Finger injury often occurs in domestic accident due to collision with home appliances or due to pinching in door or window. However, an injury criterion for finger fracture based on experimental data under dynamic loading condition has not yet been proposed. Present study was conducted in order to investigate the fracture threshold of small-diameter long bone under dynamic bending and pinching loading as a first step in developing an injury criterion. Dynamic responses of porcine fibulas were obtained using drop weight testing device equipped with an accelerometer, a load cell, a laser displacement meter and an acoustic emission (AE) sensor. AE sensor was considered useful to identifying the exact starting time of fracture. Furthermore, differences in the mechanical parameters at fracture were found between bending and pinching conditions.

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Occupants sustain injuries frequently to the chest under a high deceleration vehicles in frontal crashes, and mitigations of occupant chest injuries are needed for the occupant protection. In this research, a sled test under high deceleration crash pulse was conducted to investigate the chest protection of occupants in the high deceleration vehicle. The results of finite element analysis using Hybrid III dummy was validated based on the experiments and the mechanism of chest deflection was investigated. It was shown that the forward displacement of dummy pelvis in this high deceleration was large, and caused large shoulder inner belt force. This force resulted in a large chest deflection. It is concluded that the lower the pelvis displacement is needed to reduce the dummy chest deflection.

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In car accidents abdominal organ injuries are frequently caused by seat belts which induce compression to the abdomen. Therefore much attention has been paid to reducing the injuries caused by the protection device. Accordingly there is a need for injury assessment tool abdominal organs. The purpose of this study is developing the injury analysis model that can be expressed liver damage state by the MPS (Moving Particle Semi-implicit) method. At first to represents the viscoelastic behavior of liver tissue, we modified the Navier-Stokes equations by adopting Voigt elements between every neighboring particles. Next we set the material properties of the liver by simulating tensile test and compression test using the simplified geometric model. Finally we conducted a simulation of the impact test of the liver. As a result the liver model represents a qualitatively the mechanical properties. However the Liver model has different maximum stress, it is not possible to quantitatively express the mechanical properties.

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More than 30% of total car accidents involved rear-end collisions, and minor neck injuries account for 90% of these injuries. Whiplash Associated Disorders (WAD) is one kind of minor neck injury. WAD causes giddiness and shoulder stiffness, and symptoms tend to become chronic and lasting, however the mechanism is unknown. The previous study indicated that the whole spine alignment affects mechanism of WAD. Therefore, it is important to obtain accurate whole spine alignment for WAD study. However, because of the difficulty of capturing the whole spine alignment, alignment patterns of occupant are unknown. The objective of this study is to analyze and categorize the spinal alignment patterns of the occupant and estimate the representative spine alignment of each pattern by using the upright open MRI data. The whole spine alignment MRI data of 15 volunteers were analyzed using Multi Dimensional Scaling (MDS) method, and classified with the spine alignment patterns. The representative alignments on the 50% probability ellipsoid on the distribution map were reconstructed by using shape composition method.

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The objectives of this study are to develop and validate a simplified human body finite element (FE) model integrated with active ID muscle model, called "KIMBAR (Kinetic model Integrated with Muscles for Biomechanical Applied Research)". This model includes musculoskeletal structure and can be used with very short CPU times. Skeletal parts of this model were represented by rigid bodies connected with spherical joints. Muscle models have capabilities of force generation according to their activation levels. The KIMBAR was modeled using Hill-type muscle models with 800 muscle-tendon compartments of ID truss and seatbelt elements covered whole joints in the neck, thorax, lumber, and upper and lower extremities. This study reports validation results of KIMBAR for head-neck kinetic responses in frontal and rear impact loadings. The head-neck angles estimated from the model agreed with the experimental data in previous studies. In addition, kinetic motions due to muscle tone were represented in flexion, extension, lateral flexion, and rotation modes. Parametric studies on frontal and rear impact analysis during the kinetic motions of head-neck were conducted and found that initial muscle activation levels and head-neck postures would alter the head-neck responses in post impacts.

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The aim of this study was the clarification of the threshold of occurrence of head trauma through comparison between the number of damaged cells generated in the brain and the stress generated in the brain that were calculated with computer simulations. As a result of a comparison between the number of axonal injury and stress distribution for 11 locations in the brain, the threshold stress that generate head trauma was calculated to at least approximately 40kPa.

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Even if brain injury was doubted in the diagnosis at the hospital as a social problem in the head damage by MRI or CT, workmen's accidents include what is not recognized and that people more than several times of the death toll by the traffic accident suffer from aftereffects when the views on the image are not seen. The number of the injured people and the death toll of the whole traffic accident of Japan have second most cyclists next to a car crew. In the case of the dead of the bicycle crew, the most frequently injured body region is the head. It is necessary to clarify dynamic behavior to evaluate the head damage. Therefore this study reproduces the behavior in the brain when the head was impacted using the finite element analysis in frequent bicycle accidents and inspects an evaluation of the cerebral damage and the damage reduction effect of the helmet for bicycles. The condition of a patient of the head damage is elucidated dynamically by this study and gives a head damage patient appropriate emergency measures in the clinical spot and can provide right information for the prevention of the secondary damage.

