Flow visualization was conducted to clarify the low flow conditions or the leakage flow conditions to prevent thrombus formation in MERA centrifugal pump for extracorporeal circulation. A 3x similarity model was used to analyze precise flow in the impeller-casing gap using a high-speed video camera (Phantom) and a particle tracking velocimetry (4-frame PTV). The laser light sheet (4W) illuminated the 20%-position plane from the inner top plane of the casing, where the maximum velocity was expected in the gap. The pump conditions were selected to keep the ratio of rotational speed and flow rate. Obtained normal velocities to the integral path were integrated to obtain the leakage flow rate. The obtained leakage flow rate in the upper gap was almost 20-30% of the outflow rate for all 5 conditions. Future visualization would clarify whether the leakage flow is constant or not if the rotational speed, namely the pump pressure, is constant.

抄録全体を表示

Rotary blood pumps are used as blood pumps in the recent mechanical circulatory support, MCS. The magnetic suspension technique is a key to develop durable and bio-compatible rotary blood pumps for MCS. One of advantages of the magnetically suspended blood pump, MSBP, is a wide blood gap with the active magnetic suspension mechanism. The magnetic suspension mechanism can maintain wide blood gap between the rotated impeller and the fixed inner casing with a range of several hundreds micrometers. The wide blood gap guarantees better anti-hemolysis and anti-thrombogenicity properties of the pump with an enhanced blood stream in the gap. Also, the suspension of the impeller can be maintained under a wide range of rotating speeds from low speeds to high speeds. This feature contributes easier operation and wider usage of the mechanical circulatory support. The MSBP with a magnetic bearing has been designed based on the finite element simulation methods in magnetic field and fluid mechanics. The MSBP has indicated sufficient suspended performance and pump performance.

抄録全体を表示

Non pulsatile blood pump is one of the most important therapeutic option for the patients with profound heart failure. However, multiple organ failure has been the limiting factor for the prognosis of the patients after implantation. Non invasive measurements may be the good option to evaluate the organ function. Charge-Coupled Device image sensors will be one of the solution for the measurement with economical advantage. In this study, Charge-Coupled Device image sensors had been used for the evaluation of the renal blood flow in the animal experiments with left ventricular assistance using non pulsatile blood pump. As the results, useful evaluation of the renal blood flow had been embodied, suggesting the clinical usefulness of this device.

抄録全体を表示

In late years accidents due to health and the state of the driver increase. For those accident prevention, we developed the steering sensor which could measure the Vital signs of the driver for non-restriction. This sensor measures an electrocardiogram (the first instruction) and the pulse wave of the driver by holding a steering with both hands. Using two indexes, RRI and PTT (pulse wave propagation time) provided from these electrocardiograms and pulse waves, we tried the stress evaluation of the driver this time. First, we gave plural stress (mental workload) to five subjects in a laboratory and evaluated a change of RRI and PTT and confirmed that stress was discriminative. Then, we acquired RRI and PTT in plural driving environment and compared them with the subjectivity evaluation. As a result, we found the possibility that can distinguish plural driver's stress by using the steering sensor which we developed.

抄録全体を表示

In order to achieve safe, comfortable, and healthy life, products and services are needed to be developed on the basis of an understanding of human psychophysiological characteristics. To this end, I am engaged in research to develop technology for assessing mental state of human by mathematically analyzing physiological signals. Heart rate variability is one of the few physiological signals that can be measured stably without bothering ones daily life activity. We have done daily life experiments to clarify the relationship between autonomic nervous system physiological signals such as heart rate variability and mental state. Based on the daily life experiment, we have developed technologies such as ‘personal adaptive method to assess mental tension during daily life using heart rate variability’, ‘detecting “Hiyari-Hat” (“Startled”,“Near-Miss”) state using physiological signals’, and so on. In this presentation, I present about these technologies and discuss about the possibility and limitation for the future study.

抄録全体を表示

Many studies have investigated the relationship between mental load and biological signals such as heart rate and blood pressure. In such studies, the experiments involved attaching sensors on the bodies of test subjects to measure biological signals. However, there are concerns regarding the additional psychological stress on the subjects caused by these sensors. To solve this problem, we propose a new non-contact method to measure not only heart rate but also blood pressure variability. In this method, the time delay is calculated between two pulse waves obtained from different parts of a subject's body captured by a video camera. This index is considered to have a negative correlation with blood pressure variability because it approximates the pulse transit time obtained from a photoplethysmograph. The proposed index was calculated from video images of 20 healthy subjects performing the Valsalva maneuver. The results showed that the correlation coefficient between blood pressure and the proposed index was approximately 0.6.

