National Institute Of Radiological Sciences Research Articles

Evaluation of Spatial Resolution for Heavy Ion CT System Based on the Measurement of Residual Range Distribution With HIMAC

We report experimental results from a heavy ion CT system based on the measurement of residual range distribution using an X-ray intensifying screen and a charged coupled device (CCD) camera system. This technique was first investigated by Zygmanski (2000) for proton beams, and they reported that the spatial resolution was significantly degraded by multiple Coulomb scattering (MCS) effects in the irradiated medium. Experiments were done on the spatial resolution phantom by using helium and carbon beams accelerated up to 120 MeV/u and 230 MeV/u by the Heavy Ion Medical Accelerator in Chiba (HIMAC), installed in the National Institute of Radiological Sciences (NIRS) in Japan, using a high performance intensified CCD (ICCD) camera. We show that the MCS blurring effect can be significantly reduced in the reconstructed image by using a carbon beam with this technique. Our results suggest that heavier particles such as carbon would be more useful if this technique is envisioned as a clinical tool to obtain data that would aid proton and/or heavy ion treatment planning.

Specifications of a neutron exposure accelerator system for biological effects experiments (NASBEE) in NIRS

We developed a neutron irradiation facility, neutron exposure accelerator system for biological effect experiments (NASBEE) for biological studies in National Institute of Radiological Sciences, Japan. Irradiation field of 2 MeV average neutrons generated by a Be(d–n)B reaction is established. Dose uniformity of 240 mm in diameter irradiation field is producible within ±2.5% with a dose rate of 0.87 Gy/h at sample target distance of 1170 mm. Two irradiation rooms, a specific pathogen-free (SPF) conditioned one and a conventional, are now available. Irradiation protocols for in vitro experiments are now established and demonstrated by obtaining a relative biological effectiveness (RBE) of cell inactivation measured to be 3.54 with 10% survival dose ( D 10).

Comparison of Biological Effectiveness of Carbon-Ion Beams in Japan and Germany

To compare the biological effectiveness of 290 MeV/amu carbon-ion beams in Chiba, Japan and in Darmstadt, Germany, given that different methods for beam delivery are used for each. Murine small intestine and human salivary gland tumor (HSG) cells exponentially growing in vitro were irradiated with 6-cm width of spread-out Bragg peaks (SOBPs) adjusted to achieve nearly identical beam depth-dose profiles at the Heavy-Ion Medical Accelerator in Chiba, and the SchwerIonen Synchrotron in Darmstadt. Cell kill efficiencies of carbon ions were measured by colony formation for HSG cells and jejunum crypts survival in mice. Cobalt-60 gamma rays were used as the reference radiation. Isoeffective doses at given survivals were used for relative biological effectiveness (RBE) calculations and interinstitutional comparisons. Isoeffective D(10) doses (mean +/- standard deviation) of HSG cells ranged from 2.37 +/- 0.14 Gy to 3.47 +/- 0.19 Gy for Chiba and from 2.31 +/- 0.11 Gy to 3.66 +/- 0.17 Gy for Darmstadt. Isoeffective D(10) doses of gut crypts after single doses ranged from 8.25 +/- 0.17 Gy to 10.32 +/- 0.14 Gy for Chiba and from 8.27 +/- 0.10 Gy to 10.27 +/- 0.27 Gy for Darmstadt, whereas isoeffective D(30) doses after three fractionated doses were 9.89 +/- 0.17 Gy through 13.70 +/- 0.54 Gy and 10.14 +/- 0.20 Gy through 13.30 +/- 0.41 Gy for Chiba and Darmstadt, respectively. Overall difference of RBE between the two facilities was 0-5% or 3-7% for gut crypt survival or HSG cell kill, respectively. The carbon-ion beams at the National Institute of Radiological Sciences in Chiba, Japan and the Gesellschaft für Schwerionenforschung in Darmstadt, Germany are biologically identical after single and daily fractionated irradiation.

International intercomparisons of integrating radon detectors in the NIRS radon chamber

An international intercomparison of integrating detectors was conducted at NIRS (National Institute of Radiological Science, Japan) with a 24.4m3 inner volume walk-in radon chamber that has systems to control radon concentration, temperature and humidity.During the first intercomparison (05.2007) four groups participated from four countries and for the second intercomparison (10.2007) 17 participants were involved from 11 countries.Most of detectors are in good agreement with each other when compared to the radon level provided by the radon chamber. It appeared that the 70% of detectors are unified within the 20% margin of uncertainty.