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Typical injury in judo is concussion and acute subdural hematoma by head collision to the judo tatami, but effective guideline for prevention based on biomechanical point of view has not been proposed. In this study some Waza to cause a risk to hit a head on a tatami were performed by judo players and recorded by VICON system. These motions were reconstructed by MADYMO by using VICON data and kinetic data and hit part of a head on the tatami, which were used as input data for a FE human head model, were obtained. The strain and stress of the brain tissue were calculated in detail by the FE human head model and injury risk was predicted.

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Recently, the amount of traffic accidents involving elderlies has increased considerably. Due to that, further analysis is required, and anthropometric dummy testing would be too time and resource consuming. This research focus is to study and evaluate, through the use of HIC (Head Injury Criterion), the outcome of accidents involving a car and elderlies riding bicycles. The core of this research lies within MADYMO simulation software. The simulation itself utilizes three bodies that are: A frontal part of a car, an elderly male or female and a bicycle, previously validated in other research. A simplified typical sedan model, which consists of a frontal hood, bumpers and windshield, is set at default speeds of 10, 20, 30 and 40 kilometers per hour, respectively. In addition to that, the situations in which braking at maximum capability is considered have also been conducted to evaluate the efficiency of breaking for injury prevention. The elderly cyclist models have been developed scaling down from AM50. The bicycle-elderly impact configuration is set in different situations: Frontal, sideways and back collision. Also, the situation where the cyclist also has its own speed has been taking into account, for proper comparisons. The expected results are: To see a decrease in HIC when the car is under maximum braking situation, and higher HIC accordingly to the Sedan speed. The extra goals are to study at what speed braking becomes most efficient in preventing head injury to the cyclist and comparing the difference in HIC depending on cyclist positioning and speed.

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Here, we observed fibroblasts seeded onto a glass substrate on which Forster/fluorescence resonance energy transfer (FRET)-based tension sensors were immobilized. While the observation, actin or microtubule depolymerizers (cytochalasin D or nocodazole, respectively) were added to the culture medium to induce cell deformation. Cells began contracting within 5 min after the addition of cytochalasin D and assumed a round shape. During this contraction process, cell protrusions gradually shrank and disappeared. At the tip of these protrusions, there appeared dash-like areas with a low FRET index, indicating strong tension, and these areas disappeared within 90 min. These results suggest that the FRET-based tension sensor enabled the real-time visualization of tension induced by actin cytoskeletal reorganization and focal adhesion formation This is also supported by the observation of cells treated with nocodazole, which depolymerizes microtubules to increase tension across actin fibers. The distribution of areas with a low FRET index changed by the nocodazole treatment. The FRET-based tension sensor is useful to evaluate mechanical interactions between cells and materials.

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In this study, we observe intracellular calcium signaling response to stretch in a single osteoblastic cell with video rate temporal resolution. Our originally developed cell stretching microdevice enables in situ observation of stretched cell without excessive motion artifact such as focus drift. Minor effect of motion artifact was corrected by using fluorescent ratiometry method with calcium indicators Fluo 8H and Fura Red. We succeed to detect intracellular calcium signaling response to stretch with video rate temporal resolution.

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It is believed that mechanical stimuli such as stretch deformation of extracellular matrix is transmitted into the cell via focal adhesion complex and actin cytoskeleton. In osteoblasts and vascular endothelial cells, thick actin stress fibers form aligned network structure. We expect that intracellular strain distribution transmitted from outside is affected by such heterogeneous cytoskeletal structure. In this study, we observed cellular morphological dynamics during stretch application by using cell stretching microdevice. We succeed to obtain time lapse images of stretched cell, and tried to measure the distribution of intracellular strain during stretch application by using digital image correlation method.

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Fluorescence imaging of cells under mechanical stretching require technical overcomes because cells go out of observation fields. In this study, horizontal movements of cells under mechanical stretching were attempted to be adjusted with fluorescent beads and PIV analysis. As a result, this method realized adjustment when mechanical stretching was below 15%. Furthermore, intracellular Ca^<2+> increase was observed in endothelial cells with mechanical stretching.

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Gap junction communication is known to play essential roles in tenocyte functions in response to mechanical loading. In our previous study, it was exhibited that an application of static tensile strain with a physiological amplitude for 1h promoted gap junction communication in tenocytes while overloading strain suppressed gap junction communication. However, temporal regulation of gap junction communication during an extended static loading has not been characterized. Accordingly, the present study tested a hypothesis that gap junction communication is regulated in a manner depending on the duration of mechanical loading. Gap junction communication was investigated using a fluorescence loss in photobleaching (FLIP) technique. It was demonstrated that the level of gap junction communication was fluctuated under physiological 4% static strain during 24h period, while it was gradually increased under 8% static strain.

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Epithelial tissue constitutes many kinds of organs of multicellular organisms. During morphogenesis, tissue deformation is driven by forces generated by cell activities such as cell proliferation, cell migration and apical constriction. Because shape of organs is accomplished appropriately by a series of tissue deformation, force generation at cell level can be controlled by a result of tissue shaping in a feedback manner. As such a mechanism, we suggest a function of modifying apical constriction in response to cell shape change by mechanosensitivity of alpha-catenin, leading to the feedback relationship between apical constriction and cell shape. In this study, we construct a mathematical model of the feedback relationship and investigate its role in formation of tissue shape. Simulation results suggest that the modification is based on the shapes of adjacent cells, and that the function maintains roundness of epithelial tissue by averaging the cell shapes.

