Small Capillaries Research Articles

Microvasculopathy and biomarkers in sickle cell disease: the promise of non‐invasive real‐time in vivo tools

Microvasculopathy and biomarkers in sickle cell disease: the promise of non‐invasive real‐time <i>in vivo</i> tools

Trash Your Agar Plates! Blood Stream Bacteria Are Now Quantified by in vivo Flow Cytometry.

© 2020 International Society for Advancement of Cytometry.

Florbetapir Regional Distribution in Cerebral Amyloid Angiopathy and Alzheimer's Disease: A PET Study.

Background:Sporadic cerebral amyloid angiopathy shows progressive amyloid-β deposition in the wall of small arterioles and capillaries of the leptomeninges and cerebral cortex.Objective:To investigate whether amyloid load and distribution, assessed by florbetapir positron emission tomography (PET), differs between patients with probable CAA-related intracerebral hemorrhage (CAA-ICH) and mild cognitive impairment due to Alzheimer’s disease (MCI-AD).Methods:We assessed [18F]florbetapir uptake in 15 patients with probable CAA-ICH and 20 patients with MCI-AD patients. Global and regional florbetapir retention were assessed using standard uptake values ratio (SUVr) in region-based and voxel-wise approaches. Visual reading of florbetapir scans was performed for all participants. Group comparisons were performed using univariate and multivariate analysis.Results:Global florbetapir retention was lower in patients with CAA-ICH than MCI-AD (median SUVr, 1.33 [1.21–1.41] versus 1.44 [1.35–1.66]; p = 0.032). In the region-based analysis, regional florbetapir distribution was similar between the two groups. There was a trend for an increased occipital/global ratio in CAA-ICH patients compared to MCI-AD (p = 0.060). In the voxel-wise approach, two clusters, one in parietal regions and the other in temporal regions, had higher uptake in MCI-AD relative to CAA patients.Conclusions:Patients with CAA-ICH had a lower global florbetapir PET burden than patients with MCI-AD. Relative florbetapir retention in the posterior regions tended to be higher in CAA patients in region-based analysis but was not statistically different between groups. Investigation on differences in amyloid deposits distribution between groups required a fine-grained voxel-wise analysis. In future studies, selective amyloid tracers are needed to differentiate vascular from parenchymal amyloid.

A rant about a SANT: A rare mimic of splenic haemangioma

Sclerosing angiomatoid nodular transformation (SANT) of the spleen is a rare, benign, vascular lesion with characteristic histological features. Often an incidental finding, full excision of the lesion has been shown to be curative. We describe a case of SANT in a 35-year-old woman who presented with a purported splenic haemangioma with atypical imaging features including an uncharacteristic enlargement over a two-year period. Gross examination of the splenectomy specimen revealed a circumscribed 42 mm white, lobulated mass with prominent central sclerosis and dilated vascular spaces at the periphery. Histological examination showed a hyalinised lesion with a nodular architecture imparted by nodules of small capillary channels with red cell extravasation, and scattered admixed chronic inflammatory cells. A rare lesion of indeterminate aetiology, SANT remains a curiosity and an essential diagnostic consideration among vascular lesions of the spleen with features not typical of haemangioma.

In vivo brain imaging with multimodal optical coherence microscopy in a mouse model of thromboembolic photochemical stroke

.We used a new multimodal imaging system that combines optical coherence microscopy and brightfield microscopy. Using this in vivo brain monitoring approach and cranial window implantation, we three-dimensionally visualized the vascular network during thrombosis, with high temporal (18 s) and spatial (axial, ; lateral, ) resolution. We used a modified mouse model of photochemical thromboembolic stroke in order to more accurately parallel human stroke. Specifically, we applied green laser illumination to focally occlude a branch of the middle cerebral artery. Despite the recanalization of the superficial arteries at 24 h after stroke, no blood flow was detected in the small vessels within deeper regions. Moreover, after 24 h of stroke progression, scattering signal enhancement was observed within the stroke region. We also evaluated the infarct extent and shape histologically. In summary, we present a novel approach for real-time mouse brain monitoring and ischemic variability analysis. This multimodal imaging method permits the analysis of thrombosis progression and reperfusion. Additionally and importantly, the system could be used to study the effect of poststroke drug treatments on blood flow in small arteries and capillaries of the brain.

