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Biomedical subjects

Eiji Okamoto

Publications and source records attributed to Eiji Okamoto.

15 recordsLinked to original sources

Numerical estimation of heat distribution from the implantable battery system of an undulation pump LVAD.

We have been developing an implantable battery system using three series-connected lithium ion batteries having an energy capacity of 1,800 mAh to drive an undulation pump left ventricular assist device. However, the lithium ion battery undergoes an exothermic reaction during the discharge phase, and the temperature rise of the lithium ion battery is a critical issue for implantation usage. Heat generation in the lithium ion battery depends on the intensity of the discharge current, and we obtained a relationship between the heat flow from the lithium ion battery q(c)(I) and the intensity of the discharge current I as q(c)(I) = 0.63 x I (W) in in vitro experiments. The temperature distribution of the implantable battery system was estimated by means of three-dimentional finite-element method (FEM) heat transfer analysis using the heat flow function q(c)(I), and we also measured the temperature rise of the implantable battery system in in vitro experiments to conduct verification of the estimation. The maximum temperatures of the lithium ion battery and the implantable battery case were measured as 52.2 degrees C and 41.1 degrees C, respectively. The estimated result of temperature distribution of the implantable battery system agreed well with the measured results using thermography. In conclusion, FEM heat transfer analysis is promising as a tool to estimate the temperature of the implantable lithium ion battery system under any pump current without the need for animal experiments, and it is a convenient tool for optimization of heat transfer characteristics of the implantable battery system.

Electric Power Supplies↗

Estimation of early-stage malfunction using implantable artificial heart sound in animal experiments.

We have developed an automatic diagnosis system of an artificial heart in order to ensure the safety of the patient implanted with the artificial heart. The automatic diagnosis system is composed of an electro-stethoscope system, adaptive noise canceller (ANC), and artificial neural network (ANN). The ANC effectively eliminates ambient noise from the sound signal of the artificial heart detected by the electro-stethoscope, and a filtered sound signal is separated into each frequency components by fast Fourier transformation. Each frequency component of an artificial heart's acoustic signal is fed into the ANN in order to make a diagnosis of pump condition. The automatic diagnosis system was evaluated in mock circulatory tests and a long-term animal experiment using a goat implanted with an undulation pump ventricular assist device (UPVAD). In mock circulatory tests, the ANN was able to detect pump failing conditions, which were occlusion of inflow and outflow cannula and deterioration of the ball bearing. In a long-term animal experiment, after training the ANN using UPVAD's sound signal in normal condition, the diagnosis system continuously monitored UPVAD's sound signal detected by the electro-stethoscope placed on the surface of the left thoracic cavity of the goat. The UPVAD was stopped by rupture of a diaphragm in the pump on the ninth day of operation. We were able to identify initial signs of malfunction of the pump on the eighth day, while the UPVAD was able to operate normally. In conclusion, the automatic diagnosis system for malfunction of the artificial heart has enough performance to detect early stages of malfunction of the artificial heart, and it contributes to ensure the patient's safety.

Animals↗

Development of integrated electronics unit for drive and control of undulation pump-left ventricular assist device.

In this study, we have developed an implantable electronics unit (IEU) for driving an undulation pump-left ventricular assist device (UP-LVAD). The IEU consists of a pump driver, three series-connected lithium ion batteries (1800 mAh), a charger, and a transcutaneous information transmission system. These electronic subunits were encapsulated in a case (110 x approximately 80 x approximately 30 mm) made of epoxy resin. The IEU was evaluated in two animal experiments using goats implanted with the UP-LVAD. The lithium ion batteries in the IEU provided 30-min energy supply daily to the UP-LVAD. The transcutaneous information transmission system transmitted data bidirectionally between the IEU and the personal computer at the data transmission ratio of 56 kbps without any transmission error. We could obtain survival days of 27 and 28 days supporting cardiac function with the UP-LVAD system. The temperature inside the IEU case was maintained under 45 degrees C, and there was evidence of a burn on the surrounding tissue in autopsies in each experiment. Based on the results, the IEU is promising to be suitable for drive and control of an implantable UP-LVAD.

Animals↗

Enzyme-linked immunosorbent assay using bacterial recombinant proteins of human BP230 as a diagnostic tool for bullous pemphigoid.