Development of a multi-layer ionization chamber for heavy-ion radiotherapy

A multi-layer ionization chamber (MLIC) which consists of a stack of parallel plate-type ionization chambers in which the parallel configuration is in the depth direction was developed at the National Institute of Radiological Science (NIRS) and has been used as a field dosimeter for MU calibration since 2002. Although the MLIC can measure depth dose distributions at one time, a correction is needed to obtain an accurate dose at the center of the spread-out Bragg peak (SOBP) in a water phantom. We attributed the observed difference between the correct dose at the center of the SOBP and the measured dose to the lack of water equivalence of the MLIC. In order to overcome this problem, a new MLIC was developed. It consists of polymethyl-methacrylate (PMMA) plates and graphite electrodes instead of flame retardant type 4 (FR4) and copper electrodes. The calibration coefficients of the MLICs were obtained by 160 MeV proton beam irradiation. For carbon-ion beams, the PMMA type MLIC has the capability to measure depth dose distributions in the water phantom with less than 2% error, including the fragment tail region.

Biological studies using mammalian cell lines and the current status of the microbeam irradiation system, SPICE

The development of SPICE (single-particle irradiation system to cell), a microbeam irradiation system, has been completed at the National Institute of Radiological Sciences (NIRS). The beam size has been improved to approximately 5 μm in diameter, and the cell targeting system can irradiate up to 400–500 cells per minute. Two cell dishes have been specially designed: one a Si 3N 4 plate (2.5 mm × 2.5 mm area with 1 μm thickness) supported by a 7.5 mm × 7.5 mm frame of 200 μm thickness, and the other a Mylar film stretched by pressing with a metal ring. Both dish types may be placed on a voice coil stage equipped on the cell targeting system, which includes a fluorescent microscope and a CCD camera for capturing cell images. This microscope system captures images of dyed cell nuclei, computes the location coordinates of individual cells, and synchronizes this with the voice coil motor stage and single-particle irradiation system consisting of a scintillation counter and a beam deflector. Irradiation of selected cells with a programmable number of protons is now automatable. We employed the simultaneous detection method for visualizing the position of mammalian cells and proton traversal through CR-39 to determine whether the targeted cells are actually irradiated. An immuno-assay was also performed against γ-H2AX, to confirm the induction of DNA double-strand breaks in the target cells.

Prognostic impact of mitotic index of proliferating cell populations in cervical cancer patients treated with carbon ion beam

: The authors previously reported that the mitotic index of a proliferating cell population (pMI) was a potent prognostic factor in cervical cancer patients treated with photon beam therapy. In this study, they investigated whether the pMI accurately predicted prognosis in cervical cancer patients treated with carbon ion beam. : Tissue sections were obtained from 27 consecutively treated patients with stage IIIB bulky (19 patients) and stage IVA (8 patients) squamous cell carcinomas of the cervix treated with carbon ion beam at the National Institute of Radiological Sciences, Japan, as a phase I/II study with dose escalation methodology (52.8-72 grays equivalent radiation dose/24 fractions). The mitotic index (MI) and Ki-67 labeling index (Ki-67-LI) were determined by hematoxylin and eosin staining and immunohistochemical staining, respectively. The pMI was calculated using the following formula: pMI = MI/Ki-67-LI. : The pMI ranged from 0.6 to 8.9 (mean, 3.9 +/- 2.6; median, 3.2). Twelve of the 27 specimens had a pMI >3.5. The local control rate in tumors with a pMI >3.5 was 17%, significantly lower than the 73% in the tumors with a pMI <3.5 (P = .005). Multivariate analysis indicated that the pMI had the strongest impact on local control (standard regression coefficient = 0.48, P = .002) among the variables, including clinical stage, irradiated dose, age, and tumor volume. : These results suggest that a high pMI is an indication of a poorer prognosis, and is a powerful prognostic factor in patients with squamous cell carcinomas of the cervix treated with carbon ion beam therapy. Cancer 2009. (c) 2009 American Cancer Society.

Carbon Ion Radiotherapy for Skull Base Chordoma

To present the results of the clinical study of carbon ion radiotherapy (CIRT) for skull base and paracervical spine tumors at the National Institute of Radiological Sciences in Chiba, Japan. The study is comprised of three protocols: a pilot study, a phase I/II dose escalation study, and a phase II study. All the patients were treated by 16 fractions for 4 weeks with total doses of 48.0, 52.8, 57.6, and 60.8 Gy equivalents (GyE). As a result of the dose escalation study of CIRT for skull base tumors, a dose fractionation of 60.8 GyE/16 fractions for 4 weeks was decided as the recommended dose because of acceptable normal tissue reactions and good local tumor control. Preliminary results of the phase II clinical study of CIRT for skull base chordoma showed local control at 5 years at 100%, and normal tissues showed a mild reaction without any severe morbidity of important organs.

