The goal of this study was to find feasible indices for quantitative evaluation of sagittal stratum abnormalities in schizophrenic patients, by automatically establishing the region of interest during fiber tracking of a target bundle. We analyzed the sagittal stratum, including the inferior longitudinal fasciculus and the inferior fronto-occipital fasciculus, using a fiber tracking and tractography technique with magnetic resonance diffusion tensor imaging. Diffusion tensor images were acquired from patients with schizophrenia and healthy subjects (controls), group-matched for age, sex, and handedness. We calculated thirteen indices representing the features of the tracked fibers. These were derived from the cross-sectional area of the tracked fibers in the starting area, fractional anisotropy, mean diffusivity, and curvature of the tracked streamline. These indices were compared between patients and control groups, and between the right and left hemispheres. We found significant differences in two indices between the patient and control groups;four indices indicating significant hemisphere effects in the patient group, and three indices showing significant differences between hemispheres in the control group. These results suggest that it may be possible to perform quantitative evaluation of sagittal stratum abnormalities in schizophrenia using these indices.

View full abstract

The laparoscopic stapler is a surgical instrument that automatically creates visceral anastomosis. Although the laparoscopic stapler is widely used, objective ergonomic assessments are lacking. The purpose of this study was to quantitatively assess the force and muscle activities involved during the use of a laparoscopic stapler. The mechanical force needed to create anastomosis in a cattle colon was measured using a tensile tester. Three different loads (150N, 200N, and 250N) were applied individually to compare the anastomosis conditions. The force and muscle activities of the operators of the laparoscopic stapler were also examined. Eleven healthy female subjects (age, 27.4±10.7 years) participated in the study. Force and surface electromyography (EMG) of the flexor digitorum superficialis and flexor digitorum profundus muscles during the use of the laparoscopic stapler were measured and compared to each subject's maximum grip strength. Approximately 250N was necessary to operate the laparoscopic stapler appropriately. Although the mean grip strength of the subjects was 27.1±6.8kg, the mean force applied when they gripped the laparoscopic stapler was 15.1±4.1kg. Integrated EMG showed no differences between operating the laparoscopic stapler and gripping the hand dynamometer. This study demonstrated that the current design of laparoscopic stapler requires too much force to operate for individuals with small hands and/or low grip strength. In addition, the EMG results indicated that the enormous upper extremity muscular effort is not transmitted efficiently into power to operate the laparoscopic stapler, because of its handle design. Therefore, reconsidering the mechanism of the laparoscopic stapler is crucial to improve the usability of the laparoscopic stapler.

View full abstract

Death rate of accidental drowning in the bathtub was the highest among casualties occurring at home, according to the annual report of the Japanese Ministry of Health, Labour and Welfare in 2007. To prevent accidental drowning during bathing at home, we obtained respiratory waveforms from bioelectric impedance (BEI) measurement using non-contact electrodes. The BEI measurement is an involuntary measurement method, from which respiratory waveform during bathing can be extracted. In the present study, to find the most appropriate electrode configuration as well as the optimal measuring frequency, we calculated the frequency dependence of impedance amplitude by numerical technique based on a three-dimensional finite difference method for a composite system consisting of a human body submerged in bath water. The results of model calculation agreed with the experimental results. Next, to obtain respiratory waveforms with large amplitudes, we investigated the optimal frequency experimentally. The frequency of 1MHz was suitable for involuntary measurement of respiratory waveform during bathing.