BACKGROUND: By immunoblot analyses of normal human epidermal extracts, the 230kDa bullous pemphigoid antigen (BP230) is recognized by most bullous pemphigoid (BP) sera. We produced different recombinant glutathione-S-transferase-fusion proteins, which roughly presented N-terminal domain, central rod domain and C-terminal domain of human BP230. OBJECTIVE: In the present study, we developed an enzyme-linked immunosorbent assay (ELISA) using the recombinant proteins for detection of anti-BP230 IgG antibodies and assessed the usefulness of this assay in conjunction with an anti-BP180 ELISA to establish the diagnosis of BP. METHODS: Using the bacterial recombinant proteins of N-terminal and C-terminal domains, we developed an ELISA. A receiver-operating-characteristic (ROC) analysis was performed to determine a cut-off value for the BP230 ELISA. RESULTS: By this BP230 ELISA, 173 (72.4%) of 239 BP sera were positive, while only one (1.1%) of 94 sera from pemphigus vulgaris and pemphigus foliaceus patients was positive and all the 109 normal control sera were negative. Thus, the sensitivity and specificity of the BP230 ELISA were 72.4 and 99.5%, respectively. Interestingly, while 54 (84.4%) of 64 BP sera in active stage and 113 (64.6%) of 175 BP sera in remission were positive in BP180 ELISA, 37 (57.8%) of 64 BP sera in active stage and 136 (77.7%) of 175 BP sera in remission were positive in BP230 ELISA. These results indicate that the titer of anti-BP230 antibodies is not related with disease activity in some BP cases. Most significantly, by combining the results of BP230 ELISA and BP180 ELISA, 232 (97.1%) of 239 BP sera were positive. CONCLUSION: The combination of BP230 ELISA and BP180 ELISA is the highly sensitive method for the diagnosis of BP.

Autoantigens↗

Development of a bidirectional transcutaneous optical data transmission system for artificial hearts allowing long-distance data communication with low electric power consumption.

We have developed a wavelength division bidirectional transcutaneous optical data transmission system using amplitude shift keying (ASK) modulation. The bidirectional optical data transmission system consists of two kinds of light emitting diodes (LEDs) having different wavelengths and an ASK modulator and demodulator. Two narrow directional visible LEDs with a peak output wavelength of 590 nm were used to transmit data from inside the body to outside the body, and a narrow directional near-infrared LED with a peak output wavelength of 940 nm was used for transmission from outside the body to inside the body. The ASK modulator employs a carrier pulse signal (50 kHz) to support a maximum data transmission rate of 9600 bps. An in vitro experiment showed that the maximum tissue thickness of near-infrared optical data transmission without error was 45 mm; the figure was 20 mm for visible optical data transmission. There was no interference between the signals under full-duplex data transmission. Electric power consumption for the data transmission links was 122 mW for near-infrared light and 162 mW (81 mW x 2) for visible light. From the above results, a bidirectional transcutaneous optical data transmission system promises adequate performance for monitoring and control of an artificial heart.

Equipment Design↗

Development of an electro-stethoscope system and design of an optimum filter based on tissue sound transmission for noninvasive early diagnosis of malfunction of an implanted mechanical total artificial heart.

Early diagnosis of the malfunction of a mechanical artificial heart implanted in a patient who has been discharged from hospital is very important. We have developed an electro-stethoscope system that enables the malfunction of an artificial heart to be detected from the analysis of sound signals from the artificial heart. The sound data can be transmitted to a hospital via a mobile telephone or the Internet, so that doctors can examine the condition of the artificial heart. The optimum frequency characteristics of a low-pass filter for the elimination of ambient sound through the electro-stethoscope casing were obtained by simulating sound transmission through tissue. We evaluated the usefulness of the electro-stethoscope system using a goat in which an undulation pump total artificial heart had been implanted. A frequency analysis of the sound signal provided information on the degree of degradation of each mechanical component of the artificial heart. The results of this study showed that the electro-stethoscope system is useful for the early detection of the malfunction of an artificial heart at home, and that the use of the system contributes to improvement in the quality of life of patients.

Animals↗

Design of a miniature implantable left ventricular assist device using CAD/CAM technology.

In this study, we developed a new miniature motor-driven pulsatile left ventricular assist device (LVAD) for implantation into a Japanese patient of average build by means of computer-aided design and manufacturing (CAD/CAM) technology. A specially designed miniature ball-screw and a high-performance brushless DC motor were used in an artificial heart actuator to allow miniaturization. A blood pump chamber (stroke volume 55 ml) and an inflow and outflow port were designed by computational fluid dynamics (CFD) analysis. The geometry of the blood pump was evaluated using the value of index of pump geometry (IPG) = (Reynolds shear stress) x (occupied volume) as a quantitative index for optimization. The calculated value of IPG varied from 20.6 Nm to 49.1 Nm, depending on small variations in pump geometry. We determined the optimum pump geometry based on the results of quantitative evaluation using IPG and qualitative evaluation using the flow velocity distribution with blood flow tracking. The geometry of the blood pump that gave lower shear stress had more optimum spiral flow around the diaphragm-housing (D-H) junction. The volume and weight of the new LVAD, made of epoxy resin, is 309 ml and 378 g, but further miniaturization will be possible by improving the geometry of both the blood pump and the back casing. Our results show that our new design method for an implantable LVAD using CAD/CAM promises to improve blood compatibility with greater miniaturization.

