Optical coherence microangiography of the mouse kidney for diagnosis of circulatory disorders

Optical coherence tomography (OCT) has become widespread in clinical applications in which precise three-dimensional functional imaging of living organs is required. Nevertheless, the kidney is inaccessible for the high resolution OCT imaging due to a high light attenuation coefficient of skin and soft tissues that significantly limits the penetration depth of the probing laser beam. Here, we introduce a surgical protocol and fixation scheme that enables functional visualization of kidney’s peritubular capillaries via OCT microangiography. The model of reversible/irreversible glomerulus embolization using drug microcarriers confirms the ability of OCT to detect circulatory disorders. This approach can be used for choosing optimal carriers, their dosages and diagnosis of other blood flow pathologies

Characterization of cerebral blood flow dynamics with multiscale entropy

Based on the laser speckle contrast imaging (LSCI) and the multiscale entropy (MSE), we study in this work the blood flow dynamics at the levels of cerebral veins and the surrounding network of microcerebral vessels. We discuss how the phenylephrine-related acute peripheral hypertension is reflected in the cerebral circulation and show that the observed changes are scale-dependent, and they are significantly more pronounced in microcerebral vessels, while the macrocerebral dynamics does not demonstrate authentic inter-group distinctions. We also consider the permeability of blood–brain barrier (BBB) and study its opening caused by sound exposure. We show that alterations associated with the BBB opening can be revealed by the analysis of blood flow at the level of macrocerebral vessels

Организационно-технологическое моделирование процессов устройства кровельных покрытий с модульной системой озеленения

Введение. Представлен подход к разработке организационно-технологических моделей процессов устройства эксплуатируемых кровельных покрытий с системами озеленения, позволяющих выполнить систематизацию конструктивно-технологических решений. Приводятся организационно-технологические параметры устройства кровельных покрытий с озеленением. В настоящее время недостаточно изучены проблемы, связанные с исследованием организационно-технологических параметров при устройстве нетрадиционных энергосберегающих инженерных систем. Материалы и методы. Проведен анализ научно-технических исследований отечественных и зарубежных ученых в области технологий зеленого строительства применительно к устройству кровельных покрытий. Сформулированы организационно-технологические параметры технологических процессов и технологических операций при производстве работ устройства покрытий. Использованы методы математического моделирования, а также методы структурно-функционального моделирования. Результаты. Определены организационно-технологические параметры устройства кровельных покрытий с озеленением, состав и последовательность технологических процессов и операций при устройстве кровельных покрытий с системами озеленения. Упорядочены рабочие операции технологических процессов устройства модульных систем озеленения эксплуатируемых кровельных покрытий. Построены пространственно-технологические и функциональные модели технологических процессов устройства эксплуатируемых кровельных покрытий с системами озеленения, позволяющие выявить резервы и устранить технологические непроизводственные перерывы в процессе производства. Выводы. Установлено, что в области технологий зеленого строительства имеется необходимость разработки новых стандартов и дополнения положений нормативно-технической базы, содержащих руководящие принципы, которые охватывают процессы проектирования и строительства с подробным описанием организационно-технологических и конструктивно-технических характеристик. Построенные пространственно-технологические и функциональные модели технологических процессов устройства эксплуатируемых кровельных покрытий с системами озеленения позволяют выявить резервы и устранить технологические непроизводственные перерывы в процессе производства работ

Intravital molecular tagging velocimetry of cerebral blood flow using Evans Blue

The effects of light-driven enhancement of Evans Blue dye complexes with blood plasma proteins were observed for the first time, both in vitro and in vivo. The possible background of the effect concerns the photochemical cis-trans isomerization of the azo dye molecules. The effect was induced in the solution with a red laser with a wavelength of 638 nm, which corresponds to the peak of the dye absorption. The lifetime of the enhanced fluorescence is approximately 1 second and enables its use as an optically tagged molecular flow tracer for blood flow velocity measurements. Utilizing the effect, we performed for the first time the intravital molecular tagging velocimetry of the blood velocity in blood vessels in a living animal. The results of the measurements of the blood flow velocities in the cerebral veins of a group of healthy mice are presented

Optical coherent tomography and fluorescent microscopy for the study of meningeal lymphatic systems

The development of novel technologies for the imaging of meningeal lymphatic vessels is one of the amazing trends of biophotonics thanks to discovery of brain lymphatics over several years ago. However, there is the limited technologies exist for the study of lymphatics in vivo because lymphatic vessels are transparent with a low speed flow of lymph. Here we demonstrate the successful application of fluorescent microscopy for the imaging of lymphatic system in the mouse brain in vivo

Detection of melanoma cells in whole blood samples using spectral imaging and optical clearing