View full abstract

For continuous evaluation of the effects of visually induced motion sickness (VIMS), we previously proposed a physiological index ρ_max that represents the maximum cross-correlation coefficient between blood pressure (BP) and heart rate, the frequency components of which are limited to the Mayer wave-related band. However, ρ_max requires continuous BP measurement using a bulky measuring device that is difficult to handle. Thus, we previously proposed an easier method for obtaining ρ_max without continuous measurement of BP, which uses only a finger photoplethysmogram (PPG). In this method, independent component analysis (ICA) is used to extract BP-related signals from the PPG signals. However, continuous BP measurement is needed to determine the mixing matrix used in ICA. In order to achieve practical application of the method, this study aim to verify whether each subject's mixing matrix can be estimated based on short-term continuous BP measurement. Being able to do so would mean that ρ_max can be obtained from an estimated mixing matrix without continuously measuring BP during an experiment that presents a visual image to a subject. The validity of the proposed method was assessed by experiments performed on 28 subjects watching a swaying video image. From the ex-perimental results, we verified that the proposed method is able to extract independent components related to BP to yield ρ_max between heart rate and each independent component used to evaluate the effects of VIMS. This result suggests that the effects of VIMS can be evaluated using short-term continuous BP measurement before the evaluation task.

View full abstract

In the management of patients with unstable hemodynamics as seen in myocardial infarction or after cardiac surgical procedures, cardiovascular drugs such as inotropes and/or vasodilators are commonly infused to control systemic arterial pressure and/or cardiac output. Since responses to these agents 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. Closed-loop systems to automate drug infusion have been developed to facilitate this process. In the clinical setting, although closed-loop control of hemodynamics has been suggested to be useful and improve patient outcomes, this approach has not yet been widely adopted. In this review, we introduce several closed-loop systems that have been developed so far and our novel approach to control overall hemodynamics, address issues in their clinical application, and discuss future perspectives in this field.

View full abstract

This study aimed to provide a simulation model for virtual ablation of soft tissue, focusing on simulating soft tissue deformation and destruction. The authors applied two hypotheses, the maximum shear stress hypothesis and the crack stress hypothesis, to simulate soft tissue rupture progression based on stress distribution. This combination of hypotheses realizes dynamic definition of the direction of rupture progression. The proposed model also supports multiple sources of manipulation, i.e. two or more hands working on the tissue simultaneously, because the direction definition algorithm requires only the stress distribution of the entire object. The simulation model was implemented on a thin square board model. The first experiment evaluated the direction of rupture progression when the board model was expanded at two manipulation points. The second experiment compared the simulated crack progression with crack progression in a silicon rubber. The third experiment assessed the length of rupture progression resulting from the same force applied to different positions. The fourth experiment evaluated the effect of rupture direction related to pressures. The final experiment was conducted to estimate the calculation time required for the rupture model to run. The simulations revealed that final crack length is strongly affected by the preset crack length. A similar phenomenon occurs in real-world crack progression. Also, the direction of rupture progression is affected plausibly by manipulations. Therefore, the authors conclude that the proposed model accurately represents the dynamic ablation of soft tissue.

View full abstract

Functional magnetic resonance imaging (fMRI) is one of the techniques capable of detecting human brain function noninvasively. Although many fMRI studies have adopted echo-time (TE) of 30 to 40ms aiming to maximize blood oxygen level-dependent (BOLD) signal change, large distortion and signal dropout occur near air-filled spaces such as frontal sinus in functional imaging because of the magnetic field irregularities. Theoretically, shorter TE could decrease the magnetic distortion and signal dropout near air. However, it has not been determined whether short TE of less than 30ms may affect the statistical t value of functional image, which is the most important factor to evaluate results of fMRI study. In the present study, we assessed whether shorter TE can be utilized for fMRI study of the human brain. Nineteen healthy volunteers were scanned using fMRI during finger tapping and viewing checker-circle tasks. Signal dropout near the sinus, statistical t value, percent signal change, and modified temporal signal to noise ratio (mtSNR) of functional images were evaluated in the primary motor cortex and primary visual cortex while TE was varied between 20 and 35ms. Signal dropout was the smallest at a TE of 20ms, whereas there was no significant effect of TE on the statistical t value both in the primary motor cortex and in the primary visual cortex activity. These findings suggest that 20ms is the optimal TE value in the range of 20ms to 35ms for fMRI.