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Fibrils were self-assembled in vitro from collagen molecules by controlling the pH and temperature of purified collagen solution. The reconstituted fibrils were stretched to failure. The diameter of the fibrils was 367±24 nm (Mean±S.E., n=7). The tensile strength, strain at failure, and tangent modulus of the fibrils were 77.9±28.4 MPa, 38.7±7.6 %, 188±37 MPa, respectively.

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In this paper, the degenerated model for the Keller Segel equations which describe the cell aggregation of cellular slime molds is presented. When the chemotactic term is sufficiently small compared to the diffusion term, the system equations of the original Keller Segel equations become the simple, linear systems. We analyze the degenerated linear systems and state the time evolution characteristics for the solutions.

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A two dimensional biased random walk model was applied to calculate bacterial cells' distribution around an attractant chemical in a line. This model follows the properties of bacterial chemotaxis. In a uniform chemical concentration, a bacterial cell tumbles every a certain period of time and randomly changes its swimming direction. However, a bacterial cell suppresses tumbling when the cell senses that the chemical concentration around it has increased. Thus, a bacterial cell gradually approaches the highest concentration. This produces chemotaxis as a collective behavior of many bacterial cells. In the present model, a model cell moves a certain distance during one time step. When the model cell approached a line that is assumed to be a chemical attractant during the previous time step, the cell continues moving in the same direction in the current time step with probability α, or changes its direction randomly with probability 1-α. On the contrary, when the model cell receded from the line, the cell randomly changes its direction. The parameter a means the strength of bias; α = 0 corresponds to random walk and α = 1 the strongest biased motion. The calculated model cells' steady distribution around the attractant line is an exponential distribution which depends on α. The dependence on α is not such a simple one appeared in the previous one dimensional model. The effect of directivity at tumbling was also investigated. The directivity has little impact on the cells' distribution.

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Stem cell-based self-assembled tissue (scSAT) biosynthesized from synovium-derived mesenchymal stem cells (MSCs) has a great potential for repairing and regenerating ligaments, tendons and cartilage. However, the mechanical and structural properties of the scSAT were insufficient for clinical applications. A candidate solution to the problem is to promote the generation of the extracellular matrix in the scSAT using a special culture on static magnetic field. A magnetic exposure system Halbach cylinder-like array was manufactured with 8 neodymium magnets. A preliminary test revealed that the magnetic exposure system generated 0.674 T magnetic field. MSC was cultured on 0.674 T static magnetic field generated the magnetic exposure system. As a result, orientation intensity, cell adhesion area and aspect ratio of MSC cultured on static magnetic field were same as MSC cultured without static magnetic field. Cell occupation area of MSC cultured on static magnetic field was higher than MSC cultured without static magnetic field.

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Stem cell-based self-assembled tissue (scSAT) biosynthesized from synovium-derived mesenchymal stem cell (MSC) has a great potential for the repair and regeneration of cartilage. For the improvement of the mechanical properties of the scSAT it is a candidate solution to promote chondrogenic differentiation of MSCs. In the present study, cell/tissue culture substratum having various elastic moduli were developed using a polydimethylsiloxane (PDMS) with different mixing ratios of main agent and curing agent. Rabbit synovium-derived mesenchymal stem cells were cultured on the substrates. Results revealed that cell adhesion area became narrower and aspect ratio became higher as the substratum became softer. It is suggested that the differentiation of MSCs is dependent on the elasticity of culture substratum.

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This paper reports a new method for investigating the changes in and the distribution of higher-order structures of native chromatin fibers in response to changes in salt concentration. To achieve this, we developed a microfluidic platform that enabled us to isolate chromatin fibers non-destructively from single cells and then tag them with microbeads as positional markers. These were observed that chromatin fibers were elongated non-uniformly and continuously along a chromatin fiber as the salt concentration was increased from 0 mM to 250 mM NaCl and stepwisely between 500 mM and 750 mM NaCl, and their fluorescence of histone H3-RFP decreased over 1000 mM NaCl. These results suggest that binding proteins dissociate between 500 mM and 750 mM NaCl, and histones dissociate over 1000 mM NaCl.

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Lung branching structure is the one of the most complex pattern formation and the mechanisms of branching morphogenesis has not been fully understood yet. Computational simulation methods like a Reaction-Diffusion (RD) model will be strong tools to elucidate the developing mechanisms by calculating molecular dynamics, which is hard to be visualized by experiments. We recently found that two-dimensional branching morphogenesis when cells were set with high concentration gradient on a glass slide covered by extracellular matrix. The cell position control is relatively easy for 2D culture and our system does not require heterotypic cell-cell interactions but epithelial cells can produce the branches by themselves. Here we employed photolithography technologies to control initial cell position on a glass slide in order to match the in-vitro experimental conditions and simulation conditions exactly. By conducting branching experiments and developmental simulations simultaneously with the same initial cell positions, quality of the analysis can be improved significantly to elucidate the lung branching mechanisms.

