Characteristic of Mayer Waves in Electrophysiological, Hemodynamic and Vascular Signals.

We evaluated the properties of oscillations in the Mayer waves (MW) frequency range (∼0.1Hz) detected in blood pressure, heart rate variability, cerebral blood oxygenation changes and evolution of electroencephalographic (EEG) rhythms to elucidate the mechanisms of MW generation. We examined the persistence of MW in different signals and stability of their oscillations on the level of individual MW waveforms, which was achieved by applying matching pursuit (MP). MP yields adaptive time-frequency approximation of signal's structures in terms of frequency, amplitude, time occurrence, and time-span. The number of waveforms contributing to 95% of the energy of the signals was vastly different for the time series, but the average number of waveforms conforming to the MW criteria was almost the same (3.5 ± 0.4 per 120s epoch). In all the investigated signals, MW had the same distributions of frequency and the number of cycles. We show that the MW energy ratios in different signals varied strongly, p < 0.001. The highest percentage of MW energy was observed in blood pressure signals, heart rate variability, and reduced hemoglobin, in contrast to brain signals and oxygenated hemoglobin. The percentage of MW energy was related to the strength of causal influence exerted by them on the other signals. Our results indicate existence of a common mechanism of MW generation and support the hypothesis of MW generation in the baroreflex loop; however, they do not exclude the action of a central pacemaker.

Causal Coupling Between Electrophysiological Signals, Cerebral Hemodynamics and Systemic Blood Supply Oscillations in Mayer Wave Frequency Range.

The aim of the study was to assess causal coupling between neuronal activity, microvascular hemodynamics and blood supply oscillations in the Mayer wave frequency range. An electroencephalogram, cerebral blood oxygenation changes, an electrocardiogram and blood pressure were recorded during rest and during a movement task. Causal coupling between them was evaluated using directed transfer function, a measure based on the Granger causality principle. The multivariate autoregressive model was fitted to all the signals simultaneously, which made it possible to construct a complete scheme of interactions between the considered signals. The obtained pattern of interactions in the resting state estimated in the 0.05-0.15 Hz band revealed a predominant influence of blood pressure oscillations on all the other variables. Reciprocal connections between blood pressure and heart rate variability time series indicated the presence of feedback loops between these signals. During movement, the pattern of connections did not change dramatically. The number of connections decreased, but the couplings between blood pressure and heart rate variability signal were not significantly changed, and the strong influence of the decreased blood hemoglobin concentration on the oxygenated hemoglobin concentration persisted. For the first time our results provided a comprehensive scheme of interactions between electrical and hemodynamic brain signals, heart rate and blood pressure oscillations. Persistent reciprocal connections between blood pressure and heart rate variability time series suggest possible feedforward and feedback coupling of cardiovascular variables which may lead to the observed oscillations in Mayer wave range.

Human skull translucency: post mortem studies.

Measurements of optical translucency of human skulls were carried out. An incandescent light source and a CCD camera were used to measure the distribution of light transmitted through the skull in 10 subjects post-mortem. We noticed that intra-individual differences in optical translucency may be up to 100 times but inter-individual translucency differences across the skull reach 105 times. Based on the measurement results, a "theoretical" experiment was simulated. Monte-Carlo calculations were used in order to evaluate the influence of the differences in optical translucency of the skull on results of NIRS measurements. In these calculations a functional stimulation was done, in which the oxyhemoglobin and deoxyhemoglobin concentrations in the brain cortex change by 5µM and -5µM respectively. The maximal discrepancies between assumed hemoglobin concentration changes and hemoglobin concentration changes estimated with Monte-Carlo simulation may reach 50% depending of the translucency of the skull.

Travel-associated and autochthonous Zika virus infection in mainland France, 1 January to 15 July 2016.

During summer 2016, all the conditions for local mosquito-borne transmission of Zika virus (ZIKV) are met in mainland France: a competent vector, Aedes albopictus, a large number of travellers returning from ZIKV-affected areas, and an immunologically naive population. From 1 January to 15 July 2016, 625 persons with evidence of recent ZIKV infection were reported in mainland France. We describe the surveillance system in place and control measures implemented to reduce the risk of infection.