View full abstract

Auditory steady-state responses (ASSR) to sinusoidal amplitude-modulated (SAM) tones or to repeated clicks presented at rates between 10 and 70Hz have been recorded since the 1980's and some of the important studies are reviewed here. First, the basic methods of elicitation and measurement of ASSRs are presented, and studies on localization of ASSRs and elucidation of the generation mechanisms are reviewed. The amplitude and phase of ASSRs as functions of stimulation parameters are then reviewed. The effects of attention have also been studied and their implications for online ASSR-based brain-computer interface system are mentioned. Finally, possible applications of ASSRs for clinical use and for brain function studies are introduced. ASSRs provide a useful tool both for basic auditory studies and clinical uses such as audiometry.

View full abstract

A functional magnetic resonance imaging (fMRI) method that focuses on neural magnetic fields has great potential to detect neural activities more directly than the conventional method. Because this fMRI method does not depend on blood-oxygenation-level-dependent contrast, improved temporal and spatial resolutions can be expected. Among various approaches of this fMRI method, the one that uses a spin-lock imaging sequence has attracted wide attention because of the possibility to detect small oscillating magnetic fields. To understand the mechanism of this approach, we visualized magnetization behavior during the spin-lock module with externally applied oscillating magnetic fields. A fast-and-simple method with matrix operations was used to solve a time-dependent Bloch equation. In addition, we investigated the influence of the duration of the spin-lock pulse in the spin-lock module, which interacts with the external oscillating magnetic fields, on magnetic resonance signals. Furthermore, to detect minute magnetic fields in the order of sub-nT, we carried out phantom studies on the practical use of this method as an fMRI approach. A single-loop coil generating oscillating magnetic fields was placed inside a saline-filled phantom. Time-dependent performance of magnetization during the spin-lock module was thus visually demonstrated to aid understanding of the mechanism of the fMRI method with the spin-lock imaging sequence. In addition to this visualization, we found that the decrease in magnetization depends on the duration of the spin-lock pulse. Longer durations are appropriate for detecting minute sub-nT magnetic fields such as neural magnetic fields. Furthermore, we were able to detect magnetic fields of approximately 200 pT by choosing a spin-lock pulse of long duration and increasing the number of MR image acquisitions. Our results provide useful information for the understanding of the mechanism of direct detection of oscillating neural magnetic fields using MRI with a spin-lock imaging sequence. In addition, we propose an improved selection scheme for the duration of the spin-lock pulse and the feasibility of detecting oscillating magnetic fields of 200 pT considering practical application of fMRI.

View full abstract

We investigated the effects of forced response-like movements on serial reversal learning of a sensorimotor task in normal and hemiplegic (unilateral cortical lesion in the forepaw sensorimotor area) rats. The rats were trained to respond to an air-puff stimulus applied to one forepaw; the response involved releasing either the stimulated or non-stimulated forepaw from a lever. During the training, an error trial was followed by a correction trial wherein a lever on the correct-response side (n=4 in each group) or the incorrect-response side (n=4 in each group) was automatically elevated at 220 ms after the air-puff stimulation, mimicking the rats' lever-release movement. No lever activation was applied to the rats in the control condition (n=4 in each group). We found that learning speed was generally facilitated by the lever activation procedure on the incorrectresponse side, but not on the correct-response side. As an exception, however, lever activation on the correctresponse side facilitated learning in the contralesional (paralyzed side) forepaw of the hemiplegic group. Reaction time was not affected by the lever activation procedure, although it was longer for the contralesional forepaw compared to the ipsilesional forepaw in the hemiplegic group and both forepaws in the normal group. We conclude that the sensory inputs induced by the same forced response-like movement facilitate learning or rehabilitation differently in normal and hemiplegic rats. The results and the animal model in this study are useful for the development of more efficient motion-assisting devices for rehabilitation.

