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Background Using an optical method based on tunable diode laser absorption spectroscopy, we previously assessed oxygen (O2) and water vapor (H2O) content in a tissue phantom of the preterm infant lung. Here we applied this method on newborn piglets with induced lung complications. Methods Five mechanically ventilated piglets were subjected to stepwise increased and decreased fraction of inspired oxygen (FiO2), to atelectasis using a balloon catheter in the right bronchus, and to pneumothorax by injecting air in the pleural cavity. Two diode lasers (764 nm for O2 gas absorption and 820 nm for H2O absorption) were combined in a probe delivering light either externally, on the skin, or internally, through the esophagus. The detector probe was placed dermally. Results Calculated O2 concentrations increased from 20% (IQR 17−23%) when ventilated with room air to 97% (88−108%) at FiO2 1.0. H2O was only detectable with the internal light source. Specific light absorption and transmission patterns were identified in response to atelectasis and pneumothorax, respectively. Conclusions The optical method detected FiO2 variations and discriminated the two induced lung pathologies, providing a rationale for further development into a minimally invasive device for real-time monitoring gas changes in the lungs of sick newborn infants. Impact Optical spectroscopy can detect pulmonary complications in an animal model.Oxygen concentrations can be evaluated in the lungs.Presents a novel minimally invasive method to detect lung oxygenation and complications.Potential to be developed into a lung monitoring method in newborn infants.Potential for bed-side detection of pulmonary complications in newborn infants.

Background Vasomotion is the spontaneous oscillation in vascular tone in the microcirculation and is believed to be a physiological mechanism facilitating the transport of blood gases and nutrients to and from tissues. So far, Laser Doppler flowmetry has constituted the gold standard for in vivo vasomotion analysis. Materials and methods We applied vasomotion analysis to speed-resolved perfusion, oxygen saturation, red blood cell tissue (RBC) tissue fraction, and average vessel diameter from five healthy individuals at rest measured by the newly developed Periflux 6000 EPOS system over 10 minutes. Magnitude scalogram and the time-averaged wavelet spectra were divided into frequency intervals reflecting endothelial, neurogenic, myogenic, respiratory, and cardiac function. Results Recurrent high-intensity periods of the myogenic, neurogenic, and endothelial frequency intervals were found. The neurogenic activity was considerably more pronounced for the oxygen saturation, RBC tissue fraction, and vessel diameter signals, than for the perfusion signals. In a correlation analysis we found that changes in perfusion in the myogenic, neurogenic, and endothelial frequency intervals precede changes in the other signals. Furthermore, changes in average vessel diameter were in general negatively correlated to the other signals in the same frequency intervals, indicating the importance of capillary recruitment. Conclusion We conclude that vasomotion can be observed in signals reflecting speed resolved perfusion, oxygen saturation, RBC tissue fraction, and vessel diameter. The new parameters enable new aspects of the microcirculation to be observed.

Significance: Developing algorithms for estimating blood oxygenation from snapshot multi-spectral imaging (MSI) data is challenging due to the complexity of sensor characteristics and photon transport modeling in tissue. We circumvent this using a method where artificial neural networks (ANNs) are trained on in vivo MSI data with target values from a point-measuring reference method. Aim: To develop and evaluate a methodology where a snapshot filter mosaic camera is utilized for imaging skin hemoglobin oxygen saturation (S-O2), using ANNs. Approach: MSI data were acquired during occlusion provocations. ANNs were trained to estimate S-O2 with MSI data as input, targeting data from a validated probe-based reference system. Performance of ANNs with different properties and training data sets was compared. Results: The method enables spatially resolved estimation of skin tissue S-O2. Results are comparable to those acquired using a Monte-Carlo-based approach when relevant training data are used. Conclusions: Training an ANN on in vivo MSI data covering a wide range of target values acquired during an occlusion protocol enable real-time estimation of S-O2 maps. Data from the probe-based reference system can be used as target despite differences in sampling depth and measurement position. (C) The Authors. Published by SPIE under a Creative Commons Attribution 4.0 International License. Funding Agencies|VINNOVA Grants via the Swelife and MedTech4Health programsVinnova [2016-02211, 2017-01435, 2019-01522]

Significance: For optical methods to accurately assess hemoglobin oxygen saturation in vivo, an independently verifiable tissue-like standard is required for validation. For this purpose, we propose three hemoglobin preparations and evaluate methods to characterize them. Aim: To spectrally characterize three different hemoglobin preparations using multiple spectroscopic methods and to compare their absorption spectra to commonly used reference spectra. Approach: Absorption spectra of three hemoglobin preparations in solution were characterized using spectroscopic collimated transmission: whole blood, lysed blood, and ferrous-stabilized hemoglobin. Tissue-mimicking phantoms composed of Intralipid, and the hemoglobin solutions were characterized using spatial frequency-domain spectroscopy (SFDS) and enhanced perfusion and oxygen saturation (EPOS) techniques while using yeast to deplete oxygen. Results: All hemoglobin preparations exhibited similar absorption spectra when accounting for methemoglobin and scattering in their oxyhemoglobin and deoxyhemoglobin forms, respectively. However, systematic differences were observed in the fitting depending on the reference spectra used. For the tissue-mimicking phantoms, SFDS measurements at the surface of the phantom were affected by oxygen diffusion at the interface with air, associated with higher values than for the EPOS system. Conclusions: We show the validity of different blood phantoms and what considerations need to be addressed in each case to utilize them equivalently. Funding: This research was financially supported by VINNOVA grants via the Swelife and MedTech4Health programs (Grant Nos. 2016-02211, 2017-01435, and 2019-01522) and the Knut and Alice Wallenberg Foundation’s Center for Molecular Medicine at Linköping University (WCMM).