Computer-Aided Design↗

Artificial myocardium with an artificial baroreflex system using nano technology.

Where is the place which should be helped in a patient with congestive heart failure? The answer may be contraction of the heart. At Tohoku University, development research of "the artificial myocardium" has been conducted, using a ball screw type electromagnetic motor. Furthermore, super-miniaturization is being attempted at present. Thus, a system with shape memory alloy is being developed. The cooling speed problem was solved by the application of the Peltier element. A drive at a speed equal to that of a heartbeat was realized by the application of this system. At present, a ventricular assist device is used for patients waiting for a heart transplant in Japan. An air driven type system disturbs a patient's QOL remarkably because it is connected to the drive device. With our concept, energy is provided by using the electromagnetic force from outside of the body by the use of transcutaneous energy transmission system. Magnetic shielding by amorphous fibers was used at Tohoku University to improve the total efficiency. A natural heart can alter the cardiac output corresponding to the demand. Artificial internal organs must participate in the system of the living body, too. Tohoku University has developed a resistance based artificial heart control algorithm, which simulated a baroreflex system to cope with every demand. Nano level sensing equipment is now under development at Tohoku University. At present, development is being conducted aiming at an "intelligent artificial myocardium".

Baroreflex↗

An estimation method of hemolysis within an axial flow blood pump by computational fluid dynamics analysis.

Evaluation of hemolysis within a blood pump on a computer is useful for developing rotary blood pumps. The flow fields in the axial flow blood pump were analyzed using computational fluid dynamics (CFD). A blood damage index was calculated based on the changes in shear stress with time along 937 streamlines. Hemolysis of the pumps was measured using bovine blood. A good correlation between the computed and measured hemolysis results was observed. CFD analysis is useful for estimating hemolysis of rotary blood pumps on a computer.

Animals↗

Blood compatible design of a pulsatile blood pump using computational fluid dynamics and computer-aided design and manufacturing technology.

Thrombus formation is a critical issue when designing a long-term implantable left ventricular assist system (LVAS). Fluid dynamic characteristics of blood flow are one of the main factors that cause thrombus formation. In this study, we optimized the fluid dynamics of a sac blood pump in our LVAS to ensure minimization of shear-related blood damage that could lead to thrombus formation. A pump housing and a sac chamber were designed with computer-aided design (CAD) software, and fluid dynamics were estimated by computational fluid dynamic (CFD) analysis. We adopted distribution of CFD results for qualitative evaluation, and we also tried to estimate normalized index of hemolysis (NIH) from the results of CFD analysis as a quantitative index of optimization for geometry of the blood pump chamber. A prototype model of the optimized blood pump was made using a three-axis computer machine tool by whittling pieces of nonfoamed polyurethane. Shear stress and theoretical NIH in the redesigned model were lower than those in the first model. Area of flow stagnation that was observed in the first model was not seen in the redesigned model. The results demonstrate that application of CAD/CAM technology to design an artificial heart contributes to optimizing a blood pump chamber for the purpose of reducing thrombus formation.

Biomedical Technology↗

Computational fluid dynamics analysis of an intra-cardiac axial flow pump.

A low rate of hemolysis is an important factor for the development of a rotary blood pump. It is, however, difficult to identify the areas where hemolysis occurs. Computational fluid dynamics (CFD) analysis enables the engineer to predict hemolysis on a computer. In this study, fluid dynamics throughout intracardiac axial flow pumps with different designs were analyzed three-dimensionally using CFD software. The computed pressure-flow characteristics of the pump were in good agreement with the measurements. The Reynolds shear stress was computed along particle trace lines. Hemolysis was estimated on the basis of shear stress (tau) and its exposure time (Deltat): dHb/Hb = 3.62 x 10(-7)(tau)(i)(2.416) x Delta(t)(i)(0.785). Particle damage increased with time along the particle trace lines. Hemolysis of each of the pumps was measured in vitro. The computed hemolysis values were in good agreement with the experimental results. CFD is a useful tool for developing a rotary blood pump.

Computational Biology↗

[Improving diffusion-weighted imaging of liver with SENSE technique: a preliminary study].

