Carbon range verification with 718 keV Compton imaging.

Carbon ion radiotherapy is a sophisticated radiation treatment modality because of its superiority in achieving precise dosage distribution and high biological effectiveness. However, there exist beam range uncertainties that affect treatment efficiency. This problem can be resolved if the clinical beam could be monitored precisely in real-time, such as by imaging the prompt gamma emission from the target. In this study, we performed real-time detection and imaging of 718 keV prompt gamma emissions using a Si/CdTe Compton camera. We conducted experiments on graphite phantoms using clinical carbon ion beams of 290 MeV/u energy. Compton images were reconstructed using simple back-projection methods from the energy events of 718 keV prompt gamma emissions. The peak intensity position in reconstructed 718 keV prompt gamma images was few millimeters below the Bragg peak position. Moreover, the dual- and triple-energy window images for all positions of phantoms were not affected by scattered gammas, and their peak intensity positions were approximately similar to those observed in the reconstructed 718 keV prompt gamma images. In conclusion, the findings of the current study demonstrate the feasibility of using our Compton camera for real-time beam monitoring of carbon ion beams under clinical beam intensity.

Crosstalk Reduction Using a Dual Energy Window Scatter Correction in Compton Imaging.

Compton cameras can simultaneously detect multi-isotopes; however, when simultaneous imaging is performed, crosstalk artifacts appear on the images obtained using a low-energy window. In conventional single-photon emission computed tomography, a dual energy window (DEW) subtraction method is used to reduce crosstalk. This study aimed to evaluate the effectiveness of employing the DEW technique to reduce crosstalk artifacts in Compton images obtained using low-energy windows. To this end, in this study, we compared reconstructed images obtained using either a photo-peak window or a scatter window by performing image subtraction based on the differences between the two images. Simulation calculations were performed to obtain the list data for the Compton camera using a 171 and a 511 keV point source. In the images reconstructed using these data, crosstalk artifacts were clearly observed in the images obtained using a 171 keV photo-peak energy window. In the images obtained using a scatter window (176-186 keV), only crosstalk artifacts were visible. The DEW method could eliminate the influence of high-energy sources on the images obtained with a photo-peak window, thereby improving quantitative capability. This was also observed when the DEW method was used on experimentally obtained images.

Improved iterative reconstruction method for Compton imaging using median filter.

A Compton camera is a device for imaging a radio-source distribution without using a mechanical collimator. Ordered-subset expectation-maximization (OS-EM) is widely used to reconstruct Compton images. However, the OS-EM algorithm tends to over-concentrate and amplify noise in the reconstructed image. It is, thus, necessary to optimize the number of iterations to develop high-quality images, but this has not yet been achieved. In this paper, we apply a median filter to an OS-EM algorithm and introduce a median root prior expectation-maximization (MRP-EM) algorithm to overcome this problem. In MRP-EM, the median filter is used to update the image in each iteration. We evaluated the quality of images reconstructed by our proposed method and compared them with those reconstructed by conventional algorithms using mathematical phantoms. The spatial resolution was estimated using the images of two point sources. Reproducibility was evaluated on an ellipsoidal phantom by calculating the residual sum of squares, zero-mean normalized cross-correlation, and mutual information. In addition, we evaluated the semi-quantitative performance and uniformity on the ellipsoidal phantom. MRP-EM reduces the generated noise and is robust with respect to the number of iterations. An evaluation of the reconstructed image quality using some statistical indices shows that our proposed method delivers better results than conventional techniques.

Imaging of 99mTc-DMSA and 18F-FDG in humans using a Si/CdTe Compton camera.

