Blood Cell Flow Research Articles

Interplay between endothelial glycocalyx layer and red blood cell in microvascular blood flow: A numerical study.

The endothelial glycocalyx layer (EGL) plays a crucial role in regulating blood flow in microvessels. Experimental evidence suggests that there is greater blood flow resistance in vivo compared to in vitro, partially due to the presence of the EGL. However, the complex relationship between EGL deformation and blood cell behavior in shear flow and its quantification remains incompletely understood. To address this gap, we employ a particle-based numerical simulation technique to examine the interaction of the EGL with flowing red blood cells (RBCs) in microtubes. We examine changes in EGL deformation in response to variations in shear rate, EGL graft density, and contour height. Our results indicate that the alterations in EGL height are influenced by the mechanical properties of the EGL, flow conditions, and the RBC-EGL interaction. The flowing RBC compresses the EGL, causing a notable reduction in EGL height near the RBC flow. Additionally, we find that the presence of the EGL in the microtube results in increased RBC deformation and a wider gap between the RBC and tube wall due to spatial occupancy. The significant impact of the EGL on RBC flow is particularly evident in microtubes with diameters ranging from 7 to 10µm, a range consistent with notable differences in vascular flow resistance observed between in vivo and in vitro experiments. The simulation results shed insight on the dynamic interplay between RBC and the EGL in microvascular blood flow.

Microfluctuations in Capillary Lumens Independent of Pericyte Lining Density in the Anesthetized Mouse Cortex.

This study aimed to examine the spatiotemporal coherence of capillary lumen fluctuations in relation to spatial variations in the pericyte lining in the cortex of anesthetized mice. Two-photon microscopic angiography data (previously published) were reanalyzed, and spatial variations in capillary diameter fluctuations at rest and in capillary lining with vascular mural cells were measured along capillary centerlines. Relatively large diameters of the capillaries (5.5 μm) coincided with a dense pericyte lining, while small capillaries (4.3 μm) had a sparse pericyte lining. Temporal variations had a frequency of about 0.1 Hz with an amplitude of 0.5 μm, which were negatively correlated with pericyte lining density. Spatial frequency analysis further revealed a common pattern of spatial variations in capillary diameter and pericyte lining, but temporal variations differed. The temporal variations in capillary lumens were locally distinct from those in neighboring locations, suggesting intrinsic fluctuations independent of the pericyte lining. Capillary lumens in the brain exhibit slow microfluctuations that are independent of pericyte lining. These microfluctuations could affect the distribution of flowing blood cells and may be important for homogenizing their distribution in capillary networks.

Photothermal Enhancement of Ion Current for Red Blood Cell Flow Cytometry.

Blood cell counting typically requires complex machinery. Flow cytometers used for this purpose involve precise optical alignment, costly detectors, and pretreatment with fluorescent labels. Coulter countertype devices, which monitor ion current, are simpler. However, conventional Coulter counters provide only information about size, making it impossible to distinguish similarly sized lymphocytes from red blood cells (RBCs). Inspired by the fact that RBCs have an exceptionally high propensity to absorb light and convert it to heat, i.e., photothermal effect, this study proposes integrating photothermal phenomena into a microfluidic Coulter counting chip. Photothermal heat selectively amplifies the ion current from RBCs over other components including lymphocytes. The combination of ion current monitoring and the photothermal effect for RBC counting suggests an evolution toward versatile flow cytometers.

Exposure to nitrate and nitrite disrupts cardiovascular development through estrogen receptor in zebrafish embryos and larvae.

