When trying to sense and transmit intra-corporeal biological signal(s), unpowered passive telemetry is known solution for simplicity, size and weight and complexity reduction, and longer lifetime of sensor device, in spite of variety of design restriction. In our prior researches for encapsulated intra-corporeal pressure and/or soundscape telemetry sensor we used both powered (active) and unpowered (passive) methods, such as primary cell, secondary cell, body-fluid fuel cell, electromagnetic feeding, optical feeding, etc., however, all having its intrinsic pros and cons to prevent more extensive development for actual clinical use devising. In this study we use passive (non-power fed) sensor device on site with either ultrasonic or optical excitation and electromagnetic response reception. The method and system have unique affordable characteristics such that, unlike bidirectional electromagnetic coupling, system do not need T-R (transmission and reception) separation within a same kind of signal energy.

In this study, we studied the method of estimating continuous blood pressure only in one part of the body using PPG or non-contact Doppler radar. We performed regression analysis considering relationship between time of one heartbeat cycle and systolic blood pressure. The time of one heartbeat cycle was acquired using PPG and Doppler radar. Since the obtained regression equation included individual differences, we obtained a regression equation that does not include individual differences by using the time of one heartbeat cycle and the systolic blood pressure at rest as individual parameters. Comparing the blood pressure estimated using this regression equation with the reference blood pressure, we obtained the correlation coefficient of 0.9, which was sufficiently high. The potential of non-contact blood pressure measurement using Doppler radar is also shown.

At present, a method to confirm the presence of MSU crystals which are the cause of gout is desired. We have already reported the possibility of non-invasively detecting MSU crystals from outside by using their magnetic properties and near-infrared light. In this study, we investigated the behavior of crystals in a high viscous solution assuming joint fluid and the improvement of detection sensitivity using a polarizer. First, MSU crystals were grown in serum to be similar to those obtained from gout patients and dispersed in a highly viscous liquid. The transmitted light intensity increased when the magnetic field was switched on, and decreased when it was switched off. Next, the polarizing microscope was placed in the electromagnet and the behavior of the crystal was observed. As a result, the reflected light were disappeared. That is, the magnetic field were caused crystal rotation and a change in light contrast.

This paper reports on a magnetic resonance imaging (MRI) system for observing small samples. This system comprises micro gradient coils, a precise positioning mechanism, and a sample holder with a micro RF coil.The sample holder was fabricated by 3D printer, and the RF coil was fabricated by winding a copper wire onto the holder. Since small samples could be aligned at the center of the RF coil by using this holder, high-sensitive MRI images could be obtained. The gradient magnetic field could be strengthened by downsizing the gradient coils fabricated by assembling flexible substrate to 3D printed jigs.MRI images of the cooking oil were taken by our MRI system. The SNR of the MRI image was 61.5. The gradient magnetic efficiency of the gradient coils was about 57.8 mT/m/A. As a result, we realized that the MRI image measurement with pixel size of 50 × 50 μ m2.

Sentinel lymph node biopsy (SLNB) using magnetic tracers is a promising technique in the treatment of breast cancer to evaluate the presence of metastasis in sentinel lymph nodes (SLNs). Selection of the first SLN, which contains the largest amount of iron of magnetic nanoparticles, in some resected nodes can help to investigate the metastasis because cancer most likely metastasizes to that node. However, iron distributions in SLNs of varied sizes (generally 3-20 mm) are unidentified.In this study, we developed a device can quantify iron amount in SLNs without the dependencies of the distributions and sizes. The device, currently, quantified the iron in magnetic phantoms that is the size of 3-20 mm with varied iron-distributions, within the error of 10%. These results indicate the developed device is useful for quantifying the magnetic nanoparticles accumulating in SLNs.

The magnetic technique consisting of a magnetic tracer and a handheld magnetometer, is a promising alternative technique for sentinel lymph node biopsy (SLNB) and was shown to be non-inferior to the standard technique in terms of identification rates. In this study, injection characteristics (iron volume, dilution, time of injection and massaging) were evaluated to optimise magnetic tracer uptake in the sentinel lymph nodes (SLN) of a rat model. 202 successful SLNBs were performed. Iron uptake in the SLN is proportional (10% utilisation rate) to the amount of iron injected up to 1000 ug, showing a plateau uptake of 100 ug. Linear regression showed that time had a higher impact than dilution, on the SLN iron uptake. Massaging showed no significant change on iron uptake. The magnetic technique should be optimised for humans and a randomised controlled trial is required comparing the magnetic with the standard technique to change clinical practice.