The Compton camera can simultaneously acquire images of multiple isotopes injected in a body; therefore, it has the potential to introduce a new subfield in the field of biomedical imaging applications. The objective of this study is to assess the ability of a prototype semiconductor-based silicon/cadmium telluride (Si/CdTe) Compton camera to simultaneously image the distributions of technetium (99mTc)-dimercaptosuccinic acid (DMSA) (141 keV emission) and 18F-fluorodeoxyglucose (FDG) (511 keV emission) injected into a human volunteer. 99mTc-DMSA and 18F-FDG were injected intravenously into a 25-year-old male volunteer. The distributions of 99mTc-DMSA and 18F-FDG were simultaneously made visible by setting a specified energy window for each radioisotope. The images of these radiopharmaceuticals acquired using the prototype Compton camera were superimposed onto computed tomography images for reference. The reconstructed image showed that 99mTc-DMSA had accumulated in both kidneys, which is consistent with the well-known diagnostic distribution determined by clinical imaging via single-photon emission computed tomography. In the 18F-FDG image, there is broad distribution around the liver and kidneys, which was expected based on routine clinical positron emission tomography imaging. The current study demonstrated for the first time that the Si/CdTe Compton camera was capable of simultaneously imaging the distributions of two radiopharmaceuticals, 99mTc-DMSA and 18F-FDG, in a human body. These results suggest that the Si/CdTe Compton camera has the potential to become a novel modality for nuclear medical diagnoses enabling multi-probe simultaneous tracking.

Compton imaging with 99mTc for human imaging.

We have been developing a medical imaging system using a Compton camera and demonstrated the imaging ability of Compton camera for 99mTc-DMSA accumulated in rat kidneys. In this study, we performed imaging experiments using a human body phantom to confirm its applicability to human imaging. Preliminary simulations were conducted using a digital phantom with varying activity ratios between the kidney and body trunk regions. Gamma rays (141 keV) were generated and detected by a Compton camera based on a silicon and cadmium telluride (Si/CdTe) detector. Compton images were reconstructed with the list mode median root prior expectation maximization method. The appropriate number of iterations of the condition was confirmed through simulations. The reconstructed Compton images revealed two bright points in the kidney regions. Furthermore, the numerical value calculated by integrating pixel values inside the region of interest correlated well with the activity of the kidney regions. Finally, experimental studies were conducted to ascertain whether the results of the simulation studies could be reproduced. The kidneys could be successfully visualised. In conclusion, considering that the conditions in this study agree with those of typical human bodies and imaginable experimental setup, the Si/CdTe Compton camera has a high probability of success in human imaging. In addition, our results indicate the capability of (semi-) quantitative analysis using Compton images.

Annihilation gamma imaging for carbon ion beam range monitoring using Si/CdTe Compton camera.

In this study, we performed on-beam monitoring of 511 keV annihilation gamma emissions using a Compton camera. Beam monitoring experiments were conducted using carbon ion beams of 290 MeV/u irradiated on a polymethyl methacrylate (PMMA) phantom. The intensity of the beams was 3 × 109 particles per pulse, with 20 pulses per minute. A Compton camera based on a silicon/cadmium telluride (Si/CdTe) detector was used to monitor the annihilation gamma rays emitted from the phantom. We successfully reconstructed the energy events of 511 keV annihilation gamma rays and developed Compton images using a simple back-projection method. The distribution of the annihilation gamma ray generation traced the beam trajectory and the peak intensity position was a few millimeters shorter than the Bragg peak position. Moreover, the effect of the beam range shifter with 30, 60, and 90 mm water equivalent thickness (WET) was clearly visualized in the reconstructed Compton images. The experimentally measured values of the corresponding range shifts in the PMMA phantom (28.70 mm, 52.49 mm, and 76.77 mm, respectively) were consistent with the shifts of the Bragg peak position (25.50 mm, 51.30 mm and 76.70 mm, respectively) evaluated by Monte Carlo simulation. The results show that the Si/CdTe Compton camera has strong potential for on-beam monitoring of annihilation gamma rays in particle therapy in clinical situations.

Effect of number of views on cross-sectional Compton imaging: A fundamental study with backprojection.

