Motion Of Red Blood Cells Research Articles

Optical Microangiography: High-Definition Magnification Colonoscopy with Narrow Band Imaging (NBI) for Visualizing Mucosal Capillaries and Red Blood Cells in the Large Intestine

Recent advances in zoom endoscopy have enabled the subepithelial capillary network (SECN) in different organs of the gastrointestinal tract to be visualized. Ex vivo studies have suggested that the SECN demonstrates a honeycomb-like structure in the large intestine, but this has not yet been visualized in vivo. The high clarity and resolution of narrow-band imaging (NBI) may allow visualization at the single red-blood-cell (RBC) level and more accurate visualization of the SECN. We investigated whether high-definition magnification colonoscopy with NBI is useful for visualizing capillaries and RBCs in the large intestine. Sixteen patients with bowel symptoms undergoing routine colonoscopy with normal findings in a tertiary referral academic gastroenterology and endoscopy unit were included in the study. Total colonoscopies were performed using a high-definition magnification colonoscope (CF-H260AZI, Olympus, Tokyo) and a prototype high-definition electronic endoscopy system capable of NBI. Each part of the large intestine (cecum, ascending, transverse, descending, and sigmoid colon, and rectum) was observed at the maximum magnification with white-light imaging (WLI) and NBI. The normal honeycomb-like SECN and RBC movement by high-definition magnification colonoscopy with either WLI or NBI was prospectively successfully visualized for each part of the large intestine. In all subjects, high-definition magnification colonoscopy with NBI allowed the visualization of a honeycomb-like SECN together with RBC movement in each segment of the large intestine except for the rectum. In contrast, with WLI alone, neither this SECN structure nor RBC movement could be detected. High-definition magnification colonoscopy with NBI could be a new optical method for facilitating noninvasive investigations of both the microvascular architecture and microcirculation without the need for contrast materials.

Radial dispersion of red blood cells in blood flowing through glass capillaries: The role of hematocrit and geometry

The flow properties of blood in the microcirculation depend strongly on the hematocrit (Hct), microvessel geometry, and cell properties. Previous in vitro studies have measured the radial displacement of red blood cells (RBCs) at concentrated suspensions using conventional microscopes. However, to measure the RBCs motion they used transparent suspensions of ghost red cells, which may have different physical properties than normal RBCs. The present study introduces a new approach (confocal micro-PTV) to measure the motion of labeled RBCs flowing in concentrated suspensions of normal RBCs. The ability of confocal systems to obtain thin in-focus planes allowed us to measure the radial position of individual RBCs accurately and to consequently measure the interaction between multiple labeled RBCs. All the measurements were performed in the center plane of both 50 and 100 μm glass capillaries at Reynolds numbers ( Re) from 0.003 to 0.005 using Hcts from 2% to 35%. To quantify the motion and interaction of multiple RBCs, we used the RBC radial dispersion ( D yy ). Our results clearly demonstrate that D yy strongly depends on the Hct. The RBCs exhibited higher D yy at radial positions between 0.4 and 0.8 R and lower D yy at locations adjacent to the wall (0.8–1 R) and around the middle of the capillary (0–0.2 R). The present work also demonstrates that D yy tends to decrease with a decrease in the diameter. The information provided by this study not only complements previous investigations on microhemorheology of both dilute and concentrated suspensions of RBCs, but also shows the influence of both Hct and geometry on the radial dispersion of RBCs. This information is important for a better understanding of blood mass transport mechanisms under both physiological and pathological conditions.

Dragging Along

See related article, pages 770–776 The glycocalyx is a complex and highly dynamic polymeric meshwork that coats the surfaces of most cells and consists of proteoglycans, glycosaminoglycans (GAGs), and glycoproteins, as well as adherent plasma proteins.1,2 In the microvasculature, the glycocalyx layer on the endothelial cell surface plays a critical role in regulating vessel permeability, modulating the dynamics of near-wall movement of red blood cells, and coordinating interactions between leukocytes and the vascular wall during inflammation. In large-vessel endothelium, perturbation of the glycocalyx appears to be associated with vascular damage, as well as increased vulnerability to the development of atherosclerosis.3–5 A number of studies have demonstrated that the presence of an intact glycocalyx is essential for endothelial cell sensitivity and responsiveness to fluid mechanical stimulation, thereby supporting the idea of a central role for the glycocalyx in endothelial cell flow-mediated mechanotransduction.6–12 In this issue of Circulation Research , Potter and Damiano13 use fluorescent microparticle image velocimetry (μ-PIV) to demonstrate that the hydrodynamically relevant endothelial cell glycocalyx surface layer observed in vivo in mouse cremaster muscle venules is absent from the surfaces of human umbilical vein endothelial cells (HUVECs) and bovine aortic endothelial cells (BAECs) grown in circular collagen microchannels and maintained in vitro under standard cell culture conditions. The μ-PIV technique allows the measurement of the velocity profile of fluid flow within the venule or microchannel. A linear regression analysis of the near-wall velocity is performed, and the resulting fit is extrapolated to the venule or microchannel wall. If this extrapolation leads to a negative velocity at the wall, …