Increasing nitrate concentration on surface and groundwater due to anthropogenic activities is an environmental concern. In this study, Tg(fli1: EGFP) zebrafish embryos were exposed to nitrate (NO3-) and nitrite (NO2-), and their cardiovascular development were investigated. Exposure to 10mg/L NO3-N and 1 and 10mg/L NO2-N decreased heart rate at 48-96-h post-fertilization (hpf), ventricular volume, and red blood cell flow rate at 96 hpf. Similar concentrations increased the number of embryos and larvae with pericardial edema and missing intersegmental and parachordal vessels in the caudal region at 48-96 hpf. Addition of ICI 182,720 (ICI) reversed the effects of nitrate and nitrite, suggesting estrogen receptors (ER) are involved. 10mg/L NO3-N and 1mg/L NO2-N decreased cardiovascular-related genes, gata4,5,6, hand2, nkx2.5, nkx2.7, tbx2a, tbx2b, and fgf1a. Gene expressions of ovarian aromatase and brain aromatase (cyp19a1a and cyp19a1b, respectively) decreased in the exposed groups, whereas ERs (esr1, esr2a, and esr2b) and nitric oxide synthase 2a (nos2a) increased. The effects on gene expression were also reversed by addition of ICI. Taken together, nitrate and nitrite disrupt cardiovascular system through ER in developing zebrafish, implying that environmental nitrate and nitrite contamination may be harmful to aquatic organisms.

Novel physiological analysis using blood flow velocity for colonic polyps: Pilot study.

Real-time visualization of red blood cell flow inside subepithelial microvessels is performed with magnifying endoscopy. However, microvascular blood flow velocity in the colorectum has not been investigated. Here, we aimed to evaluate the blood flow velocity of microvessels of colonic polyps and to compare it with that of surrounding mucosa. We examined 50 lesions, including 30 adenomas (ADs) and 20 hyperplastic polyps (HPs). Blood flow velocities of lesions and their surrounding mucosa were evaluated using magnifying blue laser imaging (BLI) prior to endoscopic resection. Calculation of mean blood flow velocities was based on mean movement distance of one tagged red blood cell using split video images of magnifying BLI. Mean microvascular blood flow velocity was significantly lower in ADs (1.65±0.66 mm/sec; range 0.46-2.90) than in HPs (2.83±1.10 mm/sec; 1.07-4.50) or the surrounding mucosa (3.73±1.11 mm/sec; 1.80-6.20; P <0.001). The blood flow velocity rate compared with the surrounding mucosa was significantly lower in ADs (0.41±0.16; 0.10-0.82) than in HPs (0.89±0.25; 0.46-1.51; P <0.001). We found that mean microvascular blood flow velocity was significantly lower in ADs than in HPs and the surrounding non-neoplastic mucosa. These findings indicate that a novel dynamic approach with microvascular blood flow velocity using magnifying endoscopy may be useful in assessing physiological differences between ADs and HPs.

Blood cell characterization based on deep learning and diffraction phase microscopy

Quantitative characterization of blood cells is very important for medical diagnosis and life science research. This study presents a novel label-free and high-throughput approach for analyzing flowing blood cells in a microfluidic channel by combining deep learning with partially coherent illumination-based diffraction phase microscopy (PCI-DPM). Diluted blood was injected into a microchannel and imaged with PCI-DPM, yielding high-contrast phase images for the blood cells. A modified YOLOv5-s neural network was used to perform automatic identification and analysis of blood cells in the phase image of PCI-DPM, revealing the diameter, dry mass, volumetric density, and speed of blood cells precisely. The proposed approach allows quick and accurate assessment of blood samples, providing valuable insights for patients in different pathological states, such as hematological disorders and infections.

Clinical application and development of OCT and OCTA in fundus diseases

Optical coherence tomography (OCT), which uses light wave as the imaging method, is a new medical imaging technology based on optical coherence. Optical coherence tomography angiography (OCTA) is a non-invasive imaging method gradually emerging in recent years. This technique can detect flowing blood and evaluate tissue morphology by detecting normal flow of red blood cells in blood vessels. Because of the advantages of high resolution, easy operation and three-dimensional imaging, it is widely used in the diagnosis and evaluation of fundus diseases (such as diabetic retinopathy, choroidal neovascularization, retinal vein occlusion, etc.). This article reviews the application status and progress of OCT and OCTA in clinical diagnosis and treatment of fundus diseases.

Confinement effect on the microcapillary flow and shape of red blood cells.