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Tendinopathy has been one of major health concerns in orthopaedic surgery, not only for active athletes but also for others like office workers. Although the exact etiology of tendinopathy has yet to be elucidated, it has been demonstrated that tendon core temperature elevated up to 43 to 45 degree Celsius when humans or racehorses are subjected to extensive exercises (harsh running). A long exposure to such high temperature could induce cell death. However, effects of the exposure to the high temperature for relatively short terms (simulating running activity) on tenocyte functions are still not understood. Therefore, the present study was performed to investigate how tenocyte anabolism and catabolism are altered by a short thermal stimulation. In addition, the present study tested a hypothesis that such alterations of tenocyte functions are dependent in the presence of gap junction intercellular communication (GJIC). It was demonstrated that tenocyte GJIC was not significantly altered by a 30 minutes exposure to 43 degree. However, catabolic and inflammatory gene expressions were significantly upregulated following a 24 h post-heating culture period. With the presence of GJ blocker, upregulation of catabolic genes by the thermal stimulation was inhibited, although inflammatory gene expression was further enhanced. These results may indicate that GJIC in part contribute to alterations in tenocyte functions in response to thermal stimulation in a complicated manner.

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Permeability changes of an endothelial cell (EC) monolayer are related to many diseases. This study evaluated permeability of the EC monolayer under normoxia and hypoxia by using fluorescent dextrans of two different molecular weights in a microfluidic device with controllability of oxygen tension. As the results, permeability of the EC monolayer increased by hypoxic exposure, and the increase of the permeability measured by fluorescent dextran of 10 kDa was smaller than that measured by fluorescent dextran of 70 kDa. The results indicated that the size-selectivity of EC monolayer became weaken under hypoxia.

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Measurement of cell deformability has been of a great interest among researchers because it is known that cell deformability may be closely related to physiology and pathology of tissues where the cells are located. However, it requires an amount of time and cost to measure cell deformability with conventional methods. In this study, a microfluidic device has been developed for a high-throughput measurement of cell deformability. The microfluidic device includes a parallel array of tapered microchannels where cells are trapped. In the experiments, cells introduced in the microchannels are trapped at a certain position based on cell diameter and deformability. Because the cell-trapped position in the microchannel reflects cell deformability, the Young's moduli of cells can be determined through microscopic observation. As a proof of study, we tested bovine chondrocytes and obtained the Young's modulus of 3.85 kPa.

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The contractile forces in individual cells drive the tissue dynamics, such as morphogenesis and wound healing, and maintain tissue integrity. In these processes, α-catenin molecule plays as a tension sensor at cadherin-based adherens junctions (AJs), accelerating the positive feedback of intercellular tension. Under tension, α-catenin is activated to recruit vinculin, which recruits actin filaments to AJs. Here, we revealed how α-catenin retains its activated state while avoiding unfolding under tension. By using single-molecule force spectroscopy employing atomic force microscopy (AFM), we found that mechanically activated (under approximately 10 pN) α-catenin exhibited higher mechanical stability than a non-activated fragment. In addition, we demonstrated that mechanically activated α-catenin was further reinforced by vinculin binding. Our data suggest that the plastic characteristics of α-catenin, revealed in response to both mechanical and biochemical cues, enable the functional-structural dynamics at the cellular and tissue levels.

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Adherens junction (AJ), which directly links actin cytosketons in adjacent cells, transmits tension derived from acto-myosin activities. As a mechano-sensitive molecule at AJ, α-catenin senses and balances intercellular tension. α-Catenin changes its conformation under intercellular tension and opens auto-inhibited structure for vinculin, resulting in a local actin remodeling. However, it is unknown how firmly α-catenin and vinculin interact with each other, both of which are exerted on intercellular tension. Also, little is known about changes in conformation and vinculin affinity after α-catenin opens auto-inhibited structure. Here, we measured binding force between α-catenin and vinculin by using single-molecule force spectroscopy employing atomic force microscopy. Furthermore, we revealed changes in the conformation of α-catenin and vinculin affinity. As a result, we revealed that activated α-catenin can firmly bind to vinculin. Furthermore, AFM images showed the drastic conformational changes occurred in α-catenin after opening auto-inhibited structure, resulting in increase in vinculin affinity.

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Shock wave irradiation accelerates therapeutic effects including angiogenesis. One mechanism underlying those effects is cellular responses evoked by shock wave irradiation. It is known that mechanical stress like shear stress induces intracellular Ca^<2+> increase. In our previous study, it was observed that shock wave irradiation induced the intracellular Ca^<2+> increase similar to that by other mechanical stresses. It implies that shock wave irradiation is likely to evoke some mechanotransductions. Therefore, the objective of this study is to investigate an involvement of cytoskeletons in intracellular Ca^<2+> increase induced by shock wave irradiation using Bovine Aortic Endothelial Cells (BAEC). We observed the intracellular Ca^<2+> increase by shock wave irradiation with Fluo4-AM and performed inhibition experiment related to cytoskeletons using cytochalasin D and blebbistatin. Then, the role of the cytoskeletons in the intracellular Ca^<2+> increase in response to the shock wave irradiation was examined. As a result, no statistical significance of the difference was observed by the inhibition experiment This suggests that cytoskeletons may not involve the intracellular Ca^<2+> increase induced by shock wave irradiation and we should investigate not only the cytoskeletal response to shock wave but also other intracellular structure and functions responsible for Ca^<2+> signaling.

