performances are comparable to those of state-of-the-art time-domain instrumentation, thus opening a new way to compact, low-cost and high-performance time-resolved devices for diffuse optical imaging and spectroscopy.

Mannose-binding lectin promotes local microvascular thrombosis after transient brain ischemia in mice.

BACKGROUND AND PURPOSE: Several lines of evidence support the involvement of mannose-binding lectin (MBL) in stroke brain damage. The lectin pathway of the complement system facilitates thrombin activation and clot formation under certain experimental conditions. In the present study, we examine whether MBL promotes thrombosis after ischemia/reperfusion and influences the course and prognosis of ischemic stroke. METHODS: Middle cerebral artery occlusion/reperfusion was performed in MBL-deficient (n=85) and wild-type (WT; n=83) mice, and the brain lesion was assessed by MRI at days 1 and 7. Relative cerebral blood flow was monitored up to 6 hours after middle cerebral artery occlusion with laser speckle contrast imaging. Fibrin(ogen) was analyzed in the brain vasculature and plasma, and the effects of thrombin inhibitor argatroban were evaluated to assess the role of MBL in thrombin activation. RESULTS: Infarct volumes and neurological deficits were smaller in MBL knockout mice than in WT mice. Relative cerebral blood flow values during middle cerebral artery occlusion and at reperfusion were similar in both groups, but decreased during the next 6 hours in the WT group only. Also, the WT mice showed more fibrin(ogen) in brain vessels and a better outcome after argatroban treatment. In contrast, argatroban did not improve the outcome in MBL knockout mice. CONCLUSIONS: MBL promotes brain damage and functional impairment after brain ischemia/reperfusion in mice. These effects are secondary to intravascular thrombosis and impaired relative cerebral blood flow during reperfusion. Argatroban protects WT mice, but not MBL knockout mice, emphasizing a role of MBL in local thrombus formation in acute ischemia/reperfusion.

Optical bedside monitoring of cerebral blood flow in acute ischemic stroke patients during head-of-bed manipulation.

BACKGROUND AND PURPOSE: A primary goal of acute ischemic stroke (AIS) management is to maximize perfusion in the affected region and surrounding ischemic penumbra. However, interventions to maximize perfusion, such as flat head-of-bed (HOB) positioning, are currently prescribed empirically. Bedside monitoring of cerebral blood flow (CBF) allows the effects of interventions such as flat HOB to be monitored and may ultimately be used to guide clinical management. METHODS: Cerebral perfusion was measured during HOB manipulations in 17 patients with unilateral AIS affecting large cortical territories in the anterior circulation. Simultaneous measurements of frontal CBF and arterial flow velocity were performed with diffuse correlation spectroscopy and transcranial Doppler ultrasound, respectively. Results were analyzed in the context of available clinical data and a previous study. RESULTS: Frontal CBF, averaged over the patient cohort, decreased by 17% (P=0.034) and 15% (P=0.011) in the ipsilesional and contralesional hemispheres, respectively, when HOB was changed from flat to 30°. Significant (cohort-averaged) changes in blood velocity were not observed. Individually, varying responses to HOB manipulation were observed, including paradoxical increases in CBF with increasing HOB angle. Clinical features, stroke volume, and distance to the optical probe could not explain this paradoxical response. CONCLUSIONS: A lower HOB angle results in an increase in cortical CBF without a significant change in arterial flow velocity in AIS, but there is variability across patients in this response. Bedside CBF monitoring with diffuse correlation spectroscopy provides a potential means to individualize interventions designed to optimize CBF in AIS.

Diffuse correlation spectroscopy for non-invasive, micro-vascular cerebral blood flow measurement.

Diffuse correlation spectroscopy (DCS) uses the temporal fluctuations of near-infrared (NIR) light to measure cerebral blood flow (CBF) non-invasively. Here, we provide a brief history of DCS applications in the brain with an emphasis on the underlying physical ideas, common instrumentation and validation. Then we describe recent clinical research that employs DCS-measured CBF as a biomarker of patient well-being, and as an indicator of hemodynamic and metabolic responses to functional stimuli.

Hardware simulator for optical correlation spectroscopy with Gaussian statistics and arbitrary correlation functions.

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

Continuous optical monitoring of cerebral hemodynamics during head-of-bed manipulation in brain-injured adults.