A Small Field, High Resolution γ-Camera System dedicated to SPECT Imaging

A small field, high resolution γ-Camera system dedicated to radiopharmaceutical research and other clinical SPECT (Single Photon Emission Computed Tomography) applications is currently being developed in our group. The system is equipped with the 3” HAMAMATSU R2486 Position Sensitive PhotoMultiplier Tube (PSPMT) with a 16X+16Y-crossed wire anode and various pixelated and ho- mogeneous scintillation crystals. Planar images are created from the recorded charge signals by applying the resistive chain technique. The main part of this work focuses on the development of new correction methods for the improvement of the spatial resolution and the uniformity of the γ-Camera. The spatial distortion correction technique is based on lookup tables with the coordinates of reference points which are selected during the calibration phase of the system for a given set of collimator and scintillation crystal. The applied algorithm incorporates 2D-interpolation tech- niques and has been developed on a full automated graphics environment making use of the HIGZ (High Level Interface to Graphics and ZEBRA) program libraries from CERN. Both correction methods for the spatial distortion and non-uniformity have been applied to phantom images using several combinations of small capillaries filled with water solution of 99mTc. Comparative studies are shown on planar im- ages for different phantom geometries. The method is also extended to tomographic images and the obtained SPECT improvement in resolution is discussed.

Optical Properties of Continuous and Pixelated Scintillation Crystals

The optical photon distribution produced inside continuous and pixelated scintillation crystals by the absorption of a γ-ray have been studied with the photon transport program DETECT 2000. With this program the charge signals recorded by a multi-wired anode system, like the Position Sensitive PhotoMultiplier Tube (PSPMT) of a γ-Camera, are simulated. Based on the analytical parametrization which is fitted to experimental data, a new position reconstruction method for PSPMTs is proposed in this work. Planar images have been reconstructed with the new method and compared to the traditional charge center of gravity technique. Data are obtained from a small field, high resolution γ-Camera system with a multi- wired crossed anode using the R2486 (HAMAMATSU) PSPMT. Systematic studies for continuous and pixelated inorganic scintillation crystals of CsI(Tl) have been performed for different phantom geometries using small capillaries of 99mTc. The developed method seems to drastically improve the resolution of the reconstructed planar information, even when homogeneous crystals are used.

Using a capillary mat as a shallow heat exchanger for a ground source heat pump system

The ground heat exchanger is an important part of a ground source heat pump system. The site selection and arrangement affect the thermal performance of the entire system. A horizontal (shallow) ground heat exchanger has lower initial cost than a borehole heat exchanger. However, it has a larger physical footprint and its thermal performance is strongly affected by surface heat flux and rainfall infiltration. The capillary mat heat exchanger comprises small parallel capillary tubes and provides larger effective heat transfer area per unit footprint installation area. Additionally, it is more easily prepared and installed. This paper reports experimental result and numerical validation of ground source heat pump cooling application using shallow horizontal capillary mat ground heat exchangers. From the experiment, it was found that the installed capillary mat heat exchangers provide sufficient heat rejection rate for the heat-pump's thermal load. A numerical model for capillary mat heat exchangers is developed and the numerical result are validated using experimental data, within 1.54% root-mean-square error. A new and simple numerical relationship is also proposed to express the rate of heat transfer from capillary pipes to the surrounding soil. The extended numerical simulation found that currently installed ground heat exchangers can provide higher thermal load. The estimation of the pressure drop suggests that for a given pressure drop and flow rate, a single capillary mat having a surface area of 13.18 m2 is equivalent to a 40-m high-density polyethylene pipe with a standard diameter of 3.2 cm and a surface area of 8.05 m2.