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Cells have mechanosensors that convert mechanical forces into biochemical signals to respond to mechanical forces. According to recent reports, a variety of mechanosensors have been identified. One of them is focal adhesions that form multi-protein structures having mechanical links between intracellular cytoskeletons and extracellular matrices. The cellular mechanisms of sensing and responding to the mechanical stimulations at focal adhesions have not been clarified yet. We developed a micropillar substrate embedding micron-sized magnetic particles and enabling the micropillars to be cyclically deflected by a time-varied magnetic field. Our previous experiments suggest the direction of cell migration is changed by the cyclic deflection of magnetic micropillars because a cell may detach its pseudopod from micropillars cyclically deflected. Here we apply cyclic strain of some amplitudes and frequencies to a single osteoblast through focal adhesions to understand the effects of frequency and amplitude of cyclic strain. Our data indicate that cells tends to detach micropillars whose deflection are higher than 0.08 μm which means cells may sense cyclic strain caused by a micropillar cyclically deflected at the amplitude. Furthermore, the rates that cells detached micropillars cyclically deflected at 0.1 Hz after adhering to them were not significantly different from those at 5 Hz. The study leads to the technique of clarifying the mechanism of sensing and responding to some amplitudes and some frequencies of mechanical stimulations as well as controlling cell migration by applying mechanical stimulations.

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This paper describes a novel method to investigate a cell mechanosensing system and the quantitative relationship between the deformation of cytoskeletal structure and the change of intracellular calcium ion concentration as biochemical response in a living cell stimulated by a micropipette. Gene transfection of green fluorescent protein enabled visualization of actin cytoskeleton in cells. Local deformation was applied to a cell by a micropipette and the displacement distribution of actin cytoskeleton in the whole cell was automatically obtained from the two images of the cell before and after deformation by using Kanade-Lucas-Tomasi method which is one of the feature tracking algorithms. Intracellular calcium ion response to the same mechanical stimulation was measured as the spatial and temporal changes of intensity of a fluorescent marker loaded to osteoblasts. These measurement were simultaneously conducted in order to clarify the mechanism of converting mechanical deformation into calcium signaling in a cell. As a result, the change of intracellular calcium ion concentration increases with increasing the displacement of actin cytoskeleton and calcium ion response starts in the area of large cytoskeletal displacement. These indicate that the deformation distribution of actin cytoskeleton is highly related to the cell mechanosensing system.

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There have not been any preceding research which refer to the relationship between morphological characteristics of cerebral artery and risks of cerebral aneurysm initiation from the perspective of blood flow. The objective of this research is to evaluate risks of cerebral aneurysm initiation using CFD analysis focusing on WSS vector variations due to impinging flow by investigating the correlation between morphological parameter and WSS vector variation for 13 healthy volunteers. The result indicated impingement of blood flow at MCA bifurcations in all cases. The average values of WSS vector variation was 357.7 degrees, bifurcation angle was 90.9 degrees, and inclination angle was 19.3 degrees. Results showed a low correlation coefficient (R^2=0.232) between bifurcation angles and WSS vector variations. In addition, no correlation for inclination angles and WSS vector variations was observed. This result suggests that widening of bifurcation angles due to morphological change by aging may resulted in larger WSS vector variation due to impinging flow, and larger risks of cerebral aneurysm initiation.

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One of the problems with the cerebrovascular bypass surgery is that the adaptation mechanisms of the cerebral arteries are not clear for the medical professionals to prevent postoperative complications. In order to avoid postoperative complications, elucidation of the adaptation system in human cerebral arteries is necessary. It has been postulated that mean wall shear stress is maintained at a constant value in the arterial system; however, the credibility of the argument needs to be improve to apply the theory at clinical sites. This study investigates the consistency of the wall shear stress of the major cerebral arteries in 7 healthy volunteers using PC-MRI. The blood flowrate and the diameter of the arteries were plotted in the graph with blood flow rate against the third power of the diameter. The linear regression has been performed to see the correlation coefficient (R^2) to study the consistency of the arterial wall shear stress. Results showed a strong correlation coefficient (R^2=0.730±0.204) for the arteries with lower Wormersley number where the Hagen-Poiseuille assumption can be made. Therefore, it can be concluded that the wall shear stress is constant for the major cerebral arteries where the Hagen-Poiseuille flow can be produced.

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This research investigated the properties of endothelial cells and wall structure of unruptured cerebral aneurysms to aim elucidation of cerebral aneurysm growth mechanism. Seven aneurysms were categorized into blood blister-like (under 80 μm), transition (80-100 μm), and hypertrophic (above 100 μm) lesion by its thickness and each lesion was observed with transmission electron microscope. The results showed that endothelial cell and wall property both improves as the thickness increases. In addition, number of layers constructing the aneurysm wall increased as the thickness increased. These results suggested that existence of endothelial cell may induce the thickening process of cerebral aneurysms and part of the thickening process may be creation of new layer from migration of smooth muscle cells and creation of fibrous layer.

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This research investigated mural cell densities in different wall thickness of five human unruptured cerebral aneurysms to evaluate the tissue healing ability of aneurysmal wall. Five aneurysms were dissected after craniotomy with markings to confirm the orientation of specimens. Harvested tissue were than fixed in 4% paraformaldehyde, embedded in paraffin, sliced in semi serial sections of 3 μm thickness, and stained with hematoxylin-eosin (HE) method. To investigate mural cell densities, wall thickness was measured, and the aneurysmal wall was sectioned into 100 μm increments from histological analysis. All sections were divided into two parts of inside and outside regions from the center of the wall, and inspection areas were focused on the inside region. The characteristics of mural cell densities were classified into three types. First type was that mural cell densities in under 100 μm regions was higher than in 100-200 μm regions, which were observed in case 1 and 4-1. Second type was that the mural cell densities increased in 100-300 μm wall regions, whereas in 300-500 μm regions, the mural cell densities decreased, which were observed in case 2 and 3. Third type was the mural cell densities increased as wall thickness increased, which were observed in case 4-2. These results suggested that the tissue healing ability was different depending on wall thickness and each case.