Breast conserving surgery is a common surgery to treat localized breast cancer. Once the tissue is removed, it is sent to get an X-ray to check the margin. This process requires such set-up and radiology expert to do so. This research work proposes a method to detect the hook-wire by using a magnetometer. The magnetometer with a permanent magnet and hall sensor inside (Masaki Sekino et al, 2018) can be used to detect the location of the hook-wire having magnetic property. Normally this hook-wire makes different angels inside the tissue and considering the possibilities of different angles made by hook-wire, the calculation is done to detect the location of the hook-wire by this magnetometer which can detect magnetic particles in three-dimensional direction (Kuwahata et.al, 2017). Experimental data shows the magnetic sensitivity to be maximum when the asymmetry part faces the probe. Real surgery conditions would be considered in further experiments.

The magnetic technique was developed for lesion localisation and sentinel lymph node biopsy in breast cancer. A search for alternative techniques, due to susceptibility artefacts on breast MRI created by residual magnetic tracer led to the development and evaluation of four magnetic markers (with solid, barrel, spring and butterfly shapes). Different characteristics were evaluated: (a) marker detectability and repeatability, (b) marker migration, (c) MRI artefacts at 1.5T, 3.0T and 7.0T MRI and (d) biocompatibility of the marker. Sensitivity experiments demonstrated a lateral and anterior detection of 12.5-16.8 mm and 12.8-16.0 mm, respectively. Marker migration was not detected in a magnetic field up to 7.0T. On MRI, in all three dimensions, the smallest artefacts were seen with the butterfly marker. No leaching was found up to seven days after marker injection. The magnetic markers have promising characteristics for lesion localisation and a feasibility trial is required to determine proof of principle.

[Object] We evaluated the low frequency noise generated by two types of dispersive electrodes.[Method] Eight healthy subjects were enrolled in this study. The dispersive electrodes were set to the femur using two types of electrodes: conductivity type and capacitive type. The recording electrodes were placed on the inner vastus medialis (VM) and the rectus femoris muscle (RF). The low frequency noises (1-200 Hz) were compared between two types of dispersive electrodes.[Result] With respect to noises in VM, the mean volumes with capacitive type and conductivity type were 53.9± 3.16 dB and 48.0±1.03 dB, respectively. The mean RF noises with capacitive and conductivity type were 63.2± 1.73 dB, 56.5±1.51 dB, respectively. The noises of the capacitive type were significantly larger than the conductivity type.[Discussion] Our results indicate that the capacitive type of dispersive electrodes more affect IOM recordings than the conductivity type.

The purpose of this study is to examine whether frequency response of electric impedance can be used as a new evaluation method for cell survival. A sample chamber (inside diameter 22 mm) by which 64 micro electrodes to the inside of the area of 50 x 50 micrometers of central parts were arranged was used, the surface of the chamber was covered by collagen, and rat heart striated myocytes were cultured. The cells in the chamber were extinguished by heating, frequency response of the cells before and after heating was measured in the range of 10 to 100 kHz, and then extinction of the cells were evaluated using trypan blue exclusion assay. As a result, cellular impedance after heating was lower than that before heating in low frequency. Therefore, it was suggested that frequency response of impedance measurement could be used as a survival evaluation of cells.

In the study of biological effects of ELF electric field, we found the change of blood flow in the field exposure. We also found more aggregated RBC's in the blood which was sampled right after the field exposure to a human body. To elucidate the mechanism of the blood flow change, human blood was exposed to a controlled electric field in vitro. In this study, we newly introduced transparent ITO electrodes to realize more realistic and higher (100 kV/m) field exposure than before. In the sham-exposure condition, apparent change in blood property was not observed. In the field exposure, we found the significant (p<0.01-0.05) increase in the aggregated RBC's than that in the sham-exposure. The evidence by dose-response characteristics was confirmed. This suggested that the blood flow change in field exposure is caused not only by the physiological changes but also by the physical change of blood properties.

The dielectrophoretic movement of biological cells around the tip of the surface electrode in the flow channel has been observed in vitro. The surface electrodes of titanium are made along the edges of the parallel-piped micro flow channel by the photolithography technique. The electrode at the one of the edges has the triangle shape. One of three modes of cyclic electric stimulations (0.01 ms period) was applied between the surface electrodes: sinusoidal, pulse, or rectangular. The suspension of cells of C2C12 (mouse myoblast cell line originated with cross-striated muscle of C3H mouse) was injected to the flow channel, and the flow rate was controlled by the syringe pump. The experiment shows the following results. The movement of myoblasts around the tip of the electrode changes by the electric stimulation through the surface electrodes during the flow along the channel. The movement depends on the tip angle of the electrode.