The ability to change shape is essential for the proper functioning of red blood cells (RBCs) within the microvasculature. The shape of RBCs significantly influences blood flow and has been employed in microfluidic lab-on-a-chip devices, serving as a diagnostic biomarker for specific pathologies and enabling the assessment of RBC deformability. While external flow conditions, such as the vessel size and the flow velocity, are known to impact microscale RBC flow, our comprehensive understanding of how their shape-adapting ability is influenced by channel confinement in biomedical applications remains incomplete. This study explores the impact of various rectangular and square channels, each with different confinement and aspect ratios, on the in vitro RBC flow behavior and characteristic shapes. We demonstrate that rectangular microchannels, with a height similar to the RBC diameter in combination with a confinement ratio exceeding 0.9, are required to generate distinctive well-defined croissant and slipper-like RBC shapes. These shapes are characterized by their equilibrium positions in the channel cross section, and we observe a strong elongation of both stable shapes in response to the shear rate across the different channels. Less confined channel configurations lead to the emergence of unstable other shape types that display rich shape dynamics. Our work establishes an experimental framework to understand the influence of channel size on the single-cell flow behavior of RBCs, providing valuable insights for the design of biomicrofluidic single-cell analysis applications.

Automatic identification and analysis of cells using digital holographic microscopy and Sobel segmentation

Counting and analyzing of blood cells, as well as their subcellular structures, are indispensable for understanding biological processes, studying cell functions, and diagnosing diseases. In this paper, we combine digital holographic microscopy with cell segmentation guided by the Sobel operator using Dice coefficients for automatic threshold selection and aimed to automatic counting and analysis of blood cells in flow and different kinds of cells in the static state. We demonstrate the proposed method with automatic counting and analyzing rat red blood cells (RBCS) flowing in a microfluidic device, extracting quickly and accurately the size, concentration, and dry mass of the sample in a label-free manner. The proposed technique was also demonstrated for automatic segmentation of different cell types, such as COS7 and Siha. This method can help us in blood inspection, providing pathological information in disease diagnosis and treatment.

Clinical relevance of transcranial Doppler in a cardiac surgery setting: embolic load predicts difficult separation from cardiopulmonary bypass

BackgroundDuring cardiac surgery, transcranial Doppler (TCD) represents a non-invasive modality that allows measurement of red blood cell flow velocities in the cerebral arteries. TCD can also be used to detect and monitor embolic material in the cerebral circulation. Detection of microemboli is reported as a high intensity transient signal (HITS). The importance of cerebral microemboli during cardiac surgery has been linked to the increased incidence of postoperative renal failure, right ventricular dysfunction, and hemodynamic instability. The objective of this study is to determine whether the embolic load is associated with hemodynamic instability during cardiopulmonary bypass (CPB) separation and postoperative complications.MethodsA retrospective single-centre cohort study of 354 patients undergoing cardiac surgery between December 2015 and March 2020 was conducted. Patients were divided in tertiles, where 117 patients had a low quantity of embolic material (LEM), 119 patients have a medium quantity of microemboli (MEM) and 118 patients who have a high quantity of embolic material (HEM). The primary endpoint was a difficult CPB separation. Multivariate logistic regression was used to determine the potential association between a difficult CPB separation and the number of embolic materials.ResultsPatients who had a difficult CPB separation had more HITS compared to patients who had a successful CPB separation (p < 0.001). In the multivariate analysis, patients with MEM decreased their odds of having a difficult CPB weaning compared to patients in the HEM group (OR = 0.253, CI 0.111–0.593; p = 0.001). In the postoperative period patients in the HEM group have a higher Time of Persistent Organ Dysfunction (TPOD), a longer stay in the ICU, a longer duration under vasopressor drugs and a higher mortality rate compared to those in the MEM and LEM groups.ConclusionThe result of this study suggests that a high quantity of cerebral embolic material increases the odds of having a difficult CPB separation. Also, it seems to be associated to more complex surgery, a longer CPB time, a higher TPOD and a longer stay in the ICU. Six out of eight patients who died in this cohort were in the HEM group.

Modeling Anisotropic Electrical Conductivity of Blood: Translating Microscale Effects of Red Blood Cell Motion into a Macroscale Property of Blood.