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Foam cells are caused by excessive infiltration of lipid into the artery wall. In the current cerebral aneurysm study the presence of lipids has been shown in the aneurysm wall. However association of foam cells in the aneurysm wall has not been studied. This research 11 aneurysms foam cells accumulation whether in the aneurysm wall and characterized the distribution of foam cells. Tissues were collected from 9 patients after microsurgical clipping of the aneurysm neck. Harvested tissue were than fixed in 4% paraformaldehyde, embedded in paraffin, sliced in semi serial sections of 2 μm thickness, and stained with hematoxylin-eosin(HE) method. The sections were observed after HE staining. Foam cells were found in 4/11 unruptured cerebral aneurysms. Foam cells were different integrated distribution by location. These results suggested that accumulation of foam cells depends on the patients medical history and the blood components.

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In blood flow through microvessels, platelets are known to have enhanced concentrations near the vessel wall, which is the so-called "near-wall excess" (NWE). Since this characteristic of platelets plays an important role in hemostasis, there have been intensive studies on the platelet behavior in microchannel flows. In the present study, we examine the effects of red blood cell (RBC) deformability on the NWE in microchannel flows. The RBC deformability was altered by fixing RBCs in 40-4000 ppm glutaraldehyde solution (GA_RBC). The viscosity of RBC suspension fixed by 4000 ppm glutaraldehyde was significantly higher than that of normal intact RBC suspensions (p<0.05). Fluorescent platelet-sized particles were mixed in the suspension of RBCs with altered deformability, and the cross-sectional distributions of the particles were observed in microchannels with square cross-sections of 50μm width, utilizing a confocal laser scanning microscope at various heights from the bottom of the channel. In the case of intact RBC suspensions, the platelet-sized particles showed an apparent NWE. In the case of 4000 ppm GA_RBC suspensions, in contrast, the particles exhibited nearly uniform distributions in the channel cross-section.

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In blood flow through microvessels, platelets have high concentrations near the vessel wall, which is referred to as "Near Wall Excess (NWE)" and plays an important role in restoration and hemostasis of injured vessel walls. In the present study, we measured the distributions of platelet sized fluorescent particles in red blood cell (RBC) suspensions flowing through microchannels with circular or square cross-sections and compared their results. The measurements were performed at various heights from the channel bottom, by the use of a confocal laser scanning microscope. In the absence of RBCs, the platelet-sized particles showed nearly uniform distributions in the channel cross-section for both of circular and square channels. In square channel flows with RBCs, higher concentrations of the particles were observed near the channel walls and this NWE was more conspicuous near the channel bottom than that in the mid-plane of the channel. This result suggests that the particles are accumulated near the corners in the square cross-section. In circular channel flows with RBCs, in contrast, the highest NWE was observed in the mid-plane. The extent of NWE was larger in circular channels than in square channels at comparable flow conditions.

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[Introduction] The blood's apparent viscosity decreases, when the inner diameter of micro-tube becomes less than 300μm. This phenomenon is called as the Fahraeus-Lindqvist effect, and it is understood that the large deformable erythrocytes can easily escape from the abrupt flow change region near the wall, and then the cell density at near the wall region becomes low. Consequently, this phenomenon results in the decrease of the blood apparent viscosity at near the wall. It has also known that the erythrocyte's density increases and the erythrocyte's deformability deteriorates with their aging. Additionally, conventional studies reported that the production and decomposition of erythrocytes are repeated every day within our body. Therefore, erythrocytes are with the variety of age levels. Thereby it should result in the existence of different deformability levels. Therefore, the microvascular flow behavior would differ because of the difference in the erythrocyte's deformability. The objective of this study is to evaluate relationship of the erythrocyte's density and its rheological behavior in the micro-tube flow. [The method] Erythrocytes were divided into ten density levels by pipetting the centrifuged blood sample. Then, the 40% Hematocrit blood was prepared using only same density erythrocytes and PBS Solution. The special sample blood was inserted into our specially made micro-tube with the variation of the volume flow rate. Then the blood flow behavior was recorded through the microscopy. [Result] The result of our image analysis suggested the relative increase in hematocrit at around the center axis at higher flow rate condition than 5μm/min.

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In the blood, cells are observed to move perpendicular to the direction of the blood flow in a process called lateral migration. This lateral migration occurs due to several hydrodynamic factors, such as the presence of the vessel wall, the applied Poiseuille flow within the vessel, and cell-cell interactions. However, the effect of these factors has not been well understood. Thus, using the boundary integral method, we have been numerically investigating the effect of the wall and the effect of the curvature of the applied flow on the lateral migration of a single cell. We have shown that the effect of the wall on cell lateral migration is dominant relative to the effect of the flow curvature, even at large distances between the cell and the wall. We have also derived a semi-analytical equation representing the relative effects of the wall and flow curvature, which allows us to predict the migration velocity in slit flows or microvessels. Our results can also be used to develop simplified models, based on the position of the cell within the vessel, for biophysical phenomena such as cell margination and axial migration.