抄録全体を表示

Nowadays, each of mental disorders is conceptualized as a clinically significant behavioral or psychological syndrome or pattern that occurs in an individual and that is associated with present distress (e.g., a painful symptom) or disability (i.e., impairment in one or more important areas of functioning) or with a significantly increased risk of suffering death, pain, disability, or an important loss of freedom. Whatever its original causes, it must currently be considered a manifestation of a behavioral, psychological, or biological dysfunction in the individual. Therefore, it must be admitted that no definition adequately specifies precise boundaries for the concept of mental disorder. In other words, at the moment we do not have any objective methodology which can distinguish normal from abnormal in mental symptoms and/or measure psychological stress. Based on the facts, we will discuss the possibility of measurement of psychological stress using medical engineering techniques.

抄録全体を表示

First, we aim to realize effective human-robot interaction in two scenarios: a robot (1) recommends short breaks for a person performing lengthy computer work and (2) promotes light exercise while a person is watching television in a living room. We study detection methods for reduced concentration levels to determine the appropriate timing of the robot's interruptions. Our results confirmed that heart rate and respiratory signals vary with concentration, and non-intrusive measurements are required in such cases; therefore, we introduced a chair with sensors. We use capacity-coupled electrodes for ECG measurements, and respiration is measured by changes in the back pressure detected by sensors attached to air bags. Second, we develop tools that assist users to learn breathing methods that can relax their minds and bodies. To guide the respiratory rhythm, we propose three easy-to-use prototypes: (1) a chair-type tool that applies music and illusory sensations called “phantom sensations,” (2) an iPad app that measures respiration using an embedded accelerator and controls the tempo of music, and (3) a stuffed toy for children that guides their respiration by inflating its abdomen.

抄録全体を表示

Model-based decision making requires representation of predicted states that are updated by action-dependent state transition models. To investigate their neural implementation, mice were trained to do a virtual navigation task and neural activity was recorded in the posterior parietal cortex (PPC) with the genetically encoded calcium indicator GCaMP6f and 2-photon microscopy.
A mouse was head restrained and maneuvered a spherical treadmill. 12 speakers around the treadmill provided an auditory virtual environment. When the mouse reached a virtual sound source and licked a spout, it got a water reward. The task had two conditions: continuous condition in which the guiding sound was presented continuously and intermittent condition in which the sound was presented intermittently.
We recorded activities of up to 600 neurons simultaneously in layers 2, 3 and 5 of PPC. From population activities, we decoded the distance to sound source; the predicted distances had no significant differences between continuous and intermittent conditions. The predictions were thus preserved irrespective of auditory inputs, suggesting the important role of PPC in action-dependent state prediction.

抄録全体を表示

Two-photon imaging is a powerful tool used to examine molecular and cellular functions in living tissues. In particular, calcium imaging can quantitatively measure neuronal activity i.e. action potential firing. Two-photon calcium imaging can detect the multicellular activity of neuronal circuits in the brain at the single cell level while animals perform behavioral tasks. Motor performance improves with repetitive training, and it has been proposed that this is mediated by functional and structural reorganization of the motor cortex. However, even without long-term training, animals can rapidly adapt to environmental change. To clarify how neuronal activities in the primary motor cortex (M1) are reorganized for long-lasting training and rapid adaptation, we conducted two-photon calcium imaging in the mouse M1 during 14-day training sessions of a self-initiated lever-pull task (Masamizu et al., Nat. Neurosci., 2014) and 15-min operant conditioning of single neurons (Hira et al., Nat. Commun., 2014), respectively. We found that the dynamics of neuronal activity during motor learning and fast neuronal operant conditioning depends on the layer structure and temporal timing of the activity.

抄録全体を表示

Functional loss of limb control in individuals with spinal cord injury (SCI) or stroke is attributed to interruption of descending pathways to spinal network. Although neural circuits locate below and above the lesion remain most of their function. I will show an artificial neuronal connection (ANC) that bridges supra-spinal system and spinal network beyond the lesion site restores lost function. The ANC was produced by a brain-computer interface that can detect the neural activity and converted in real-time to activity-contingent electrical stimuli delivered to nervous system. A promising application is to bridge impaired biological connections, as demonstrated for cortically-controlled electrical stimulation to muscles. Our results document that monkey utilized the artificial connection instead of residual connections. Recent work has shown that volitionally-controlled walking in individuals with SCI can be restored by musle-controlled magnetic stimulation to lumbar spinal cord. Thus, ANC can compensate for interrupted descending pathways. Furthermore, these paradigms have numerous potential applications, depending on the input signals, the computed transform and the output targets.

抄録全体を表示

This paper proposes a novel method of the risk assessment of sudden cardiac death based on 3-channel Holter ECG data. The proposed method intends to realize an accurate and efficient TWA detection on the data recorded under non-controlled common daily activity. A new index named α percentile of alternans ratio values ARP (α) is proposed as a useful measure for the risk assessment. The method examines the change in T-wave morphology based on singular value decomposition (SVD). The T-Loop divided into five sections is utilized for calculating the AR ratio defined as the relative frequency power at the Nyquist frequency. Then α percentile of ordered AR values ARP (α) are compared between subject with high cardiac risk and control subjects. It was shown that the index ARP(0.05) effectively classifies the high risk subject group. The method will be useful for the risk assessment of sudden cardiac death from the ECG data during the daily common activity.