Significance: Hemoglobin oxygen saturation and red blood cell (RBC) tissue fraction are important parameters when assessing microvascular status. Functional information can be attained using temporally resolved measurements performed during stimulus–response protocols. Pointwise assessments can currently be conducted with probe-based systems. However, snapshot multispectral imaging (MSI) can be used for spatial–temporal measurements. Aim: To validate if hemoglobin oxygen saturation and RBC tissue fraction can be quantified using a snapshot MSI system and an inverse Monte Carlo algorithm. Approach: Skin tissue measurements from the MSI system were compared to those from a validated probe-based system during arterial and venous occlusion provocation on 24 subjects in the wavelength interval 450 to 650 nm, to evaluate a wide range of hemoglobin oxygen saturation and RBC tissue fraction levels. Results: Arterial occlusion results show a mean linear regression R2 = 0.958 for hemoglobin oxygen saturation. Comparing relative RBC tissue fraction during venous occlusion results in R2 = 0.925. The MSI system shows larger dynamic changes than the reference system, which might be explained by a deeper sampling including more capacitance vessels. Conclusions: The snapshot MSI system estimates hemoglobin oxygen saturation and RBC tissue fraction in skin microcirculation showing a high correlation (R2 > 0.9 in most subjects) with those measured by the reference method. Funding: Swedens Innovation Agency VINNOVA via the programs Swelife and MedTech4Health [2017-01435, 2019-01522]; CENIIT research organization within Linkoping University [11.02]

Chronic limb-threatening ischemia (CLTI) has a major impact on patient's lives and is associated with a heavy health care burden with high morbidity and mortality. Treatment by endovascular intervention is mostly based on macrocirculatory information from angiography and does not consider the microcirculation. Despite successful endovascular intervention according to angiographic criteria, a proportion of patients fail to heal ischemic lesions. This might be due to impaired microvascular perfusion and variations in the supply to different angiosomes. Non-invasive optical techniques for microcirculatory perfusion and oxygen saturation imaging have the potential to provide the interventionist with additional information in real-time, supporting clinical decisions during the intervention. This study presents a novel multimodal imaging system, based on multi-exposure laser speckle contrast imaging and multi-spectral imaging, for continuous use during endovascular intervention. The results during intervention display spatiotemporal changes in the microcirculation compatible with expected physiological reactions during balloon dilation, with initially induced ischemia followed by a restored perfusion, and local administration of a vasodilator inducing hyperemia. We also present perioperative and postoperative follow-up measurements with a pulsatile microcirculation perfusion. Finally, cases of spatial heterogeneity in the observed oxygen saturation and perfusion are discussed. In conclusion, this technical feasibility study shows the potential of the methodology to characterize changes in microcirculation before, during, and after endovascular intervention. Funding: Swedish Research CouncilSwedish Research CouncilEuropean Commission [2014-6141]; Swedens Innovation Agency VINNOVAVinnova [2017-01435, 2019-01522]

The objective of this study was to explore the associations between skin microcirculatory function and established cardiovascular risk factors in a large Swedish cohort. As part of the Swedish CArdioPulmonary bioImage Study (SCAPIS), microcirculatory data were acquired at Linkoping University hospital, Linkoping, Sweden during 2016–2017. The subjects, aged 50–64 years, were randomly selected from the national population register. Microcirculatory reactivity was assessed using a 5-min arterial occlusion-release protocol. Comprehensive skin microcirculatory data were continuously acquired by using a fiberoptic probe placed on the lower right arm. After exclusion of missing data (208), 1557 subjects were remaining. Among the parameters, skin microcirculatory peak oxygen saturation after occlusion release, had the strongest relationship to the cardiovascular risk factors. The linear associations between peak oxygen saturation and cardiovascular risk factors were analyzed adjusted for age and sex. We found a negative association with peak oxygen saturation (standardized regression coefficient) for blood pressure (systolic −0.05 (95% CI: −0.10;-0.003) and diastolic −0.05 (−0.10; −0.003)), BMI −0.18 (−0.23; −0.13), waist circumference (males −0.20 (−0.32; −0.16), females −0.18 (−0.25; −0.11)), prevalent diabetes −0.31 (−0.49; −0.12), hypertension −0.30 (−0.42; −0.18), hyperlipidemia −0.24 (−0.40; −0.09), fasting glucose level −0.06 (−0.12; −0.01), HbA1c −0.07 (−0.12; −0.02), triglyceride level −0.09 (−0.14; −0.04), hsCRP −0.12 (−0.17; −0.07), and current smoker versus never smoked −0.50 (−0.67; −0.34). A positive association with peak oxygen saturation was found for cholesterol level 0.05 (0.005; 0.11) and HDL 0.11 (0.06; 0.17). This is the first study showing that post-ischemic skin microvascular peak oxygen saturation is associated with virtually all established cardiovascular risk factors in a population-based middle-aged cohort.

Significance: Diffuse reflectance spectroscopy (DRS) is frequently used to assess oxygen saturation and hemoglobin concentration in living tissue. Methods solving the inverse problem may include time-consuming nonlinear optimization or artificial neural networks (ANN) determining the absorption coefficient one wavelength at a time. Aim: To present an ANN-based method that directly outputs the oxygen saturation and the hemoglobin concentration using the shape of the measured spectra as input. Approach: A probe-based DRS setup with dual source-detector separations in the visible wavelength range was used. ANNs were trained on spectra generated from a three-layer tissue model with oxygen saturation and hemoglobin concentration as target. Results: Modeled evaluation data with realistic measurement noise showed an absolute root-mean-square (RMS) deviation of 5.1% units for oxygen saturation estimation. The relative RMS deviation for hemoglobin concentration was 13%. This accuracy is at least twice as good as our previous nonlinear optimization method. On blood-intralipid phantoms, the RMS deviation from the oxygen saturation derived from partial oxygen pressure measurements was 5.3% and 1.6% in two separate measurement series. Results during brachial occlusion showed expected patterns. Conclusions: The presented method, directly assessing oxygen saturation and hemoglobin concentration, is fast, accurate, and robust to noise. (C) The Authors. Published by SPIE under a Creative Commons Attribution 4.0 Unported License. Funding Agencies|Swedish Research CouncilSwedish Research Council [2014-6141]; Swedens innovation agency VINNOVA via the program MedTech4Health [2016-02211]; Swedens innovation agency VINNOVA via the program Swelife and MedTech4Health [2017-01435]

This talk highlights a novel instrument for real-time video-rate imaging of microcirculation blood flow. The instrument utilizes multi-exposure laser speckle contrast imaging (MELSCI) with a high-speed camera, custom integrated electronics, and machine learning for massive computational bandwidth. This instrument enables, for the first time, continuous in vivo imaging of blood flow at frame rates sufficiently high to track dynamic changes, with perfusion estimates strongly correlated with that of laser Doppler flowmetry (LDF). This is an important step enabling a better understanding of the role of the microcirculation in several cardiovascular diseases. A pilot study on healthy subjects is presented.