Direct evidence of milk consumption from ancient human dental calculus.

Milk is a major food of global economic importance, and its consumption is regarded as a classic example of gene-culture evolution. Humans have exploited animal milk as a food resource for at least 8500 years, but the origins, spread, and scale of dairying remain poorly understood. Indirect lines of evidence, such as lipid isotopic ratios of pottery residues, faunal mortality profiles, and lactase persistence allele frequencies, provide a partial picture of this process; however, in order to understand how, where, and when humans consumed milk products, it is necessary to link evidence of consumption directly to individuals and their dairy livestock. Here we report the first direct evidence of milk consumption, the whey protein ß-lactoglobulin (BLG), preserved in human dental calculus from the Bronze Age (ca. 3000 BCE) to the present day. Using protein tandem mass spectrometry, we demonstrate that BLG is a species-specific biomarker of dairy consumption, and we identify individuals consuming cattle, sheep, and goat milk products in the archaeological record. We then apply this method to human dental calculus from Greenland's medieval Norse colonies, and report a decline of this biomarker leading up to the abandonment of the Norse Greenland colonies in the 15(th) century CE.

Determination of reference values for optical properties of liquid phantoms based on Intralipid and India ink.

A multi-center study has been set up to accurately characterize the optical properties of diffusive liquid phantoms based on Intralipid and India ink at near-infrared (NIR) wavelengths. Nine research laboratories from six countries adopting different measurement techniques, instrumental set-ups, and data analysis methods determined at their best the optical properties and relative uncertainties of diffusive dilutions prepared with common samples of the two compounds. By exploiting a suitable statistical model, comprehensive reference values at three NIR wavelengths for the intrinsic absorption coefficient of India ink and the intrinsic reduced scattering coefficient of Intralipid-20% were determined with an uncertainty of about 2% or better, depending on the wavelength considered, and 1%, respectively. Even if in this study we focused on particular batches of India ink and Intralipid, the reference values determined here represent a solid and useful starting point for preparing diffusive liquid phantoms with accurately defined optical properties. Furthermore, due to the ready availability, low cost, long-term stability and batch-to-batch reproducibility of these compounds, they provide a unique fundamental tool for the calibration and performance assessment of diffuse optical spectroscopy instrumentation intended to be used in laboratory or clinical environment. Finally, the collaborative work presented here demonstrates that the accuracy level attained in this work for optical properties of diffusive phantoms is reliable.

Assessment of speed distribution of red blood cells in the microvascular network in healthy volunteers and type 1 diabetes using laser Doppler spectra decomposition.

We applied a recently reported method of decomposition of laser Doppler power density spectra for in vivo monitoring of speed distributions of red blood cells (RBCs) in the microvascular network. The spectrum decomposition technique allows us to derive the distribution of RBC speed (in absolute units (mm s(-1))) versus RBC concentration (in arbitrary units). We carried out postocclusive reactive hyperaemia (PORH) test in 15 healthy volunteers and 21 diabetic patients in which the duration of type 1 diabetes was longer than 10 years. Measurements were carried out simultaneously with the use of a typical laser Doppler commercial instrument and speed resolved laser Doppler instrument utilizing the new technique based on decomposition of the laser Doppler spectra. We show that for the classical laser Doppler instrument, none of the PORH parameters revealed a statistical significance of difference between the groups analyzed. In contrast, the RBC speed distributions obtained from laser Doppler spectra during rest in the control group and type 1 diabetes are statistically significant. This result suggests that speed distribution measurements in the rest state (without any kind of stimulation test) allows for the assessment of microcirculation disorders. Measurements carried out in healthy subjects show that the first moment of speed distributions (mean speed of the distributions) is 2.32 ± 0.54 mm s(-1) and 2.57 ± 0.41 mm s(-1) for optodes located on the toe and finger of the hand, respectively. Respective values in type 1 diabetes were higher: 3.00 ± 0.36 mm s(-1) and 3.10 ± 0.48 mm s(-1).

Assessment of cerebral perfusion in post-traumatic brain injury patients with the use of ICG-bolus tracking method.