Evidence for accessory chemosensory cells in the adult human nasal cavity

The existence of functionally relevant accessory olfactory organs in humans is still a matter of controversy. A vomeronasal organ (VNO) with sensory and non-sensory epithelia exists only in macrosmatic mammals. A similar structure is regularly observed in humans during fetal development. The postnatal persistence of a VNO like epithelial duct has been described in about 10 %. Here we studied tissue samples of nasal mucosa from adults. In all individuals we found epithelial cells in the lower part of the nasal septum which exhibited morphological features of sensory neurons and which showed immunostaining for olfactory marker protein OMP. These cells were interposed by ciliated cells, goblet cells and small intraepithelial capillaries. Only occasionally we found such cells within a morphologically defined epithelial duct. A clear separation of sensory and non-sensory epithelia could not be observed. In most cases we found OMP positive groups of cells either in epithelial cavities or just embedded in respiratory epithelium. With RT-PCR we could confirm the presence of OMP encoding mRNA thus supporting the idea of intrinsic expression of this protein in the nasal mucosa. We conclude that accessory chemosensory structures are regularly conserved in adult humans in the approximate anatomical location of the VNO of microsmatic animals. Their functional importance is yet to be determined.

Cutaneous Intravascular/Angiotropic Lymphoma Following a Septic Shock Episode. Case Report and Literature Review

Angiotropic lymphoma is a rare aggressive disease characterized by exclusive or predominant accumulation of malignant lymphoid cells within the lumen of small arteries, veins and capillaries. We describe a 74-year-old female patient who presented at the department of dermatology with widespread cutaneous telangiectasia and generalized edema. No neurologic symptoms were present during the course of these clinical manifestations. After close-up examination and further laboratory and radiological studies, the final diagnosis of cutaneous intravascular lymphoma was made in the histopathological report. Immunochemistry evaluation confirmed a B-cell subtype. Diagnosis of this rare disease, in most cases, is achieved by surgical biopsy. The biopsy and immunohistochemistry have increased the chances of an ante mortem diagnosis. Afterward, the patient was referred to Hematologic Department to follow the combined chemotherapy treatment, which resulted to be successful, and the cutaneous lesions began to disappear

A Case of an Isolated Peripheral Giant Cell Granuloma in the Parotid Gland

Peripheral giant cell granuloma (PGCG) is an benign non-neoplastic lesion most commonly occurring in oral cavity but extraoral PGCG is extremely rare. Recently, we experienced a case of an isolated PGCG in the parotid gland in 59-year-old man. FNAB findings and radiologic findings including CT and US were suggestive of Warthin’s tumor. Partial parotidectomy was performed. Pathologic findings showed fibrillar connective tissue stroma with spindled, ovoid, and round histiocytes-like cells mixed with uneven multinuclear giant cells, small capillaries, hemorrhage, hemosiderin-laden macrophages, and necrosis which were consistent with giant cell granuloma. We report a case of an PGCG in parotid with a review of literature. Key Words: Peripheral giant cell granuloma, PGCG, Parotid gland

Enzyme-Ligand Interaction Monitored by Synchrotron Radiation Circular Dichroism.

CD spectroscopy is the essential tool to quickly ascertain in the far-UV region the global conformational changes, the secondary structure content, and protein folding and in the near-UV region the local tertiary structure changes probed by the local environment of the aromatic side chains, prosthetic groups (hemes, flavones, carotenoids), the dihedral angle of disulfide bonds, and the ligand chromophore moieties, the latter occurring as a result of protein-ligand binding interaction. Qualitative and quantitative investigations into ligand-binding interactions in both the far- and near-UV regions using CD spectroscopy provide unique and direct information whether induced conformational changes upon ligand binding occur and of what nature that are unattainable with other techniques such as fluorescence, ITC, SPR, and AUC.This chapter provides an overview of how to perform circular dichroism (CD) experiments, detailing methods, hints and tips for successful CD measurements. Descriptions of different experimental designs are discussed using CD to investigate ligand-binding interactions. This includes standard qualitative CD measurements conducted in both single-measurement mode and high-throughput 96-well plate mode, CD titrations, and UV protein denaturation assays with and without ligand.The highly collimated micro-beam available at B23 beamline for synchrotron radiation circular dichroism (SRCD) at Diamond Light Source (DLS) offers many advantages to benchtop instruments. The synchrotron light source is ten times brighter than a standard xenon arc light source of benchtop instruments. The small diameter of the synchrotron beam can be up to 160 times smaller than that of benchtop light beams; this has enabled the use of small aperture cuvette cells and flat capillary tubes reducing substantially the amount of volume sample to be investigated. Methods, hints and tips, and golden rules to measure good quality, artifact-free SRCD and CD data will be described in this chapter in particular for the study of protein-ligand interactions and protein photostability.

