The efficiency of axial gas dispersion during ventilation with high-frequency oscillation (HFO) is improved by manipulating the oscillatory flow waveform so that intermittent oscillatory flow occurs. We therefore measured the arterial CO₂ pressure and expired CO₂ concentration during high-frequency intermittent oscillatory flow in rabbits to verify the intermittency augmentation effect on gas exchange. In this work, the oscillatory frequency was fixed at 15 Hz so as to apply the results to a HFO respirator. Tidal volume was varied from 2.0 to 3.0mL/kg. The waveform of the intermittent oscillatory flow was set using an intermittent parameter, τ=0.5, where τ represents the ratio of the advection to the oscillation period. When tidal volume was small, the arterial CO₂ pressure was dependent on the flow patterns and decreased when using intermittent oscillatory flow. It was also found that the expired CO₂ concentration becomes greater than that in sinusoidal oscillatory flow. In addition, the use of intermittent oscillatory flow effectively augments gas exchange for ventilation in surfactantdeficient rabbits.

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A novel automated computerized scheme has been developed to assist radiologists for distinction between benign and malignant pulmonary nodules on radiographs using temporal subtraction images. Fifty-one chest radiographs including 26 malignant nodules and 25 benign nodules were used. The CAD system was developed based on features extracted from both chest radiographs and temporal subtraction images. The nodule was segmented automatically on both chest radiographs and subtraction images once the location of the nodule was indicated on the chest radiograph by a radiologist and/or computer. The nodule on the subtraction image was then segmented by thresholding with various pixel values, which were determined from the area of the histogram of pixel values on the temporal subtraction image. Twenty-three image features for each nodule were obtained from both subtraction images and current chest radiographs. The nodule image features included three morphological features obtained from the subtraction image and 10 gray-level features obtained from a histogram analysis of pixel values within the nodule on both subtraction and current images. A linear discrimination analysis (LDA) with six features was applied to determine the likelihood of pulmonary nodule malignancy. A receiver operating characteristic (ROC) analysis was used in the area under the ROC curve (Az) of the computer output obtained by use of the LDA. The six image features selected were the area, irregularity, mean, squared mean, and contrast obtained from the subtraction image and contrast obtained from the current image, which provided the highest Az value of the computer output obtained using the LDA. LDA was employed to separate benign from malignant nodules by use of a hyperplane. The output value of LDA represented the distance of either a benign or a malignant nodule from the hyperplane. In fact, the Az value of the computer output with six features obtained using the LDA for distinction between benign and malignant nodules was 0.851, which was obtained from a leave-oneout method. Our CAD system has the potential to assist radiologists in distinguishing between benign and malignant pulmonary nodules on chest radiographs using temporal subtraction images.

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We have been developing a computer-aided diagnosis (CAD) system for mammograms. We developed a triple-ring filter for detecting microcalcifications, and the prototype detection system is nearly complete. However, our prototype system does not allow for the detection of subtle microcalcifications, which have a low contrast and can be confused with circumferences of almost the same density. The purpose of this study is to develop a new pattern recognition method using the higher-order autocorrelation features (HOAFs) specially created for subtle microcalcifications. The ROI (region of interest) for extracting the feature was experimentally determined as 9×9 in consideration of the size of microcalcifications in the mammography. We employed 120 ROIs including subtle microcalcifications and 120 normal ROIs for training. Forty-five features calculated from the triple-ring filter (8 features), the mean and the variance of the pixel values of the local area (2 features), and the HOAFs (35 features) were extracted from these ROIs. The various features of microcalcifications and FP (false-positive) shadows were extracted and trained using the multi-regression analysis. As a result of comparing those performances using a FROC (free-response receiver operating characteristic) curve, the proposed method always performed better than the current method. It seems that the HOAFs, which reflect local features, are effective in detecting subtle microcalcifications. As a result of applying the new clustered microcalcification system, which combined this method and the current method with 556 unknown images, sensitivity was 94.2%, and the number of FPs per image was 0.61. In our prototype system, the sensitivity was 92.4% and the number of FPs per image was 0.61. The results of our experiment proved that this method can identify subtle microcalcifications that cannot be detected using the current system, and detection performance might be improved by combining it with our prototype system.