INTRODUCTION: We have been developing a medical imaging technique using a Compton camera, which is expected to reconstruct three-dimensional images. If the number of views is not sufficient, star-shaped artifacts (streak artifacts) could arise in cross-sectional images. Therefore, we estimated the point spread function (PSF) of cross-sectional Compton images and the effect of the number of views by Monte Carlo simulations and experimental studies. MATERIALS AND METHODS: A cross-sectional Compton image was reconstructed using a dataset comprising 719 view directions and PSF was analyzed using a radial distribution. The peak height, full width at half maximum (FWHM), background (BG), and residual sum of squares (RSS) were calculated from the obtained PSF. In addition, RSSs were plotted against the number of views to estimate the required number to suppress star-shaped artifacts. RESULTS: There was no correlation found between the number of views and both FWHM (16 mm) and peak/BG ratio (∼1 × 104). RSSs were reduced with the number of views and approached the minimum asymptotically. Correlation was observed between the required number of views and the number of Compton events used for image reconstruction. CONCLUSION: We determined the PSF of cross-sectional Compton images and the effect of the number of views on the images. The required number of views to suppress the star-shaped artifact is related to the square root of the number of Compton events used to reconstruct the image. From this study, we concluded that 21 or more views are required for clinical purposes.

In vivo simultaneous imaging with 99mTc and 18F using a Compton camera.

We have been developing a medical imaging technique using a Compton camera. This study evaluates the feasibility of clear imaging with 99mTc and 18F simultaneously, and demonstrates in vivo imaging with 99mTc and/or 18F. We used a Compton camera with silicon and cadmium telluride (Si/CdTe) semiconductors. We estimated the imaging performance of the Compton camera for 141 keV and 511 keV gamma rays from 99mTc and 22Na, respectively. Next, we simultaneously imaged 99mTc and 18F point sources to evaluate the cross-talk artifacts produced by a higher energy gamma-ray background. Then, in the in vivo experiments, three rats were injected with 99mTc-dimercaptosuccinic acid and/or 18F-fluorodeoxyglucose and imaged. The Compton images were compared with PET images. The rats were euthanized, and the activities in their organs were measured using a well counter. The energy resolution and spatial resolution were measured for the sources. No apparent cross-talk artifacts were observed in the practical-activity ratio (99mTc:18F = 1:16). We succeeded in imaging the distributions of 99mTc and 18F simultaneously, and the results were consistent with the PET images and well counter measurements. Our Si/CdTe Compton camera can thus work as a multi-tracer imager, covering various SPECT and PET probes, with less cross-talk artifacts in comparison to the conventional Anger cameras using a collimator. Our findings suggest the possibility of human trials.

Imaging of monochromatic beams by measuring secondary electron bremsstrahlung for carbon-ion therapy using a pinhole x-ray camera.

A feasibility study on the imaging of monochromatic carbon-ion beams for carbon-ion therapy was performed. The evaluation was based on Monte Carlo simulations and beam-irradiation experiments, using a pinhole x-ray camera, which measured secondary electron bremsstrahlung (SEB). The simulation results indicated that the trajectories of the carbon-ion beams with injection energies of 278, 249 and 218 MeV/u in a water phantom, were clearly imaged by measuring the SEB with energies from 30 to 60 keV, using a pinhole camera. The Bragg-peak positions for these three injection energies were located at the positions where the ratios of the counts of SEB acquisitions to the maximum counts were approximately 0.23, 0.26 and 0.29, respectively. Moreover, we experimentally demonstrated that it was possible to identify the Bragg-peak positons, at the positions where the ratios coincided with the simulation results. However, the estimated Bragg-peak positions for the injection energies of 278 and 249 MeV/u were slightly deeper than the expected positions. In conclusion, for both the simulations and experiments, we found that the 25 mm shifts in the Bragg-peak positions can be observed by this method.

Monte Carlo simulation of photon emission below a few hundred kiloelectronvolts for beam monitoring in carbon ion therapy.