Noninvasive in vivo imaging of microcirculatory blood flow or perfusion (average speed times concentration of moving red blood cells) is of interest in several clinical applications, including monitoring of burn wounds1,2 and investigation of peripheral arterial disease,3 as well as several others.4 One technique that has gained a lot of focus in the last decades is laser speckle contrast imaging [LSCI; sometimes laser speckle contrast analysis (LASCA)] in which tissue is illuminated with a laser and the resulting speckle pattern is detected with a camera. Light that scatters when interacting with moving particles in the tissue will obtain a Doppler frequency shift depending on the velocity of the particles. The interference of light with different frequencies will give rise to fluctuations in the speckle pattern formed on the imaging sensor. The movement of the speckles on the sensor will cause an image blur that increases with exposure time. The local spatial statistics of this blur can be related to the movement of particles in the tissue, as is done in LSCI.5 LSCI has been increasingly used over laser Doppler imaging mainly due to its simple setup and fast acquisition and data processing. However, conventional LSCI has drawbacks such as a nonlinear response to perfusion, dependency to static scattering contrast, and a high variability in the presence of noise.5,6 Recent work has gone into calibrating and correcting for these issues to make LSCI a more accurate technique.7 Despite this, while it is generally accepted that LSCI is related to microcirculatory perfusion, the relationship is complex and a direct mapping is still not known.4,8 For the older laser Doppler flowmetry (LDF) technique, the relation to microcircular perfusion is better understood, where it is, for example, possible to theoretically show that the perfusion estimate is linearly related to the flow speed.9,10 To address the nonlinearity of LSCI to perfusion, Parthasarathy et al.11 proposed a new setup using multiple exposure times. The technique, called multi-exposure laser speckle contrast imaging (MELSCI, sometimes MESI), obtains information about the speckle motion blur at various exposures, enabling more advanced models to be used when estimating perfusion from the contrast.5,12 Several approaches to capture multi-exposure images have been proposed. The initial approach by Parthasarathy et al.11 was to use a time-modulated laser to achieve multi-exposure images. By capturing all images with a fixed exposure time but only illuminating the tissue during parts of that time, multi-exposures can be generated. However, a problem with this approach is that images with different exposure times are separated in time since they are captured sequentially. Dragojevic et al.13 suggested another approach that addressed this drawback. This was based on a high-speed camera, only capturing images at the shortest exposure time required, and in postprocessing adding successive images together to create longer exposure times. These synthetic exposure times are valid if the interframe delay in the camera is negligible. This method is faster and more accurate than previous methods due to all exposure times essentially being captured simultaneously, but it produces immense amounts of data that must be transferred and processed. At the time, this was, therefore, limited to an offline technique. Hence, MELSCI has so far been held back by technical limitations in both the imaging setup and the computation time of the models. To address this problem of a data and processing bottleneck, we have previously presented a system for synthetic MELSCI,14 based on a high-speed 1000-frames per second (fps) 1-megapixel camera directly interfaced to a field programmable gate array (FPGA) performing the multi-exposure contrast algorithm outlined by Dragojevic13 in real-time. Processed contrast images were sent to a computer, massively reducing the data throughput requirements. This system could produce multi-exposure contrast images at 15.6 fps, using all available frames from the 1000-fps camera, without any loss of data. However, due to insufficient processing power, the system was not able to transfer the processed images to the computer fast enough, and thus could not provide a real-time video-rate output. Furthermore, while the calculation of multi-exposure contrast images was fast enough, at the time there was no multi-exposure perfusion algorithm fast enough to keep up with the continuous stream of contrast images. The model proposed by Parthasarathy et al.11 and later refined by Kazmi et al.15 requires nonlinear fitting to extract perfusion-related parameters from the multi-exposure contrast. This process must be performed individually in each pixel for full field perfusion images, which is not feasible in real-time with satisfactory frame rates.6 We have previously presented a method using machine learning and simulated data from thousands of Monte Carlo tissue models from which we train an artificial neural network (ANN) to translate multi-exposure contrast to laser Doppler perfusion. We showed that this technique not only achieves a model-inference time of

Several studies have shown that advanced glycation end products (AGE) play a role in both the microvascular and macrovascular complications of diabetes and are closely linked to inflammation and atherosclerosis. AGEs accumulate in skin and can be detected using their auto fluorescence (AF).A significant correlation exists between AGE AF and the levels of AGEs as obtained from skin biopsies. A commercial device, the AGE Reader, has become available to assess skin AF for clinical purposes but, while displaying promising results, it is limited to single-point measurements performed in contact to skin tissue. Furthermore, in vivo imaging of AGE accumulation is virtually unexplored.We proposed a non-invasive, contact-less novel technique for quantifying fluorescent AGE deposits in skin tissue using a multispectral imaging camera setup (MSI) during ultraviolet (UV) exposure. Imaging involved applying a region-of-interest mask, avoiding specular reflections and a simple calibration. Results of a study conducted on 16 subjects with skin types ranging from fair to deeply pigmented skin, showed that AGE measured with MSI in forearm skin was significantly correlated with the AGE reference method (AGE Reader on forearm skin, R=0.68, p=0.005). AGE measured in facial skin was borderline significantly related to AGE Reader on forearm skin (R=0.47, p=0.078). These results support the use of the technique in devices for non-touch measurement of AGE content in either facial or forearm skin tissue over time. SEMEOTICONS

Gate-defined quantum dots (QDs) are such a highly-tunable quantum system in which single spins can be electrically coupled, manipulated, and measured. However, the spins in gate-defined QDs are lacking its interface to free-space photons. Here, we verify that a circularly-polarized single photon can excite a single electron spin via the transfer of angular momentum, measured using Pauli spin blockade (PSB) in a double QD. We monitor the inter-dot charge tunneling which only occur when the photo-electron spin in one QD is anti-parallel to the electron spin in the other. This allows us to detect single photo-electrons in the spin-up/down basis using PSB. The photon polarization dependence of the excited spin state was finally confirmed for the heavy-hole exciton excitation. The angular momentum transfer observed here is a fundamental step providing a route to instant injection of spins, distributing single spin information, and possibly towards extending quantum communication., Gate-defined quantum dots offer a way to engineer electrically controllable quantum systems with potential for information processing. Here, the authors transfer angular momentum from the polarization of a single photon to the spin of a single electron in a gate-defined double quantum dot.