抄録全体を表示

This paper proposes an efficient algorighm to classify the autonomic nervous activity based on the heart rate variability (HRV). Data has been provided by MIT-Harvard division of health sciences and technology. 14 volunteers'data were collected at 8 distinct states by drug administration. Binary decision scheme with three layered perceptron (3LP) was shown to be effective for the classification. Careful data cleaning and classification indices for each binary decision lead us to the accurate classification of sensitivity 0.897 and specificity 0.979. The pattern classification with Support Vector Machine (SVM) showed comparable performance with (3LP). The method employs relative power spectra hence useful for individualized health monitoring.

抄録全体を表示

This paper shows a method of evaluating the accuracy of the instantaneous heart rate reconstruction. A general evaluation scheme and a new evaluation index have been proposed and three reconstruction methods, Derivative of Cubic Spline Interpolation (DCSI), Resampled Instantaneous Heart Rate (RIHR) and Spline Smoothed Instantaneous Heart Rate (SIHR), are compared. Computer simulation based on Integrated pulse frequency modulation (IPFM) model with modulating signals having 1/f power spectrum characteristics has been carried out for comparison. A new index named the Effective bandwidth showed better performance in the following order, i.e. DCSI > SIHR > RIHR. It is also noted that SIHR have less estimation bias compared to DCSI in high frequency region. The method will be useful for precise characterization of the frequency domain characteristics of the heart rate.

抄録全体を表示

Motion After Effects (MAE) is a phenomenon that a stationary object seems to move in the opposite direction after observing the one-side movement for a while. MAE has been used to isolate neural activity related to the processing of motion perception in human. It has been reported that direction-specific activity can be detected from the steady-state visual evoked potential (SSVEP) (Ales & Norcia, 2008, Momose et al , 2014). Here we used the method, and investigated the effect of motion velocity on direction specific response in SSVEP. Four healthy university students (two males, 22.25±0.43 years old) with normal vision participated in the experiment. Stimulus was vertical sinusoidal grating of 2 c/deg. Test stimulus was 12 sec oscillating grating (4, 9, or 18 Hz) that presented immediately after the adaptor of 25.6 sec drifting grating (2, 4.5 or 9 deg/s). EEG was recorded during the test stimulus using a 64-channel Geodesic Sensor Net with 0.1-50Hz filtering. Fourier analysis was used to extract 1F and 2F responses. The phase of 1F responses depended on direction of adaptor agreeing with the previous studies. The brain area shown the MAE direction specific responses was dependent on the velocity of the adaptor.

抄録全体を表示

The objective of this study is to investigate the response properties of a spherical bushy neuron model in the antero-ventral cochlear nucleus in response to sinusoidally modulated pulsatile electric stimuli using computer simulations. In the computer simulation, we used a single compartment model of the modified Hodgkin-Huxley type consisting of sodium, high- and low-threshold potassium, and cation channels. The pulsatile electric stimuli was applied intra-cellularly to the neuron model, and then the transmembrane potentials were computed using the 4-th order Runge-Kutta method to generate the spike trains. To quantitatively evaluate the response properties, the period histogram was generated and then the vector strength was estimated from the spike trains. The simulation results show that as the modulation depth increases, the vector strength tends to increase, and that a modulation depth greater than 8% can encode information into the spike trains with an appropriate vector strength, like that observed in feline experiments. These results may give an insight into the better design of auditory brain-stem prostheses.

抄録全体を表示

It has been reported that therapeutic value of cancer chemotherapy depends on a period of treatment time of the day. This effect, circadian time-dependency of treatment, has been considered to come from interactions between cell cycle and circadian rhythm. In this study, we aimed to clarify a biological background of this effect by means of simulating therapeutic effect based on a model of cell cycle controlled by circadian rhythms. Here we constructed a cell proliferation model using a framework of stochastic automaton. During the cell cycle process, a cell is subject to DNA damage with a certain probability. Then the damaged cell dies or returns to the cell cycle, causing a phase response to the cellular circadian clock system. In the simulations, a cancer cell is characterized by prolonged or shortened duration of G1 phase of the cell cycle. We simulated proliferation of 10,000 cells population treated by a drug that increases death rate of cells in S phase. As a result, we found that morning treatment is most effective to maximize the damage to the cancer cells and minimize the normal cell's death.

抄録全体を表示

As for the novel technique supporting a medical intervention, two procedures exist. Blindness in one eye is completely an exploitation of novel medical equipment. Medical equipment was without carrying out an improved for a long time. However, I can develop the medical equipment to a fair human being by building two respects which connect a therapeutist, an instrumental, and a pt now. The second is the viscus model creation for a realistic understanding of human construction. The phantom of a trouble site is required again. I can conduct a positive surgery by performing a simulation using a phantom before surgery. A syngamy and integration of these two ways can perform an innovative medical.