The purpose of this study is to determine whether the main component of the low-energy (63-68 keV) particles emitted perpendicularly to the 12C beam from the 12C-irradiated region in a water phantom is secondary electron bremsstrahlung (SEB). Monte Carlo simulations of a 12C-beam (290 MeV/u) irradiated on a water phantom were performed. A detector was placed beside the water phantom with a lead collimator between the phantom and the detector. To move the Bragg-peak position, a binary filter was placed in an upper stream of the phantom. The energy distributions of the particles incident on the detector and those deposited in the detector were analyzed. The simulation was also performed with suppressed delta-ray and/or bremsstrahlung generation to identify the SEB components. It was found that the particles incident on the detector were predominantly photons and neutrons. The yields of the photons and energy deposition decreased with the suppression of SEB generation. It is concluded that one of the predominant components of the yields in the regions shallower than the Bragg-peak position is due to SEB generation, and these components become significantly smaller in regions deeper than the Bragg-peak position.

An analytical model of dynamic sliding friction during impact.

Dynamic sliding friction was studied based on the angular velocity of a golf ball during an oblique impact. This study used the analytical model proposed for the dynamic sliding friction on lubricated and non-lubricated inclines. The contact area A and sliding velocity u of the ball during impact were used to describe the dynamic friction force Fd = λAu, where λ is a parameter related to the wear of the contact area. A comparison with experimental results revealed that the model agreed well with the observed changes in the angular velocity during impact, and λAu is qualitatively equivalent to the empirical relationship, µN + µÎ·'dA/dt, given by the product between the frictional coefficient µ and the contact force N, and the additional term related to factor η' for the surface condition and the time derivative of A.

Objective and subjective comparison of the visibility of three echogenic needles and a nonechogenic needle on older ultrasound devices.

OBJECTIVE: This study evaluated the visibility of echogenic needles with older ultrasound devices in an in vitro phantom study. METHODS: We compared three echogenic needles from B. Braun (BB), Unisis (UN), and Hakko (HK) with a nonechogenic needle. Each needle was inserted into an ultrasound phantom 10 times at 30° and 45° with the bevels up. The captured images of the needle and background contrast were digitally analyzed, and the median of 10 insertions for each angle was calculated to determine objective needle visibility. Needle images were also shown to 12 anesthesiologists to evaluate subjective visibility on a five-point Likert scale. RESULTS: The shafts of all the echogenic needles were significantly more objectively visible than the nonechogenic needles. Subjective visibilities of the BB and UN needles were significantly higher than that of the nonechogenic needle. Therefore, the BB and UN needles were judged to have more than fair subjective visibility. However, subjective visibility of the HK needle was consistently and significantly lower than that of the BB and UN echogenic needles. At 45°, the HK needle had nearly the same poor visibility as the nonechogenic needle. CONCLUSION: The results of our study indicate that the BB and UN needles are more visible than nonechogenic needles in an ultrasound phantom, even on older devices.

Three-dimensional and multienergy gamma-ray simultaneous imaging by using a Si/CdTe Compton camera.

PURPOSE: To develop a silicon (Si) and cadmium telluride (CdTe) imaging Compton camera for biomedical application on the basis of technologies used for astrophysical observation and to test its capacity to perform three-dimensional (3D) imaging. MATERIALS AND METHODS: All animal experiments were performed according to the Animal Care and Experimentation Committee (Gunma University, Maebashi, Japan). Flourine 18 fluorodeoxyglucose (FDG), iodine 131 ((131)I) methylnorcholestenol, and gallium 67 ((67)Ga) citrate, separately compacted into micro tubes, were inserted subcutaneously into a Wistar rat, and the distribution of the radioisotope compounds was determined with 3D imaging by using the Compton camera after the rat was sacrificed (ex vivo model). In a separate experiment, indium 111((111)In) chloride and (131)I-methylnorcholestenol were injected into a rat intravenously, and copper 64 ((64)Cu) chloride was administered into the stomach orally just before imaging. The isotope distributions were determined with 3D imaging after sacrifice by means of the list-mode-expectation-maximizing-maximum-likelihood method. RESULTS: The Si/CdTe Compton camera demonstrated its 3D multinuclear imaging capability by separating out the distributions of FDG, (131)I-methylnorcholestenol, and (67)Ga-citrate clearly in a test-tube-implanted ex vivo model. In the more physiologic model with tail vein injection prior to sacrifice, the distributions of (131)I-methylnorcholestenol and (64)Cu-chloride were demonstrated with 3D imaging, and the difference in distribution of the two isotopes was successfully imaged although the accumulation on the image of (111)In-chloride was difficult to visualize because of blurring at the low-energy region. CONCLUSION: The Si/CdTe Compton camera clearly resolved the distribution of multiple isotopes in 3D imaging and simultaneously in the ex vivo model.