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It has been reported that magnetic stimulation effectively eliminates urinary incontinence. However, this type of therapy has not been established as a practical treatment for urinary incontinence because of poor power conversion efficiency and the leakage of current to regions other than that targeted for stimulation. It is therefore necessary to develop magnetic stimulators that can stimulate the sphincter muscles and peripheral nerves more efficiently, and are more convenient than those presently available. By using a large-diameter coil, the magnetic stimulation method offers a larger current distribution over a wider area of the target region than the electrical stimulation method, and the placement of the coil can be relatively easily changed to obtain better therapeutic results. Utilizing a computer simulation model of the female abdomen, we attempted to simulate the distribution of the induced current density on the basis of biological tissue conductivity. Finally, we determined which method of stimulation is the most efficient by varying the stimulator coil location and size. A genetic algorithm (GA) was used for optimization.

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Surface electromyography (SEMG) during an arm curl task was analyzed using the time-frequency technique of continuous wavelet transform (CWT) in order to evaluate muscle fatigue. Eleven healthy male volunteers performed arm curls with a 5kg dumbbell until exhaustion. SEMG was recorded from the biceps brachii muscle. Instantaneous mean frequency (IMF), median frequency (IMDF), and proportion of high-frequency components were calculated from coefficients of CWT, which was applied to six SEMG recordings of 1-s duration acquired at 5, 10, 15, 20, 25 and 30 trials of the task. The results showed that IMF and IMDF significantly shifted towards the lower frequency, and that the proportion of high-frequency components was significantly decreased. We were thus able to demonstrate a fluctuation in SEMG as a sign of muscle fatigue during dynamic contraction such as arm curls. The time-frequency analysis of SEMG using CWT is a useful method for evaluating muscle fatigue during dynamic contractions.

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We have developed a computer-aided diagnosis system to detect abnormalities in fundus images. In Japan, ophthalmologists usually diagnose hypertensive changes by identifying narrowing arteriolar with a focus on irregularities. The purpose of this study is to develop an automated method for detecting narrowing arteriolar with a focus on irregularities in fundus images. The blood vessel candidates were detected by the density analysis method. Next, the blood vessels to be observed for diagnosis were detected by tracking the vessel candidates extending from the optic disk. In this step, the direction of a vector was determined by the angle made by a bifurcation point and a furcation. After the connectivity of the vessel segments was adjusted based on the recognized intersections, the true tree-like structure of the retinal blood vessels was established. The abnormal blood vessels were finally detected by measuring their diameters. The comparison between the results obtained using our system and the diagnostic results of ophthalmologists showed that our proposed method automatically detected an irregularity in diameter in 75.0% of all 24 narrowing arteries with a focus on irregularities in 70 fundus images. However, approximately 2.9 normal vessel segments per image were determined to be abnormal. The automated detection of narrowing arteriolar with a focus on irregularities could help ophthalmologists in diagnosing ocular diseases.

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In certifying eligibility for long-term care, in order to determine the level of need for long-term care, an examiner visits the applicant to evaluate their actual physical condition. However, the period of evaluation interview is usually limited, and thus assessment of the actual physical condition tends to be difficult. Taking these circumstances into consideration, we designed an ambulatory sensor system aimed at discriminating whether or not a subject uses assistance when standing up from a chair and sitting up in bed during daily activities. The system is composed of two accelerometers, one attached on the subject's chest and the other to the forearm. The chest accelerometer measures the angle in the gravitational direction and up-down motion acceleration. The forearm accelerometer measures the angle in the horizontal direction. In addition the sensor outputs are recorded in a compact data-logger. From experiments using 12 healthy subjects aged from 20 to 50 yrold, the present system could discriminate between the use of assistance (cane, desk and armrest) and no use of assistance when standing up. The periods of sitting up in bed were also detectable and the present system could discriminate between the use of assistance (bed handrail) and no use of assistance. The discriminating accuracy of the system was experimentally evaluated using four healthy subjects (aged 20 yr-old) and two elderly subjects (aged 72 and 73 yr-old). Preliminary experiments of ambulatory monitoring in normal living were also carried out using two elderly subjects (aged 72 and 69 yr-old). The results clearly demonstrated that the new system is able to distinguish with excellent accuracy (>90%) between using and not using assistance when standing up and sitting up in bed. We suggest that the system could be a useful means obtaining giving objective information in the procedure of certifying eligibility for long-term care.