The PeriFlux 6000 EPOS system combines diffuse reflectance spectroscopy (DRS) and laser Doppler flowmetry (LDF) for the assessment of oxygen saturation (expressed in percentage), red blood cell (RBC) tissue fraction (expressed as volume fraction, %RBC), and perfusion (%RBC × mm / s) in the microcirculation. It also allows the possibility of separating the perfusion into three speed regions (0 to 1, 1 to 10, and10 mm / s). We evaluate the speed-resolved perfusion components, i.e., the relative amount of perfusion within each speed region, using a blood-flow phantom. Human blood was pumped through microtubes with an inner diameter of 0.15 mm. Measured DRS and LDF spectra were compared to Monte Carlo-simulated spectra in an optimization routine, giving the best-fit parameters describing the measured spectra. The root-mean-square error for each of the three speed components (0 to 1, 1 to 10, and10 mm / s, respectively) when describing the blood-flow speed in the microtubes was 2.9%, 8.1%, and 7.7%. The presented results show that the system can accurately discriminate blood perfusion originating from different blood-flow speeds, which may enable improved measurement of healthy and dysfunctional microcirculatory flow.

Spectroscopic imaging of human tissue analyzes backscattered light intensity separated by wavelength. We used a DLP-projector illuminating sinusoidal patterns with varying phase and varying spatial frequency on forearm skin. Detection was done with: 1) a snap-shot filter mosaic camera with 16 wide-band sensitive pixels; 2-3) a four cameras setup with narrow and wide bandwidth optical bandpass filters in the 450-700 nm range, respectively. The detected images were processed with a demodulation scheme, assessing tissue optical parameters, involving light absorption. Calibration was done using an optical phantom with known optical properties. From the absorption coefficient the concentration of skin blood and its oxygenation was determined. We will present results from forearm arterial occlusion and release experiments using the three setups above. Specifically, the effect of the filter bandwidth will be evaluated using data from the multi-camera setups. Furthermore, the snap-shot filter mosaic camera data may be explained by the calculation of modulation using an illumination and detector setup with a broad spectral transmission bandwidth, with considerable variation in μ_a of included chromophores. Approaches for either reducing the effective bandwidth of the filters or by including their characteristic in a light transport model for SFDI modulation, will be proposed.

The aim of this study was to determine the optical absorption and scattering properties in a large Swedish cohort including 1765 subjects. The study was performed in the Linkoping site within the national multicenter Swedish CArdioPulmonary bioImage Study (SCAPIS), a world unique study including detailed imaging and functional analysis of heart, vessels and lungs in 30 000 men and women in Sweden to predict and prevent cardiovascular disease and chronic obstructive pulmonary disease. The subjects, men and women between 50 and 64 years old, were randomly selected and recruited from the population registry in Sweden. Measurements on the volar forearm were performed at baseline and during a systolic occlusion provocation with an integrated system, including spatially resolved diffuse reflectance spectroscopy and laser Doppler flowmetry. Data were analyzed with an inverse Monte Carlo algorithm, accounting for both scattering, geometrical and absorbing properties of the tissue. The absorption coefficient was assumed to differ between the epidermis and the two dermis layers, while the reduced scattering coefficient was equal in all layers. The reduced scattering coefficient (@ 650 nm) was (M ± SD) = 1.68 ± 0.34 mm-1. Gender was found to significant change the fraction of small scattering particles and the reduced scattering coefficient. The absorption coefficient (@ 650 nm) for the dermis layers was 0.010 ± 0.005 mm-1. This large study on optical properties of skin can serve as reference values and provide new knowledge on how factors like gender, age, BMI etc. affect the optical properties.

Quantum state transfer from a single photon to a single electron following selection rules can only occur for a spin-resolved light-hole excitation in GaAs quantum dots; however, these phenomena have yet to be experimentally realized. Here, we report on single-shot readout of a single electron spin via the Zeeman-resolved light-hole excitation using an optical spin blockade method in a GaAs quantum dot and a Pauli spin blockade method in a double GaAs quantum dot. The observed photoexcitation probability strongly depends on the photon polarization, an indication of angular momentum transfer from a single photon to an electron. Our demonstration will open a pathway to further investigation of fundamental quantum physics and applications of quantum networking technology.

Newborn infants may have pulmonary disorders with abnormal gas distribution, e.g., respiratory distress syndrome. Pulmonary radiography is the clinical routine for diagnosis. Our aim was to investigate a novel noninvasive optical technique for rapid nonradiographic bedside detection of oxygen gas in the lungs of full-term newborn infants.Laser spectroscopy was used to measure contents of oxygen gas (at 760 nm) and of water vapor (at 937 nm) in the lungs of 29 healthy newborn full-term infants (birth weight 2,900-3,900 g). The skin above the lungs was illuminated using two low-power diode lasers and diffusely emerging light was detected with a photodiode.Of the total 390 lung measurements performed, clear detection of oxygen gas was recorded in 60%, defined by a signal-to-noise ratio of3. In all the 29 infants, oxygen was detected. Probe and detector positions for optimal pulmonary gas detection were determined. There were no differences in signal quality with respect to gender, body side or body weight.The ability to measure pulmonary oxygen content in healthy full-term neonates with this technique suggests that with further development, the method might be implemented in clinical practice for lung monitoring in neonatal intensive care.