Liver Microcirculation Analysis by Red Blood Cell Motion Modeling in Intravital Microscopy Images

Intravital microscopy has been used to visualize the microcirculation by imaging fluorescent labeled red blood cells (RBCs). Traditionally, microcirculation has been modeled by computing the mean velocity of a few, randomly selected, manually tracked RBCs. However, this protocol is tedious, time consuming, and subjective with technician related bias. We present a new method for analyzing the microcirculation by modeling the RBC motion through automatic tracking. The tracking of RBCs is challenging as in each image, as many as 200 cells move through a complex network of vessels at a wide range of speeds while deforming in shape. To reliably detect RBCs traveling at a wide range of speeds, a window of temporal template matching is applied. Then, cells appearing in successive frames are corresponded based on the motion behavior constraints in terms of the direction, magnitude, and path. The performance evaluation against a ground truth indicates the detection accuracy up to 84% TP at 6% FP and a correspondence accuracy of 89%. We include an in-depth discussion on comparison of the microcirculation based on motion modeling from the proposed automated method against a mean velocity from manual analysis protocol in terms of precision, objectivity, and sensitivity.

Point:Counterpoint: There is/is not capillary recruitment in active skeletal muscle during exercise

#### Focus. The key issue here is whether resting skeletal muscle is fully perfused. We will make the case that it is not, and thus there exists a reserve of unperfused capillaries (capillary reserve) that are recruited to carry flow not only by muscle contraction, but also by insulin. #### Our

Two-Dimensional Simulation of Red Blood Cell Deformation and Lateral Migration in Microvessels

A theoretical method is used to simulate the motion and deformation of mammalian red blood cells (RBCs) in microvessels, based on knowledge of the mechanical characteristics of RBCs. Each RBC is represented as a set of interconnected viscoelastic elements in two dimensions. The motion and deformation of the cell and the motion of the surrounding fluid are computed using a finite-element numerical method. Simulations of RBC motion in simple shear flow of a high-viscosity fluid show "tank-treading'' motion of the membrane around the cell perimeter, as observed experimentally. With appropriate choice of the parameters representing RBC mechanical properties, the tank-treading frequency and cell elongation agree closely with observations over a range of shear rates. In simulations of RBC motion in capillary-sized channels, initially circular cell shapes rapidly approach shapes typical of those seen experimentally in capillaries, convex in front and concave at the rear. An isolated RBC entering an 8-mum capillary close to the wall is predicted to migrate in the lateral direction as it traverses the capillary, achieving a position near the center-line after traveling a distance of about 60 mum. Cell trajectories agree closely with those observed in microvessels of the rat mesentery.

Mesoscale Simulation of Blood Flow in Small Vessels

Computational modeling of blood flow in microvessels with internal diameter 20–500 μm is a major challenge. It is because blood in such vessels behaves as a multiphase suspension of deformable particles. A continuum model of blood is not adequate if the motion of individual red blood cells in the suspension is of interest. At the same time, multiple cells, often a few thousands in number, must also be considered to account for cell-cell hydrodynamic interaction. Moreover, the red blood cells (RBCs) are highly deformable. Deformation of the cells must also be considered in the model, as it is a major determinant of many physiologically significant phenomena, such as formation of a cell-free layer, and the Fahraeus-Lindqvist effect. In this article, we present two-dimensional computational simulation of blood flow in vessels of size 20–300 μm at discharge hematocrit of 10–60%, taking into consideration the particulate nature of blood and cell deformation. The numerical model is based on the immersed boundary method, and the red blood cells are modeled as liquid capsules. A large RBC population comprising of as many as 2500 cells are simulated. Migration of the cells normal to the wall of the vessel and the formation of the cell-free layer are studied. Results on the trajectory and velocity traces of the RBCs, and their fluctuations are presented. Also presented are the results on the plug-flow velocity profile of blood, the apparent viscosity, and the Fahraeus-Lindqvist effect. The numerical results also allow us to investigate the variation of apparent blood viscosity along the cross-section of a vessel. The computational results are compared with the experimental results. To the best of our knowledge, this article presents the first simulation to simultaneously consider a large ensemble of red blood cells and the cell deformation.