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It is widely accepted that the perception of pure tone is mostly determined in the early sites of the auditory pathway: e. g., at the external acoustic meatus pathway and the basilar membrane. We measured EEG signals for pure tones that have the same A-weighted sound pressure level (73 dB) at several frequencies. Correction of the amplitude with A-weighted sound pressure level allows us to isolate the effects that occur at the upper cognitive sites from those at earlier sites, since the A-weighted sound pressure level compensates for the gain lost at the earlier sites. Eight normal subjects participated in the experiment. We measured alpha wave fluctuation and alpha power spectra that responded to the pure tones. We used pure tones at 12 different frequencies as test stimuli and white noise as a control stimulus. Alpha wave fluctuation was calculated from the slope of the fluctuation spectrum, obtained from the Fp1 and Fp2 electrodes. The results showed that the slope varied depending on the frequency of the pure tones and formed a U-shaped curve as a function of the frequency of the pure tones. The trough of the curve was around 1-2kHz and became close to zero as the frequency increased/decreased, suggesting that the pure tones around 1-2kHz induce the largest comfort and lowest arousal. The alpha power spectrum peaked at around 0.4-5.0kHz. Since the alpha power spectrum increases when subjects feel relaxed, it appears that pure tones around 1-4kHz induce relaxation, consistent with the results of alpha wave fluctuation.

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Electric stimulation of a peripheral nerve generates a magnetic field produced by action currents within nerve fibers. The conduction characteristics of these action currents of the nerve affect the magnetic field produced, which also reflects the characteristics of each bundle of fibers, though these consist of thousands of nerve fibers. Therefore, a method to estimate the distribution of the diameters of nerve fibers was investigated. A nerve was modeled as a bundle of nerve fibers of different diameters. Then stimulation of the bundle and the generation of a magnetic field around it were attempted. Stimulation of the bundle at two points with different intensities makes it possible to activate only the low-threshold nerve fibers within the bundle. This method was applied to estimate the distribution of the diameters of nerve fibers from magnetic field measurements. To obtain the distribution of the diameters of nerve fibers with relatively high estimation accuracy, using the peak position analysis of a magnetic field was suggested.

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Oscillatory neural activities, such as theta rhythm (4-12Hz) and high-frequency burst waves (>100Hz) in the hippocampus, are expected to play an important role in the learning and memory functions of the brain. Neural oscillations are also observed in a hippocampal slice preparation in the presence of carbachoL Therefore, this preparation has been used as an in vitro model for studying the rhythms. In this study, local field potentials and multi-neuron activities were simultaneously recorded at two sites that are 0.4mm apart from each other in the pyramidal cell layer of the CA3b area in the slices because the rhythmic activities are often initiated in this area. This study was carried out in order to study the manner in which the rhythmic activities initiate and spread in the area. It was shown that the generation and disappearance of the theta, beta (12-25Hz), and gamma (25-80Hz) rhythms were spatially coherent. Neural spike timings of CA3 neurons tended to lock to a particular phase of the field potential oscillations. In contrast, in the case of high-frequency burst waves, the phase gap between the recording sites changed with the passage of time. These results suggest that the generation and synchronization mechanism of high-frequency burst waves are completely different from those of the other rhythmic waves: the theta, beta, and gamma waves.

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To date, there has been no standard method for predicting blood glucose in clinical use. In this paper, we discuss the development of a new controlling method that can improve the hyperglycemia state in Type II diabetes. Since the fasting blood glucose level is regulated by the balance of insulin secretion and resistance, a chaotic model is created by embedding the theorem of Takens from a stabilized time series of the fasting blood glucose level incorporating the mathematical model of the glucose-insulin metabolism. The fasting blood glucose level of the next morning can be predicted using a semi-fuzzy reconstruction method, and the optimal amount for the insulin injection before going to bed can also be calculated from the prediction. As a result, patients can regulate their lifestyle using this quantitative perspective. Under this regulation, both the chaotic model and the prediction become more stable and accurate over a long period of use.