A round-robin test on the identification of GSR particles by SEM/EDX and involving eleven Institutes was conducted on a real sample, in order to evaluate the possibilities/limitations of using such sample to get additional information (compared to the analysis of the usual synthetic sample used within the framework of the ENFSI proficiency test) about the performances of the SEM/EDX systems. Each Institute was asked to analyse this sample following its own standard operating procedure, and by using all the systems in house, whenever available. Between each Institute, a check of the sample was performed by the organizing Institute (NICC), in order inter alia to monitor any degradation and/or contamination of the sample. A total of about 30 analyses were performed on the sample. For each particle of interest identified on the real sample, the detection effectiveness was monitored, as well as the classification allotted by each Institute. The Institutes were also asked to report some of their measurement parameters, and to send the results as they would have been communicated in their own case report. A quite good agreement was observed with regard to the classification of the particles of interest, since a broad consensus was reached for approximately 75% of these particles. A different classification risk exists for some classes, the barium/antimony classes being probably the most critical, as traces of lead may cause the particles to shift (or not) from the consistent with GSR upper-class to the characteristic of GSR upper-class; in the end, the decision to shift from one class to another strongly depends on local rules. At the end of the campaign, a survey sent to collect experience and lessons learned from this exercise showed that analysing a real sample definitively offers an added value, especially in terms of classification process (during the automatic run and when performing the manual review) of particles.

Laser speckle contrast imaging (LSCI) enables video rate imaging of blood flow. However, its relation to tissue blood perfusion is nonlinear and depends strongly on exposure time. By contrast, the perfusion estimate from the slower laser Doppler flowmetry (LDF) technique has a relationship to blood perfusion that is better understood. Multiexposure LSCI (MELSCI) enables a perfusion estimate closer to the actual perfusion than that using a single exposure time. We present and evaluate a method that utilizes contrasts from seven exposure times between 1 and 64 ms to calculate a perfusion estimate that resembles the perfusion estimate from LDF. The method is based on artificial neural networks (ANN) for fast and accurate processing of MELSCI contrasts to perfusion. The networks are trained using modeling of Doppler histograms and speckle contrasts from tissue models. The importance of accounting for noise is demonstrated. Results show that by using ANN, MELSCI data can be processed to LDF perfusion with high accuracy, with a correlation coefficient R = 1.000 for noise-free data, R = 0.993 when a moderate degree of noise is present, and R = 0.995 for in vivo data from an occlusion-release experiment.

We have determined in vivo optical scattering properties of normal human skin in 1734 subjects, mostly with fair skin type, within the Swedish CArdioPulmonary bioImage Study. The measurements were performed with a noninvasive system, integrating spatially resolved diffuse reflectance spectroscopy and laser Doppler flowmetry. Data were analyzed with an inverse Monte Carlo algorithm, accounting for both scattering, geometrical, and absorbing properties of the tissue. The reduced scattering coefficient was found to decrease from 3.16 ± 0.72 to 1.13 ± 0.27 mm-1 (mean ± SD) in the 475- to 850-nm wavelength range. There was a negative correlation between the reduced scattering coefficient and age, and a significant difference between men and women in the reduced scattering coefficient as well as in the fraction of small scattering particles. This large study on tissue scattering with mean values and normal variation can serve as a reference when designing diagnostic techniques or when evaluating the effect of therapeutic optical systems.

Intranasal oxytocin (OT) has previously been found to increase spirituality, an effect moderated by OT-related genotypes. This pre-registered study sought to conceptually replicate and extend those findings. Using a single dose of intranasal OT vs placebo (PL), we investigated experimental treatment effects, and moderation by OT-related genotypes on spirituality, mystical experiences, and the sensed presence of a sentient being. A more exploratory aim was to test for interactions between treatment and the personality disposition absorption on these spirituality-related outcomes. A priming plus sensory deprivation procedure that has facilitated spiritual experiences in previous studies was used. The sample (N = 116) contained both sexes and was drawn from a relatively secular context. Results failed to conceptually replicate both the main effects of treatment and the treatment by genotype interactions on spirituality. Similarly, there were no such effects on mystical experiences or sensed presence. However, the data suggested an interaction between treatment and absorption. Relative to PL, OT seemed to enhance spiritual experiences in participants scoring low in absorption and dampen spirituality in participants scoring high in absorption.

Spatial frequency domain imaging (SFDI) utilizes a digital light processing (DLP) projector for illuminating turbid media with sinusoidal patterns. The tissue absorption (μ a ) and reduced scattering coefficient (μ , s ) are calculated by analyzing the modulation transfer function for at least two spatial frequencies. We evaluated different illumination strategies with a red, green and blue light emitting diodes (LED) in the DLP, while imaging with a filter mosaic camera, XiSpec, with 16 different multi-wavelength sensitive pixels in the 470-630 nm wavelength range. Data were compared to SFDI by a multispectral camera setup (MSI) consisting of four cameras with bandpass filters centered at 475, 560, 580 and 650 nm. A pointwise system for comprehensive microcirculation analysis was used (EPOS) for comparison. A 5-min arterial occlusion and release protocol on the forearm of a Caucasian male with fair skin was analyzed by fitting the absorption spectra of the chromophores HbO 2 , Hb and melanin to the estimatedμ a . The tissue fractions of red blood cells ( f RBC), melanin (/mel) and the Hb oxygenation ( S 0 2 ) were calculated at baseline, end of occlusion, early after release and late after release. EPOS results showed a decrease in S 0 2 during the occlusion and hyperemia during release ( S 0 2 = 40%, 5%, 80% and 51%). The f RBC showed an increase during occlusion and release phases. The best MSI resemblance to the EPOS was for green LED illumination ( S 0 2 = 53%, 9%, 82%, 65%). Several illumination and analysis strategies using the XiSpec gave un-physiological results (e.g. negative S 0 2 ). XiSpec with green LED illumination gave the expected change in /RBC , while the dynamics in S 0 2 were less than those for EPOS. These results may be explained by the calculation of modulation using an illumination and detector setup with a broad spectral transmission bandwidth, with considerable variation in μ a of included chromophores. Approaches for either reducing the effective bandwidth of the XiSpec filters or by including their characteristic in a light transport model for SFDI modulation, are proposed.