抄録全体を表示

Concerning the medical device patent application in the Japanese Patent Office, as shown in Fig1, in 2013, the number of Japanese patent became less than that of the China and became the fourth. Fortunately, according to the medical patent data published by the U.S.P.T.O, Japanese patent is still the second in 2013. However, we must recognize this fact so as to establish a new patent strategy with design patent. Note that mixing design patents into a patent portfolio add new dimension of protection, in the biomedical engineering field. That is, inventors and/or companies that strategically procure design patents can add a key layer of protection to their medical device patent portfolio.

抄録全体を表示

The properties of cardiovascular device is closely correlated with blood flows. Because they depend on fluid force, excessive high shear stress related to hemolysis, and flow stagnation related to thrombogenesis. Thus, fluid dynamics analysis is a key technology to optimize the geometric design. There are two fluid dynamic analyses which are the CFD (computational fluid dynamics) analysis and EFD (experimental fluid dynamics) analysis. The CFD analysis is mainly used for simple geometry and steady flow with the result's validation of EFD analysis. On the other hand, the EFD analysis is mainly used for complicated geometry and/or unsteady flow. The important thing is that the results from those analyses should be corresponded with the pump properties. The correspondence is easily confirmed concerning the fluid force. But it is not so easily confirmed concerning the hemo-compatibility such as hemolysis or thrombogenesis because it requires enough clinical experiences. The rule of thumb turns to the quantitative index for evaluation established by several experts. Those evaluation technologies should be the powerful tool when developing various cardiovascular devices.

抄録全体を表示

We introduce examples of computational fluid dynamics (CFD) analysis of blood flow in continuous flow blood pumps as shown below. In all analyses, blood was assumed to be an incompressible Newtonian fluid, and Reynolds-average Navier-Stokes equations were calculated. Turbulence model which is suitable for wide range of Reynolds number was chosen.
VALVO Pump
An estimation method of hemolysis within blood pumps by CFD analysis was proposed.By applying this method, the design modification of the pump was carried out in order to improve the hemolytic performance.
VALVO Pump 2
Numerical analysis of the blood flow in the axial flow pump was conducted and the pump hydraulic performance and the hydrodynamic forces acting on the impeller were calculated to determine the parameters for the passive magnetic bearing.
Catheter-type VAD
Blood flow in the left ventricle under support with a catheter-type continuous flow blood pump was investigated numerically and experimentally. Assessment based on average wall shear stress on the left ventricular wall indicated that some of the combinations of the catheter tip shape and insertion depth improved the washout effect.

抄録全体を表示

To avoid the thrombus in artificial organs, especially rotary blood pumps and heart valves, it is necessary to understand the fundamental physical mechanism for thrombus formation on shear flows. The mechanism of thrombus formation is complicated because it includes biochemical factors. The main physical factors of thrombus formation are considered to be shear stress (shear rate), wall properties for blood's adhesion and transport process of aggregation factor in the flow. In spite of this complicacy, it is preferable for mechanical engineer to design the devices using the simple prediction tool such as CFD software. Concerning about CFD method, we have proposed two CFD approaches such as finite volume method (FVM) and lattice Boltzmann method (LBM) to predict thrombus formation.In this presentation, to establish the prediction method for thrombus formation by this CFD (FVM), the orifice flow with simple geometry and separation and reattachment flow as seen in the blood pumps is used for analysis. The CFD results are compared with the experiments to validate this prediction method by CFD.

抄録全体を表示

Performance criteria such as Pressure Gradient and Effective Orifice Area (EOA) are influenced by the change of flow passage profile which affect on the generation of vortices and turbulence. Consideration on shear stress is also becoming important if blood trauma is considered.In this presentation, relationship between prosthetic heart valve performance and blood trauma will be discussed through experimental flow analysis of heart valve. Ball, Tilting-Disk, and Bileaflet-type mitral prosthetic heart valve's performance was compared using Pressure Gradient and turbulent shear stress downstream of a valve using LDA system. Turbulent shear stress distribution and shear stress history at immediately downstream of aortic bileaflet mechanical prosthetic heart valves were compared using Dynamic PIV system.Based on the experimental analysis, following conclusion can be made. Valve profile and leaflet opening angle influence on generation of flow separation and turbulence which in turn will affect on Pressure Gradient, turbulent shear stress, and history of turbulent shear stress. Therefore, it is very important to consider detailed analysis of the flow field associated with heart valve.

抄録全体を表示

The present study aims to clarify the blood flow in a blood vessel perfused from a cannula during cardiac surgery with extracorporeal circulation. Figure shows the calculations of velocity profile in an aortic arch by STAR-CD. The three-dimensional calculation model of an aortic arch was made by Mimics using several hundred CT images. After the flow perfused from a cannula firstly impinges on the lesser curvature wall of an aortic arch, it flows along the wall. Then the flow leaves the lesser curvature wall and impinges on the greater curvature wall. The flow separates into right and left directions and generates vortices right and left sides of the impingement point.

