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It has been shown that Ginkgo biloba Extract (EGb 761) increases peripheral and cerebral blood flow and microcirculation and improves myocardial ischemia reperfusion injury. This study was designed to investigate the effect of EGb 761 on hepatic endothelial cells and hepatic microcirculation. Sixty male Wister rats were divided into normal, carbon tetrachloride (CCl₄) and EGb groups, and were given normal saline, CCl₄ and CCl₄ plus EGb 761, respectively, for 10 weeks. Samples were taken from the medial lobe of the rat livers ten weeks later. Hepatic sinusoidal endothelial cells and other parameters of hepatic microcirculation were observed under transmission electron microscopy (TEM). The amount of malondialdehyde (MDA), endothelin (ET-1), platelet-activating factor (PAF) and nitric oxide (NO) in liver tissue was determined by spectrophotometry and radioimmunoassay, respectively. Compared with the CCl₄ group, aggregation of blood cell or micro thrombosis in hepatic sinusoids, deposition of collagen in hepatic sinusoids and space of Disse, injury of endothelial cells and capillization of hepatic sinusoid was significantly reduced in the EGb group. The amount of MDA, ET-1 and PAF was markedly reduced in the EGb group than in the CCl₄ group, while no significant difference in the amount of NO was observed between the two groups. The results demonstrate that EGb 761 has protective effect on hepatic endothelial cells and hepatic microcirculation in rats with chronic liver injury induced by CCl₄. The mechanisms may involve its inhibition on ET-1, PAF and lipid peroxidation.

The intestine plays a vital role in the pathophysiology of sepsis development. The objective of the present study was to explore the effects of rhubarb on intestinal microcirculation in septic rats. We used moorFLPI laser speckle imaging to detect the blood flow of the intestinal mucosa and wall. Using an ELISA, we assayed the concentration of lactate (L) and pyruvic acid (P) in the intestinal tissue to calculate the ratio of lactate to pyruvic acid (L/P ratio). To observe the intestinal mucosal capillaries, gelatin and ink were perfused into the intestine and subsequently stained with hematoxylin and eosin (HE) to measure the ratio of the vessel area. We then used immunohistochemistry to measure CD31 expression. Using an MTT assay, the effect of the rhubarb extract on the proliferation of human umbilical vein endothelial cells (HUVECs) was analyzed. The blood flow in the intestinal wall and mucosa of the control, sham and rhubarb-treated groups was significantly higher, while the sepsis group had relatively low blood flow. The L/P ratio in the intestinal tissue was larger in the sepsis group than in the other three groups. The microvascular area (MVA) in the sepsis group was smaller than in the control group, sham group or rhubarb group. Positive expression for CD31 was observed in the cytoplasm of vascular endothelial cells. The intestinal mucosal capillaries were reduced in septic rats as compared to the other three groups. HUVEC proliferation was enhanced by the rhubarb extract monomers at 1 μmol/L, but suppressed at higher concentrations of 10 to 100 μmol/L. These results suggest that pre-treatment with rhubarb prior to sepsis induction promotes the expansion of the intestinal mucosal capillaries, protects intestinal mucosal capillary endothelial cells and increases the number of functional intestinal capillaries.

We have determined the wavelet phase coherence between simultaneously recorded microvascular blood flow and oxygen saturation signals from 88 healthy subjects, thus enabling us to study their common fluctuations. Measurements were taken for 30 min from the arm and leg, at two depths. In the skin, blood flow and oxygen saturation were found to be coherent both at the cardiac frequency and below 0.1 Hz down to about 0.01 Hz. Coherence in the arm extends to lower frequencies than that in the leg. From the deeper recordings, no coherence was found on either limb. The existence of coherence between skin blood flow and oxygen saturation demonstrates causal connections between them within certain frequency ranges. The method has yielded the first detailed insight into the dynamics of blood oxygenation.

This paper presents a mathematical model and a computational framework for the resolution of large networks of distensible blood microvessels characterized by a hierarchy of different diameters. We analyze the contribution of different distensibility relations, representing both active and passive responses in the case of the microvascular network in the eye retina. Model predictions indicate that, depending on the geometrical (hierarchical) location in the network, distensibility effects may be significantly different and lead, over long times, to possible geometrically-driven remodeling processes.