Real-time detection of local behaviors of systemically administered drugs in vivo is necessary to develop effective medical therapies. Yet, conventional methods require considerable samples quantities and have poor sampling rates. Moreover, they cannot address how drug kinetics correlates with target function over time. Here, we construct a system equipped with two different sensors. One is a needle-type of boron-doped diamond microsensor, and the other is a classical glass microelectrode. We first tested a diuretic, bumetanide, which can induce deafness. In the guinea-pig cochlea, changes of bumetanide concentration and the extracellular potential underlying hearing were simultaneously measured in real time. In the rat brain, the kinetics of an antiepileptic drug, lamotrigine, was tracked at the same time as the extracellular potentials representing neuronal activities. The actions of an anticancer drug, doxorubicin, was also monitored in vivo. This microsensing system would clarify local pharmacokinetics and pharmacodynamics of different drugs in various organs.

We are developing a 4D human body model in which all the internal structures operate while deforming in real-time without "anatomical contradiction", by using a whole-body 3D human model (including internal structures such as major organs, skeleton, vascular system, etc.) reconstructed from MRI data and driven by the motion captured data of the participant.Regarding the evaluation of model deformation, the upper limb and the lower limb were targeted, and the measurement was performed using MRI. However, it is difficult for MRI currently used clinically to measure a certain volume as measured by MDCT of volume data at high speed. Therefore, we developed a device in which the participant could repeat the motion in a stable manner in the gantry to obtain a 4D dataset.We report here our examinations about deformation methods and the possibilities for their clinical applications of the human body model under development.

In this paper, we propose sparse feature extraction methods using virtual planning data in mandibular reconstruction. Although research to automatically generate surgical plans has been done, the mechanism of estimation was empirically designed based on insights of researchers. If relationships between clinically designed surgical procedures and quantitatively extracted features are clarified, the findings will contribute to the surgery. The proposed method estimates the number of segments and extracts the features by sparse modeling using a past planned data. We conducted experiments to extract dominant features for binary classification on the number of fibular segments. The results showed that three of the front lower jaw angle, the distance between the right angle and the right cutting plane, and the distance between the left mental tubercle and the right cutting plane are particularly important for classification.

Motion analysis of finger trajectory and posture is useful for evaluating the high precision manipulation in medical and sports fields. Measurements of the force acting between hand and tool are important for a quantitative evaluation of motion. However the insertion of force sensor has undesirable effects in the experiment because the thickness of sensor gives a sense of incongruity to the operator during actual motions.Force myography (FMG) is proposed for the estimation method of muscle activities. This method focuses on the local rise and down of the body segment surfaces accompanying the muscle contraction. And the response of the pressure sensor array wound around the target is used for detection of motion. In this study, we developed a FMG measurement device and applied the finger motion analysis in the case of catheter wire pinching. The possibility of quantitative pinch force estimation was shown in the experiments.

Stroke often leaves with spasticity which increases muscle tone. For an accurate assessment of ankle spasticity, automatic devices that measure a resistance torque during passive dorsiflexion have been developed. However, conventional methods have not been successfully distinguishing spastic, elastic, viscous, and inertial torques around the ankle joint. The distinguish among these torques is essential to determine treatment. In this paper, therefore, we developed a novel device which dorsiflexes the ankle joint and measures the resistance torque and ankle angle. As the first step, we formulated the relationship between the elastic torque and the angle. The proposed model includes an elastic model of three muscles; tibialis anterior (TA), agastrocnemius (GC), and soleus (SL).

Most of conventional methods to evaluate the design of knee prosthesis need the assumption about joint load, contact location or so, and they usually are calculated two-dimensional simple model without considering the joint shape. Therefore we created the 3D mathematical model to analyze the knee mechanics. The features of the model are that, driven by the muscle forces, including both patellofemoral and tibiofemoral joints connected by patellar tendon, including the condition of point contact using free-form surface, outputting the muscle forces to achieve the force/moment equilibrium, and targeting the deep knee flexion to consider the contact of muscles and bones or include thigh-calf contact force. We tested the model to check the effect of tibial rotational alignment to a patellofemoral joint. As a result, we could achieve the solutions during deep knee flexion, and confirmed the medial patellofemoral contact force increased by tibial internal rotational alignment.