Diffusion-weighted imaging (DWI) has not commonly been performed for assessment of the liver because of technical and physiologic problems. The sensitivity-encoding (SENSE) technique enables the acquisition time to be shortened and reduces artifacts on DWI. We compared the DWI without SENSE, with SENSE only, and with SENSE and half-Fourier technique using a 1.5 Tesla MRI unit. In general, imaging quality was improved and fewer artifacts were observed in DWI with SENSE. DWI of liver with SENSE is expected to be a useful tool for clinical application.

Aged↗

Optimum selection of an implantable secondary battery for an artificial heart by examination of the cycle life test.

An implantable secondary battery is one of the key components in a total artificial heart system. Because a 2 year cycle life is required, the cycle life of the secondary battery as well as its charge and discharge properties are important parameters for selection of an appropriate battery. We carried out cycle life tests on four kinds of rechargeable batteries (a Ni-MH secondary battery, a Ni-Cd secondary battery, a Li-ion battery with a graphite anode, and a Li-ion battery with a nongraphitizable carbon electrode) to determine their suitability as implanted back-up batteries. Each of the batteries was charge/discharge cycled at 37 degrees C to 39 degrees C using a charge current of 1 C ampere, and they were each fully discharged under either pulsatile discharge loads, which mimicked pulsatile operation, or a nonpulsatile load equivalent to the average of the pulsatile loads. The two Li-ion batteries made by different manufacturers both met the minimum requirement of cycle life of more than 1,500 cycles, considering safety coefficient regardless of the discharge pattern. In addition, the temperature increase of these Li-ion batteries (3 degrees C) was lower than that of Ni-Cd and Ni-MH batteries (15-25 degrees C). Out of these four batteries, the two Li-ion batteries are the most suitable for use in a totally implantable artificial heart system.

Cadmium↗

Ten-year NEDO BVAD development program: moving forward to the clinical arena.

Since 1995, the Baylor Group has been developing a totally implantable NEDO BVAD system. This 10-year program was completed in March 2005, and preparation for clinical trials is underway. This article summarizes the entire 10-year NEDO program and describes the strategy for clinical trials. The project aimed to achieve: (1) dual centrifugal pumps with the ability of full biventricular support, (2) a compact system implantable into small adults, (3) a totally implantable system with transcutaneous energy transmission system (TETS), (4) a durable system with a lifetime of over 5 years, and (5) a system free of thrombus and with minimal hemolysis. The final goals are to complete preclinical system evaluations and commence the clinical trials in the near future. In vitro studies have demonstrated a pump capacity of over 8.5 l/min and an Index of Hemolysis of <0.004 g/100 l. The pump-bearing life expectancy was over 5 years. To date, eight pumps endured in vivo studies of over 3 months without complications, including thromboembolic events. The in vitro endurance studies of eight pumps are longer than 1 year. There were no mechanical malfunctions or pump failure. A stepwise clinical trial is being planned: Step1, a wearable BVAD/VAD will be clinically studied; Step 2, the BVAD/VAD will be implanted intracorporeally without TETS; and, Step 3, a totally implantable system will be clinically evaluated. The NEDO BVAD system has completed preclinical testing. Clinical trial preparation is underway.

Animals↗

Paradoxical effects by preoperative oral low-dose tegafur administration in human gastric carcinomas: enhanced apoptosis and increased intratumoral microvessel density.

This study examined the effect of preoperative low-dose tegafur treatment in human gastric carcinomas. Among 55 patients with gastric carcinoma, 33 received an oral administration of tegafur 600 mg/body/day for 7 days before. Formalin-fixed, paraffin-embedded specimens were immunostained for Ki-67, P53, P21, CD34, Bax, VEGF, and dThdPase and also examined by the terminal deoxynucleotidyl transferase-mediated dUTP-digoxigenin nick end labeling procedure. The apoptotic index (AI), Ki-67 labeling index (KI) and intratumoral microvessel density (IMVD) were counted. Mean AI and IMVD were 3.4+/-1.60 and 126.1+/-36.56 in the treated carcinomas, and 2.3+/-0.88 and 98.0+/-44.40 in the non-treated carcinomas, both values being significantly higher in the former (P<0.05). The treatment resulted in a significant increase of mean AI in the intestinal type, in the early, and in the P53-positive carcinomas (P<0.05), while the treatment brought a significant increase of IMVD in the diffuse type, in the early and in the P53-negative carcinomas (P<0.05, respectively). No significant difference was noted on the frequency of P53, P21, BAX, VEGF and dThdPase expressions between the two groups. Ki-67 expression did not correlate with any factors. Preoperative low-dose tegafur treatment resulted in a paradoxical effect; enhanced apoptosis and increased IMVD in human gastric carcinomas.

Aged↗