INTRODUCTION: Head-of-bed manipulation is commonly performed in the neurocritical care unit to optimize cerebral blood flow (CBF), but its effects on CBF are rarely measured. This pilot study employs a novel, non-invasive instrument combining two techniques, diffuse correlation spectroscopy (DCS) for measurement of CBF and near-infrared spectroscopy (NIRS) for measurement of cerebral oxy- and deoxy-hemoglobin concentrations, to monitor patients during head-of-bed lowering. METHODS: Ten brain-injured patients and ten control subjects were monitored continuously with DCS and NIRS while the head-of-bed was positioned first at 30° and then at 0°. Relative CBF (rCBF) and concurrent changes in oxy- (ΔHbO2), deoxy- (ΔHb), and total-hemoglobin concentrations (ΔTHC) from left/right frontal cortices were monitored for 5 min at each position. Patient and control response differences were assessed. RESULTS: rCBF, ΔHbO2, and ΔTHC responses to head lowering differed significantly between brain-injured patients and healthy controls (P < 0.02). For patients, rCBF changes were heterogeneous, with no net change observed in the group average (0.3 ± 28.2 %, P = 0.938). rCBF increased in controls (18.6 ± 9.4 %, P < 0.001). ΔHbO2, ΔHb, and ΔTHC increased with head lowering in both groups, but to a larger degree in brain-injured patients. rCBF correlated moderately with changes in cerebral perfusion pressure (R = 0.40, P < 0.001), but not intracranial pressure. CONCLUSION: DCS/NIRS detected differences in CBF and oxygenation responses of brain-injured patients versus controls during head-of-bed manipulation. This pilot study supports the feasibility of continuous bedside measurement of cerebrovascular hemodynamics with DCS/NIRS and provides the rationale for further investigation in larger cohorts.

Assessment of Microvascular Hemodynamic Adaptations in Finger Flexors of Climbers.

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.

Dynamic Light Scattering in Biomedical Applications: feature issue introduction.

The feature Issue on "Dynamic Light Scattering in Biomedical Applications" presents a compilation of research breakthroughs and technological advancements that have shaped the field of biophotonics, particularly in the non-invasive exploration of biological tissues. Highlighting the significance of dynamic light scattering (DLS) alongside techniques like laser Doppler flowmetry (LDF), diffusing wave spectroscopy (DWS), and laser speckle contrast imaging (LSCI), this issue underscores the versatile applications of these methods in capturing the intricate dynamics of microcirculatory blood flow across various tissues. Contributions explore developments in fluorescence tomography, the integration of machine learning for data processing, enhancements in microscopy for cancer detection, and novel approaches in optical biophysics, among others. Innovations featured include a high-resolution speckle contrast tomography system for deep blood flow imaging, a rapid estimation technique for real-time tissue perfusion imaging, and the use of convolutional neural networks for efficient blood flow mapping. Additionally, studies delve into the impact of skin strain on spectral reflectance, the sensitivity of cerebral blood flow measurement techniques, and the potential of photobiomodulation for enhancing brain function. This issue not only showcases the latest theoretical and experimental strides in DLS-based imaging but also anticipates the continued evolution of these modalities for groundbreaking applications in disease detection, diagnosis, and monitoring, marking a pivotal contribution to the field of biomedical optics.

Study protocol to examine the effects of acute exercise on motor learning and brain activity in children with developmental coordination disorder (ExLe-Brain-DCD).

INTRODUCTION: Developmental coordination disorder (DCD) is one of the most prevalent pediatric chronic conditions. Without proper intervention, significant delays in motor skill performance and learning may persist until adulthood. Moderate-to-vigorous physical exercise has been proven to improve motor learning (adaptation and consolidation) in children with or without disorders. However, the effect of a short bout of physical exercise on motor adaptation and consolidation in children with DCD has not been examined. Furthermore, the role of perceptual-motor integration and attention as mediators of learning has not been examined via neuroimaging in this population. OBJECTIVES: Therefore, the primary aims of this project will be to compare children with and without DCD to (a) examine the effect of acute exercise on motor learning (adaptation and consolidation) while performing a rotational visuo-motor adaptation task (rVMA), and (b) explore cortical activation in the dorsolateral- and ventrolateral-prefrontal cortex areas while learning the rVMA task under rest or post-exercise conditions. METHODS: One hundred twenty children will be recruited (60 DCD, 60 controls) and within-cohort randomly assigned to either exercise (13-minute shuttle run task) or rest prior to performing the rVMA task. Adaptation and consolidation will be evaluated via two error variables and three retention tests (1h, 24h and 7 days post adaptation). Cortical activation will be registered via functional near-infrared spectroscopy (fNIRS) during the baseline, adaptation, and consolidation. DISCUSSION: We expect to find exercise benefits on motor learning and attention so that children with DCD profiles will be closer to those of children with typical development. The results of this project will provide further evidence to: (a) better characterize children with DCD for the design of educational materials, and (b) establish acute exercise as a potential intervention to improve motor learning and attention.

Comprehensive workflow and its validation for simulating diffuse speckle statistics for optical blood flow measurements.

Diffuse optical methods including speckle contrast optical spectroscopy and tomography (SCOS and SCOT), use speckle contrast (κ) to measure deep blood flow. In order to design practical systems, parameters such as signal-to-noise ratio (SNR) and the effects of limited sampling of statistical quantities, should be considered. To that end, we have developed a method for simulating speckle contrast signals including effects of detector noise. The method was validated experimentally, and the simulations were used to study the effects of physical and experimental parameters on the accuracy and precision of κ. These results revealed that systematic detector effects resulted in decreased accuracy and precision of κ in the regime of low detected signals. The method can provide guidelines for the design and usage of SCOS and/or SCOT instruments.

Erratum: 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 corrects the article on p. 5994 in vol. 14, PMID: 38021143.].