In univentricular Fontan circulations, morphological variations of systemic ventricles make it difficult to evaluate the negative impact of asynchronous contraction and widened QRS duration on hemodynamics. A computational simulation of Fontan circulation was performed using a time-varying elastance chamber model combined with a three-element Windkessel vascular model. Systemic ventricles were divided into two ventricular compartments (Vnt₁, Vnt₂) by ventricular septal defects, which had various ratios of end-diastolic volumes (EDV₁/EDV₂, α). We introduced contraction delay between Vnt₁ and Vnt₂ (T_dys) and simulated hemodynamic changes. Compared with the ventricles with α > 1, those with α < 1 exhibited significantly decreased cardiac output as T_dys increased. These deteriorations were characterized by the increased reverse flow from Vnt₂ to Vnt₁ during mid-systole. Delayed contraction in more distensible compartment can exacerbate mechanical dyssynchrony with the dilation of less distensible compartment in mid-systole, which contributes to the pathogenesis of heart failure in the univentricular heart.

Heart failure with a preserved ejection fraction (HFpEF) now accounts for half of patients seen. These patients have life expectancy similar to patients with reduced systolic function. Some echocardiographic studies show that patients with HFpEF have reduced peak strain. However it seems to be strange that reduced systolic function and preserved ejection fraction are both consistent. We feature initial thickness of cardiac muscle, it is calculated cardiac contractive force to accomplish ejection fraction of 50% with thick-walled cylinder models, which adopt 40-50mm in inner diameter and 8-16mm in thickness. It is simulated under considerations of slightly compressibility, Newtonian viscosity, anisotropic elastic force and contractive force along cardiac muscle fiber. As the result, higher contractive force are necessary for thick wall model, in spite of average circumfential strain is reduced. It is indicated that more contractive force for cardiac muscle of HFpEF are needed for same work because of myocardial hypertrophy.

We have proposed a new methodology for tachyarrhythmia catheter ablation using a photosensitization reaction to reduce complications. To understand the necessary time for electrical conduction block on myocardial cells against the photosensitization reaction, we investigated the intracellular Ca²⁺ synchronicity on electrical conduction wire of cultured myocardial cells. By fitting with the measured data, we constructed a mathematical model of the three-compartment of conductive, vulnerable, and blocked. Rate parameters between the compartments were optimized. We estimated the change of vulnerable cell ratio, which would risk the tachyarrhythmia recurrent, using the constructed model with the optimized rate constants to evaluate the stability of the treatment.

The cause of VT/VF is spiral wave reentry(SWR). In recent years, an endoscope was inserted into the left atrium of the sheep heart, and action potential of left atrium was measured simultaneously by optical mapping method using two high speed cameras, endocardium and epicardium at the same time research has been reported. As a result, it has been suggested that I-shaped type filament, which is the SWR center, stays in a site where the myocardial wall thickness changes drastically. However, in the ventricle, anatomical structure is complicated and measurement signals require high resolution, so simultaneous measurement of action potential signals is not done sufficiently. Therefore, in this research, we developed a system that can simultaneously measure action potential signals using two high speed cameras, and we report the phase analysis method which quantitatively shows the correlation between anatomical structure and I-shaped type filament which is the SWR center.

Although it is believed that excessive action potential (AP) prolongation leads to the development of early afterdepolarizations (EADs), the triggering mechanism of EAD-induced ventricular arrhythmias is not yet fully understood. Combining computer simulations with numerical computations based on dynamical system theory, we have investigated dynamical stability changes of AP observed in a paced human ventricular myocyte model with decreasing and/or increasing the rapid component of delayed rectifying K+ current (IKr) and the slow component of delayed rectifying K+ current (IKs). We found that upon reducing IKr, EAD emergence resulted from the dynamical stability change in AP. Furthermore, reducing the repolarization currents evoked multi-stable dynamics including AP with EADs depending on initial ion circumstances within the myocyte. This multi-stability in cardiac AP dynamics might be responsible for the EAD-induced arrhythmias with decreases in the repolarization currents.

The mainstream method for cuffless blood pressure is that based on pulse transit time. However, there are many inconveniences in this method such as requiring simultaneous measurement of electrocardiogram and photoplethysmogram and frequent calibration using a cuff sphygmomanometer. So, we developed a far simpler method to estimate blood pressure only using a heart rate and modified normalized pulse volume that can be measured using a smartphone alone. In this study, we examined its accuracy against conventional brachial cuff sphygmomanometer. Mental arithmetic task was used to alter blood pressure in 13 healthy subjects. Analysis revealed that the correlation coefficients between these two were .73, .73, and .72 for mean blood pressure, systolic blood pressure, and diastolic blood pressure, respectively. Results suggest that this simple method can yield moderately reliable measures of blood pressure.