This paper is aimed at examining the effect of convection–diffusion on oxygen transport at the micro-level. A coupled model of the convection–diffusion and molecular diffusion of oxygen is developed, and the solid deformation resulting from capillary fluctuations and the seepage of tissue fluid are incorporated into this model. The results indicate that (1) the oxygen concentration calculated from this coupled model is higher than that given by molecular diffusion models, both within the capillaries and tissue (maximum difference of 16%); (2) convection–diffusion has the greatest effect in tissue surrounding the middle of the capillary, and enhances the amount of oxygen transported to cells far from the oxygen source; (3) larger permeability coefficients or smaller diffusion coefficients produce a more obvious convection–diffusion effect; (4) a counter-current flow occurs near the inlet and outlet ends of the capillary. This model also provides a foundation for the study of how oxygen affects tumor growth.

It is generally assumed that influence of the red blood cells (RBCs) is predominant in blood rheology. The healthy RBCs are highly deformable and can thus easily squeeze through the smallest capillaries having internal diameter less than their characteristic size. On the other hand, RBCs infected by malaria or other diseases are stiffer and so less deformable. Thus it is harder for them to flow through the smallest capillaries. Therefore, it is very important to critically and realistically investigate the mechanical behavior of both healthy and infected RBCs which is a current gap in knowledge. The motion and the steady state deformed shape of the RBCs depend on many factors, such as the geometrical parameters of the capillary through which blood flows, the membrane bending stiffness and the mean velocity of the blood flow. In this study, motion and deformation of a single two-dimensional RBC in a stenosed capillary is explored by using smoothed particle hydrodynamics (SPH) method. An elastic spring network is used to model the RBC membrane, while the RBC's inside fluid and outside fluid are treated as SPH particles. The effect of RBC's membrane stiffness (k_b), inlet pressure (P) and geometrical parameters of the capillary on the motion and deformation of the RBC is studied. The deformation index, RBC's mean velocity and the cell membrane energy are analyzed when the cell passes through the stenosed capillary. The simulation results demonstrate that the k_b, P and the geometrical parameters of the capillary have a significant impact on the RBCs' motion and deformation in the stenosed section.

This study focuses on the movement of particles and extracellular fluid in soft tissues and microvessels. It analyzes modeling applications in biological and physiological fluids at a range of different length scales: from between a few tens to several hundred nanometers, on the endothelial glycocalyx and its effects on interactions between blood and the vessel wall; to a few micrometers, on movement of blood cells in capillaries and transcapillary exchange; to a few millimetres and centimetres, on extracellular matrix deformation and interstitial fluid movement in soft tissues. Interactions between blood cells and capillary wall are discussed when the sizes of the two are of the same order of magnitude, with the glycocalyx on the endothelial and red cell membranes being considered. Exchange of fluid, solutes, and gases by microvessels are highlighted when capillaries have counter-current arrangements. This anatomical feature exists in a number of tissues and is the key in the renal medulla on the urinary concentrating mechanism. The paper also addresses an important phenomenon on the transport of macromolecules. Concentration polarization of hyaluronan on the synovial lining of joint cavities is presented to demonstrate how the mechanism works in principle and how model predictions agree to experimental observations quantitatively.

Diabetic neuropathy (DN) is, at least in part, associated with the functional attenuation of vasa nervorum, the microvascular structure of peripheral nerves. Microvascular imaging options for vasa nervorum still remain limited. In this work, optical microangiography (OMAG), a volumetric, label-free imaging technique, is utilized for characterizing, with high resolution, blood perfusion of peripheral nerve in diabetic mice. We demonstrate that OMAG is able to visualize the structure of microvasculature and to quantify the changes of dynamic blood flow and vessel diameters during administration of vessel stimulant in both diabetic and normal mice. The results indicate the potential of OMAG to assess the blood supply of nerve involved in the pathology and treatment of DN.

The wireless distributed acquisition system for near infrared spectroscopy (WDA-NIRS) is a portable, ultra-compact, continuous wave (CW) NIRS system. Its main advantage is that it allows continuous synchronized multi-site hemodynamic monitoring. The WDA-NIRS system calculates online changes in hemoglobin concentration based on modified Beer–Lambert law and the tissue oxygenation index based on the spatial-resolved spectroscopy method. It consists of up to seven signal acquisition units, sufficiently small to be easily attached to any part of the body. These units are remotely synchronized by a PC base station for independent acquisition of NIRS signals. Each acquisition module can be freely adapted to individual requirements such as local skin properties and the microcirculation of interest, e.g., different muscles, brain, skin, etc. For this purpose, the light emitted by each LED can be individually, interactively or automatically adjusted to local needs. Furthermore, the user can freely create an emitter time-multiplexing protocol and choose the detector sensitivity most suitable to a particular situation. The potential diagnostic value of this advanced device is demonstrated by three typical applications.