Influence of curing light power and energy on shrinkage force and acoustic emission characteristics of a dental composite restoration.

PURPOSE: To evaluate the density effects of light power and energy on the volumetric polymerization shrinkage and acoustic emission (AE) characteristics of a dental resin composite in the cavities of human teeth. METHODS: Two experiments were performed at different power levels (1,000 and 4,000 mW/cm2) using a light curing unit: (1) cylindrical cavities with diameters of 4 mm and depths of 2 mm were constructed using two symmetric steel molds. The cavities were filled with resin, and the shrinkage force during polymerization was measured using a load cell attached to the mold. Polymerization shrinkage forces were measured under four conditions (1,000 mW/cm2 x 10 seconds, 1,000 mW/cm2 x 20 seconds, 4,000 mW/cm2 x 3 seconds, and 4,000 mW/cm2 x 5 seconds); (2) tooth specimens with cavity diameters of 6 mm and depths of 2 mm were made from human molars. AE signals during polymerization shrinkage were monitored in real time for 10 minutes after irradiation and two AE factors (amplitude for defect size and hit number for defect number) were assessed in the examination of defects. Two levels of light energy (20 J/cm2 = 1,000 mW/cm2 x 20 seconds and 12 J/cm2 = 4,000 mW/cm2 x 3 seconds) were used. RESULTS: Shrinkage occurred more quickly at 4,000 mW/cm2 than at 1,000 mW/cm2 during the initial phase. The shrinkage force became almost the same for equivalent light energy as time increased. Higher light energy (20 J/cm2) under low-power conditions (1,000 mW/cm2) caused larger cumulative numbers of AE hits than did lower light energy (12 J/cm2) under high-power conditions (4,000 mW/cm2). At 4,000 mW/cm2 and 12 J/cm2 (i.e., high power, low energy), the average amplitude of the AE signals was larger than at 1,000 mW/cm2 and 20 J/cm2 (low power, high energy).

Beam range estimation by measuring bremsstrahlung.

We describe a new method for estimating the beam range in heavy-ion radiation therapy by measuring the ion beam bremsstrahlung. We experimentally confirm that the secondary electron bremsstrahlung process provides the dominant bremsstrahlung contribution. A Monte Carlo simulation shows that the number of background photons from annihilation gamma rays is about 1% of the bremsstrahlung strength in the low-energy region used in our estimation (63-68 keV). Agreement between the experimental results and the theoretical prediction for the characteristic shape of the bremsstrahlung spectrum validates the effectiveness of our new method in estimating the ion beam range.

Quantitative analysis of cisplatin sensitivity of human esophageal squamous cancer cell lines using in-air micro-PIXE.