抄録全体を表示

Numerical analysis studies for oxygenator have been conducted using a method focused on blood flow calculation, or a method that coupled flow with empirical formula or mass transfer equation. These results of each analysis would be useful information as design indexes for reduction of pressure drop, improvement of thromb-resistant property and enhancement of gas transfer performance to be a prerequisite for miniaturization required for the next generation of oxygenator. However, in most of oxygenators, it is not elucidated that the relationship between thrombus distribution and blood stagnant flow region after long-term use. Furthermore, most of investigations of gas transfer employ simplified numerical analysis method by focusing on oxygen transfer only. In this study, we compared the calculated flow velocity with thrombus distributions after 2 or 5 weeks continuous ECMO use in order to investigate thromb-resistant property, and compared the estimated gas transfer rates using our invented analysis method including reactions with the measured gas transfer rates in a part of oxygenator in order to investigate oxygen and carbon dioxide distributions between blood layer and gas layer.

抄録全体を表示

Introduction: Coronary stent fracture is recognized as causes of restenosis or thrombosis. We conducted finite element analysis (FEA) of coronary stent to predict fatigue failure under cyclic bend loading. Methods: Matched with manufacturing steps of coronary stent, a stent with a diameter, length and thickness of 1.8mm, 18mm, and 81μm was modeled. The stent was crimped on a balloon by applying enforced displacement until the outer diameter became 1.0mm. Next, the stent was deployed into a bended coronary artery model with an angulation of 125 degrees. Then, cyclic bend from 125 degrees to 105 degrees was applied to the stent. Results and Discussions: FEA of alternating stress, mean stress, and fatigue safety factor showed that there were nodes in unsafe zone in Goodman diagram. FEA suggested a threshold of cyclic bend angulation of the coronary stent on fatigue failure. Fracture locations observed in the cyclic-bend accelerated durability tests was consistent with the nodes of the stents which exceeded fatigue safety factor of 1. Conclusion: The comparison between FEA and accelerated durability tests indicated that FEA was useful to predict fatigue failure of the coronary stent.layer and gas layer.

抄録全体を表示

Therapeutic environment is highly developed but increasingly complicated by emergence of a new minimally invasive surgical technique, the development of various diagnostic and treatment equipment. Computer Aided Surgery (CAS) technologies contribute for the advancement of minimally invasive surgery using precise guidance system based on diagnostic imaging and robotics technologies. And it also provide us digital operation room environment, in which we can easily measure and analyze the surgical information. We are developing the technologies for guiding surgeons precisely and technologies for measuring and analyzing the digital information on the surgical navigation system to detect and evaluate the characteristics of surgical procedures and environments and also to predict the future outcome and effectiveness of the treatment. In this presentation, I introduces the results of trial experiments using these new navigation technologies and the possibility of the future navigation technologies for recording and evaluating a therapeutic procedure and environment in operation room.

抄録全体を表示

We have developed a multimodal nonlinear optical microscopy system to observe stimulated Raman scattering (SRS), coherent anti-Stokes Raman scattering (CARS), second harmonic generation (SHG), and two photon excitation fluorescence (TPEF) images simultaneously. By using the developed system, we observed atheroscleortic plaques formed in the aorta samples of spontaneously hyperlipidemic mice with apolipoprotein E deficiency. The histological structure of lipid, collagen, and elastin were visualized with SRS/CARS, SHG, and TPEF, respectively. The usefulness of SRS comparing with CARS for imaging of lipid distribution was also demonstrated because CARS images have high background signals originated from non-resonant background and/or autofluorescence of elastin. Three-dimensional reconstruction images of SRS/CARS/SHG/TPEF enabled to visualize the non-invasive three-dimensional tissue structure and detection of factors determining the plaque vulnerability including abnormally produced collagen and fibrous cap. The usefulness of the multimodal nonlinear optical microscopy system for the histological assessment and quantitative evaluation of the atherosclerotic lesion was demonstrated.

抄録全体を表示

In this talk, firstly we will introduce our developing 14T MRM(Magnetic Resonance Microscopy) system, of which minimum voxel size is about 20μ. And then, we will introduce our project of in vivo imaging of medaka fish for human disease model. It is expected that the development of disease will be able to be visualized at an individual level.Figure on the right column shows PDFF(Proton Density Fat Fraction) map of a medaka fish obtained by using 3d MRM in vivo imaging.

抄録全体を表示

Rapid advances in bioimage data acquisition technology made that image becomes the shining star in modern biology. Such image information of bioscience provides multidimensional digital data which quantitatively estimates complex natural phenomena. In future, numerical simulations with biophysics based on the image information may reveal mystery of living materials. We think that the key to reach such future from current biology is to integrate advanced image processing techniques into biology. Therefore, our team consisting of engineers, computer scientists, and biologists together has been working on developing new imaging and image processing techniques for biomedical data which are rich in variety of physical scales from organ to intracellular images. Medical image processing is highly advanced in computer science. However applying conventional methods to cellular and intracellular images is extremely difficult because of low signal-to-noise ratio imposed by hardware limitations and complex biological structures. On the other hand, these new problems raise a very challenging and interesting new field of study. Let's start with the bio-image processing together