Effect of Systemic Polyelectrolyte Microcapsule Administration on the Blood Flow Dynamics of Vital Organs.

Polyelectrolyte microcapsules and other targeted drug delivery systems could substantially reduce the side effects of drug and overall toxicity. At the same time, the cardiovascular system is a unique transport avenue that can deliver drug carriers to any tissue and organ. However, one of the most important potential problems of drug carrier systemic administration in clinical practice is that the carriers might cause circulatory disorders, the development of pulmonary embolism, ischemia, and tissue necrosis due to the blockage of small capillaries. Thus, the presented work aims to find out the processes occurring in the bloodstream after the systemic injection of polyelectrolyte capsules that are 5 μm in size. It was shown that 1 min after injection, the number of circulating capsules decreases several times, and after 15 min less than 1% of the injected dose is registered in the blood. By this time, most capsules accumulate in the lungs, liver, and kidneys. However, magnetic field action could slightly increase the accumulation of capsules in the region-of-interest. For the first time, we have investigated the real-time blood flow changes in vital organs in vivo after intravenous injection of microcapsules using a laser speckle contrast imaging system. We have demonstrated that the organism can adapt to the emergence of drug carriers in the blood and their accumulation in the vessels of vital organs. Additionally, we have evaluated the safety of the intravenous administration of various doses of microcapsules.

Pore Structure Characteristics of RAP-Inclusive Cement Mortar and Cement Concrete Using Mercury Intrusion Porosimetry Technique

Abstract The pore structure characteristics of cement mortar and concrete incorporating reclaimed asphalt pavement (RAP) fine aggregates as part replacements of natural fine aggregates (NAs) were studied using mercury intrusion porosimetry (MIP) technique. NAs were replaced by RAP at 25, 50, 75, and 100 % by volume of total fine aggregates. Mineral admixtures, namely silica fume and activated sugarcane bagasse ash, were incorporated as part replacements of cement as well. MIP technique could identify the mesopores and macropores in the cementitious mixture. Porosity increases with an increase in RAP content in cementitious mixture, owing to larger and porous interfacial transition zone. Total intrusion pore volume increases with an increase in RAP content and is greater than the control mix irrespective of RAP content and mineral admixture. Mesopores and macropores follow a similar trend as total intrusion pore volume, suggesting finer and larger pores in RAP-inclusive cementitious mixtures. Threshold diameters were observed to initially decrease until 50 % RAP content and to increase thereafter for RAP-inclusive cement mortar, suggesting easy penetration of chemical species for higher RAP content mixes. From pore classification studies, entrained air, large capillaries, medium capillaries, and small capillaries were also analyzed. Large capillaries follow a similar trend to threshold diameter, in which the former affects the transport processes in cementitious mixture. RAP-inclusive cementitious mixtures have the ability to resist freeze as well as thaw and salt decay; this is concluded indirectly from pore structure studies. The pore-mass fractal dimension has the ability to describe the pore-solid structure, whereas the pore-surface fractal dimension failed to do so for RAP-inclusive cementitious mixtures.