Cardiovascular diseases are a leading global cause of mortality. The current standard diagnostic methods, such as imaging and invasive procedures, are relatively expensive and partly connected with risks to the patient. Bioimpedance measurements hold the promise to offer rapid, safe, and low-cost alternative diagnostic methods. In the realm of cardiovascular diseases, bioimpedance methods rely on the changing electrical conductivity of blood, which depends on the local hemodynamics. However, the exact dependence of blood conductivity on the hemodynamic parameters is not yet fully understood, and the existing models for this dependence are limited to rather academic flow fields in straight pipes or channels. In this work, we suggest two closely connected anisotropic electrical conductivity models for blood in general three-dimensional flows, which consider the orientation and alignment of red blood cells (RBCs) in shear flows. In shear flows, RBCs adopt preferred orientations through a rotation of their membrane known as tank-treading motion. The two models are built on two different assumptions as to which hemodynamic characteristic determines the preferred orientation. The models are evaluated in two example simulations of blood flow. In a straight rigid vessel, the models coincide and are in accordance with experimental observations. In a simplified aorta geometry, the models yield different results. These differences are analyzed quantitatively, but a validation of the models with experiments is yet outstanding.

Automated Hematological Approach and Protein Electrophoretic Pattern in Tilapia (Oreochromis niloticus): An Innovative and Experimental Model for Aquaculture

This study aimed to assess the usefulness of two innovative automated methods (automated blood count counters and flow cytometry) for hematological investigation in Tilapia to make a contribution to the clinical diagnostics of this farmed species. Moreover, serum total proteins and their electrophoretic fractions (prealbumin, albumin, α-, β-, and γ-fraction), as health condition indicators, were assessed. The analysis of serum total proteins and electrophoretic fraction showed a normal and typical electrophoretic pattern of healthy fish (serum total proteins, 3.70 ± 0.62 g/dL; prealbumin, 0.44 ± 0.20 g/dL; albumin, 1.17 ± 0.66 g/dL; α-fraction, 1.49 ± 0.64 g/dL; β-fraction, 0.32 ± 0.16 g/dL; and γ-fraction, 0.29 ± 0.13 g/dL). The relationships between the values of red blood cells (RBCs), white blood cells (WBCs), and thrombocytes (TCs) obtained with the two automated methods were determined using Pearson correlation analysis. The results showed a significant positive correlation between automatic blood cell counting and flow cytometry analysis for RBCs (r = 0.97, p &lt; 0.0001) and WBCs (r = 0.91, p &lt; 0.0001), whereas no correlation was found for TCs (r = −0.11, p = 0.66). The preliminary results gathered in this study seem to highlight the usefulness of the new analytical techniques herein investigated in tilapia, suggesting their application in the hematological investigation of farmed fish species and their usefulness for monitoring the health and well-being of fish reared in aquaculture.

Local Dialogues Between the Endocrine and Exocrine Cells in the Pancreas.

For many years, it has been taught in medical textbooks that the endocrine and exocrine parts of the pancreas have separate blood supplies that do not mix. Therefore, they have been studied by different scientific communities, and patients with pancreatic disorders are treated by physicians in different medical disciplines, endocrinologists and gastroenterologists, respectively. The conventional model that every islet in each pancreatic lobule receives a dedicated arterial blood supply was first proposed in 1932 and it has been inherited to date. Recently, in vivo intravital recording of red blood cell flow in mouse islets as well as in situ structural analysis of 3D pancreatic vasculature from hundreds of islets provided evidence for preferentially integrated pancreatic blood flow in 6 mammalian species. The majority of islets have no association with the arteriole and there is bidirectional blood exchange between the two segments. Such vascularization may allow an entire downstream region of islets and acinar cells to be simultaneously exposed to a topologically and temporally specific plasma content, which could underlie an adaptive sensory function as well as common pathogeneses of both portions of the organ in pancreatic diseases including diabetes.

Morphology, repulsion, and ordering of red blood cells in viscoelastic flows under confinement.