Background: Baroreflex function stratifies cardiovascular risks, however, the method to estimate its loop gain (G) has never been identified in patients. We hypothesized that the ratio of power spectral density (PSD) of arterial pressure (AP) considering baroreflex frequencies yields G. The aim of this study is to examine the feasibility to estimate G in rats and in humans. Method: We created graded severity of baroreflex failure in 21 rats, estimated their G from AP, and compared them with those obtained via actual measurement. To examine their clinical applicability, we estimated G from AP in 25 volunteers, and verified as age-dependent decrease. Results: In rats, G estimated from PSD correlated linearly with those measured (R2=0.87). In human, G in young (28.7±6.2 y.o.) was markedly higher than that in elderly (85.8±3.8 y.o.) (2.54±1.06 vs. 0.66±0.65, p<0.01). Conclusions: G can be estimated from PSD of AP.

Introduction: Although autonomic dysfunction is recognized as a central mechanism of orthostatic hypotension after microgravity exposure, how microgravity affects the baroreflex remains unclear. We elucidated the effect of simulated microgravity on the baroreflex by using open-loop analysis.Methods: We unloaded hindlimb (HU) of Sprague-Dawley rats to simulate microgravity. Two weeks after HU, we isolated carotid sinuses from the systemic circulation. We compared the carotid sinus pressure (CSP)-sympathetic nerve activity (SNA) (central arc) and SNA-arterial pressure (AP) relationships (peripheral arc) between HU (N=7) and control (N=3). Results: Compared to control, HU reset the central arc to the higher pressure range, and flattened the slope of peripheral arc. Those changes in baroreflex synergistically and markedly decreased the total baroreflex loop gain (CSP-AP relationship) at the operating point(0.21±0.14 vs. 1.33±0.23, p<0.01).Conclusion: The microgravity induced loss of baroreflex gain may play an important role in the pathogenesis of orthostatic hypotension after regravitation.

A prudent investigation of the features space of electrocardiogram (ECG) will propel the performance of machine learning algorithms in arrhythmias detection. features in the morphological and temporal domain are sometimes blurry in a noisy signal, which is very common in wearable devices. In this study, we assume that for one ECG waveform (one cardiac cycle), its statistical features and its relation with preceding and following ECG waveforms, which are represented by R-R interval, can give us enough physiological/pathological information to isolate the arrhythmias from heartbeats of normal sinus rhythm. The atrial fibrillation, the ventricular bigeminy, and ventricular trigeminy waveforms are extracted from MIT-BIH arrhythmia database and long-term atrial fibrillation database to take into account the inter-individual difference. self-organizing map and bagging tree ensemble are used to analyze and classify the heartbeats.

Atrioventricular (AV) node is one of the cardiac conduction system of the heart. The AV node is the only electrical conduction pathway between the atria and ventricles. Therefore, the AV node acts as important roles in cardiac function. However, the detailed mechanisms of the AV node have not been understood. The purposes of this study are to construct a three-dimensional anatomical model of the AV node and to simulate electrical excitation conduction and arrhythmias in the AV node. The anatomical model constructed in this study includes the right atrium, three AV node regions and right ventricle. Action potential models to calculate electrical activity were included into the anatomical model. Using our model, electrical excitation conduction from the right atrium to the bundle of His via the AV node properly and reentrant beat in the AV node. Our model is useful to analyze function of the AV node.

This report proposes a method to improve the vascular age estimation from the acceleration pulse waveform (APW). There are some cases where the expected peaks in the APW are not separated. These cases frequently happen for the young subjects aged 20-30. We have shown that the introduction of the third derivative of the original pulse wave enables to differentiate the missing APW peaks. The adaptive procedure of pulse wave selection is proposed to obtain the representative parameter values for the subject. The procedure adopts the correlation between parameter vector obtained from each beat with median parameter vector of the subject. Finally, principal component analysis of the derived indices is applied to determine the vascular age estimation coefficients. The proposed method is applied to 522 subjects aged from 3 to 87. For the subject age range between 20-60, the significant improvement for the vascular age estimation has been confirmed.

Background: Although interatrial shunting device (IAS) for heart failure patients has been launched in clinical, its quantitative impact on hemodynamics remains unknown. We developed the circulatory equilibrium framework to estimate the impact of IAS on hemodynamics.

Theoretical consideration: Circulatory equilibrium framework describes hemodynamics by cardiac output curve and venous return surface. We incorporated IAS in it and estimated hemodynamics under IAS.

Method: In 5 mongrel dogs, we connected the atria with a centrifugal pump to mimic IAS hemodynamics. We changed shunt flow and compared estimated hemodynamics with those measured.

Result: The estimated systemic flow (r²=0.93, SEE 12.3 ml/min/kg), pulmonary flow (r²=0.93, SEE 11.7 ml/min/kg), left atrial pressure (r²=0.81, SEE 0.72 mmHg) and right atrial pressure (r²=0.86, SEE 0.59 mmHg) matched well with those measured irrespective of volume status.