We present a first evaluation of a new multi-exposure laser speckle contrast imaging (MELSCI) system for assessing spatial variations in the microcirculatory perfusion. The MELSCI system is based on a 1000 frames per second 1-megapixel camera connected to a field programmable gate arrays (FPGA) capable of producing MELSCI data in realtime. The imaging system is evaluated against a single point laser Doppler flowmetry (LDF) system during occlusionrelease provocations of the arm in five subjects. Perfusion is calculated from MELSCI data using current state-of-the-art inverse models. The analysis displayed a good agreement between measured and modeled data, with an average error below 6%. This strongly indicates that the applied model is capable of accurately describing the MELSCI data and that the acquired data is of high quality. Comparing readings from the occlusion-release provocation showed that the MELSCI perfusion was significantly correlated (R=0.83) to the single point LDF perfusion, clearly outperforming perfusion estimations based on a single exposure time. We conclude that the MELSCI system provides blood flow images of enhanced quality, taking us one step closer to a system that accurately can monitor dynamic changes in skin perfusion over a large area in real-time.

The lipid–protein mixture that covers the lung alveoli, lung surfactant, ensures mechanical robustness and controls gas transport during breathing. Lung surfactant is located at an interface between water-rich tissue and humid, but not fully saturated, air. The resulting humidity difference places the lung surfactant film out of thermodynamic equilibrium, which triggers the buildup of a water gradient. Here, we present a millifluidic method to assemble multilamellar interfacial films from vesicular dispersions of a clinical lung surfactant extract used in replacement therapy. Using small-angle X-ray scattering, infrared, Raman, and optical microscopies, we show that the interfacial film consists of several coexisting lamellar phases displaying a substantial variation in water swelling. This complex phase behavior contrasts to observations made under equilibrium conditions. We demonstrate that this disparity stems from additional lipid and protein gradients originating from differences in their transport properties. Supplementing the extract with cholesterol, to levels similar to the endogenous lung surfactant, dispels this complexity. We observed a homogeneous multilayer structure consisting of a single lamellar phase exhibiting negligible variations in swelling in the water gradient. Our results demonstrate the necessity of considering nonequilibrium thermodynamic conditions to study the structure of lung surfactant multilayer films, which is not accessible in bulk or monolayer studies. Our reconstitution methodology also opens avenues for lung surfactant pharmaceuticals and the understanding of composition, structure, and property relationships at biological air–liquid interfaces., Composition gradients develop across lung surfactant films under physiologically relevant nonequilibrium conditions, yielding a structural heterogeneity that is suppressed by cholesterol addition.

We analyze the importance of different asset holdings for the interdependence of the yield curves in the Euro area using a spatial VAR model. We find that the cross-border holdings of long-term debt and bank lending are important for the interdependence. We also find that comovement in the Euro area declines after 2008. We show that this decline is not related to the difference among countries in reacting to shocks from the US during the financial crisis. Rather, it largely reflects the segmentation between GIIPS and non-GIIPS countries. Our analysis of dispersion in sovereign-CDS-spread term structure shows that the differential in sovereign creditworthiness in the Euro area is a main driver of the yield-curve divergence after 2008.

Quantum entanglement between different forms of qubits is an indication of the universality of quantum mechanics. Entanglement transfer between light and matter, especially photon and spin, has long been studied as the central concept, but it remains technically challenging for single photons and spins. In this paper, we show paired generation of a single electron in a GaAs quantum dot and a single photon from a single polarization-entangled photon pair. We measure temporal coincidence between the single photo-electron detection and the single photon detection. Considering a single photon polarization is converted to an electron spin via an optical selection rule, the present result indicates the capability of photon to spin entanglement transfer. This may be useful to explore the physics of entanglement transfer and also for applications to quantum teleportation based quantum communication.

Background Mesenchymal stromal cells (MSCs) are currently being evaluated in numerous pre-clinical and clinical cell-based therapy studies. Furthermore, there is an increasing interest in exploring alternative uses of these cells in disease modelling, pharmaceutical screening, and regenerative medicine by applying reprogramming technologies. However, the limited availability of MSCs from various sources restricts their use. Term amniotic fluid has been proposed as an alternative source of MSCs. Previously, only low volumes of term fluid and its cellular constituents have been collected, and current knowledge of the MSCs derived from this fluid is limited. In this study, we collected amniotic fluid at term using a novel collection system and evaluated amniotic fluid MSC content and their characteristics, including their feasibility to undergo cellular reprogramming. Methods Amniotic fluid was collected at term caesarean section deliveries using a closed catheter-based system. Following fluid processing, amniotic fluid was assessed for cellularity, MSC frequency, in-vitro proliferation, surface phenotype, differentiation, and gene expression characteristics. Cells were also reprogrammed to the pluripotent stem cell state and differentiated towards neural and haematopoietic lineages. Results The average volume of term amniotic fluid collected was approximately 0.4 litres per donor, containing an average of 7 million viable mononuclear cells per litre, and a CFU-F content of 15 per 100,000 MNCs. Expanded CFU-F cultures showed similar surface phenotype, differentiation potential, and gene expression characteristics to MSCs isolated from traditional sources, and showed extensive expansion potential and rapid doubling times. Given the high proliferation rates of these neonatal source cells, we assessed them in a reprogramming application, where the derived induced pluripotent stem cells showed multigerm layer lineage differentiation potential. Conclusions The potentially large donor base from caesarean section deliveries, the high yield of term amniotic fluid MSCs obtainable, the properties of the MSCs identified, and the suitability of the cells to be reprogrammed into the pluripotent state demonstrated these cells to be a promising and plentiful resource for further evaluation in bio-banking, cell therapy, disease modelling, and regenerative medicine applications. Electronic supplementary material The online version of this article (doi:10.1186/s13287-017-0582-6) contains supplementary material, which is available to authorized users.