Red blood cells (RBC), the primary carriers of oxygen in the body, play a crucial role across several biomedical applications, while also being an essential model system of a deformable object in the microfluidics and soft matter fields. However, RBC behavior in viscoelastic liquids, which holds promise in enhancing microfluidic diagnostic applications, remains poorly studied. We here show that using viscoelastic polymer solutions as a suspending carrier causes changes in the clustering and shape of flowing RBC in microfluidic flows when compared to a standard Newtonian suspending liquid. Additionally, when the local RBC concentration increases to a point where hydrodynamic interactions take place, we observe the formation of equally-spaced RBC structures, resembling the viscoelasticity-driven ordered particles observed previously in the literature, thus providing the first experimental evidence of viscoelasticity-driven cell ordering. The observed RBC ordering, unaffected by polymer molecular architecture, persists as long as the surrounding medium exhibits shear-thinning, viscoelastic properties. Complementary numerical simulations reveal that viscoelasticity-induced repulsion between RBCs leads to equidistant structures, with shear-thinning modulating this effect. Our results open the way for the development of new biomedical technologies based on the use of viscoelastic liquids while also clarifying fundamental aspects related to multibody hydrodynamic interactions in viscoelastic microfluidic flows.

Analysis of the Suitability of an Effective Viscosity to Represent Interactions Between Red Blood Cells in Shear Flow.

Many methods to computationally predict red blood cell damage have been introduced, and among these are Lagrangian methods that track the cells along their pathlines. Such methods typically do not explicitly include cell-cell interactions. Due to the high volume fraction of red blood cells (RBCs) in blood, these interactions could impact cell mechanics and thus the amount of damage caused by the flow. To investigate this question, cell-resolved simulations of red blood cells in shear flow were performed for multiple interacting cells, as well as for single cells in unbounded flow at an effective viscosity. Simulations run without adjusting the bulk viscosity produced larger errors unilaterally and were not considered further for comparison. We show that a periodic box containing at least 8 cells and a spherical harmonic of degree larger than 10 are necessary to produce converged higher-order statistics. The maximum difference between the single-cell and multiple-cell cases in terms of peak strain was 3.7%. To achieve this, one must use the whole blood viscosity and average over multiple cell orientations when adopting a single-cell simulation approach. The differences between the models in terms of average strain were slightly larger (maximum difference of 6.9%). However, given the accuracy of the single-cell approach in predicting the maximum strain, which is useful in hemolysis prediction, and its computational cost that is orders of magnitude less than the multiple-cell approach, one may use it as an affordable cell-resolved approach for hemolysis prediction.

Energy spectrum analysis on a red blood cell model.

It is important to understand the dynamics of red blood cells (RBCs) in blood flow. This requires the formulation of coarse-grained RBC models that reproduce the hydrodynamic properties of blood accurately. One of the models that successfully reproduces the rheology and morphology of blood has been proposed by Fedosov et al. [Comput. Methods Appl. Mech. Eng. 199, 1937-1948 (2010)]. The proposed RBC model contains several parameters whose values are determined by either various experiments or physical requirements. In this study, we developed a new method of determining parameter values precisely from the fluctuations of the RBC membrane. Specifically, we studied the relationship between the spectra of the fluctuations and model parameters. Characteristic peaks were observed in the spectra, whose peak frequencies were dependent on the parameter values. In addition, we investigated the spectra of the radius of gyration. We identified the peaks originating from the spring potential and the volume-conserving potential appearing in the spectra. These results lead to the precise experimental determination of the parameters used in the RBC model.

Analysis of the microcirculation state in children with acute bronchitis

Background. The purpose was to evaluate the peculiarities of microcirculation (MC) according to biomicroscopy data in respiratory diseases in children on a model of acute bronchitis. Materials and methods. The paper presents data on the study of MC in children with acute bronchitis (n = 30) compared with healthy individuals. The state of microcirculation was evaluated using nail bed biomicroscopy and by qualitative and semi-quantitative indicators. Results. In children with acute bronchitis compared to healthy persons, a number of changes were noted: in the arterioles — an increase in tortuosity, in the venular parts — the phenomena of sludge and spasms, in the capillaries — a decrease in the number of functioning microvessels and changes in their shape, slowing blood flow and sludging of red blood cells. Conclusions. Digital nail bed biomicroscopy in children is an accessible, simple and informative method for studying the state of MC in acute respiratory diseases. In acute bronchitis, even with a mild course, there are changes in the MC pattern at the level of all microvessels, with a predominance of changes in the capillaries.

Assessment of microcirculation variables and endothelial glycocalyx using sidestream dark field videomicroscopy in anesthetized dogs undergoing cardiopulmonary bypass.