High frequency of GNA14, GNAQ, and GNA11 mutations in cherry hemangioma: a histopathological and molecular study of 85 cases indicating GNA14 as the most commonly mutated gene in vascular neoplasms

Cherry hemangioma is the most common hemangioma in adult life. Neoplastic and non-neoplastic theories had both been proposed for its pathogenesis, but its nature is still poorly understood. We noted a significant subset of anastomosing hemangiomas and congenital hemangiomas harbored a population of small capillaries surrounded by a perivascular hyaline layer, reminiscent of the vessels seen in cherry hemangioma. Both anastomosing hemangioma and congenital hemangioma harbor recurrent mutations in exon 5 of GNAQ and its paralogues. In this study, we analyzed 68 cherry hemangiomas and 17 cherry hemangioma-like hemangiomas exhibiting additional non-classical features including markedly dilated, cavernous vessels, and/or a deep component extending to the deep dermis. By Sanger sequencing, GNAQ, GNA11, and GNA14 exon 5 mutations were identified in 12, 4, and 32 cherry hemangiomas, respectively, and 5, 3, and 3 cherry hemangioma-like hemangiomas, respectively. MassARRAY analysis detected mutations (including exon 2 GNAQG48V mutations) in additional 8 cherry hemangiomas and 3 cherry hemangioma-like hemangiomas. Overall, the cherry hemangiomas and cherry hemangioma-like hemangiomas had equal GNA mutation rates (82%), and GNA14 and GNAQ mutations were present in approximately half of cherry hemangiomas and cherry hemangioma-like hemangiomas, respectively. All mutations were mutually exclusive. KRASG12V mutation was also detected in one cherry hemangioma-like hemangioma without GNA mutations. In summary, our study demonstrated recurrent GNA14/GNAQ/GNA11 mutations were present in the majority of this very common hemangioma and established its neoplastic nature. Our results also expanded the morphological spectrum of GNA-mutated hemangiomas to include tumors composed of cavernous-like vessels and indicated GNA14 was the most commonly mutated gene in vascular tumors.

Calcium Channels and Calcium-Regulated Channels in Human Red Blood Cells.

Free Calcium (Ca2+) is an important and universal signalling entity in all cells, red blood cells included. Although mature mammalian red blood cells are believed to not contain organelles as Ca2+ stores such as the endoplasmic reticulum or mitochondria, a 20,000-fold gradient based on a intracellular Ca2+ concentration of approximately 60nM vs. an extracellular concentration of 1.2mM makes Ca2+-permeable channels a major signalling tool of red blood cells. However, the internal Ca2+ concentration is tightly controlled, regulated and maintained primarily by the Ca2+ pumps PMCA1 and PMCA4. Within the last two decades it became evident that an increased intracellular Ca2+ is associated with red blood cell clearance in the spleen and promotes red blood cell aggregability and clot formation. In contrast to this rather uncontrolled deadly Ca2+ signals only recently it became evident, that a temporal increase in intracellular Ca2+ can also have positive effects such as the modulation of the red blood cells O2 binding properties or even be vital for brief transient cellular volume adaptation when passing constrictions like small capillaries or slits in the spleen. Here we give an overview of Ca2+ channels and Ca2+-regulated channels in red blood cells, namely the Gárdos channel, the non-selective voltage dependent cation channel, Piezo1, the NMDA receptor, VDAC, TRPC channels, CaV2.1, a Ca2+-inhibited channel novel to red blood cells and i.a. relate these channels to the molecular unknown sickle cell disease conductance Psickle. Particular attention is given to correlation of functional measurements with molecular entities as well as the physiological and pathophysiological function of these channels. This view is in constant progress and in particular the understanding of the interaction of several ion channels in a physiological context just started. This includes on the one hand channelopathies, where a mutation of the ion channel is the direct cause of the disease, like Hereditary Xerocytosis and the Gárdos Channelopathy. On the other hand it applies to red blood cell related diseases where an altered channel activity is a secondary effect like in sickle cell disease or thalassemia. Also these secondary effects should receive medical and pharmacologic attention because they can be crucial when it comes to the life-threatening symptoms of the disease.

3D Shape Modeling and Analysis of Retinal Microvasculature in OCT-Angiography Images.