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Cells change their own states, stopping replication or repressing protein syntheses in order to adapt to the external environment such as temperature change, lack of nutrition or other stressful stimuli. As a result of these changes, they transform from the exponential growth phase into a stationary phase or into an anaerobic condition, etc. In conventional studies of microarray time series analyses, a fixed transcriptional regulatory formation is assumed through all data series. On the contrary, we assume that the regulatory formations can be changed, and estimate the transition time points from a statistical viewpoint. Using a linear dynamical system and microarray data, we estimate cellular internal states that are unobservable by experiments and detect transitions of internal states based on the temporary descent of log-likelihood values. Combining the results with the classification results based on a self-organizing map, significant cellular transition points can be detected and activation of particular functional genes concerned with each state of transition extracted. This approach gives us an objective standard for understanding cellular changes and the estimation of unknown gene functions in microarray time series analyses.

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In this paper, we discuss the development of a beat-to-beat model of the cardiovascular system that qualitatively simulates the characteristic patterns of cardiovascular variability in response to mental task stress. First, we improved Deboer's model by: (1) representing delay function related to the baroreflex as a function of time, (2) setting sympathetic nervous activity and parasympathetic nervous activity as dynamic variables, (3) adding a term describing sympathetic influence and afterload effect on stroke volume, and (4) representing the total effect of the autonomic nervous system on the heart rate by the product of sympathetic influence factor and parasympathetic influence factor. Next, we showed that the presented model can qualitatively reproduce characteristic patterns of cardiovascular variability in response to mental arithmetic stress by decreasing the values of parameters related to parasympathetic nervous activity. The characteristic response patterns are: (a) decrease in heart beat interval, (b) increase in systolic blood pressure, (c) increase in diastolic blood pressure, (d) decrease in heart rate variability (HRV), (e) decrease in amplitude of low-frequency (0.04-0.15Hz) band HRV, and (f) increase in mean frequency of low-frequency band HRV. On the contrary, Deboer's model could not reproduce these patterns by changing the values of parameters related to autonomic nervous activity in a valid manner. Finally, we discuss the generation mechanism of the characteristic patterns of cardiovascular variability in response to mental task stress using the presented model.

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In recent years, the number of patients complaining of abnormal bowel movements has increased, and the incidence of abnormal bowel movements in the Japanese population over the age of 15 years old has been estimated to have increased to approximately 20%. Clarification of the intestinal peristalsis of the digestive tract is important for elucidating the pathology of digestive disorders. Existing assessment systems have problems with quantification and reproducibility. With this background, the present study was conducted to develop a system for analyzing intestinal peristalsis using three-dimensional (3D) position sensors. By creating 3D position sensors out of permanent magnets, we were able to directly measure the movements of intestinal contents and assess the state of intestinal peristalsis using strain gauges attached to the intestinal wall. The results of in vitro experiments showed that the maximum measurement error was 6.5mm within 250mm of the sensor. A preliminary animal study was conducted using wired position sensors. Radiographic findings showed that the sensors detected the movement of the intestinal contents, and the movement detected by the sensors correlated with the output of the strain gauges attached to the intestinal wall.

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Magnetic micromachines are driven by magnetic fields and can be operated wirelessly. The devices themselves require no batteries and no controlling parts or machinery. Given these advantages, micromachines are expected to be applied widely in the medical field. As one example, a micromachine equipped with a heating element for hyperthermia and capable of maneuvering within the human body can be used to provide a new cancer therapy for local hyperthermia. In this study, we fabricated a magnetic micromachine capable of moving in the liver, one of the targets of local hyperthermia. The machine consisted of a cutting tip to cut the liver tissue, a cylindrical permanent magnet and a spiral structure made with a tungsten wire. The magnet was magnetized in the direction of its diameter. The machine was designed with a small diameter of only 0.9mm in order to permit the insertion of an 18G injector. When a rotational magnetic field was applied, the magnet rotated and the spiral structure produced thrust force. The micromachine was able to move a distance of 40mm in a porcine liver and 45mm in a bovine liver. These results confirm that the micromachine has excellent potential for medical applications.