The influence of ischemia–reperfusion (I/R) action on pancreatic blood flow (PBF) and the development of acute pancreatitis (AP) in laboratory rats is evaluated in vivo by using the laser speckle contrast imaging (LSCI). Additionally, the optical properties in norm and under condition of AP in rats were assessed using a modified integrating sphere spectrometer and inverse Monte Carlo (IMC) software. The results of the experimental study of microcirculation of the pancreas in 82 rats in the ischemic model are presented. The data obtained confirm the fact that local ischemia and changes in the blood flow velocity of the main vessels cause and provoke acute pancreatitis.

Laser speckle contrast imaging (LSCI) is a noninvasive, label-free technique that allows real-time investigation of the microcirculation situation of biological tissue. High-quality microvascular segmentation is critical for analyzing and evaluating vascular morphology and blood flow dynamics. However, achieving high-quality vessel segmentation has always been a challenge due to the cost and complexity of label data acquisition and the irregular vascular morphology. In addition, supervised learning methods heavily rely on high-quality labels for accurate segmentation results, which often necessitate extensive labeling efforts. Here, we propose a novel approach LSWDP for high-performance real-time vessel segmentation that utilizes low-quality pseudo-labels for nonmatched training without relying on a substantial number of intricate labels and image pairing. Furthermore, we demonstrate that our method is more robust and effective in mitigating performance degradation than traditional segmentation approaches on diverse style data sets, even when confronted with unfamiliar data. Importantly, the dice similarity coefficient exceeded 85% in a rat experiment. Our study has the potential to efficiently segment and evaluate blood vessels in both normal and disease situations. This would greatly benefit future research in life and medicine.

Pulse parameters calculated from the LDF waveform based on a time-domain synchronized averaging analysis were shown to be able to discriminate the difference in microvascular resistance. However, its applicability may depend on the validation of signal stationarity. In this study, our aim is to investigate the effect of pulse number, which may destroy the signal stationarity, on various pulse LDF parameters. Analysis was performed in data obtained on healthy volunteers. When one pulse parameter is deviated from the standard value for more than 10%, it was regarded as an error; EP (error probability) was then defined as the occurring probability of error. It was revealed in this study that average parameter deviations for FDT and PDT were smaller than 5% for all tested pulse numbers. If we set 10% as the parameter-deviation criterion as well as the acceptable EP range, there should be at least 120 pulses for FDT and PDT, and 210 pulses for FNA and PW. The study presented here has established the criteria for appropriate pulse number to achieve the signal stationarity; we can thus get accurate pulse parameters so that the microcirculatory discriminability of the pulse-based time-averaging analysis on LDF signal can be improved. The proposed quantitative method to verify the validation of signal stationarity when utilizing time-averaging can also be applied to analysis of other bio-signals.

Vascular complications are responsible for most of the morbidity and mortality in diabetic patients. Effective strategies to improve circulation appear to be another important issue in addition to the interventions of blood glucose control. Previous studies have shown that the biological effects on humans after using the materials containing ceramic particles emits far infrared radiation (FIR). The present study is to investigate the warming effect of the fabrics containing specified metals in diabetic patients. A total of 28 diabetic patients were blinded and randomly assigned to treatment group ($N=18$) and control group ($N=10$), respectively. The subjects of treatment group were ministered with the blankets with fibers containing the specified metals, while the subjects of control group were provided with blankets of ordinary material. The skin temperature and microcirculatory perfusion were monitored before and after 20-min use of the blankets at shoulder and bilateral calves. After warming with blankets, the treatment group revealed a higher increased ratio of skin perfusion than control ($p<0.05$), while there was no prominent variation on the wavelet spectrum of the perfusion signal. Although it is already a known fact that passive FIR warming has the advantages of safety and convenience, our results suggest that warming by wearing the textiles containing the specified metals with high FIR emissivity is a solution for daily skin care of diabetic patients.

