Cerebral venous circulatory disturbance as an informative prognostic marker for neonatal hemorrhagic stroke

Neonatal hemorrhagic stroke (NHS) is a major problem of future generation’s health due to the high rate of death and cognitive disability of newborns after NHS. The incidence of NHS in neonates cannot be predicted by standard diagnostic methods. Therefore, the identification of prognostic markers of NHS is crucial. There is evidence that stress-related alterations of cerebral blood flow (CBF) may contribute to NHS. Here, we assessed the stroke-associated CBF abnormalities for high prognosis of NHS using a new model of NHS induced by sound stress in the pre- and post-stroke state. With this aim, we used interdisciplinary methods such as a histological assay of brain tissues, laser speckle contrast imaging and Doppler coherent tomography to monitor cerebral circulation. Our results suggest that the venous stasis with such symptoms as progressive relaxation of cerebral veins, decrease the velocity of blood flow in them are prognostic markers for a risk of NHS and are an informative platform for a future study of corrections of cerebral venous circulatory disturbance related to NHS

The stress and vascular catastrophes in newborn rats: mechanisms preceding and accompanying the brain hemorrhages

In this study, we analyzed the time-depended scenario of stress response cascade preceding and accompanying brain hemorrhages in newborn rats using an interdisciplinary approach based on: a morphological analysis of brain tissues, coherent-domain optical technologies for visualization of the cerebral blood flow, monitoring of the cerebral oxygenation and the deformability of red blood cells (RBCs). Using a model of stress-induced brain hemorrhages (sound stress, 120 dB, 370 Hz), we studied changes in neonatal brain 2, 4, 6, 8 h after stress (the pre-hemorrhage, latent period) and 24 h after stress (the post-hemorrhage period). We found that latent period of brain hemorrhages is accompanied by gradual pathological changes in systemic, metabolic, and cellular levels of stress. The incidence of brain hemorrhages is characterized by a progression of these changes and the irreversible cell death in the brain areas involved in higher mental functions. These processes are realized via a time-depended reduction of cerebral venous blood flow and oxygenation that was accompanied by an increase in RBCs deformability. The significant depletion of the molecular layer of the prefrontal cortex and the pyramidal neurons, which are crucial for associative learning and attention, is developed as a consequence of homeostasis imbalance. Thus, stress-induced processes preceding and accompanying brain hemorrhages in neonatal period contribute to serious injuries of the brain blood circulation, cerebral metabolic activity and structural elements of cognitive function. These results are an informative platform for further studies of mechanisms underlying stress-induced brain hemorrhages during the first days of life that will improve the future generation's health

Microfluidic System for In-Flow Reversible Photoswitching of Near-Infrared Fluorescent Proteins

We have developed a microfluidic flow cytometry system to screen reversibly photoswitchable fluorescent proteins for contrast and stability of reversible photoconversion between high- and low-fluorescent states. A two-color array of 20 excitation and deactivation beams generated with diffractive optics was combined with a serpentine microfluidic channel geometry designed to provide five cycles of photoswitching with real-time calculation of photoconversion fluorescence contrast. The characteristics of photoswitching in-flow as a function of excitation and deactivation beam fluence, flow speed, and protein concentration were studied with droplets of the bacterial phytochrome from Deinococcus radiodurans (DrBphP), which is weakly fluorescent in the near-infrared (NIR) spectral range. In agreement with measurements on stationary droplets and HeLa S3 mammalian cells expressing DrBphP, optimized operation of the flow system provided up to 50% photoconversion contrast in-flow at a droplet rate of few hertz and a coefficient of variation (CV) of up to 2% over 10 000 events. The methods for calibrating the brightness and photoswitching measurements in microfluidic flow established here provide a basis for screening of cell-based libraries of reversibly switchable NIR fluorescent proteins

Noninvasive Hemoglobin Measurements With Photoplethysmography in Wrist

This paper describes the application of multiwavelength photoplethysmography (MW-PPG) in reflectance mode for noninvasive measurements of total hemoglobin concentration. Consumer wrist-wearable devices (smartwatches, wristbands) typically contain a photoplethysmography sensor operating in reflectance mode, as opposed to clinical pulse-oximetry sensors operating in transmittance mode. We assume that the generally accepted approach to the analysis of the transmittance-mode MW-PPG signal, based on the direct implementation of the Beer-Lambert law, is not applicable to the analysis of reflectance-mode MW-PPG signals. We propose that the shape of the MW-PPG signal carries information regarding the distribution of optical paths at different wavelengths within the tissue, which is crucial for the correct estimation of the absorption of light in the probe volume. We have developed and tested several machine-learning algorithms to analyze the reflectance-mode MW-PPG signal and to estimate the total hemoglobin concentration based on this analysis. To train and validate the algorithms, we collected a dataset of 840 MW-PPG signals measured from 170 volunteers by using a wrist-wearable PPG sensor. Three reference devices were used to label the data and test the performance of the developed algorithms: an invasive laboratory blood test, minimally invasive HemoCue Hb 201+, and noninvasive Masimo Radical-7 transmittance mode pulse-oximeter. The best performance achieved with the developed algorithm, mean absolute error MAE $\approx 12.6\pm$ 1.7 g/L and correlation coefficient R $\approx 0.66\pm$ 0.09, is comparable with the performance of the clinical noninvasive device

WAVELET-BASED ANALYSIS OF CEREBROVASCULAR DYNAMICS IN NEWBORN RATS WITH INTRACRANIAL HEMORRHAGES

Intracranial hemorrhage (IH) is a major problem of neonatal intensive care. The incidence of IH is typically asymptomatic and cannot be effectively detected by standard diagnostic methods. The mechanisms underlying IH are unknown but there is evidence that stress-induced disorders in adrenergic regulation of cerebral venous blood flow (CVBF) are among the main reasons. Quantitative and qualitative assessment of CVBF could significantly advance understanding of the nature of IH in newborns. In this work, we analyze variations of CVBF in newborn rats with an experimental model of stress-induced IH and adrenaline injection. Our analysis is based on the Doppler optical coherence tomography (DOCT) and a proposed adaptive wavelet-based approach that provides sensitive markers of abnormal reactions of the sagittal vein to external factors. The obtained results demonstrate that the incidence of IH in newborn rats is accompanied by a suppression of CVBF with the development of venous insufficiency and areactivity to adrenaline. We introduce a numerical measure θ, quantifying reactions of CVBF and show that the values θ < 1.23 estimated in the low-frequency (LF) spectral range corresponding to the sympathicus indicate abnormal reactions associated with the development of IH. We conclude that the revealed areactivity of the cerebral veins to adrenaline represents a possible mechanism responsible for pathological changes in CVBF