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In this paper, the authors propose applying a magnetic actuator to a capsule endoscope. We fabricated a capsule-type magnetic actuator and investigated its moving properties in a silicone tube and in pig intestines. The device consists of a dummy capsule measuring 11mm in diameter and 40mm in length, a magnetic actuator composed of a permanent magnet inside the dummy capsule and a 1-mmφ spiral structure outside the capsule. The permanent magnet is magnetized in the direction of the diameter. When a rotational magnetic field is applied, the magnetic actuator rotates and moves wirelessly. In this study, we measured the effect of the spiral shape on the velocity and thrust properties. According to our experimental results using the silicone tube, the optimal actuator was formed with 4 spirals set at a spiral angle of 45 degrees. In the subsequent moving test performed in pig intestines, the actuator traveled a distance of 450mm to its destination in the large intestine in 150s, and a distance of 400mm to its destination in the small intestine in 110s. This result confirms the potential applicability of the actuator as a guidance system for capsule endoscopes.

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To realize the augmented reality (AR) visualization of pre- or intra-operative 3-dimensional (invisible) information about the interior of tissues such as a tumor in a 2-dimensional endoscopic view, we proposed a novel method for endoscopic image overlay called “direct calibration of endoscopic camera (DCEC)” and developed a prototype of the system based on the three-dimensional measurement using micro-fluxgate magnetic sensors in combination with the DCEC. The DCEC requires neither pre-operative camera calibration nor intra-operative endoscopic camera tracking. Using the DCEC, the world-to-endoscopic image transformation can be directly calculated in an intra-operative stage. The calibration protocol is flexible and applicable to a variety of endoscopic cameras such as oblique-viewing endoscopic cameras, and easily usable in the operating room. To evaluate the performance of the DCEC and applicability of the developed system in clinical use, we performed an in vivo experiment. As a result, our system could overlay the position of a magnet embedded in the vicinity of a target tumor in real-time.

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In this study, we measured the ability of children with learning disabilities (LD) to adapt to changes when reaching for visual targets. The rotation and reverse motions of the cursor, representing the subject's hand position, resulted in a change in visual feedback. In the experiment, we measured the changes in adaptation ability for two groups of children, children with LD and normal children, when rotation and reverse motions were varied and the distance from the body to starting point was varied. The results showed the adaptability of children with LD differs with that of normal children in right and left reversed tasks. The motor ability of children with LD was significantly lower even when identical rotation and reverse motions were used for the two groups of children in an exocentric task. The results suggest the probability of a reduced ability or functional impairment in the brain function of children with LD when perceiving depth.

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A simple type of passive exercise training equipment has been newly developed that allows people with knee joint pain to train by exercising their legs. The equipment has only one AC motor and consists of only one component, so is smaller and lighter than the former type. This device is equipped with a seat that is driven by the motor and two foot-plates for the user's legs. In order to induce muscle contraction, mainly at the user's femur utilizing his/her own weight, the seat can be inclined repetitiously toward the knee joint alternating each leg. In addition, in order to reduce knee joint pain by maintaining the angle of the knee joint, the foot-plate will drops down owing to the user's weight when the seat inclines, so that the distance between the seat and foot-plate maintained almost the same. In a laboratory experiment using the equipment, it was indicated that:(1) muscle oxygenation in the femur was promoted as observed via near infra-red spectroscopy, (2) glucose uptake was significantly enhanced as observed in a euglycemic clamp study, and (3) knee joint pain was smaller than that experienced when walking on a flat surface area as determined from a subjective evaluation by persons with knee joint osteoarthritis.