Conclusion: Our proposed framework estimated hemodynamics under IAS quantitatively. It may contribute to the safe management of IAS for heart failure patients.

To treat stenotic artery, short-term thermal angioplasty named Photo-thermo Dynamic Balloon (PTDB) has been proposed. According to our previous study, smooth muscle cells (SMCs) were stretch-fixed after this vascular dilatation. If this formation is cytotoxic, there might be a risk of restenosis because of enhancement in SMC migration ability. To estimate SMC migration ability after PTDB, we studied the respiratory activity of SMCs by a short-term heating/stretch-fixing up to 96 hours in vitro. SMCs on the stretch chamber were heated (50°C or 60°C, 15 s) with stretching (up to 50%). As a result, the activity of 60°C heated SMCs was drastically decreased in every stretching rate. On the other hand, the activity of 50°C heated SMCs was decreased more gradually than that of 60°C. We think that heating SMCs over 60°C might sufficiently suppress the migration of SMCs and chronic restenosis in PTDB.

During dialysis, patients had often been in shock state by sudden fall in blood pressure. To prevent this situation, paramedical had measured their blood pressure using a cuff-type sphygmomanometer. However, those measurements are not enough to detect the accident as the measurement interval is over 30 minutes. Furthermore, frequent pressuring by the sphygmomanometer causes a patient discomfort and pain. Therefore, we studied methodology for continuous blood pressure monitoring without pressure measurement.The measurement principle is prediction of Pulse Wave Velocity (PWV) at a section of aorta using Electrical Impedance Tomography (EIT) data and estimation of blood pressure. As a previous stage of PWV measurement, we verified correlation between Pulse Arrival Time (PAT) and blood pressure using EIT data in this study. Then we calculated PAT and verified the correlation coefficient as 0.70 in a normal subject. The result indicated that continuous blood pressure measurement would be possible using EIT technology.

The purpose of this study to expand the construction of blood vessel network in multiple ultrasound volumes from different directions using a vascular network structure, and to reconstruct a wider range of vascular network information.

The structure of blood vessel networks was extracted from an ultrasound volume to graph with three-dimensional thinning processing. Next, we performed spatial registration using the common branch point between adjacent volumes, and calculate the homogeneous transformation matrix between the volumes. Then, blood vessel networks were expanded by placing them in the same coordinate system.

We examined with the ultrasound volumes of a porcine liver, which was obtained from different directions. By comparing the calculated network with that in the CT volume, we confirmed that there were 23 common bifurcation points between them to indicate the possibility of extension using this method. We also applied this method to human livers.

(Introduction) The body consist of water about 60%, is controled intracellular and extracellular fluids in various ways. And this fluid has specific frequency characteristics by its structure and composition. The organ take necessary elements from the outside, and emit unnecessary ones. This movement is chemically and physically methods. Several diseases break down these mechanism. So, detecting these changes is applied for diagnosis and treatment.(Object) Measuring the bioelectrical impedance method, we can get the information of body, which makes for diagnosis and treatment applications.(Method) We try to make for the application for diagnosis and treatment by this measurement of the change of bioelectrical impedance.(Result) We accumulated a database of frequency characteristics of fluids, skin, subcutaneous tissues and muscles in body. We made for the applications of diagnosis and treatment method.(Conclusion) It is possible to acquire biological information, for making diagnosis, and treatment by transmitting information from outside.

Recently, for the ECG measurement, wearable heart rate (HR) devices using textile electrodes has been developed. Because the conducting property of non-adhesive textile electrodes are largely affected by body posture and movement, a stable and reliable ECG analysis technique is required. As a new technique of ECG analysis, here we investigate the application of the multi-scale Savitzky-Golay (S-G) differential filter. The S-G filter is the FIR filter that smooths a signal by least squares polynomial fitting. Furthermore, the S-G differential filter is given by the differential coefficient of the fitted polynomial. Since the S-G differential filter is represented as a FIR filter, the filtering is implemented by a convolution. In this paper, we develop the fast algorithm of the S-G differential filter and introduced the multiple scale approach of the filtering. Using this approach, we propose peak and waveform detection algorithms.

The purpose of this study is to evaluate precision of heart rate variability by pulse wave on different postures to R wave. Simple wearable devices with pulse wave are attracting for not only many experts but also ordinary people concerned with health promotion.In this study, ECG and pulse wave were simultaneously recorded on each of different postures for 5 minutes. The differential intervals between R-wave and pulse wave peak were detected. Then, heart rate variability on Tone-Entropy analysis was examined whether or not the differential time interval between R-wave results and pulse wave ones can be permitted as autonomic nervous system activity. From our results, entropies between sitting and upright positions have statistically significant difference with (ex.)p<0.05. In conclusion, our results show that heart rate variability with pulse rate should prevent to measure autonomic nervous system activity in, especially, sitting and upright positions as much as possible.