抄録全体を表示

Cancer is the leading cause of morbidity and mortality worldwide. So many researches have been studied to overcome the disease. We have studied sonodynamic therapy (SDT). Our SDT is based on cellcidal effects of reactive oxygen species that are produced by the interaction between drug delivery system (DDS) and high intensified focused ultrasound (HIFU). A pharmaceutical company now investigates the DDS in a human clinical trial for conventional chemotherapy. The efficacy of the SDT has been demonstrated in a mouse model, and has been expected to realize a novel cancer therapy that is excellent in low invasiveness and little side effects, because the treatment will be provided by applying a combination of a low-energy HIFU and a minute quantity injection of DDS (1/6 dose injection compared with conventional chemotherapy). A clinical trial of the SDT has been projected in collaboration with medical devise companies (HIFU), pharmaceutical companies (DDS). We have started a discussion with PMDA (Pharmaceutical and Medical Devise Agency, Japanese regulatory agency).

抄録全体を表示

Molecular oxygen is one of the most important and a key molecule in aerobic organism. Recently, we reported that red phosphorescent iridium(III) complexes (BTP, BTPDM1) can be used as an optical probe for visualizing the oxygen levels of living cells and tissues. Here, we present the evaluation of the quantitative analysis of oxygen in living cells and tissues based on the phosphorescence lifetime measurements of BTPDM1 by using time-correlated single-photon counting (TCSPC) system. We measured the phosphorescence decay profiles of BTPDM1 delivered in the normal and tumor tissues of tumor-bearing mice by using a bifurcated fiber combined with the TCSPC system. The decay profiles of both tissues could be analyzed by double exponential decay functions. The average decay lifetime of the tumor tissue was remarkably increased as compared with that of the extratumor tissue, showing the lower oxygen levels of the tumor tissues. Based on the calibration curve constructed by using cultured cells, the oxygen levels of tumor and extratumor tissues were evaluated to be 6.1 and 50 mmHg, respectively.

抄録全体を表示

The advent of functional contrast agents and nanoparticle drug delivery systems (nano-DDSs) is opening new pathways to understanding pathophysiology using MRI. Nano-carriers for DDSs can contain multiple functional elements, such as therapeutic drugs, MRI contrast agents, fluorescent or luminescent dyes, and radioisotopes, without serious changes to the particle kinetics/dynamics. The development of such multifunctional nano-DDSs and imaging has accordingly become a subject of widespread research. Various materials have also been reported as nano-DDS carriers, including micelles, liposomes, emulsions, dendrimers, quantum dots (QDs) and carbon materials such as fullerenes, with each material providing a different set of characteristics as a nano- DDS carrier. I will summarize our recent research into nano-DDS-based contrast agents for MRI.

抄録全体を表示

The method to control the ferromagnetic drugs in the patient body using magnetic force has been studied in order to improve the efficiency of the drug treatment. In the conventional method the drugs are accumulated near the surface of the body. In this study we intend to solve the problem by rotating the magnetic field. The drugs which were given to blood vessel are attracted to the inside wall of the on-axis blood vessel by the rotating magnetic force and thus the drugs are accumulated. On the other hand the accumulation is prevented in the off-axis blood vessel because the blood flow washes out the drugs. The feasibility of this technique was confirmed experimentally.

抄録全体を表示

We established nano-particles loaded with indocyanine green (ICG) derivatives: ICG loaded lactosomes (ICGm) and investigated the diagnostic and therapeutic value of photodynamic therapy (PDT) using ICGm for experimental peritoneal dissemination of gastric cancer. Experimental peritoneal disseminaion of human gastric cancer were established in nude mice. Three weeks after intraperitoneal injection of the cancer cells, either ICGm or ICG solution was injected through the tail vein. Forty-eight hours after the administration of photosensitizer, in vivo and ex vivo imaging were performed. For PDT, 48 hours after the administration, other mice were irradiated through the abdominal wall, and the body weight and survival rate were monitored. In vivo imaging revealed that peritoneal tumors were visualized through the abdominal wall in ICGm-treated mice, whereas only non-specific fluorescence was observed in ICG-treated mice. PDT reduced the total weight of the disseminated nodules and significantly improved weight loss and survival rate in ICGm-treated mice. In conclusion, ICGm can be used as a novel diagnostic and therapeutic nano-device in peritoneal dissemination of gastric cancer.

抄録全体を表示

The heart is a mechanically functioning organ which consists of cardiomyocytes. Although it has been revealed that mechano-electric coupling plays an important role in cardiac physiology, it is difficult to investigate direct link between subcellular mechano-sensitive responses and tissue or organ functions in wet experiments. To integrate experimentally obtained findings in micro and macro study, we have developed a mathematical cardiac myocyte model based on Iribe-Kohl-Noble model. To describe mechano-sensitive properties, we implemented stretch activated channels (SACs), viscoelastic property of cytoskeleton or cytosolic structures, and shortening-rate dependency in troponin I (TnI) inactivation. Viscoelastic property in our model gave stretch-rate dependency in SACs activation, which reasonably reproduced mechanically induced ectopic beat after quick stretch and delayed increase in developed force after slow stretch. Shortening-rate dependent TnI inactivation reproduced afterload dependency in muscle mechanics previously reported. Our modeling study suggests advantages of computational biology in macro-micro integration in cardiac physiology.