Researches in National Institute of Radiological Sciences (NIRS) for radiation protection of non-human biota and ecosystems in Japanese environment

This paper summarizes research activities in National Institute of Radiological Sciences (NIRS) for evaluation of the radiation effects on selected terrestrial and aquatic organisms as well as the ecosystems. Seven organisms, conifers, fungi, earthworms, springtails, algae, daphnia and Medaka are presently selected to study. For the estimation of possible radiation dose, transfers of radionuclides and related elements from medium to organisms are evaluated. Dose-effect relationships of acute gamma radiation on the survival, growth, and reproduction of selected organisms have been studied. Studies on the effect of chronic gamma radiation at low dose rate were also started. In order to understand the mechanism of radiation effects and to find possible indicators of the effects, information of genome- and metagenome-wide gene expression has been collected. Evaluation of ecological effects of radiation is more challenging task. Study methods by using three-species microcosm were established, and an index for the holistic evaluation of effects on various ecological parameters was proposed. The microcosm has been simulated as a computer simulation code. Developments of more complicated and practical model ecosystems have been started. The Denaturant Gradient Gel Electrophoresis (DGGE) has been applied on soil bacterial community in order to evaluate the radiation effects on soil ecosystems.

初期および二次被ばく医療機関の線量評価・汚染評価機能に関する現状調査

The questionnaire on evaluation function for contaminations and doses was sent to the primary and the secondary radiation emergency hospitals in Japan by the network council for physical dosimetry in National Institute of Radiological Sciences (NIRS) designated as the tertiary hospital. The recovery percentage from the 88 hospitals was 70%. It turned out that six primary hospitals in 37 hospitals did not have even the basic instruments on radiation measurement such as GM counter and personal dosimeter. 64% of the secondary hospitals have the whole body counter, but its operation frequency including exercise was considerably low. It is thought that the main cause originates in a chronic manpower shortage and the budget shortfall seen by all the primary and the secondary hospitals. And also peculiar difficulty of correspondence to the radiation emergency medical treatment and the few experience might promote the problem. Thus the anxiety of the site staff had been appeared to the result of the questionnaire survey in shape like the opinion and the demand, etc. It will be necessary to advance the enhancement of training and to make the manual for the contaminations and the doses evaluation in the hospitals.

Excitation functions of proton induced reactions on natural selenium up to 62 MeV

Excitation functions of proton induced nuclear reactions on nat Se leading to the formation of the radionuclides 82,80m,77,76,75 Br, 75,73 Se and 77,76,72,71 As were measured from their respective thresholds up to 62 MeV. The selenium targets were prepared by vacuum deposition onto thin Al-backings. For the cross section measurements the conventional stacked-foil technique was used. Irradiations were performed at the AVF 930 cyclotron of the National Institute of Radiological Sciences in Chiba, Japan. Our results were compared with the available data in the literature, and some of the literature data obtained using isotopically enriched targets were used to validate our data. The experimental data sets generally showed good agreement. Integral yields of 75 Br, 76 Br, 77 Br, 80m Br and 82 Br were derived from the measured cross section data. The yield of 80m Br is quite high but, due to associated radionuclidic impurities, it is not meaningful to produce 80m Br using nat Se as target material.

The Present Status and Outlook of HIMAC

This year, Heavy Ion Medical Accelerator in Chiba (HIMAC) of National Institute of Radiological Sciences celebrates its 15th anniversary of use in clinical trials. It has been brought up to the level accepted for general treatment at the suggestion of Lawrence Berkeley Laboratory (LBL). We are working on research and development aiming at further accumulation of results, the additional improvement of clinical results and overcoming obstinate cancers. While providing an outline of the present status and outlook of HIMAC, the applications of superconducting are considered.

Proton induced reactions on natural tellurium up to 63 MeV: Data validation and investigation of possibility of 124I production

Abstract Excitation functions of the reactions natTe (p,xn)120g,121,123,124,125,126,128,13I were measured from their respective thresholds up to 63 MeV via the stacked foil technique. Thin targets were prepared by a vacuum deposition method. Irradiations were performed using AVF 930 cyclotron at the National Institute of Radiological Sciences. The concord and conflict between our excitation studies and the available literature data are shown. The high values of our cross sections for 125I in comparison to some literature data are discussed. Our cross sections measurements validated some of the literature data obtained using enriched target isotopes. The integral yields of iodine radionuclides were deduced from the measured excitation curves. The estimated yield of 124I via the natTe(p,xn) process over the energy range E p= 57 → 53 MeV is 16.7 MBq/μA h. The level of the radionuclidic impurities 125I and 126I is, however, rather high, so that it is not meaningful to produce 124I using natTe as target material.