3D optical coherence tomography angiography (OCT-A) is a novel and non-invasive imaging modality for analyzing retinal diseases. The studies of microvasculature in 2D en face projection images have been widely implemented, but comprehensive 3D analysis of OCT-A images with rich depth-resolved microvascular information is rarely considered. In this paper, we propose a robust, effective, and automatic 3D shape modeling framework to provide a high-quality 3D vessel representation and to preserve valuable 3D geometric and topological information for vessel analysis. Effective vessel enhancement and extraction steps by means of curvelet denoising and optimally oriented flux (OOF) filtering are first designed to produce 3D microvascular networks. Afterwards, a novel 3D data representation of OCT-A microvasculature is reconstructed via advanced mesh reconstruction techniques. Based on the 3D surfaces, shape analysis is established to extract novel shape-based microvascular area distortion via the Laplace-Beltrami eigen-projection. The extracted feature is integrated into a graph-cut segmentation system to categorize large vessels and small capillaries for more precise shape analysis. The proposed framework is validated on a dedicated repeated scan dataset including 260 volume images and shows high repeatability. Statistical analysis using the surface area biomarker is performed on small capillaries to avoid the effect of tailing artifact from large vessels. It shows significant differences ( ) between DR stages on 100 subjects in a OCTA-DR dataset. The proposed shape modeling and analysis framework opens the possibility for further investigating OCT-A microvasculature in a new perspective.

Numerical simulation of cryosurgery in biological tissue with developed circulatory system

This paper is devoted to the modeling of the cryogenic impact on biological tissue with a developed circulatory system: large blood vessels, dense distributed small vessels and capillaries penetrating the tissue. The case of cryogenic destruction of a cancer tumor localized near a large artery is considered. The paper presents a direct numerical simulation of the temperature distribution evolution in biological tissue including the calculation of blood flow parameters in a vessel. The mathematical model is based on the Pennes bioheat transfer model with enthalpy modification and the quasi-one-dimensional hemodynamic model of blood flow in arteries, taking into account local changes in the elastic properties of the vessel walls due to strong cooling of adjacent tissue. A numerical algorithm based on explicit finite-volume approximation of the heat transfer model and the hybrid characteristic scheme (after splitting the equation with respect to physical processes) for numerical solution of hyperbolic systems is developed in order to simulate cryosurgery for the tumor near the artery. The main focus of the paper is a numerical study of the circulatory system parameters’ influence on the shape of the final distribution of the cellular necrosis zone. We study the dependence of the necrosis front penetration depth on the perfusion power which characterizes the density of capillary distribution, the peak and background rates of blood flow in the artery, the diameter of the blood vessel and the thickness of its walls.

Dispersive and propagation of shallow water waves as a higher order nonlinear Boussinesq-like dynamical wave equations

The propagation of small amplitude long capillary–gravity waves on the surface of shallow water described by the higher order nonlinear Boussinesq type wave equation. This model is arising in mathematical physics, shallow water waves, fluid dynamics and fluid flow. We applied the modified Jacobi elliptic function expansion method to obtained exact solutions in the type of solitary wave and elliptic functions solutions. These solutions helps the mathematicians and physicians to understand the physical phenomena of this model. This technique can be utilized on other models to launch further exclusively novel solutions for other categories of nonlinear PDEs occurring in mathematical Physics.

On the Influence of Capillary-Based Structural Health Monitoring on Fatigue Crack Initiation and Propagation in Straight Lugs.

This paper addresses the influence on the fatigue life induced by the implementation of a capillary-based structural health monitoring methodology, patented under the name eSHM. It consists in integrating structurally small and pressurized capillaries into the component, so that when a fatigue crack breaches the capillary network, it results in a leak flow to the open atmosphere and loss of pressure in the galleries which is detected by a pressure sensor. The novelty of the proposed system resides in the opportunity to locate the capillary according to the designer’s need, as one resorts to additive manufacturing for the part production. However, the presence of these galleries in highly stressed regions raises concerns about crack initiation at the capillary itself and accelerated fatigue crack growth. This paper aims at the quantification of the influence the eSHM has on the fatigue behavior of the component and the determination whether this influence is significant or not. To that purpose, numerical simulations on a straight lug component, using the finite elements and eXtended Finite Elements Methods (XFEM), are performed. Various capillary sizes and shapes are assessed, so as to enable a general conclusion on the impact of the eSHM methodology in straight lugs.