View full abstract

Cationic lipoplexes, which consist of cationic lipids and DNA, are widely used in gene transfection. Recently, some reports suggest that the transfection efficiency of lipoplexes is affected by its formulation and physicochemical properties. To improve the lipoplex transfection efficiency, we examined gene transfection using lipoplexes treated with high hydrostatic pressure (HHP) that affects the phase behavior of the phospholipid bilayer. Lipoplexes were prepared with different cationic lipid to DNA ratios and then subjected to hydrostatic pressure at 5,000 and 10,000 atm. Non-pressurized lipoplex and HHP-treated lipoplex (after removing pressure) were evaluated. Dynamic light scattering measurement showed that the size of HHP-treated lipoplex increased compared with non-pressurized lipoplex, suggesting that formulation change and assembly of lipoplexes occurred under high hydrostatic pressure. Lipoplexes with and without HHP treatment were transferred into HeLa and COS-7 cells. The transfection efficiency of HHP-treated lipoplex increased compared with non-pressurized lipoplex, irrespective of the mixture ratio. Also, the transfection efficiency of HHP-treated lipoplex remained higher for several days. These results suggest that high hydrostatic pressure induces structural change in lipoplex, thereby affecting the transfection efficiency.

View full abstract

The technique of mesoscopic epifluorescence tomography (MEFT) has been reported previously. Although it allows three-dimensional (3D) imaging of the concentration distribution of fluorophore reporters embedded in tissue in reflectance geometry with a resolution of hundreds of micrometers, reconstruction accuracy is unsatisfactory. In this study, a novel regularization method is proposed to improve the accuracy. The proposed method is a derivation of Tikhonov regularization but inherits the iterative reweighted nature of sparsity regularization. First, Tikhonov regularization is utilized to generate an initial estimation. Then, a weight matrix is generated on the initial estimation and then coupled to the regularization objective function for a new estimation. The new estimation leads to a new weight matrix that begins iteration. The weight is decided in a piecewise manner : a high but constant weight is set to the region of interest (ROI) where the fluorophore is highly likely to exist, while lower weights are set to background regions. The values in the ROI are thus enhanced to a similar degree in each iteration while those in the background regions are suppressed. We constructed a MEFT system and conducted a series of numerical simulations and phantom experiments to evaluate the performance of the proposed method in comparison with several general regularization methods. Our results showed that application of our method produced reconstructed distribution with more accurate values (concentrations) and a clearer boundary compared with Tikhonov regularization and LSQR algorithm (used in previous report). Moreover, due to the constant weight set for the ROI, our proposed method preserves local smoothness and completeness of actual fluorophore distribution, for which sparsity regularization is inadequate.

View full abstract

Autologous bone grafts are used to reconstruct mandibular bone defects because autologous bone is highly osteogenic and does not elicit immune reactions. Because harvesting these grafts requires an additional invasive surgical procedure, we attempted to construct bone grafts from decellularized xenogeneic bone. Fragments of porcine femur cortical bone were assembled into pairs and fastened together using suture thread. They were pressurized hydrostatically to disrupt cells, washed to remove all the cell debris, and implanted subcutaneously in rats. After implantation, few immune reactions were observed and the bone fragments were not absorbed. Cells in the gap between fragments were observed histologically one week after implantation. Two weeks and four weeks after implantation, the gap was not discernible on X-ray micro CT images, and a bone-like collagen matrix was observed in the gap histologically. These findings suggest that the assembled decellularized bone fragments induce formation of bone matrix to fill the gap. Decellularized bone has the potential to be an alternative material for bone graft.