Nail tip sensor is novel wearable sensor attaching to fingernails like gel nail. This nail tip sensor is developed as remote monitoring device in home medical care and health application for personal health care. The nail tip sensor can measure vital data without uncomfortable feeling, because sensory nerves and sweat gland is not distributed in finger nails. Multi point simultaneous measuring is also realized by the sensor, because human body has twenty nails. In this research, multi point simultaneous measuring is focused. Distance from heart to hand is different form distance from heart to foot, thus difference of pulse wave transit time (PWTT) is occurred. In this research, PWTT is measured using miniature photoplethysmography sensor attached to nail of hand and nail of foot. And pulse wave velocity (PWV) is calculated from the PWTT. It is hoped that blood pressure and arteriosclerosis is evaluated from the PWTT.

Recently, it has become to be recognized that companies should treat employee's health as the valuable business resource. In Japan, the productive age population is decreasing and the ratio of older worker in the productive age population is increasing. Thus, to maintain the productivity, the health management of employees becomes increasingly important. Here, to enable the effective health management, we study the application of a smart clothing measuring heart rate and physical activity. Through the analysis of the monitoring data of construction crews, we developed new health condition indices based on both heart rate and physical activity. Our indices showed statistically significant correlation with the subjective health condition of the workers. In our presentation, we will discuss the application of the indices.

The professional role of nursing is to accurately collect patient's biological information and living environment and to share information with doctors and co-medical. Medical information gathered by nurses is an important role in determining the quality of medical care. In this presentation, I will report the "engineering + medicine + nursing science" research conducted by the speaker.

Chronic sympathetic activation causes clinically important arrhythmias including atrial fibrillation (AF) and ventricular arrhythmias. Pharmacological inhibition of the β-adrenergic receptor (β-AR) signaling by β-AR antagonist (β-blocker) has been widely utilized in the treatment for heart failure, AF and ventricular arrhythmias. However, a major problem in introducing β-blocker therapy is the worsening of cardiac function. Adenylyl cyclase (AC), a target enzyme of β-AR signaling, expresses in multiple isoforms that differ in their tissue distribution and biochemical properties. By computer-based drug screening system, we previously found vidarabine, an anti-herpesvirus agent, as a drug to selectively inhibit the catalytic activity of cardiac AC subtype. Vidarabine and metoprolol, a β-blocker, consistently shortened the duration of AF and reduced the incidence of sympathetic activation-induced ventricular arrhythmias, whereas only vidarabine did not significantly affect cardiac function. These findings suggests that pharmacological inhibition of cardiac AC may be useful for the prevention and/or treatment of arrhythmias.

Background: Unlike ordinary diuretics, Tolvaptan minimally affects hemodynamics. We examined the impact of Tolvaptan on stressed blood volume (SBV) by circulatory equilibrium framework. Methods: In anesthetized mongrel dogs, we administered Tolvaptan (3mg/kg, N=5) or Furosemide (0.8mg/kg, N=5) intravenously. We estimated SBV from the circulatory equilibrium using the venous return surface: SBV=(CO+19.61*PRA+3.49*PLA) / (0.129*body weight); CO, cardiac output; PRA, right atrial pressure; PLA, left atrial pressure. We measured urinary volume (UV), arterial pressure (AP) and SBV simultaneously until 1 hour after the drug administration, and compared those of Tolvaptan with Furosemide. Results: Both Tolvaptan and Furosemide increased UV. In contrast, Tolvaptan decreased SBV and thus AP much less than Furosemide (p<0.05). Conclusion: Tolvaptan induces diuresis and preserves stressed blood volume, thereby stabilizes hemodynamics. Understanding hemodynamics by using circulatory equilibrium framework contributes to the safe management of patients with cardiovascular diseases.

Open-loop systems analysis is useful to understand sympathetic arterial pressure control by dividing the arterial baroreflex system into neural arc and peripheral arc subsystems. We have investigated the effects on sympathetic nerve activity (SNA) of cardiovascular agents using the open-loop systems analysis.Regarding dihydropyridine Ca2+ channel blockers (DCCB), both cilnidipine (a second-generation DCCB) and azelnidipine (a third-generation DCCB) were expected to suppress SNA. However, these drugs did not suppress SNA, as in the case with nifedipine (a first-generation DCCB). Regarding beta blockers, two of most commonly prescribed beta blockers, metoprolol and carvedilol were compared. These drugs did not acutely affect the neural arc. Carvedilol, but not metoprolol, decreased arterial pressure, suggesting that carvedilol exerted peripheral vasodilation via its alpha blocking action.The open-loop systems analysis enables quantitative descriptions of the drug effects on baroreflex neural and peripheral arcs.