The aim of this study was to verify the usefulness of the time-resolved optical method utilizing diffusely reflected photons and fluorescence signals combined with intravenous injection of indocyanine green (ICG) in the assessment of brain perfusion in post-traumatic brain injury patients. The distributions of times of flight (DTOFs) of diffusely reflected photons were acquired together with the distributions of times of arrival (DTAs) of fluorescence photons. The data analysis methodology was based on the observation of delays between the signals of statistical moments (number of photons, mean time of flight and variance) of DTOFs and DTAs related to the inflow of ICG to the extra- and intracerebral tissue compartments. Eleven patients with brain hematoma, 15 patients with brain edema and a group of 9 healthy subjects were included in this study. Statistically significant differences between parameters obtained in healthy subjects and patients with brain hematoma and brain edema were observed. The best optical parameter to differentiate patients and control group was variance of the DTOFs or DTAs. Results of the study suggest that time-resolved optical monitoring of inflow of the ICG seems to be a promising tool for detecting cerebral perfusion insufficiencies in critically ill patients.

An algorithm for assessment of inflow and washout of optical contrast agent to the brain by analysis of time-resolved diffuse reflectance and fluorescence signals.

In optical measurements of the brain oxygenation and perfusion the problem of contamination of the signals with the components related to the extracerebral tissues remains an obstacle limiting clinical applicability of the technique. In this paper we present an algorithm allowing for derivation of signals related to the changes in absorption in the intracerebral tissues based on analysis of time-resolved diffuse reflectance and fluorescence. The proposed method was validated in series of Monte Carlo simulations in which inflow and washout of an optical contrast agent into the two-layered human head model was considered. It was shown that the decomposed intracerebral component of the signal can be derived with uncertainty of about 5%. This result suggests that the method proposed can be applied in improved estimation of brain perfusion parameters based on the bolus-tracking technique.

Estimation of scattering phase function utilizing laser Doppler power density spectra.

A new method for the estimation of the light scattering phase function of particles is presented. The method allows us to measure the light scattering phase function of particles of any shape in the full angular range (0°-180°) and is based on the analysis of laser Doppler (LD) power density spectra. The theoretical background of the method and results of its validation using data from Monte Carlo simulations will be presented. For the estimation of the scattering phase function, a phantom measurement setup is proposed containing a LD measurement system and a simple model in which a liquid sample flows through a glass tube fixed in an optically turbid material. The scattering phase function estimation error was thoroughly investigated in relation to the light scattering anisotropy factor g. The error of g estimation is lower than 10% for anisotropy factors larger than 0.5 and decreases with increase of the anisotropy factor (e.g. for g = 0.98, the error of estimation is 0.01%). The analysis of influence of the noise in the measured LD spectrum showed that the g estimation error is lower than 1% for signal to noise ratio higher than 50 dB.

Assessment of brain oxygenation in term and preterm neonates using near infrared spectroscopy.

PURPOSE: The aim of this study was to determine brain oxygenation in full-term and preterm neonates using near infrared spectroscopy. MATERIAL AND METHODS: A total of 88 full-term and preterm newborn infants without hypoxic-ischaemic disorders admitted to the NICU were examined using NIRS on the first day of life and on day 28 of life. Additional measurements were taken at the end of the first week of life in the premature neonates group. Measurements of oxyhaemoglobin (HbO2), deoxyhaemoglobin (Hb), total haemoglobin (HbT) concentration and tissue oxygen saturation (Ox) were performed in 5 brain regions. Right and left frontal areas, the occipital area and right and left temporal areas were measured. RESULTS: In full-term healthy neonates a marked decrease in HbO, Hb and HbT values was observed on day 28 of life in all brain regions except the occipital area. In the neonatal period the greatest changes in brain oxygenation occurred in the right and left frontal regions of the brain. In preterm neonates constant values of HbO2 and Ox were observed in the first 28 days of life. In preterm newborn infants, as well as in full term newborn infants, similar Ox and HbO2 values were obtained on day 28 of life. CONCLUSIONS: NIRS is a safe method and can be used to evaluate brain oxygenation in newborn infants. The results of these measurements are in accordance with changes in brain oxygenation in the first month of life, which are predicated on the basis of the neonate's physiology.

Experimental estimation of the photons visiting probability profiles in time-resolved diffuse reflectance measurement.