View full abstract

Compared to the evaluation of new pharmaceutical drugs, the assessments of the design and results of clinical trials for medical devices are not well established. For medical devices, the definition of the benefit-risk balance assessed during approval by regulatory agencies is not clear, which may result in subjectivity of the decision-making process. It is possible to hypothesize that the newly approved medical device should be superior in both risk and efficacy to the already existing device, which is used as control. To test this hypothesis, we performed an independent analysis of the premarket approvals (PMA) of therapeutic medical devices based on assessment review of reports of a regulatory agency, the Food and Drug Administration (FDA). A total of 74 studies that tested various medical devices for PMA were selected. For each clinical trial, the study design was evaluated with particular emphasis on its nature (retrospective or prospective). presence of a control arm, randomization, and masking. We performed an objective analysis of the benefit-risk balance between effec-tiveness and safety in the test arm compared to that in the control arm, using an original method for data evaluation. Of the 74 studies, 56 (76%) were prospective, 1 was purely retrospective (1%). 15 were mixed (20%), and 2 (3%) did not specify the nature of study. Only 46 studies (62%) included a comparative control group, 26 of which (57%) demonstrated “equivalence” but not “superiority” of the primary effectiveness measure. Depending on the evaluation criteria (mortality, complications, adverse effects, others) the results of safety assessment revealed advantage of the test arm in only 16-38% of comparative studies. The designs of the protocols for testing therapeutic medical devices and the criteria of objective evaluation during approval for broad clinical practice are not standardized. For PMA approval, FDA does not ultimately require better effectiveness and/or safety of the new device compared to the existing control device.

View full abstract

Human movements measured by a motion capture system are often represented by the motions of a multi-rigid link model of the body, which allows mechanodynamic analysis of the movements. In such cases, the position and posture of the model at time t, denoted as J(t) parameterized by unknown constant body parameters, should be determined so that they are consistent with the spatial position x(t) of a set of reflective markers attached to the body and satisfy the rigid link assumption of the model. Challenges in constructing a map from x(t) to J(t) are associated with the so-called “skin motion error”, which is the motion artifact of the markers induced by the fact that each body segment modeled by a single rigid link is in reality a multi-link system and not rigid. The skin motion error generates inconsistency between x(t) and J(t) and lowers the accuracy of the estimation. Here, we propose a novel computational algorithm for constructing the map for a small number of markers with skin motion errors, in which J(t) is estimated iteratively so that the updated J(t) is more consistent with the marker positions and the rigid link assumption, and is less affected by the skin motion error. In particular, we determine the optimal J(t) over a range of t as a fixed point of the map that is formulated as a discrete nonlinear dynamical system. Although this study is preliminary and limited to a planar double rigid link system for simplicity, mathematical analysis suggests that the performance of posture estimation may be improved using our algorithm by determining the appropriate locations at which the markers should be attached.

View full abstract

This paper provides a robotic ultrasound transducer positioning system for minimally invasive ultrasonic therapy by manipulating microbubbles in blood vessel, aiming at effective high-intensity focused ultrasound (HIFU) and acoustic drug/gene delivery. To realize such a technique in vivo, accurate and dynamic positioning of an ultrasound transducer is required. For this purpose, we have recently developed a robotic system with a parallel link structure. The novel system consists of the newly developed robot with an ultrasound transducer, an optical tracking device, and an ultrasound imaging device. As an interface for robot control, we have also developed a planning software to plan target position and direction on an echogram. The optical tracking device is used to integrate the robot and the echogram coordinates. To validate the system feasibility, this study evaluated the system performance by conducting experiments of microbubble manipulation in an artificial blood vessel.

View full abstract

As a conventional hospital information system (HIS) requires clinical staff to record data, the introduction of an HIS deprives those staff of time for direct treatment and care. This paper introduces the first commercial automatic vital data transmission system that records patients' body temperature, blood pressure, pulse rate, and arterial oxygen saturation in the clinical environment of Kyoto University Hospital. The results of task-and-motion analysis and system logging show that the system reduces the time required to record vital data by 40%. Furthermore, the system is expected to eliminate human error that may occur due to nurses failing to input data, or inputting erroneous data. To maximize the benefit of using information and communication technologies, the development of medical sensors that can be interfaced directly with a ubiquitous health-support information environment, namely an HIS, is indispensable.