抄録全体を表示

The organization of lateral domains, called lipid rafts, in plasma membranes is essential for physiological functions, such as signaling and trafficking. Membrane domains are considered to be a form of two-dimensional phase separation that develops due to the interaction between lipid molecules. To reveal the physicochemical properties of membrane domains, we have developed model membrane systems using multi-component giant vesicles. The vesicles which are composed of saturated and unsaturated lipids together with cholesterol show phase separation into domains. We clarified the shifts in phase structures within bilayer membranes with change in tension and temperature. The miscibility transition temperature between one-liquid and two-liquid states was shown to increase under tension (Soft Matter, 7, 9061-9068, 2011). We also found that membrane domains mediate the partitioning of nanoparticles in a size-dependent manner: small particles were localized in an ordered phase, whereas large particles preferred a fluidic disordered phase (J. Am. Chem. Soc., 134, 13990-13996, 2012).

抄録全体を表示

Endothelial cells (ECs) sense the hemodynamic forces, such as shear stress and stretch, and transduce blood flow information into functional responses that play important roles in vascular homeostasis and pathophysiology. A unique feature of shear-stress-sensing is the involvement of many different types of membrane-bound molecules, including receptors, ion channels, and adhesion proteins, but the mechanisms remain unknown. To determine how hemodynamic forces influence the cell membrane, cultured ECs were exposed to shear stress and examined for changes in membrane lipid order and fluidity by Laurdan two-photon imaging and FRAP measurements. Upon flow stimulation, the lipid phases of EC membranes changed from the liquid-ordered state to the liquid-disordered state in an intensity-dependent manner, and membrane fluidity increased over the entire membranes. Notably, a similar change in lipid order occurred in the artificial membranes of giant unilamellar vesicles, suggesting that this is a physical phenomenon. These findings indicate that EC membranes directly respond to shear stress by rapidly decreasing their lipid phase order and increasing their fluidity.

抄録全体を表示

Human mesenchymal stem cells (hMSCs) are expected to use as vehicles for delivering therapeutic genes to sites of injury and exposed to shear stress in that situation. However, the effect of fluid shear stress on the migration and the mechanisms are both limited. Using a parallel plate flow chamber system, we applied steady shear stress of 0.2 ～ 6 Pa to fluorescently labelled hMSCs. Cell migration was evaluated by the rate of wound area in the scratch injury assay. In the absence of flow (control), cells reached confluence at 10 h after wound performed. Under shear stress of 0.2 Pa, it was clear that flow stimulation caused notably faster wound closure than the control, which showed confluence at 6 h, while there was no significant difference in the migration of 0.5 Pa and 1 Pa shear stress groups compared with the control. Cell migration was prominently inhibited in higher shear stresses than 2 Pa. To understand the mechanisms the inhibitory experiments for MAPK family were carried out. The results suggest that JNK inhibitor abolished the effect of shear stress on migration of hMSCs, indicating that JNK plays a prominent role in shear stress-induced migration of hMSCs than ERK.

抄録全体を表示

We show here the data suggesting that enhanced hemodynamics in the asymmetric-shaped circle of Willis initiates cerebral aneurysm (CA) formation, using CA-inducing model and CFD analysis. CA develops at the circle of Willis, where blood flow is increased by a carotid ligation and hypertension. The number of induced CA was significantly smaller in knockout mice of P2X4 purinoceptor, the endothelial shear-sensor, than wild types. Endothelium may sense an enhanced wall shear stress (WSS), which initiates CA formation. In CFD, flow velocities derived from individual physiological data, but not commonly used assumed ones calculated with the average in healthy adults, should be used as inlet boundary conditions. In CFD analyses in the human MCA aneurysm, we virtually reconstructed the arterial geometry just before CA induction, and compared hemodynamics between CA-induced side and normal side. Normalized transverse WSS is significantly larger at CA side than normal side, suggesting that WSS temporal fluctuations in transverse direction to flow are involved in CA formation. To clarify mechanisms of CA enlargement and rupture, the prospective clinical trial, CFD ABO Study was launched.