Red Blood Cells and Other Nonspherical Capsules in Shear Flow: Oscillatory Dynamics and the Tank-Treading-to-Tumbling Transition

We consider the motion of red blood cells and other nonspherical microcapsules dilutely suspended in a simple shear flow. Our analysis indicates that depending on the viscosity, membrane elasticity, geometry, and shear rate, the particle exhibits either tumbling, tank-treading of the membrane about the viscous interior with periodic oscillations of the orientation angle, or intermittent behavior in which the two modes occur alternately. For red blood cells, we compute the complete phase diagram and identify a novel tank-treading-to-tumbling transition as the shear rate decreases. Observations of such motions coupled with our theoretical framework may provide a sensitive means of assessing capsule properties.

A203 Blood Cell Motions and Interactions in Microchannels

Detailed knowledge on the motions and interactions of individual blood cells flowing in microchannels is essential to provide a better understanding on the blood rheological properties and disorders in microvessels. This paper presents the ability of a confocal micro-PTV system to track red blood cells (RBCs) through a 100 μm circular glass microchannel. The technique consists of a spinning disk confocal microscope, high speed camera and a diode-pumped solid state (DPSS) laser combined with a single particle tracking (SPT) software (MtrackJ). Detailed measurements on the motions of RBCs were measured at different haematocrits (Hct). Our results show clearly that this technique can provide detailed information about microscale disturbance effects caused by the blood cells.1) Goldsmith, H.: Red cell motions and wall interactions in tube flow, Federation Proceedings, Vol. 30, No.5 (1971) pp. 1578-1588.2) Goldsmith, H. and Marlow J.: Flow behavior of erythrocytes. 11. Particles motions in concentrated suspensions of ghost cells, Journal of Colloid and Interface Science, Vol. 71, No. 2 (1979) pp. 383-407.3) Lima, R., et al.: Confocal micro-PIV measurements of three dimensional profiles of cell suspension flow in a square microchannel, Meas. Sci. Tech., Vol. 17, (2006) pp. 797-808.4) Lima, R., et al., In vitro confocal micro-PIV measurements of blood flow in a square microchannel: the effect of the haematocrit on instantaneous velocity profiles, J. Biomech., (in press).5) Abramoff, M., et al.: Image processing with lmageJ, Biophotonics International, Vol. 11, No. 7 (2004) pp. 36-42.6) Meijering, E., et al.: Tracking in Molecular Bioimaging, , IEEE Signal Processing Magazine, Vol 23. No. 3 (2006) pp. 46-53.

High Speed Digital Video Capillaroscopy: Nailfold Capillary Shape Analysis and Red Blood Cell Velocity Measurement

Nailfold capillaroscopy has been shown to reflect microvascular disturbances mainly in connective tissue diseases, and the development of video capillaroscopy made it possible to determine capillary red blood cell velocity by measuring the displacement of plasma gaps between red cells. We improved both temporal and spatial resolutions of video capillaroscopy by developing the high speed digital video capillaroscopy, integrating high speed digital video camera, deep-focus zoom lens, appropriate light source and light collecting adaptor. The first objective of this study is to present the novel method for quantitative capillary shape analysis by using the level-set method. The capillary radius distribution along the capillary center line is obtained and described by the level-set function. Based on this mathematical description of capillary shape, more rigorous definition of the capillary red blood cell velocity than the conventional method is discussed. The second objective of this study is to propose the innovative measurement method of red blood cell velocity in nailfold capillary, and then the possibility of tracking the individual red blood cell movement, not only in the axial direction but also lateral direction, in human nailfold capillary is discussed

Theoretical model and experimental study of red blood cell (RBC) deformation in microchannels