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Telemedicine is a medical activity that shares medical environments between different facilities. In order to share these environments, it is required that all forms of medical information are exchanged via networks. However, the transmission of information across the network can become obstructed or delayed if the bandwidth available is insufficient. Consequently, lost or damaged information could lead to problems in providing proper medical diagnosis and/or treatment. Among the information and communication technologies being researched, a quality of service (QoS) control technique has been developed and applied for practical use. The ractical QoS control technique mainly controls network traffic in the transport layer of a seven-layer open systems interconnection (OSI) model. However, a higher level of intelligent control is required for the QoS of information in telemedicine. When a bandwidth is reduced, information must be efficiently reduced to understandable units simultaneously for each application. Additionally, the relative importance of information data changes as the medical procedure progresses. Therefore, transmission control must dynamically reflect the relative importance. In this paper, the authors propose the introduction of an application-level QoS control technique that controls the quality of service at the application layer of an OSI service layer model. Utilizing the aforementioned method, information can be transmitted through groups of frames (GoF)—groups of information divided into understandable units. Additionally, this paper proposes assigning priorities to each packet of communication data and each channel. In so doing, the proposed method can produce a wider bandwidth for important information sources and sufficient QoS for other information sources.

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The force applied to sliding doors and the shape and dimensions of the operating parts were examined in terms of friendliness for users including elderly people in order to determine the basic design requirements for sliding doors. The maximum force applied to operating parts installed on a wall was measured using 18 subjects (five males and five females 75 years old on average, and six males and three females 29 years old on average). The maximum force applied by elderly males was 42N on average; that for elderly females 44N; that for younger females was 60N; and that for younger males was 139N. Younger subjects produced stronger force with deeper operating parts (3-15mm); however, the relationship between the shape and size of a part and the maximum force in case of elder subjects remained unclear. A sensory evaluation test was conducted to check the influence of applied force and the shape and dimensions of operating parts on opening and closing sliding doors using a full-sized mock sliding door. Three levels of applied force (10N, 20N and 30N) were tested using five different parts: a bar handle (25.4mm in diameter, 500mm in length), convex hand grips with finger-holds of 6mm, 15mm and 30mm in size, and a concave hand grip with a depth of 15mm. Sixteen subjects, including five males and five females 77 years old on average and two males and four females 26 years old on average, performed the action of opening and closing a sliding door to evaluate its user friendliness at five levels. While the applied force of 10N was highly evaluated, 30N was poorly valued regardless of the shape and dimensions of the operating part. The most remarkable effect was observed in the case of 20N, the shallower hand grip was strictly assessed and the bar handle was highly appreciated.

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A simple structured back muscle supporter was developed and evaluated in this study. Many caregivers suffer from pain in the lower back due to severe working conditions. Though hoists and lifts are available, they are rarely used because of drawbacks related to usability. We have developed a carrying frame shape prototype that remarkably reduces lower back burden on caregivers without restricting natural movement of the body. According to the analysis carried out on a mechanical model of a person wearing the supporter, the device generates support moment of 30Nm at the torso flexion angle of 60 degrees. Experimental results show that the EMG amplitude of the erector spinae muscle decreases significantly by wearing this supporter.

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In this study, we developed a futon with a ventilation mechanism and an air-control method that measures the temperature inside the bed and maintains a comfortable temperature (32±2°C) using feedback control. We verified the performance of the temperature control system and evaluated the sleep quality of four participants by measuring PSG (polysomnogram) . The results showed that the in-bed temperature was kept in the “comfortable temperature” zone 99.84% of the time when the subjects were in the bed using the feedback control method developed. We also confirmed the following tendencies: (1) When the air-controlled method was being used, sleep latency was marginally shortened (p<0.1), meaning that the subjects fell asleep more easily; (2) the ratio of “SWS (slow wave sleep, i. e., deep sleep)” significantly increased (p<0.05), indicating that sleep rhythms improved; and (3) the effectiveness of sleep was higher than that of the method without the air-control method. These results indicate that the air-control method developed is effective for increasing the quality of sleep.