View full abstract

Although immobilization of growth factors (GFs) on culture substrates has been investigated as a cell culture technique, quantification of the bioactive stability of immobilized GFs has not been studied in detail. We developed a system of measuring GF stability using heparin-immobilized collagen substrate, vascular endothelial growth factor (VEGF). and human umbilical vein endothelial cells (HUVECs). VEGF solution was added to a heparin-crosslinked substrate and immobilized on the substrate. HUVECs were cultured on the VEGF-immobilized substrate, and the mitochondrial activity of the cells was assessed. A calibration curve showing the relation between HUVEC mitochondrial activity and immobilized VEGF density was constructed. Next, immobilized VEGF and VEGF solution were pre-incubated at 37°C, and the pre-incubated VEGF was added to heparin-crosslinked substrate. HUVEC mitochondrial activity declined as the pre-incubation period increased. Density of active immobilized VEGF was derived from HUVEC mitochondrial activity using the calibration curve, and the effect of pre-incubation of VEGF at 37°C was demonstrated quantitatively. Even after culture for 16 days, immobilized VEGF in culture medium at 37°C retained 43%of the initial bioactivity. Immobilized VEGF retained activity better than VEGF solution for at least 12 days of pre-incubation. The present results indicate that immobilization improves the stability of VEGF.

View full abstract

We developed a technique to evaluate mental fatigue quantitatively by measuring perceptual performance of visually presented flicker;namely, the flicker-perception threshold (FPT), on consumer devices. Frequency domain flicker-perception threshold (FD-FPT) or critical fusion frequency (CFF), defined as a frequency at which intermittency of light disappears into a steady state for a human observer, is known to decrease as mental fatigue increases. Although FD-FPT has a long history as a reliable index of mental fatigue in the laboratory setting, it requires a dedicated device to measure, which impedes the use of this method by the general public. Additionally, arbitrariness and subjectivity of subject responses in the conventional flicker test present a significant problem for robust measurements of mental fatigue in everyday situations. This issue is especially important under such conditions where there is no supervision for users on how to respond to the ongoing flicker stimuli. We developed (a) a new method to control the subjective flickering sensation by changing the contrast of the visual stimuli instead of changing the temporal frequency, and (b) a new paradigm in which forced-choice task performance is used to determine FPT to eliminate arbitrariness of subject responses. The proposed techniques were implemented as application software, which enables persons to measure mental fatigue quantitatively using consumer mobile devices such as smart phones and PCs.

View full abstract

Hypoxia-related mechanisms are important in tumor biology and immune responses. Oxygen is delivered to tumor tissue by blood flowing through abnormal and dysfunctional microvessels, resulting in heterogeneity of tissue oxygenation within the tumor. Hypoxic conditions play a role in directing angiogenesis, guiding immune cells, and inducing tumor metastasis. Mimicking such oxygen gradient in in vitro cellular experiments is important to clarify the mechanisms involved in tumor biology. Previous research has led to the development of cell culture devices that generate an oxygen gradient, but it was impossible to monitor the oxygen gradient during cell culture. In this study, we designed an open-well polydimethylsiloxane (PDMS) microfluidic device integrated with an oxygen-sensitive film, which permits oxygen measurement around cells and molecular analysis after cell culture experiments. Mathematical simulation and phosphorescence-based partial oxygen measurements show that the gradient can be controlled by changing the oxygen gas concentration inside the microchannels, according to the requirements of various biological models. A monoculture of endothelial cells exposed to an oxygen gradient in the device showed increased expression of oxygen-responsive genes in the hypoxic area. These results suggest that our microfluidic device can be used for in vitro experiments such as gene expression and migration assays. We believe that this new device is a powerful tool for studies of tumor biology and immunology.

View full abstract