A time-gated intensified CCD camera was applied for time-resolved imaging of light penetrating in an optically turbid medium. Spatial distributions of light penetration probability in the plane perpendicular to the axes of the source and the detector were determined at different source positions. Furthermore, visiting probability profiles of diffuse reflectance measurement were obtained by the convolution of the light penetration distributions recorded at different source positions. Experiments were carried out on homogeneous phantoms, more realistic two-layered tissue phantoms based on the human skull filled with Intralipid-ink solution and on cadavers. It was noted that the photons visiting probability profiles depend strongly on the source-detector separation, the delay between the laser pulse and the photons collection window and the complex tissue composition of the human head.

Evaluation of algorithms for microperfusion assessment by fast simulations of laser Doppler power spectral density.

In classical laser Doppler (LD) perfusion measurements, zeroth- and first-order moments of the power spectral density of the LD signal are utilized for the calculation of a signal corresponding to the concentration, speed and flow of red blood cells (RBCs). We have analysed the nonlinearities of the moments in relation to RBC speed distributions, parameters of filters utilized in LD instruments and the signal-to-noise ratio. We have developed a new method for fast simulation of the spectrum of the LD signal. The method is based on a superposition of analytically calculated Doppler shift probability distributions derived for the assumed light scattering phase function. We have validated the method by a comparison of the analytically calculated spectra with results of Monte Carlo (MC) simulations. For the semi-infinite, homogeneous medium and the single Doppler scattering regime, the analytical calculation describes LD spectra with the same accuracy as the MC simulation. The method allows for simulating the LD signal in time domain and furthermore analysing the index of perfusion for the assumed wavelength of the light, optical properties of the tissue and concentration of RBCs. Fast simulations of the LD signal in time domain and its frequency spectrum can be utilized in applications where knowledge of the LD photocurrent is required, e.g. in the development of detectors for tissue microperfusion monitoring or in measurements of the LD autocorrelation function for perfusion measurements. The presented fast method for LD spectra calculation can be used as a tool for evaluation of signal processing algorithms used in the LD method and/or for the development of new algorithms of the LD flowmetry and imaging. We analysed LD spectra obtained by analytical calculations using a classical algorithm applied in classical LD perfusion measurements. We observed nonlinearity of the first moment M1 for low and high speeds of particles (v < 2 mm s⁻¹, v > 10 mm s⁻¹). It was also noted that the first moment M(1) is less sensitive to the change of the mean RBC speed for flat speed distributions. The low-pass filter frequency f2 implemented in the LD instrument has a significant influence on the first moment of the spectrum. In particular, for a cut-off frequency lower than 10 kHz the M1 value is strongly underestimated.

Laser-Doppler spectrum decomposition applied for the estimation of speed distribution of particles moving in a multiple scattering medium.

Recently, a method for the estimation of speed distribution of particles moving in an optically turbid medium has been proposed. The method allows potentially absolute measurement of speed of the particles and can be applied in laser-Doppler perfusion measurements. However, the decomposition technique was limited to short source-detector separations for which the assumption that one photon is Doppler scattered not more than once is fulfilled. In the present paper we show a generalized decomposition technique in which photons can be scattered more than once. We show the theoretical background for decomposition in such a case. We apply a decomposition method for the analysis of laser-Doppler spectra obtained by Monte Carlo simulations. This analysis allows showing noise limits in which the technique can be effectively applied in analysis of measured spectra. We propose an approximated scattering model based on the assumption that for one photon consecutive Doppler scattering events occur on particles moving with the same speed, and we show that this approximation does not influence significantly the uncertainty of the resulting speed distribution. The proposed decomposition procedure is validated in measurements on a physical flow model. The decomposition procedure is also validated by analysis of spectra measured on a physical phantom using laser-Doppler flow meter (Oxford Optronix, UK). A diluted solution of milk was pumped through a tube fixed in an optically turbid material with speed varying from 0 mm s(-1) to 4 mm s(-1). We observed a linear relation between actual speed of milk solution and speed estimated from results of spectra decomposition.

Monte Carlo algorithm for efficient simulation of time-resolved fluorescence in layered turbid media.