To evaluate microcirculation and endothelial glycocalyx (eGC) variables using sidestream darkfield (SDF) videomicroscopy in canine cardiopulmonary bypass (CPB). Dogs undergoing CPB for surgical correction of naturally-occurring cardiac disease were prospectively included. Variables collected included patient demographics, underlying cardiac disease, red blood cell flow (Flow), 4-25 μm vessel density (Density), absolute capillary blood volume (CBVabs), relative capillary blood volume (CBVrel) and eGC width assessed by perfused boundary region (PBR). Anesthetized healthy dogs were used as control. Microcirculation and eGC variables were compared at baseline under anesthesia (T0), on CPB prior to cross clamping (T1), after cross clamp removal following surgical correction (T2) and at surgical closure (T3). Twelve dogs were enrolled, including 10 with a complete dataset. Median Flow was 233.9, 79.9, 164.3, and 136.1 μm/s at T0, T1, T2, and T3, respectively, (p = 1.00). Median Density was 173.3, 118.4, 121.0 and 155.4 mm/mm2 at T0, T1, T2, and T3, respectively, (p = 1.00). Median CBVabs decreased over time: 7.4, 6.6, 4.8 and 4.7 103μm3 at T0, T1, T2, and T3, respectively, (p < 0.01). Median CBVrel increased over time: 1.1, 1.5,1.1, and 1.3 103μm3 at T0, T1, T2, and T3, respectively, (p < 0.001). Median PBR increased over time: 1.8, 2.1, 2.4, 2.1 μm at T0, T1, T2, and T3, respectively, (p < 0.001). Compared to control dogs (n = 8), CPB dogs had lower CBVabs at T0. Alterations in eGC thickness and microvascular occur in dogs undergoing CPB for naturally-occurring cardiac disease.

Flow Heterogeneity and Factors Contributing to the Variability in Retinal Capillary Blood Flow.

Capillary flow plays an important role in the nourishment and maintenance of healthy neural tissue and can be observed directly and non-invasively in the living human retina. Despite their importance, patterns of normal capillary flow are not well understood due to limitations in spatial and temporal resolution of imaging data. Capillary flow characteristics were studied in the retina of three healthy young individuals using a high-resolution adaptive optics ophthalmoscope. Imaging with frame rates of 200 to 300 frames per second was sufficient to capture details of the single-file flow of red blood cells in capillaries over the course of about 3seconds. Erythrocyte velocities were measured from 72 neighboring vessels of the parafoveal capillary network for each subject. We observed strong variability among vessels within a given subject, and even within a given imaged field, across a range of capillary flow parameters including maximum and minimum velocities, pulsatility, abruptness of the systolic peak, and phase of the cardiac cycle. The observed variability was not well explained by "local" factors such as the vessel diameter, tortuosity, length, linear cell density, or hematocrit of the vessel. Within a vessel, a moderate relation between the velocities and hematocrit was noted, suggesting a redistribution of plasma between cells with changes in flow. These observations advance our fundamental understanding of normal capillary physiology and raise questions regarding the potential role of network-level effects in explaining the observed flow heterogeneity.

Developmental and cardiovascular toxicities of acetochlor and its chiral isomers in zebrafish embryos through oxidative stress

Acetochlor (ACT) is a widely used pesticide, yet the environmental and health safety of its chiral isomers remains inadequately evaluated. In this study, we evaluated the toxicity of ACT and its chiral isomers in a zebrafish model. Our findings demonstrate that ACT and its chiral isomers disrupt early zebrafish embryo development, inducing oxidative stress, abnormal lipid metabolism, and apoptosis. Additionally, ACT and its chiral isomers lead to cardiovascular damage, including reduced heart rate, decreased red blood cell (RBC) flow rate, and vascular damage. We further observed that (+)-S-ACT has a significant impact on the transcription of genes involved in cardiac and vascular development, including tbx5, hand2, nkx2.5, gata4, vegfa, dll4, cdh5, and vegfc. Our study highlights the potential risk posed by different conformations of chiral isomeric pesticides and raises concerns regarding their impact on human health. Overall, our results suggest that the chiral isomers of ACT induce developmental defects and cardiovascular toxicity in zebrafish, with (+)-S-ACT being considerably more toxic to zebrafish than (−)-R-ACT.