A person's well-being status is reflected by their face through a combination of facial expressions and physical signs. The SEMEOTICONS project translates the semeiotic code of the human face into measurements and computational descriptors that are automatically extracted from images, videos, and three-dimensional scans of the face. SEMEOTICONS developed a multisensory platform in the form of a smart mirror to identify signs related to cardio-metabolic risk. The aim was to enable users to self-monitor their well-being status over time and guide them to improve their lifestyle. Significant scientific and technological challenges have been addressed to build the multisensory mirror, from touchless data acquisition, to real-time processing and integration of multimodal data.

Laser speckle-based techniques are frequently used to assess microcirculatory blood flow. Perfusion estimates are calculated either by analyzing the speckle fluctuations over time as in laser Doppler flowmetry (LDF), or by analyzing the speckle contrast as in laser speckle contrast imaging (LSCI). The perfusion estimates depend on the amount of blood and its speed distribution. However, the perfusion estimates are commonly given in arbitrary units as they are nonlinear and depend on the magnitude and the spatial distribution of the optical properties in the tissue under investigation. We describe how the spatial confinement of blood to vessels, called the vessel packaging effect, can be modeled in LDF and LSCI, which affect the Doppler power spectra and speckle contrast, and the underlying bio-optical mechanisms for these effects. As an example, the perfusion estimate is reduced by 25% for LDF and often more than 50% for LSCI when blood is located in vessels with an average diameter of 40 μm, instead of being homogeneously distributed within the tissue. This significant effect can be compensated for only with knowledge of the average diameter of the vessels in the tissue.

Skin and kidney microvascular functions may be affected independently in diabetes mellitus. We investigated skin microcirculatory function in 79 subjects with diabetes type 2, where 41 had microalbuminuria and 38 not, and in 41 age-matched controls. The oxygen saturation, fraction of red blood cells and speed-resolved microcirculatory perfusion (% red blood cells × mm/s) divided into three speed regions: 0–1, 1–10 and above 10 mm/s, were assessed during baseline and after local heating of the foot with a new device integrating diffuse reflectance spectroscopy and laser Doppler flowmetry. Arterial stiffness was assessed as carotid-femoral pulse wave velocity. Subjects with diabetes and microalbuminuria had significantly higher carotid-femoral pulse wave velocity compared to subjects without microalbuminuria and to controls. The perfusion for speeds 0–1 mm/s and red blood cell tissue fraction were reduced in subjects with diabetes at baseline and after heating, independent of microalbuminuria. These parameters were correlated to HbA1c. In conclusion, the reduced nutritive perfusion and red blood cell tissue fraction in type 2 diabetes were related to long-term glucose control but independent of microvascular changes in the kidneys and large-vessel stiffness. This may be due to different pathogenic pathways in the development of nephropathy, large-vessel stiffness and cutaneous microvascular impairment.

The lipid–protein film covering the interface of the lung alveolar in mammals is vital for proper lung function and its deficiency is related to a range of diseases. Here we present a molecular-level characterization of a clinical-grade porcine lung surfactant extract using a multitechnique approach consisting of H 1 – C 13 solid-state nuclear magnetic spectroscopy, small- and wide-angle X-ray scattering, and mass spectrometry. The detailed characterization presented for reconstituted membranes of a lung extract demonstrates that the molecular structure of lung surfactant strongly depends on the concentration of cholesterol. If cholesterol makes up about 11% of the total dry weight of lung surfactant, the surfactant extract adopts a single liquid-ordered lamellar phase, L α ( o ) , at physiological temperatures. This L α ( o ) phase gradually changes into a liquid-disordered lamellar phase, L α ( d ) , when the temperature is increased by a few degrees. In the absence of cholesterol the system segregates into one lamellar gel phase and one L α ( d ) phase. Remarkably, it was possible to measure a large set of order parameter magnitudes | S CH | from the liquid-disordered and -ordered lamellar phases and assign them to specific C–H bonds of the phospholipids in the biological extract with no use of isotopic labeling. These findings with molecular details on lung surfactant mixtures together with the presented NMR methodology may guide further development of pulmonary surfactant pharmaceuticals that better mimic the physiological self-assembly compositions for treatment of pathological states such as respiratory distress syndrome.

A multiple exposure laser speckle contrast imaging (MELSCI) setup for visualizing blood perfusion was developed using a field programmable gate array (FPGA), connected to a 1000 frames per second (fps) 1-megapixel camera sensor. Multiple exposure time images at 1, 2, 4, 8, 16, 32 and 64 milliseconds were calculated by cumulative summation of 64 consecutive snapshot images. The local contrast was calculated for all exposure times using regions of 4 × 4 pixels. Averaging of multiple contrast images from the 64-millisecond acquisition was done to improve the signal-to-noise ratio. The results show that with an effective implementation of the algorithm on an FPGA, contrast images at all exposure times can be calculated in only 28 milliseconds. The algorithm was applied to data recorded during a 5 minutes finger occlusion. Expected contrast changes were found during occlusion and the following hyperemia in the occluded finger, while unprovoked fingers showed constant contrast during the experiment. The developed setup is capable of massive data processing on an FPGA that enables processing of MELSCI data in 15.6 fps (1000/64 milliseconds). It also leads to improved frame rates, enhanced image quality and enables the calculation of improved microcirculatory perfusion estimates compared to single exposure time systems.