In the management of patients with unstable hemodynamics of severe heart failure or septic shock, cardiovascular drugs such as inotropes and/or diuretics are used to restore arterial pressure, cardiac output, right/left atrial pressure. Since responses to these drugs vary between patients and within patient over time, strict monitoring of patient condition and frequent adjustments of drug infusion rates are usually required. This is a difficult and time-consuming process. Furthermore, since the number of expert care providers specialized in the management is limited, it may be difficult to provide appropriate hemodynamic management to all the patients with severe hemodynamic failure. To facilitate this process and make the management available even with non-expert providers, we have been developing closed-loop drug infusion systems to automatically restore hemodynamics in severe hemodynamic failure. We introduce our approach to control the hemodynamics and a variety of drug infusion systems developed so far.

We have the development of point of care devices using advanced photonics technology. In this paper, we show our drug measurement system based on a paper with photonic crystal and our photoacoustic system by LED light source.Our therapeutic drug monitoring system composed of a paper and photonics crystal based on the nanostructure which designed for drug monitoring.

Progress in regenerative medicine, robotics and ICT will realize the integration of artificial materials into living systems. In this regard, bio-materials interface should be compatible to chemical, physical and mechanical environments of biological tissues. Our group focused on free-standing polymeric ultra-thin films (referred to as nanosheets) with tens- to hundreds-of-nanometer thickness, which showed flexible and adhesive properties owing to their ultra-thin structure. We utilized such unique physical properties for wound dressings, sealing the tissue lesion without adhesive glue. In this study, we envisaged the development of nanosheets towards implantable device, allowing for the integration of electrical elements into the living body. Specifically, we developed "printed nanofilms" by combining nanosheets and printing technology to pattern conductive lines or embed electrical elements on the nanosheet. We also developed the nanosheet-based implantable device, and demonstrated the measurement of neuronal signals in a brain or local photoirradiation in photodynamic therapy.

Metronomic PDT (mPDT) obtains selective apoptosis of malignant tumor by delivering light at low intensity (<1.5mW/cm2) and extended period (a few days). As working with weak light, mPDT is expected as a novel therapy for malignant disease in deeply located organs by using implantable optical devices. However, few data indicated the effectiveness of mPDT.To investigate anti-cancer effects of mPDT, we used a mouse cancer model bearing two homologous intradermal tumors on their back. Following administration of photosensitizer, illuminating one tumor with an optical device resulted in significant growth suppression on both light-irradiated and non-irradiated tumors in one animal, and longer irradiation time induced stronger anti-tumor effects on both tumors. These results showed that mPDT leads to suppression of tumor growth in not onlylocal tumor but also distant disease, suggesting the activation of systemic anti-tumor immune response. This modality has a potential in the systemic treatment of advanced cancers.

Recently, flexible electronics has much attracted to realize bio medical application for their flexibility and conformability. To improve these characteristics, reducing the thickness of the device is very effective. We have developed ultra-flexible and lightweight organic electronics and photonics with few micron substrates. We fabricated the 2-V operational organic transistor which has very thin gate dielectric layers. The gate dielectrics were composed of aluminium oxide layer and self-assembled monolayers (SAMs). And also we fabricated ultra-flexible light-emitting diodes (OLEDs) have been manufactured on one-micrometer-thick substrates. The total thickness of the devices, including the substrate and encapsulation layer, is three micrometers, which is one order of magnitude thinner than the epidermal layer of the human skin. The OLEDs are directly laminated on the surface of skin and are used as indicators/displays owing to their amazing conformability. The PLEDs are integrated with organic photo detector and were used as pulse oximeter.

Diabetes mellitus is defined as a group of metabolic disorders characterized by high blood glucose levels. To control the blood glucose levels for treatment of diabetes mellitus though insulin therapy, it has been recognized important to accurately and continuously monitor the blood glucose levels. In recent years, non-enzymatic glucose sensors develop to overcome the limitations of conventional enzymatic glucose sensors.We developed a glucose sensor in which a glucose responsive fluorescent dye having diboronic acid as a glucose recognition site and anthracene derivative as a fluorophore is immobilized in a biocompatible hydrogel. The glucose sensor reversibly changes the fluorescence intensity according to the glucose concentration. And we implanted the fluorescent device equipped with the glucose sensor into the subcutaneous space of rats, and we achieved the in vivo continuous glucose monitoring.