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A new video-oculography with miniature displays to provide visual stimulus has been developed. This device enables medical doctors or clinical engineers to easily conduct clinical check-ups for the diagnosis of vertigo caused by vestibular dysfunction or central nervous system disorder. Using the headset developed, it is possible to present virtual visual stimulus images. The headset also has features for measuring the movements of both eyes simultaneously without attaching conventional, unpleasant electrodes to the face. Since the relative geometrical association with each other's coordinates system for measurement and presentation is absolutely fixed inside the headset, there is no limitation to head movement. In order to evaluate the output obtained by the developed system, eye tracking tests and optokinetic nystagmus tests were conducted. Thirty-one participants gave written informed consent. The output waveforms for eye movement compared to a conventional electro-nystagmograph demonstrated the validity of the developed system, which can contribute to time and space savings in clinical diagnosis.

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After the inhalation of hyperpolarized ¹²⁹Xe gas, in vivo spectra from the rat head revealed a dominant peak around 195ppm (Peak A) and another easily resolvable peak near 189ppm (Peak B). We have already confirmed that peak A and peak B originate from brain and non-brain tissue, respectively. In order to confirm that the properties of ¹²⁹Xe in non-brain tissue are different from those in brain tissue, a comparison is made of the washout times of ¹²⁹Xe from the brain and non-brain tissues using a strict two-pulse measurement protocol from 12 rats. The washout time of peak B (25.4±10.4sec) was consistently longer than that of peak A (14.7±1.0sec) . Blood flow through scalp tissue and muscle is approximately one-tenth of that in the brain. Hence, it is reasonable to assume that the washout time of the non-brain peak is longer.

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Although many studies have been conducted in relation to the biological effects of extremely-low frequency (ELF) magnetic fields, there is little agreement as to their total effects on living organisms. Related to this, we are concerned with the viral infection system; consisting of viruses and cells, and the following infection process: (1) absorption, (2) penetration, (3) synthesis of viral components, (4) maturation, and (5) release. This system enabled us to observe the effects of ELF magnetic fields more easily than using experimental animals. We divided these five steps into two groups. The first group is called the absorption period, which includes steps (1) and (2). The second group is called the proliferation period, which includes the remaining steps. In this investigation, we compared the two groups from the viewpoint of the effects when they were exposed to a 50Hz 62mT magnetic field. As a result, the 50Hz 62mT magnetic field inhibited the growth of the virus as compared to sham exposures. When either the absorption period or the proliferation period was exposed to the 50Hz 62mT magnetic field, growth was inhibited as well. It was clearly proven that the 50Hz 62mT magnetic field has an inhibitory action on viral infections, and the action can be observed throughout all processes in the viral infection system.

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We propose the application of a terahertz electromagnetic pulse (THz pulse) for non-contact measurement of local water content in the skin. The free-space propagating THz pulse is generated as dipole radiation from a photoconductive antenna triggered by a femtosecond pulsed light from a mode-locked Ti: Sapphire laser. Strong interaction of the electromagnetic wave with water in the THz region enables the measurement of water content in the skin using the THz pulse. The ultrashort temporal width of the THz pulse can probe depth information on the skin in the same manner as the ultrasound pulse echo method. In this paper, we demonstrate measurements of water content and thickness of the analytical region in a human skin sample based on the time-of-flight method for THz pulse echo. A relative change of water content in the sample was determined by the change in the peak height of the THz pulse echoed from the skin surface. With respect to tomographic information on the skin, we observed THz pulse echo from an air-corneum interface and that from an epidermis-dermis interface, successively. Simultaneous quantification of the water content and thickness will be a powerful tool for monitoring the hydration level with respect to morphology of the skin.

