Laser speckle contrast imaging (LSCI) has become one of the most common tools for functional imaging in tissues. Incomplete theoretical description and sophisticated interpretation of measurement ...results are completely sidelined by a low-cost and simple hardware, fastness, consistent results, and repeatability. In addition to the relatively low measuring volume with around 700 μm of the probing depth for the visible spectral range of illumination, there is no depth selectivity in conventional LSCI configuration; furthermore, in a case of high NA objective, the actual penetration depth of light in tissues is greater than depth of field (DOF) of an imaging system. Thus, the information about these out-of-focus regions persists in the recorded frames but cannot be retrieved due to intensity-based registration method. We propose a simple modification of LSCI system based on the off-axis holography to introduce after-registration refocusing ability to overcome both depth-selectivity and DOF problems as well as to get the potential possibility of producing a cross-section view of the specimen.
Abstract
Interpretation of noncoding genomic variants is one of the most important challenges in human genetics. Machine learning methods have emerged recently as a powerful tool to solve this ...problem. State-of-the-art approaches allow prediction of transcriptional and epigenetic effects caused by noncoding mutations. However, these approaches require specific experimental data for training and cannot generalize across cell types where required features were not experimentally measured. We show here that available epigenetic characteristics of human cell types are extremely sparse, limiting those approaches that rely on specific epigenetic input. We propose a new neural network architecture, DeepCT, which can learn complex interconnections of epigenetic features and infer unmeasured data from any available input. Furthermore, we show that DeepCT can learn cell type–specific properties, build biologically meaningful vector representations of cell types, and utilize these representations to generate cell type–specific predictions of the effects of noncoding variations in the human genome.
A new application of the photodynamic treatment (PDT) is presented for the opening of blood‐brain barrier (BBB) and the brain clearing activation that is associated with it, including the use of gold ...nanoparticles as emerging photosensitizer carriers in PDT. The obtained results clearly demonstrate 2 pathways for the brain clearing: (1) using PDT‐opening of BBB and intravenous injection of FITC‐dextran we showed a clearance of this tracer via the meningeal lymphatic system in the subdural space; (2) using optical coherence tomography and intraparenchymal injection of gold nanorods, we observed their clearance through the exit gate of cerebral spinal fluid from the brain into the deep cervical lymph node, where the gold nanorods were accumulated. These data contribute to a better understanding of the cerebrovascular effects of PDT and shed light on mechanisms, underlying brain clearing after PDT‐related opening of BBB, including clearance from nanoparticles as drug carriers.
It is a crucial physiological role of blood‐brain barrier to protect the central nervous system against pathogens and toxic substances. However, this protective mechanism limits 98% of the beneficial drugs delivery as well. Our results contribute to a better understanding of the cerebrovascular effects of photodynamic treatment (PDT) and shed light on mechanisms, underlying brain clearing after PDT‐related opening of blood‐brain barrier, including clearance from nanoparticles as drug carriers.
Neonatal stroke is similar to the stroke that occurs in adults and produces a significant morbidity and long-term neurologic and cognitive deficits. There are important differences in the factors, ...clinical events and outcomes associated with the stroke in infants and adults. However, mechanisms underlying age differences in the stroke development remain largely unknown. Therefore, treatment guidelines for neonatal stroke must extrapolate from the adult data that is often not suitable for children. The new information about differences between neonatal and adult stroke is essential for identification of significant areas for future treatment and effective prevention of neonatal stroke. Here, we studied the development of stress-induced hemorrhagic stroke and possible mechanisms underlying these processes in newborn and adult rats. Using histological methods and magnetic resonance imaging, we found age differences in the type of intracranial hemorrhages. Newborn rats demonstrated small superficial bleedings in the cortex while adult rats had more severe deep bleedings in the cerebellum. Using Doppler optical coherent tomography, we found higher stress-reactivity of the sagittal sinus to deleterious effects of stress in newborn vs. adult rats suggesting that the cerebral veins are more vulnerable to negative stress factors in neonatal vs. adult brain in rats. However, adult but not newborn rats demonstrated the stroke-induced breakdown of blood brain barrier (BBB) permeability. The one of possible mechanisms underlying the higher resistance to stress-related stroke injures of cerebral vessels in newborn rats compared with adult animals is the greater expression of two main tight junction proteins of BBB (occludin and claudin-5) in neonatal vs. mature brain in rats.
Stress is a major factor for a risk of cerebrovascular catastrophes. Studying of mechanisms underlying stress-related brain-injures in neonates is crucial for development of strategy to prevent of ...neonatal stroke. Here, using a model of sound-stress-induced intracranial hemorrhages in newborn rats and optical methods, we found that cerebral veins are more sensitive to the deleterious effect of stress than arteries and microvessels. The development of venous insufficiency with decreased blood outflow from the brain accompanied by hypoxia, reduction of complexity of venous blood flow and high production of beta-arrestin-1 are possible mechanisms responsible for a risk of neonatal hemorrhagic stroke.
Fluorescent microscopy of the brain clearing from the FITC‐dextran (red color) via the meningeal lymphatic vessels (green color, labelled by specific antibodies LYVE‐1 conjugated with Alexa 488). The ...FITC‐dextran injected intravenously immediately is observed in the Sagittal sinus (the main cerebral vein) and after photodynamic opening of blood‐brain barrier it is also presented in the meningeal lymphatic vessels due to activation of brain clearing from accumulated the FITC‐dextran in the brain parenchyma.
Further details can be found in the article by Oxana Semyachkina‐Glushkovskaya, Vladimir Chehonin, Ekaterina Borisova, et al. (
e201700287
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Neonatal brain hemorrhages is a major problem of future generation’s health due to the high rate of cognitive disability of newborns after vascular catastrophes in the brain. Despite the public ...health impact of neonatal brain hemorrhages, the mechanisms underlying in these pathological processes remain unknown. Here, using a model of sound-stress-induced brain hemorrhages (per diapedesis, no per rhexis) in newborn rats and optical methods, we found that brain hemorrhages in newborn rats are accompanied by the increase in perfusion of brain tissues, which closely associated with reducing of cerebral oxygenation and increasing of nitric oxide production in both the brain tissues and blood. We assume that nitric oxide contributes the dilation of cerebral vessels during hypoxia and the increasing of cerebral blood flow in newborn rats with brain hemorrhages. Hypoxic-hyperperfusion during stress-related hemorrhages in newborn animals can be an important protective mechanism against anoxia and critical changes in cerebral hemodynamics.
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