Cisplatin is a key chemotherapeutic agent for the treatment of esophageal cancer. We examined the intracellular localization of cisplatin in esophageal cancer cell lines and determined their sensitivity to cisplatin using in-air micro-PIXE (particle induced X-ray emission). Two human esophageal squamous cell carcinoma (ESCC) cell lines, TE-2 and TE-13, were examined for their response to cisplatin using MTT assay, flow cytometry, and DNA fragmentation assays. Real-time reverse transcription-polymerase chain reaction was also used to evaluate the mRNA expression of multidrug resistance protein 2 (MRP2) in both cell lines. Platinum localizations of intracellular and intranuclear were measured using in-air micro-PIXE. TE-2 cells were more sensitive to cisplatin than TE-13 cells (IC(50): 37.5 mum and 56.3 mum, respectively). Flow cytometry analysis confirmed that more TE-2 than TE-13 cells were in the sub-G1 phase. DNA fragmentation assay was analyzed to confirm the MTT assay and flow cytometry results. The expression of MRP2 mRNA in TE-13 cells was stronger than in TE-2 cells. In-air micro-PIXE showed that TE-2 cells had higher intracellular cisplatin concentrations than TE-13 cells and the ratio of intranuclear to intracellular cisplatin in individual cells was not significantly different. We observed the intracellular and intranuclear localization of cisplatin using in-air micro-PIXE. The results of this study suggest that in-air micro-PIXE could be a useful quantitative method for evaluating the cisplatin sensitivity of individual cells. Finally, we speculate that MRP2 in the cell membrane may play an important role in regulating the cisplatin sensitivity of ESCC cells.

Targeted delivery of chemotherapeutic agents using improved radiosensitive liquid core microcapsules and assessment of their antitumor effect.

PURPOSE: Radiation-sensitive microcapsules composed of alginate and hyaluronic acid are being developed. We report the development of improved microcapsules that were prepared using calcium- and yttrium-induced polymerization. We previously reported on the combined antitumor effect of carboplatin-containing microcapsules and radiotherapy. METHODS AND MATERIALS: We mixed a 0.1% (wt/vol) solution of hyaluronic acid with a 0.2% alginate solution. Carboplatin (l mg) and indocyanine green (12.5 microg) were added to this mixture, and the resultant material was used for capsule preparation. The capsules were prepared by spraying the material into a mixture containing a 4.34% CaCl(2) solution supplemented with 0-0.01% yttrium. These capsules were irradiated with single doses of 0.5, 1.0, 1.5, or 2 Gy (60)Co gamma-rays. Immediately after irradiation, the frequency of microcapsule decomposition was determined using a microparticle-induced X-ray emission camera. The amount of core content released was estimated by particle-induced X-ray emission and colorimetric analysis with 0.25% indocyanine green. The antitumor effect of the combined therapy was determined by monitoring its effects on the diameter of an inoculated Meth A fibrosarcoma. RESULTS: Microcapsules that had been polymerized using a 4.34% CaCl(2) solution supplemented with 5.0 x 10(-3)% (10(-3)% meant or 10%(-3)) yttrium exhibited the maximal decomposition, and the optimal release of core content occurred after 2-Gy irradiation. The microcapsules exhibited a synergistic antitumor effect combined with 2-Gy irradiation and were associated with reduced adverse effects. CONCLUSION: The results of our study have shown that our liquid core microcapsules can be used in radiotherapy for targeted delivery of chemotherapeutic agents.

[BNP measurement for perioperative management].

BACKGROUND: It is difficult to evaluate the tolerance to anesthesia of patients undergoing operations, who have risk factors of congestive heart failure, such as hypertension, old age or various cardiac diseases. BNP (B type natriuretic peptide) is a useful biomarker as a screening tool for LV dysfunction. Therefore we hypothesized that the measurement of BNP may be useful for perioperative management of these patients. METHODS: Subjects were 101 (58 male and 43 female) gastro-intestinal cancer patients, aged 30 to 91 years (mean 63.9 +/- 12.4) scheduled for intraperitoneal surgery. All patients' plasma BNP concentrations were measured when the patient agreed to the operation. Forty-five patients were enlisted for remeasurements on 2 or 4 postoperative days. We checked patients' backgrounds, perioperative circulatory characteristics and cardiac events. The relationship of BNP to other characteristics and cardiac events were analyzed. RESULTS: The preoperative mean BNP of patients under 55 years of age (n=20) was 20.4, in patients age 55 to 74 (n=60) it was 30.4, and in patients 75 years and over (n=21) it was 162.1. BNP in elderly patients was higher than in the younger. The mean BNP of the 44 patients with some complications (hypertension, ECG abnormality, cardiac disease etc.) was 97.8, as compared to 23.3 in the 57 patients without complications. The BNP was higher in patients who were elderly, had some cardiac disease, lower exercise capacity, chest X ray abnormality or who needed an echo cardiographic examination. Among the 45 patients who were checked pre and postoperatively, 19 patients' BNP increased postoperatively, while 26 patients showed no change or decrease. Excluding 2 patients, with newly onset congestive heart failure during the postoperative period, the preoperative mean BNP was 63.5, and the postoperative mean BNP was 54.6. During the perioperative period, there was no significant change of BNP. There was no relationship between the BNP and perioperative circulatory characteristics or cardiac events. There were 5 cases with high BNP levels (> 300). None of these patients had cardiac symptoms, and they had normal LV systolic function. It is probable that these patients had chronic heart failure due to LV diastolic dysfunction and risks of perioperative heart failure. CONCLUSIONS: We cannot predict any circulatory characteristics and cardiac events from preoperative BNP measurement; however BNP measurement is useful for screening asymptomatic chronic heart failure due to LV diastolic dysfunction.