The motion and deformation of red blood cells (RBCs) flowing in a microchannel were studied using a theoretical model and a novel automated rheoscope. The theoretical model was developed to predict the cells deformation under shear as a function of the cells geometry and mechanical properties. Fluid dynamics and membrane mechanics are incorporated, calculating the traction and deformation in an iterative manner. The model was utilized to evaluate the effect of different biophysical parameters, such as: inner cell viscosity, membrane shear modulus and surface to volume ratio on deformation measurements. The experimental system enables the measurement of individual RBCs velocity and their deformation at defined planes within the microchannel. Good agreement was observed between the simulation results, the rheoscope measurements and published ektacytometry results. The theoretical model results imply that such deformability measuring techniques are weakly influenced by changes in the inner viscosity of the cell or the ambient fluid viscosity. However, these measurements are highly sensitive to RBC shear modulus. The shear modulus, estimated by the model and the rheoscope measurements, falls between the values obtained by micropipette aspiration and laser trapping. The study demonstrates the integration of a theoretical model with a microfabricated device in order to achieve a better understanding of RBC mechanics and their measurement using microfluidic shear assays. The system and the model have the potential of serving as quantitative clinical tools for diagnosing deformability disorders in RBCs.

A Hemodynamic Study on a Marginal Cell Depletion Layer of Blood Flow Inside a Microchannel

Biological flows, especially blood flow, have attracted a great deal of attention from fluid engineering and hemodynamic investigation fields with advances in bio-technology. The flow of blood carries dissolved gases, nutrients, hormones, and metabolic waste through the circulatory system in the human body. In the present study, the characteristics of blood flow inside a microchannel are investigated by using a micro-particle image velocimetry (micro-PIV) and an optical image processing technique. The motion of red blood cells (RBCs) was visualized with a high-speed CCD camera. The microchannel is made of polydimethylsiloxane (PDMS) material and a slide-glass is attached to the top. The thickness of the margin cell depletion layer is calculated from an acquired raw image through the image processing method, with variations in microchannel width.

Particle method for computer simulation of red blood cell motion in blood flow

A particle method for the computer simulation of blood flow was proposed to analyze the motion of a deformable red blood cell (RBC) in flowing blood plasma. The RBC and plasma were discretized by particles that have the characteristics of an elastic membrane and a viscous fluid, respectively. The membrane particles were connected to their neighboring membrane particles by springs, and the motion of the particles was determined on the basis of the minimum energy principle. The incompressible flow of plasma that was expressed by the motion of the fluid particles was determined by the moving-particle semi-implicit (MPS) method. The RBC motion and plasma flow were weakly coupled. The two-dimensional simulation of blood flow between parallel plates demonstrated the capability of the proposed method to express the blood flow phenomena observed in experiments, such as the downstream motion of the RBC and the deformation of the RBC into a parachute shape.

Application of Chimera grid to modelling cell motion and aggregation in a narrow tube.

A computational scheme using the Chimera grid method is presented for simulation of three-dimensional motion and aggregation of two red blood cells (RBCs) in a narrow tube. The cells are modelled as rigid ellipsoidal particles; the computational scheme is applicable to deformable fluid-filled particles. Attractive energy between two RBCs is modelled by a depletion interaction theory and used for simulating aggregation of two cells. Through the simulation, we show that the Chimera grid method is applicable to the simulation of three-dimensional motion and aggregation of multiple RBCs in a microvessel and microvascular network.

Simulation of red blood cell deformation and radial migration in microvessels

The width of the cell-free layer near walls of microvessels strongly influences the resistance to blood flow in microvessels. However, the radial migration of red blood cells in flowing blood is not well understood from a mechanical viewpoint. Here, a theoretical method is used to simulate the motion and deformation of mammalian red blood cells in microvessels. Each red blood cell is represented as a set of interconnected viscoelastic elements in two dimensions. The motion and deformation of the cell in a microvessel and the motion of the surrounding plasma is computed using a finite-element numerical method. In simulations of red blood cell motion in capillary-sized channels, initially circular cell shapes rapidly approach shapes typical of those seen experimentally in capillaries, convex in front and convex at the rear. An isolated red blood cell entering an 8-μm capillary close to the wall is predicted to migrate in the radial direction as it traverses the capillary, achieving a position near the center-line after traveling a distance of about 60 μm. Cell trajectories agree closely with those observed in microvessels of the rat mesentery. Supported by NIH grant HL34555.