抄録全体を表示

医療機器イノベーションを実現する人材を育成する教育プログラム　スタンフォードバイオデザインのグローバルファカルティトレーニングでの経験をもとに、バイオデザインプログラムの概要、および、本経験を活かして大阪大学にて実現しようとしているグローバル人材育成プログラムについて報告する。

抄録全体を表示

医療機器イノベーションを実現する人材を育成する教育プログラム　スタンフォードバイオデザインのグローバルファカルティトレーニングでの経験をもとに、バイオデザインプログラムの概要、および、本経験を活かして東京大学にて実現しようとしているグローバル人材育成プログラムについて報告する。

抄録全体を表示

医療機器イノベーションを実現する人材を育成する教育プログラム
スタンフォードバイオデザインのグローバルファカルティトレーニングでの経験をもとに、バイオデザインプログラムの概要、および、本経験を活かして医療機器産業企業にて実現しようとしているグローバル人材育成プログラムについて報告する。

抄録全体を表示

We have been developing a novel electronic musical instrument Cymis (Cyber Musical Instrument with Score), showing that persons with neural or motor impairments such as cerebral palsy can play the piece easily. The aim of the present study is to propose a basic idea of prospective music performance on the Cymis which may attenuate cognitive impairment and reduce the risk of dementia in the elderly. In the beginning, we have tried to show that Cymis performance could be an effective cognitive stimulus. Five subjects, university female students majoring music, were instructed to perform a song, keeping the constant tempo, with pointing each head of note displayed on the touch monitor. Two popular songs that they knew well were selected, under the conditions of with and without sound production, and regular tempo of 84[BPM ] and extraordinarily fast tempo of 150[BPM]. By examining both answers to fourteen questions regarding cognitive functions and results of performance, it was indicated that Cymis performance could be an effective stimulus to cognitive function.

抄録全体を表示

In Japan, the proportion of people aged 65+ in the total population is highest in the world: 25.1% in 2013. An increase of demented patients associated with aging is receiving a lot of attention. Very early dementia (MCI) is on the burner because of the possibility of the dementia progression prevention. We have early diagnosis tools for a causative disease and an assessment tools for dementia but no specific tools for MCI and very early stage dementia. Here, the effectiveness and problems of the Stroop task as dementia early diagnosis are discussed. The area performs this task was shown to be the frontal lobes where control high-order function from other papers. True time data without wrong answers of only non-demented subjects showed significant correlation between MMSE and Seroop task performance. The Stroop task was shown to be used instead of MMSE to detect MCI and very early stage dementia.

抄録全体を表示

Sosei Sanarudai Club starts it's service since 2012 as a general type of day service. Health indexes, such as toe gap force, time up and go test, functional reach test, weight etc. have examined every month from the beginning. It is well known that toe gap force is important index keeping away from fall. As time up and go test and functional reach test also seem to be relative indexes of fall, the relationship of three indexes was investigated. The interval of the investigation is from November, 2013 to November, 2014. Subjects were 9 elderly who took about 20 minute's exercise when they came to the day service. Correlation between the changing rate of each index during one year and the frequency of coming to the day service was inspected and toe gap force (left) was only one index that had the correlation coefficient of 0.622 (P=0.041).

抄録全体を表示

A quantitative and effective evaluation of a human lower limb movement is very important in clinical gait analysis. In particular, evaluating the gait condition of the individual elderly people is required for the fall prevention. Therefore, we propose “Leg motion measurement and gait evaluation system” which can be applied for clinical gait analysis. In this paper, we measured the striding movement over a virtual obstacle of elderly people by using the proposed gait evaluation system and analyzed the changes in the gait condition.

抄録全体を表示

There are a large number of elderly who have problems in their daily life as not being able to comprehend date or schedule so give up either at-home life or single life, due to their lowering of cognitive function. This project is to develop robot systems that is able to transmit information necessary for elderly' life to realize their autonomous self-sustaining life longer. On this report issues upon actual practice as well as influences on life or human will be revealed by introducing case study of long-term installed robot that support their scheduling at houses of the senior with mild cognitive impairment.

抄録全体を表示

Previously, we developed an integrated system of clinical diagnosis and treatment using “Computational Anatomy” models. This system is based on mathematical statistics using large amounts of CT image data. However, in clinical practice, diagnosis and treatment are carried out using a variety of medical images, such as CT, MRI, and pathological image. Therefore, it is necessary to develop a new model that integrates various medical images. Now, we develop “Multidisciplinary Computational Anatomy” models that combine time, space, functional, and pathology axes (see figure). Using this new model, we will develop highly intelligent diagnosis and therapy for difficult-to-treat diseases.

抄録全体を表示

The objective of our group, A01, is to develop mathematical foundations and fundamental technologies of multidisciplinary computational anatomy (MCA). A01 consists of three subgroups, A01-1, A01-2, and A01-3. The subgroup A01-1 aims to develop the mathematical foundations of the MCA, and the research topics include image registration and statistical inference. A01-2 aims to develop the fundamental technologies for integration of multiscale spatiotemporal morphology in MCA: Expanding conventional statistical shape models (SSM), the subgroup aims to, for example, construct new SSMs that bridge between images with different resolutions and/or different modalities. A01-3 aims to develop the fundamental technologies for integration of function and pathology in MCA: Integrating multimodal information, the subgroup aims to, for example, develop parametric representation of global and local shapes of organs with pathology staging. In the study of the above-mentioned topics, the subgroups collaborate together and A02 will apply the developed foundations and technologies to clinical systems. For the collaboration, the subgroups share clinical knowledge and medical images supplied by A03.

抄録全体を表示