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Objective of this study is to develop a realistic pulmonary capillary network model at which capillaries form a random and fine mesh having a range of the capillary length. For this objective, the authors presented a method to generate such a mesh based on the bubble mesh method which is a mesh-generation technique for the finite element method. The presented method introduces some irregular type of circular nodes in addition to the ordinary circular nodes of the bubble mesh method to give a variety to the node radius, and the capillary network is generated by the Voronoi tessellation of the nodes. In this study, two-dimensional capillary networks were examined to generate for investigation of contributions of characteristics of the irregular nodes, variation of their radius and their concentration to the variation of the capillary length. Consequently, it was shown that the presented method generated a random network and the variation could be changed by those parameters. It was found, however, that too much wide variation of the radius of the irregular nodes declined mean capillary length due to limitation of number of surrounding nodes in packing them in the domain.

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It is expected that whole body vibration (WBV) is effective to prevent cancer metastasis to bone. However, the mechanics of WBV is still not clear. Therefore, in order to clarify this mechanics in detail, we simulated the behavior of a RBC in the microvessel under the microvibration, and investigated the effect of the WBV on the osteoclastic of the cancer. In the present simulation, we constructed three-dimensional model of the microvessel which diameter is 20 μm. We assumed that the vibration occur perpendicularly and parallel to the main flow. Simulated blood flow was computed using the lattice Boltzmann method in conjunction with the immersed boundary method for incorporating fluid-membrane interactions between the flow field and deformable RBC. We assumed the initial shape of the RBC as the sphere particle which diameter is about 8 (a.m. In order to investigate the advantage of the vibration, we estimated the difference in RBC trajectory as the initial position is 5 μm. The vibration perpendicularly to the main flow hardly influence the RBC trajectory, whereas the parallel vibration brought about promotion of the axial migration of the RBC as increase in the frequency. It is suggested that this effect is generated by the backward flow due to the vibration.

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When keeping blood inside a static tube, it is well known that the red blood cells (RBCs) start to sediment downward due to the density difference between inner fluid and the outer fluid plasma. In present work, we numerically investigate the orientation angle of settling RBCs. First, we confirm that the RBCs change its orientation toward vertical angle as also reported in previous experimental studies. Secondly, we find that this reorientation is faster for a red blood cell with higher Bond number or lower viscosity ratio. In this report, we also discuss how this reorientation speed would impact the overall trajectories of the RBCs.

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Relationships between impingement of blood flow and thrombus formation mechanisms in human arteries are still hypothetical. This study investigated the relationship between different conditions of impingement and thrombus formations. Impingements of whole blood were created using Y-shaped and T-shaped micro-channels that were MPC coated. The velocities of impingement were set to be 0.2 m/s and 3.0 m/s. The whole blood was obtained from a healthy male volunteer. The whole blood at the impingement area was observed with an inverted microscope and a high-speed camera. Also, areas of thrombus ware measured on the obtained images using Image-Pro Plus to quantify the thrombus volume. The results showed that thrombus formation occurred in the Y-shaped impingement flow and didn't occur in the T-shaped impingement flow in either of the velocity. The thrombus formation in the Y-shaped impingement at low velocity occurred at the position shifted to the right and left rear from the bifurcation center. The thrombus formation at high velocity occurred at the bifurcation center. In addition, thrombus at low velocity peeled off easily than at high velocity. In conclusion, it was suggested that different impingement patterns affect the formation, formation point, and detachment rate of thrombus in the micro-channels.

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Considering high-shear-induced platelet activation, we carried out a computer simulation of thrombus formation in a stenosed flow channel using a particle method. A model blood consisted of plasma and platelets, and platelet aggregation was represented by connecting platelet particles by springs. As a result of simulation, platelet particles were activated by high shear at a stenosis, and they adhered to channel wall surfaces in the rear of the stenosis. Shapes of platelet aggregates and its growth speed depended on thresholds of shear rate and exposure time to determine flow-dependent platelet activation. Platelet aggregation area at the lower channel wall whose shape changed along a main flow direction decreased with an increasing threshold of exposure time. The platelet aggregation area at the upper channel wall whose shape was straight along a main flow direction decreased with an increasing threshold of high shear rate. The platelet aggregation shapes corresponded with a previously published in vitro experimental result when a threshold shear rate was greater than 17,000 s^<-1> which is smaller than experimentally estimated value of 30,000 s^<-1> or greater. Platelet aggregation area increased faster than that observed in an in vitro experiment because a large number of platelet were assumed in simulations.

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The swelling and hemolysis behavior of human red blood cells (RBCs) due to the osmotic pressure imbalance has been investigated. Adding the 0.1wt% NaCl solution as hypotonic solution into the isotonic RBC suspension, we experimentally observed an RBC swelling from the biconcave disk to the spheroidal and spherical shape. The time evolution of the surface area and the volume of the RBC was evaluated from the lateral shape on the assumption of the axisymmetric geometry. The results show that the volume significantly increases with shape variation under the hypotonic condition, and then it decreases in a short time. Finally, the inclusion such as the hemoglobin leaks out of the RBC keeping the spherical membrane shape. Corresponding to the experimental observation, we theoretically and numerically calculated the variation in the hydrostatic pressure difference through the RBC membrane during the osmotic swelling. The calculated results enable an evaluation of the hydrostatic pressure differences at arbitrary moment in the swelling process by comparing the RBC shapes obtained experimentally and theoretically in terms of the ratio of major to minor radii.