Most cancer deaths are associated with metastases resulting from the spread of circulating tumor cells (CTCs) from the primary tumor to vital organs. The existing methods for detection of CTCs as markers of metastasis progression are time consuming with several steps of sample processing, including red blood cell removal, labeling, immunomagnetic capture and isolation, which can lead to loss of CTCs. Here we introduce a method for detection and identification of CTCs using spectral absorption imaging of melanoma cells and optical clearing of whole blood samples. Verification of this approach was performed using phantoms of human melanoma cells and suspensions of mouse melanoma cells of line B16F10 alone and in mixture with blood. A method for improving detection sensitivity has been demonstrated applying optical clearing of mouse blood using biocompatible chemical agents. The findings suggest that the proposed diagnostic platform has the potential to detect quickly CTCs in whole blood samples from patients with melanoma

Target delivery of drug carriers in mice kidney glomeruli via renal artery. Balance between efficiency and safety

Targeting drug delivery systems is crucial to reducing the side effects of therapy. However, many of them are lacking effectiveness for kidney targeting, due to systemic dispersion and accumulation in the lungs and liver after intravenous administration. Renal artery administration of carriers provides their effective local accumulation but may cause irreversible vessel blockage. Therefore, the combination of the correct administration procedure, suitable drug delivery system, selection of effective and safe dosage is the key to sparing local therapy. Here, we propose the 3-μm sized fluorescent capsules based on poly-L-arginine and dextran sulfate for targeting the kidney via a mice renal artery. Hemodynamic study of the target kidney in combination with the histological analysis reveals a safe dose of microcapsules (20 × 106), which has not lead to irreversible pathological changes in blood flow and kidney tissue, and provides retention of 20.5 ± 3% of the introduced capsules in the renal cortex glomeruli. Efficacy of fluorescent dye localization in the target kidney after intra-arterial administration is 9 times higher than in the opposite kidney and after intravenous injection. After 24 h microcapsules are not observed in the target kidney when the safe dose of carriers is being used but a high level of fluorescent signal persists for 48 h indicating that fluorescent cargo accumulation in tissues. Injection of non-safe microcapsule dose leads to carriers staying in glomeruli for at least 48 h which has consequences of blood flow not being restored and tissue damage being observed in histology

Effect of pulsed laser parameters on photoacoustic flow cytometry efficiency in vitro and in vivo

Photoacoustic flow cytometry is one of the most effective approaches to detect "alien" objects in the bloodstream, including circulating tumor cells, blood clots, parasites, and emboli. However, the possibility of detecting high-amplitude signals from these objects against the background of blood depends on the parameters of the laser pulse. So, the dependencies of photoacoustic signals amplitude and number on laser pulse energy (5–150 μJ), pulse length (1, 2, 5 ns), and pulse repetition rate (2, 5, 10 kHz) for the melanoma cells were investigated. First, the PA responses of a melanoma cell suspension in vitro was measured to directly assess the efficiency of converting laser light into an acoustic signal. After it the same dependence with the developed murine model based on constant rate melanoma cell injection into the animal blood flow was tested. Both in vivo and in vitro experiments show that signal generation efficiency increases with laser pulse energy above 15 μJ. Shorter pulses, especially 1 ns, provide more efficient signal generation as well as higher pulse rates. A higher pulse rate also provides more efficient signal generation, but also leads to overheating of the skin. The results show the limits where the photoacoustic flow cytometry system can be effectively used for detection of circulating tumor cells in undiluted blood both for in vitro experiment s and for in vivo murine models

Targeted Therapy for Glomerulonephritis Using Arterial Delivery of Encapsulated Etanercept

Complex immunosuppressive therapy is prescribed in medical practice to patients with glomerulonephritis to help them overcome symptoms and prevent chronic renal failure. Such an approach requires long-term systemic administration of strong medications, which causes severe side effects. This work shows the efficiency of polymer capsule accumulation (2.8 ± 0.4 µm) containing labeled etanercept (100 μg per dose) in the kidneys of mice. The comparison of injection into the renal artery and tail vein shows the significant superiority of the intra-arterial administration strategy. The etanercept retention rate of 18% and 8% ID in kidneys was found 1 min and 1 h after injection, respectively. The capsules were predominantly localized in the glomeruli after injection in mice using a model of acute glomerulonephritis. Histological analysis confirmed a significant therapeutic effect only in animals with intra-arterial administration of microcapsules with etanercept. The proposed strategy combines endovascular surgery and the use of polymer microcapsules containing a high molecular weight drug that can be successfully applied to treat a wide range of kidney diseases associated with glomerular pathology

Photodynamic opening of the blood-brain barrier and pathways of brain clearing

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