We have determined the wavelet phase coherence between simultaneously recorded microvascular blood flow and oxygen saturation signals from 88 healthy subjects, thus enabling us to study their common fluctuations. Measurements were taken for 30min from the arm and leg, at two depths. In the skin, blood flow and oxygen saturation were found to be coherent both at the cardiac frequency and below 0.1Hz down to about 0.01Hz. Coherence in the arm extends to lower frequencies than that in the leg. From the deeper recordings, no coherence was found on either limb. The existence of coherence between skin blood flow and oxygen saturation demonstrates causal connections between them within certain frequency ranges. The method has yielded the first detailed insight into the dynamics of blood oxygenation.

Microcirculation plays a direct role in the accomplishment of the principal purpose of the circulation system. The functions of the microcirculation incorporates oxygen supply, transport, diffusion, and exchange of nutrients and metabolites between blood and tissue, maintenance of body temperature, regulation of blood pressure, tissue defense and repair. These complex functions are carried out in the microcirculation by a number of dynamic changes in the blood within the vessels, the vessels themselves or the tissues surrounding the vessels. Intravital microscopic approaches have greatly contributed to the advancement of research in the fields of microcirculation. The techniques represent the only method that allows direct visualization and quantitative analysis of the microcirculation. In this chapter in vivo microscopic techniques with useful experimental models, which provide significant information regarding the microcirculation, are introduced.

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is the rapid acquisition of serial MRI images before, during, and after the administration of an MR contrast agent. Unlike conventional enhanced MRI, which simply provides a snapshot of enhancement at one point in time, DCE-MRI permits a fuller depiction of the wash-in and wash-out contrast kinetics, and thus provides insight into the microcirculation of the studied tissues or lesions. With the dynamic signal intensity change post-contrast agent injection, empirical measures such as maximal signal intensity enhancement and initial enhancement slope can be easily obtained. Such data are also amenable to two-compartment pharmacokinetic modeling, from which parameters based on the rates of exchange between the compartments can be generated. DCE-MRI can be used to characterize masses, stage tumors, and noninvasively monitor therapy. Measures of contrast uptake by dynamic MRI have demonstrated a convincing ability to aid in diagnosing the presence of viable tumors and to measure the response for arange of human tumors. While questions remain about how to best extract noninvasive pharmacokinetic measures of drug access from these novel dynamic imaging methods, scientists and clinicians are optimistic that these methods can provide important new clinical measures which reflect the range of biological variations within and between naturally occurring solid tumors. Efforts to standardize DCE-MRI acquisition, analysis, and reporting methods will allow wider dissemination of this useful functional imaging technique.

Cardiovascular disease has become one of the most serious diseases which not only endangers human health, but also causes death. The microcirculatory hemodynamic parameters contain abundant cardiovascular information. Through hemodynamic detection, cardiovascular health status can be understood. Results: The data measured by the fingertip pulse wave detection was transmitted to the mobile phone via Bluetooth. The data was obtained at the phone of the Android platform and finally calculated to the relevant microcirculatory hemodynamic parameters. Using this program, users can easily learn about their physical condition through their mobile phones. This equipment allows users to pay attention to their own health at home and improve their health consciousness. Not only that, it also makes the allocation of medical resources more efficient.

Automated morphometry of the microcirculation requires robust image processing programs which can identify and track microvessels in video or photographic images obtained by transillumination. We describe a model which replicates the illumination process contributing to a film or video image of the microvessels of the conjunctiva. The model provides a foundation for microvessel detection algorithms, for precise measurement of vessel dimensions and depth within a diffuse medium, and for separating neighboring vessels in complex images. In this model, a cylindrical vessel is embedded in a diffuse medium which is on a reflecting background. A light source illuminating the scene is reflected by scene components and passes through a pinhole to an image plane, which records these reflections as intensity values at discrete pixel locations. Fundamental physical principles which include Lambert's cosine law governing the illuminance of diffuse light sources and reflectors, isotropic spreading, Fresnel's reflection law, and Beer's law governing the effects of a translucent medium were systematically applied to the model. The direct and the reflected illumination at each point in the model was calculated using geometric relationships present in the scene. A video apparatus and a phantom was constructed to analyze different illumination conditions, to determine the contribution each scene component makes to the final image and to verify the completed model. Relative reflectivity data determined from video signals was used in a computer simulation of the image model. The results of the simulation compared favorably with experimental data. The validated image process model provides much needed information about the intensity values present in microvessel images. This information will be useful in finding solutions to problems which exist in vessel detection and tracking approaches based on idealized image models.