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In order to examine fetus hearing, we observed heart rate and brain waves of fetus induced by sound stimulation. In this paper, we focused on changes in the heart rate. We developed a sound device that consists of a function generator, a piezo driver and a piezoelectric vibrator. The piezoelectric vibrator was positioned on the surface of the abdomen of mother above fetal head. Continuous sounds stimuli of 2 kHz were provided to fetuses through born conduction. The intensity of the stimuli were 70 dB and 50 dB. Fetal heart rate was evaluated by a childbirth monitoring apparatus. Fetal hearing screening were applied to 19 healthy pregnant women in the period of 32 to 36 weeks gestational age. Heart rate data were examined based on 3 indexes, i.e. peak amplitude, peak latency and initial duration. Change of heart rate induced by the stimulus was compared to that which accidentally occurred without stimulus. As a result, the peak amplitude of heart rate wave induced by the stimulus was little lower than that without stimulus. In contrast, the peak latency of heart late wave induced by the stimulus was longer than that without stimulus. There is no difference in the initial duration between the heart rate waves.

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This paper discusses the design and implementation of a three dimensional magnetic tweezer system to achieve measurement of mechanical properties of living cells by touching a magnetically levitated micro probe to specimen cells. The system consists of a three dimensional magnetic tweezer, an inverted optical microscope for 3D probe position measurement, and control/interface software. For reducing assembly error in the magnetic tweezer and adjusting the gap distance between magnetic poles precisely, a pole positioning mechanism was implemented in the magnetic tweezer. By using the fabricated prototype, Trajectory tracking experiment in which magnetic particle of 4.5μm diameter was steered to follow target trajectories and homogeneity evaluation for force generation of each magnetic pole were performed.

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We have developed a navigation system for the blood vessel prosthesis replacement of aortic aneurysms, and have used it in clinical practice. This system supports surgeons to identify a target intercostal artery by using patient image. The patient image and real body are matched by registration. Reference points of registration are anatomical landmarks of skeleton such as jugular notch, sternal angle, left anterior superior iliac spine, pubis, and spinous process. However, identification of spinous process was hard to doctors in operation. We developed a new registration method which X, Y and Z axis correspond to the Head-Foot, Right-Left and Anterior-Posterior directions. The specific feature is that identification of spinous process is not necessary. We evaluated errors with the new registration method using the retrospective 6 clinical data. We calculated fiducial localization error. As a result, errors of anterior points in the Head-Foot direction were less than 10 mm. We aimed to reduce the Head-Foot error as less than 20 mm because the ribs exist at intervals of approximately 40 mm in the Head-Foot direction. The new registration method was confirmed to be effective in the decision of approach to the target artery. Moreover, even when the point of the spinous process changed to the next spinous process of the set spinous processes, error was equivalent to the original point, therefore, using the present system, the identification of the spinous process can be unnecessary. It was concluded that newly-developed registration algorism is effective for doctors in identification of intercostal artery.

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The acute coronary syndrome (ACS) is caused by a blood clot formed on a ruptured plaque. The risk factor of the ruptured plaque is strongly related to both the thickness of fibrous cap and the lipid distribution. Therefore, a noninvasively diagnostic system is required in clinical practice to identify the tissue characterization of the arteriosclerosis with microscale. In this paper, we propose a tomographically visualizing technique of tissue characterization using "Attenuation, Reflection and Variance OCT" (ARV-OCT). The present system can calculate the ratio of lipid and fibrous using optical characteristic quantities from OCT images i.e. attenuation, reflection and variance. ARV-OCT was ex vivo applied to atherosclerotic plaques of rabbit artery. As a result, the proposed technique is able to classify fibrous and lipid tissue from an OCT image of the aorta. ARV-OCT is one of clinical diagnostic criteria of the tissue characterization in atheroscherotic plaques.

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We have been developing microporous covered stents (MCSs) for the treatment of giant and wide neck intracranial aneurysms (IAs). By shielding IA neck with the microporous cover film, blood flow in IA was stagnated immediately. Subsequently, IA embolization is occurred by thrombus formation with a remarkable decrease of shear rate in IA flow. So, flow reduction performance of device placing is closely related to capability of IA embolization. In this study, we compared the flow reduction performance between MCS and flow diverter (FD), a another type stent for the IA treatment. IA flow was visualized by using in vitro flow simulator and evaluated by particle image velocimetry (PIV). Two-dimensional sidewall IA model was made from acrylic resin. Aneurysm depth, Dome size and neck width of IA model were 9.1 mm, 10.0 mm, 7.1 mm respectively. FD or MCS models were placed at the neck of the aneurysm model. Distributions of flow velocity and shear rate in IA were measured. Before stenting, high shear rate regions spread throughout IA cavity. After stenting, flow velocities in IA model stagnated remarkably. Area mean shear rate in IA flow became about 9 % by FD and 3 % by MCS. Flow reduction performance of MCS was about 3 times higher than the FD.

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