The aim of this study is to explore what motivates youth from so called “exposed” areas to commit to voluntary work, and how the youth view their own role and the role of the organisation in a context of social mobilization. In order to answer the research questions of this study, the commitment of youth in a non-profit organization has been studied using several different methods of data collection. In order to measure the function of motivation amongst the youth, the survey Volunteer Functions Index (VFI) has been used. VFI is a tool used to measure motivation based on what functions an activity performs in the life of the individual. In order to achieve a greater understanding and be able to explore aspects that the VFI does not cover, four semi-structured interviews were conducted with current and former members of the organization. In order to better understand the context of the organization and to be able to ask more questions during the interviews, a participant observation was done within the work of the organization. The study shows that the youth that participate in the study perceive their commitment in the organization as an important part of their identity and that the identity is an important aspect of what possible actions are perceived to be available and attractive. It also seems as if the commitment to the organization is tied to the opportunity to change the social conditions for one self and others. The study also shows that the organization has been more successful in achieving social mobilization amongst girls than amongst boys, and that some of the participants attribute this to the gender roles that permeate the area Denna studie syftar till att undersöka vad som motiverar ungdomar från så kallade utsatta områden till att engagera sig ideellt samt hur ungdomarna uppfattar sin egen och organisationens roll i en kontext av social mobilisering. För att kunna besvara studiens frågeställning har ungdomars engagemang i en ideell verksamhet studerats med hjälp av flera olika datainsamlingsmetoder. För att mäta ungdomarnas motivationsgrunder har enkäten Volunteer Functions Index (VFI) använts, ett verktyg som mäter motivation utifrån vilka funktioner aktiviteten har i individens liv. För att skapa en djupare förståelse och kunna fånga upp aspekter som inte täcks in av VFI har fyra semi-strukturerade intervjuer genomförts med nuvarande och före detta deltagare i organisationen. För att skapa förståelse kring kontexten och skapa förutsättningar för att ställa fler frågor under intervjuerna föregicks dessa av en deltagande observation inom organisationens verksamhet. Materialet visar på att ungdomarna som deltar i studien uppfattar engagemanget i organisationen som en viktig del av sin identitet och att identiteten är viktig för vilka handlingsalternativ som man uppfattar som möjliga och attraktiva. Det tycks dessutom som att engagemanget i organisationen är kopplat till möjligheten att förändra de sociala förutsättningarna för sig själva och andra. Studien visar också att organisationen varit mer framgångsrik med social mobilisering bland tjejer än bland killar och att vissa av deltagarna kopplar detta till de könsroller som genomsyrar området.

Lip segmentation is a non-trivial task because the colour difference between the lip and the skin regions maybe not so noticeable sometimes. We propose an automatic lip segmentation technique for hyper-spectral images from an imaging prototype with medical applications. Contrarily to many other existing lip segmentation methods, we do not use colour space transformations to localise the lip area. As input image, we use for the first time a parametric blood concentration map computed by using narrow spectral bands. Our method mainly consists of three phases: (i) for each subject generate a subset of face images enhanced by different simulated Lambertian illuminations, then (ii) perform lip segmentation on each enhanced image by using constrained morphological operations, and finally (iii) extract features from Fourier-based modeled lip boundaries for selecting the lip candidate. Experiments for testing our approach are performed under controlled conditions on volunteers and on a public hyper-spectral dataset. Results show the effectiveness of the algorithm against low spectral range, moustache, and noise.

Hyperspectral imaging (HSI) can estimate the spatial distribution of skin blood oxygenation, using visible to near-infrared light. HSI oximeters often use a liquid-crystal tunable filter, an acousto-optic tunable filter or mechanically adjustable filter wheels, which has too long response/switching times to monitor tissue hemodynamics. This work aims to evaluate a multispectral snapshot imaging system to estimate skin blood volume and oxygen saturation with high temporal and spatial resolution. We use a snapshot imager, the xiSpec camera (MQ022HG-IM-SM4X4-VIS, XIMEA (R)), having 16 wavelength-specific Fabry-Perot filters overlaid on the custom CMOS-chip. The spectral distribution of the bands is however substantially overlapping, which needs to be taken into account for an accurate analysis. An inverse Monte Carlo analysis is performed using a two-layered skin tissue model, defined by epidermal thickness, haemoglobin concentration and oxygen saturation, melanin concentration and spectrally dependent reduced-scattering coefficient, all parameters relevant for human skin. The analysis takes into account the spectral detector response of the xiSpec camera. At each spatial location in the field-of-view, we compare the simulated output to the detected diffusively backscattered spectra to find the best fit. The imager is evaluated for spatial and temporal variations during arterial and venous occlusion protocols applied to the forearm. Estimated blood volume changes and oxygenation maps at 512x272 pixels show values that are comparable to reference measurements performed in contact with the skin tissue. We conclude that the snapshot xiSpec camera, paired with an inverse Monte Carlo algorithm, permits us to use this sensor for spatial and temporal measurement of varying physiological parameters, such as skin tissue blood volume and oxygenation. Funding Agencies|Centre for Industrial Information Technology (CENIIT) at Linkoping University; SEMEOTICONS (SEMEiotic Oriented Technology for Individuals CardiOmetabolic risk self-assessmeNt and Self-monitoring) [611516]

This paper gives results from Vehicle-to-Vehicle (V2V) communication field tests in a platoon consisting of four trucks. During these tests it was assumed that large vehicles such as trucks need multiple antennas to overcome shadowing and obstruction caused by the vehicle itself, trailers and other trucks in the platoon. Therefore, in the experiments the vehicles had one antenna in each side-view mirror, and each antenna was connected to an IEEE 802.11p radio transmitting at 5.9 GHz according to the ETSI ITS-G5 standard. The purpose of the tests was to estimate the V2V channel for trucks participating in a platoon and to investigate the potential of diversity for such cooperative application. Three communication schemes for diversity were evaluated: receive diversity, transmit diversity, and transmit in combination with receive diversity. Studies were performed for two different antenna configurations in three different environments (rural, highway and tunnel).

We detect in real time interdot tunneling events in a weakly coupled two-electron double quantum dot in GaAs. At finite magnetic fields, we observe two characteristic tunneling times T_{d} and T_{b}, belonging to, respectively, a direct and a blocked (spin-flip-assisted) tunneling. The latter corresponds to the lifting of a Pauli spin blockade, and the tunneling times ratio η=T_{b}/T_{d} characterizes the blockade efficiency. We find pronounced changes in the behavior of η upon increasing the magnetic field, with η increasing, saturating, and increasing again. We explain this behavior as due to the crossover of the dominant blockade-lifting mechanism from the hyperfine to spin-orbit interactions and due to a change in the contribution of the charge decoherence.