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Human blood collected from donors is tested for viruses using nucleic acid amplification testing (NAT) because blood products are made of human blood in Japan. However, NAT cannot detect viruses if there is only slight contamination. Therefore, viral infection is often caused by blood products contaminated with viruses. To prevent viral infection through blood products, we designed a viral detection method that uses a metal-coated hollow fiber (MCH)-membrane coated with gold. The principle of this viral detection is as follows. Viruses are captured and concentrated in a MCH-membrane, a viral sample is aspirated through the membrane. The membrane is then soaked in an alkaline-sodium dodecyl sulfate (SDS)-solution, and viruses are chemically lysed. After that, the membrane is used as a cathode electrode. Viral genes are electrically released from the membrane to electrophoresis buffer when a 3.5V/cm electric field is applied for 5min. Viruses are then detected by amplifying the released genes. Our aim is realize clinical application for viral detection, and we demonstrated the system on simulated serum samples for the first time. In addition, we introduce loop-mediated isothermal amplification (LAMP) as a method of nucleic acid amplification and attempt to shorten the detection time. The viral detection method using MCH-membrane was not inhibited by the proteins contained in calf serum. Viruses were detected from simulated serum samples containing 10PFU/mL of herpes simplex virus type 1 (HSV-1) with this viral detection method. The detectable sensitivity was caused by the viral concentration of MCH-membrane. Because LAMP markedly shortens the detection time, viral detection was completed in approximately one-fourth the detection time of NAT (90min) . Viral detection using MCH-membrane will contribute to not only the inhibition of viral infection with contaminated blood products, but also to the rapid provision of platelet products, which have short expiration dates.

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Optical coherence tomography (OCT) is very promising for high-resolution cross-sectional imaging underneath the surface of biological tissue. The axial resolution of OCT is determined by the coherence length of the light source used in a low-coherence interferometer. In this paper, we demonstrate high-resolution OCT of micro-tissue structures using a femtosecond Ti: sapphire laser. A coherence length of 3.1μm is obtained using a bulk optic interferometer. In the experiment, micro-skin structures including the epidermis, dermis and stratum basale are clearly observed using high-resolution OCT. In vivo high-resolution OCT of human skin was also successfully demonstrated. Furthermore, the thickness of the stratum corneum can be measured as near as 20μm using our OCT system. Our experimental results indicate that a femtosecond laser is suitable for high-resolution OCT for basic research in dermatology.

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In a living body, cells are organized in complex three-dimensional arrangements where individual cells cooperate to perform the functions required of organs. In order to artificially reproduce the cell morphology of a living body, technology is required to control cell adhesion and extension, as well as alignment and orientation. Here, we propose and demonstrate the use of a photofabrication technique to produce unique structures that can be used as cell growth substrates. Photocurable gelatin, consisting of styrene-derivative gelatin and comphaquinone (a photoinitiator), was used to create the biocompatible structures. Near-infrared laser irradiation was focused on the gelatin and two-photon absorption occurred at the focus, inducing spatially localized polymerization and solidification of the gelatin structure with high resolution. The photofabrication technique also allows the production of three-dimensional cell scaffolding. Due to the localization of polymerization combined with scanning the position of the laser focus, it is possible to create arbitrary three-dimensional gelatin structures. After photo-induced solidification, non-solidified parts of the gelatin (i. e. the non-irradiated regions) were washed out by rinsing with deionized water. In the experiments described here, a mode-locked Ti: sapphire laser (780nm, 82MHz, 80fs) was used as the irradiation source, and a grid-like structure of micron-order resolution was fabricated by scanning the laser beam and exposing regions of gelatin on a cover glass. Rat cardiomyocytes were then cultured on the fabricated structure. Seventy percent of the cardiomyocytes on the gelatin structure showed cell extension parallel to the structure, and cell extension was observed to occur predominantly along the edges of the gelatin regions. In contrast, cardiomyocytes cultured on dishes without any structure showed disordered extension and did not align parallel to each other.

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A prototype autoclavable wire-driven microforceps for neurosurgery, which can be used with a minimally invasive surgery-support system (called the hyper-utility mechatronic assistant system, HUMAN), has been was developed. The microforceps is separated into a mechanical drive part that can be sterilized and an electric drive part, to which sterilization is not performed. A microforceps drive-system was also constructed, and its dynamic characteristics were experimentally measured by a laser-sensor system. The open-close speed is 125deg/s and the delay time is 0.04s. It was found that separating the microforceps into two parts had no influence on these characteristics. The material of the sheath serving as the channel for the drive wire can be further improved for autoclave sterilization. It is concluded that the newly developed microforceps will be a great help in further developing minimally invasive neurosurgery using HUMAN.

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