We present an efficient Monte Carlo algorithm for simulation of time-resolved fluorescence in a layered turbid medium. It is based on the propagation of excitation and fluorescence photon bundles and the assumption of equal reduced scattering coefficients at the excitation and emission wavelengths. In addition to distributions of times of arrival of fluorescence photons at the detector, 3-D spatial generation probabilities were calculated. The algorithm was validated by comparison with the analytical solution of the diffusion equation for time-resolved fluorescence from a homogeneous semi-infinite turbid medium. It was applied to a two-layered model mimicking intra- and extracerebral compartments of the adult human head.

Towards noninvasive molecular fluorescence imaging of the human brain.

Fluorescence molecular brain imaging is a new modality allowing the detection of specific contrast agents down to very low concentration ranges (picomolar) in disease models. Here we demonstrate a first noninvasive application of fluorescence imaging in the human brain, where concentrations down to about 100 nM of a nonspecific dye were detected. We argue that due to its high sensitivity, optical molecular imaging of the brain is feasible, which - together with its bedside applicability - makes it a promising technique for use in patients.

DC-magnetoencephalography and time-resolved near-infrared spectroscopy combined to study neuronal and vascular brain responses.

The temporal relation between vascular and neuronal responses of the brain to external stimuli is not precisely known. For a better understanding of the neuro-vascular coupling changes in cerebral blood volume and oxygenation have to be measured simultaneously with neuronal currents. With this motivation modulation dc-magnetoencephalography was combined with multi-channel time-resolved near-infrared spectroscopy to simultaneously monitor neuronal and vascular parameters on a scale of seconds. Here, the technique is described, how magnetic and optical signals can be measured simultaneously. In a simple motor activation paradigm (alternating 30 s of finger movement with 30 s of rest for 40 min) both signals were recorded non-invasively over the motor cortex of eight subjects. The off-line averaged signals from both modalities showed distinct stimulation related changes. By plotting changes in oxy- or deoxyhaemoglobin as a function of magnetic field a characteristic trajectory was created, which was similar to a hysteresis loop. A parametric analysis allowed quantitative results regarding the timing of coupling: the vascular signal increased significantly slower than the neuronal signal.

Cross-correlation analysis of the correspondence between magnetoencephalographic and near-infrared cortical signals.

OBJECTIVES: The study of neurovascular coupling greatly benefits from combined measurements of neuronal and vascular signals. Two-step signal processing is developed to extract parameters describing the coupling. METHODS: Using a magnetometer in an extremely well shielded room a broadband magnetoencephalogram was simultaneously measured with time-resolved near-infrared spectroscopy during a motor activity paradigm. The raw MEG and NIRS data were denoised separately using independent component analysis. RESULTS: After averaging the resulting signals showed motor activity-related changes. The temporal correspondence between MEG and NIRS was assessed plotting a combined trajectory and calculating a cross-correlation. Compared to the MEG signal, at movement onset the NIRS signal showed an onset delay in the range of seconds. CONCLUSIONS: Multi-variate signal pre-processing followed by temporal delay estimates demonstrated the extraction of neurovascular coupling parameters.

Decomposition of a laser-Doppler spectrum for estimation of speed distribution of particles moving in an optically turbid medium: Monte Carlo validation study.

A method for measurement of distribution of speed of particles moving in an optically turbid medium is presented. The technique is based on decomposition of the laser-Doppler spectrum. The theoretical background is shown together with the results of Monte Carlo simulations, which were performed to validate the proposed method. The laser-Doppler spectra were obtained by Monte Carlo simulations for assumed uniform and Gaussian speed distributions of particles moving in the turbid medium. The Doppler shift probability distributions were calculated by Monte Carlo simulations for several anisotropy factors of the medium, assuming the Hanyey-Greenstein phase function. The results of the spectra decomposition show that the calculated speed distribution of moving particles match well the distribution assumed for Monte Carlo simulations. This result was obtained for the spectra simulated in optical conditions, in which the photon is scattered with the Doppler shift not more than once during its travel between the source and detector. Influence of multiple scattering of the photon is analysed and a perspective of spectrum decomposition under such conditions is considered. Potential applications and limitations of the method are discussed.