Single-turn extraction from a K110 AVF cyclotron by flat-top acceleration.

Single-turn extraction from the Japan Atomic Energy Agency AVF cyclotron with a K number of 110 using a flat-top (FT) acceleration system has been achieved to reduce the energy spread of an ion beam for microbeam formation with energy up to hundreds of MeV and to increase extraction efficiency from the cyclotron. In order to generate a FT waveform voltage using the fifth-harmonic frequency on a dee electrode, a FT resonator was designed using MAFIA code to achieve downsizing and low power consumption. The FT resonator, coupled to the main resonator through a coupling capacitor, covered the full range of the fifth harmonic frequency from 55 to 110 MHz. Various ion beams, accelerated using different acceleration harmonic modes of h=1 and 2, such as 220 MeV (12)C(5+) (h=2), 260 MeV (20)Ne(7+) (h=2), and 45 MeV H(+) (h=1), were developed by FT acceleration. A clear turn separation of the beam bunches was successfully observed at the extraction region of the large-scale AVF cyclotron with number of revolutions greater than 200. As a result, high extraction efficiency (over 95%) from the cyclotron was achieved. Single-turn extraction was confirmed by counting the number of beam bunches out of the cyclotron for an injected beam pulsed by a beam chopping system in the injection line. The energy spread of the 260 MeV (20)Ne(7+) beam was measured using an analyzing magnet, and we verified a reduction in the energy spread from DeltaE/E=0.1% to 0.05% by single-turn extraction after FT acceleration.

Changes of heavy metal, metallothionein and heat shock proteins in Sertoli cells induced by cadmium exposure.

In this study, we examined the levels of Cadmium (Cd), iron (Fe) and zinc (Zn), which were considered to be involved in Sertoli cell damage caused by Cd exposure. We also examined metallothionein (MT), heat shock protein 70 (Hsp70) and heme oxygenase-1 (HO-1) expressions in Sertoli cells induced by Cd exposure. Evaluation by the in-air micro-particle induced X-ray emission (PIXE) method revealed that Cd and Fe distribution was increased in the cytoplasm of Sertoli cells after Cd exposure. By contrast, Zn was decreased in the cytoplasm of Sertoli cells after Cd exposure. It was suggested that the target of Cd toxicity was the cytoplasm of Sertoli cells, Fe was considered to enhance damage to Sertoli cells caused by Cd exposure. The DNA fragmentation rate was determined by ELISA after Cd exposure to Sertoli cells. It remained essentially unchanged with 2.5 microM Cd exposure of Sertoli cells; however, MT, Hsp70 and HO-1 were significantly increased by Cd exposure. As a result, Cd-induced MT was protected Sertoli cells against apoptosis, and Cd-induced HO-1 was involved in protection against oxidative stress. Incidentally, MT, Hsp70 and HO-1 showed similar responses to Cd exposure.