Simulation Study on Effects of Deformabilities of Red Blood Cells on Blood Flow Using Particle Method

A computer simulation using particle method was carried out to investigate effects of deformabilities of red blood cells (RBCs) on blood flow in microcirculation. The motion of deformable RBCs was determined by the spring model on the basis of the minimum energy principle. The motion of the plasma fluid particles was analyzed by the moving-particle semi-implicit (MPS) method assuming incompressible viscous flow. The two-dimensional simulation of blood flow between parallel plates demonstrated that RBCs moved downstream and were deformed into a parachute shape as observed in experiments. Comparison between the results for single RBC and multiple RBCs clarified that the deformation of RBCs was suppressed by their neighboring RBCs. The higher the spring constants of the RBC model, the less deformed the RBCs were, causing large blood flow resistance. These results indicate that deformability of each RBC cooperates with mechanical interaction between RBCs in determining the rheological properties of blood on blood cellular scale.

Computational Blood Flow Analysis -New Trends and Methods

Over the past few decades, a large number of novel numerical methods have been proposed to analyze blood flows and to understand the relationship between vascular diseases and hemodynamics. In this paper, we review recent computational fluid dynamics studies on macroscale hemodynamics such as blood flow in the heart and large arteries, microscale blood flows in small vessels in which blood is assumed to be a suspension of red blood cells in plasma, and single red blood cell motions in an induced flow field. The advantages and disadvantages of numerical methods are discussed, and current trends in these research fields are introduced.

Simulation Study on Effects of Hematocrit on Blood Flow Properties Using Particle Method

The effects of hematocrit (Hct) on blood flow in microcirculation were investigated by computer simulation using a particle method. Deformable red blood cells (RBCs) and blood plasma were modeled by assembly of discrete particles. It was assumed that an RBC consisted of an elastic membrane and inner viscous fluid, and that plasma was viscous fluid. The particles for the RBC membrane were connected with their neighboring membrane particles by stretch/compression and bending springs. The motion of all the particles that was subjected to incompressible viscous flow was solved by the moving particle semi-implicit (MPS) method based on Navier-Stokes (NS) equations. The forces induced by the springs to express the elastic RBC membrane were substituted into the NS equations as the external force, which enabled coupled analysis of elastic RBC motion and plasma fluid flow. Two-dimensional simulations of blood flow between parallel plates were carried out for various Hct values. As a result, it was shown that at higher Hct, RBCs were less deformed into a parachute shape during their downstream motion, indicating that mechanical interaction between RBCs restricted the RBC deformation. Mechanical interaction between RBCs had a significant influence on RBC deformation and the velocity profile of plasma flow when the Hct value was more than 0.20∼0.30. Apparent blood flow resistance increased with Hct, corresponding to previously reported in vitro experimental results compiled to an empirical formula.

MICROSCOPIC-SCALE SIMULATION OF BLOOD FLOW USING SPH METHOD

We have developed a microscopic blood model based on the Smoothed Particle Hydrodynamics (SPH) method. In the model, plasma fluid is discretized by SPH particles, and a red blood cell (RBC) is expressed by internal SPH particles surrounded by elastic membrane particles. For verifying the model, we numerically analyzed two popular phenomena of blood flow. One is the tank-tread motion of an RBC under a constant shear field. The numerical results are agreed well with the experimental data and the tank-tread motion of RBC is well reproduced. The other is the axial migration or pinch effect of RBCs in Poiseuille flow. From the numerical results, we find that the axial migration effect becomes weaker as the viscosity of cell internal fluid becomes higher. The reason is because the RBC motion changes from tank-tread motion to rigid body rotation (from axial migration effect to pinch effect) as the cell contents become thick. From these results, it is confirmed that our blood model based on the SPH method can well express microscopic and rheological properties of RBCs.

Computer Modeling of Red Blood Cell Rheology in the Microcirculation: A Brief Overview

One of the major functions of the cardiovascular system is to deliver blood to the microcirculation where exchange of mass and energy can take place. In the present article, we will provide an overview of the state-of-the-art computational methods for modeling of red blood cell (RBC) rheology and dynamics in the microcirculation. While significant progress has been made in simulation of single-file motion of deformable RBCs in capillaries and of diluted sheared suspensions of RBCs in infinite domains, detailed understanding of the mechanics of blood flow in intermediate diameter microvessels (8-1,000 microm) has presented formidable challenges. The difficulties are largely due to modeling the motion of multiple, interacting, highly deformable particles. The current computational tools consist mainly of three-dimensional (3D) boundary-integral methods for single RBC dynamics and deformation; and for rheology of large systems of droplets at large volume fractions using periodic boundary conditions and novel adaptive computational meshes. Further advances will result from combination of these tools to produce new algorithms capable of describing the motion and deformation of large systems of RBCs in microvessels at physiologically relevant volume fractions.