HETC-HEDS Code Validation Using Laboratory Beam Energy Loss Spectra Data

Recently, the Monte Carlo transport code HETC has been extended to include the interactions and transport of energetic heavy ions. Here, for the first time, we compare predictions of fragment production and energy loss with laboratory data measured at Brookhaven National Laboratory and at the National Institute of Radiological Sciences in Japan. Very good agreement is found for predicted and measured energy loss spectra for a variety of incident laboratory beams and targets.

Influence of the presence of humidity, ambient aerosols and thoron on the detection responses of electret radon monitors

This paper describes how the presence of humidity, ambient aerosols and thoron influences the detection responses of an electret passive environmental radon monitor (commercially E-PERM ®) using radon and thoron chambers of National Institute of Radiological Sciences (NIRS). From the initial experiments, the linear correlation between the conversion factor for radon and the midpoint voltage for the short-term and long-term electrets was determined. As a result, it was observed that the conversion factors were approximately 10% lower for the short-term electrets and 3% higher for the long-term electrets than those reported by the manufacturer. The evaluation of different magnitudes of radon concentration showed that the presence of humidity and ambient aerosols had little influence on the detection response for radon, with less than 10% relative standard deviation. In the case of thoron detection response, net voltage drop values increased linearly with time-integrated concentrations for both short-term and long-term electrets, as was the case with radon. The thoron responses to radon were less than 5% for both the electrets from the results of experiments and calculations.

Water Radiolysis with Heavy Ions of Energies up to 28 GeV. 3. Measurement ofG(MV·+) in Deaerated Methyl Viologen Solutions Containing Various Concentrations of Sodium Formate and Monte Carlo Simulation

Formation yields of methyl viologen cation radicals G(MV*+) (100 eV)(-1) have been measured in deaerated aqueous solutions of 0.25 mM methyl viologen (MV(2+)) containing various concentrations of formate anion (0.01-2 M) after irradiation with six different ion beams (4He(2+), 12C(6+), 20Ne(10+), 28Si(14+), 40Ar(18+) and 56Fe(26+) with incident energies varying from 0.6 to 28 GeV) provided by the Heavy Ion Medical Accelerator in Chiba (HIMAC) at the National Institute of Radiological Science (NIRS) in Japan. The sample solutions are irradiated at the incident energy of the ions using 1-cm irradiation cells. Corresponding LET values cover the range from 2.2 to 185 eV/nm. G(MV*+) increases with increasing formate concentration. In 4He(2+) radiolysis, it increases from 5.7 to 7.1 as the concentration of formate is increased from 0.01 to 2 M, while in 56Fe(26+) radiolysis, the MV*+ yield value changes from 2.2 to 4.1. The other values lie between the yields for 4He(2+) and 56Fe(26+). In addition, G(MV*+) decreases with increasing LET. In the case of 12C(6+) radiolysis, G(MV*+) increases with increasing energy of the carbon ions from 135 to 400 MeV/nucleon, i.e., with decreasing LET from 21 to 11 eV/nm. In parallel to the above measurements, Monte Carlo simulations of the radiolysis of the MV(2+)/formate solutions have been performed. Ionic strength effects on reactions between charged species are taken into account. To reproduce the experimental results, previously unreported reactions such as e(aq)(-) + MV*+, MV*(+) + *OH and *COO- + *OH have been introduced in the reaction scheme. After optimization, the rate constants of these latter two reactions are determined to be (3 +/- 0.5) x 10(10) and (5 +/- 0.5) x 10(10) M(-1) s(-1), respectively. By contrast, the reaction between e(aq)- and MV*+ is too slow to affect G(MV*+). On the basis of these calculations, characteristics of intratrack reactions induced by heavy-ion beams are discussed in reference not only to the scavenger method used for measurement of water decomposition product yields but also to the differences in the relative spatial distribution of the reactants as well as the places where their intratrack reaction occurs within the geometry of the ion track structure.

The Difference in LET and Ion Species Dependence for Induction of Initially Measured and Non-rejoined Chromatin Breaks in Normal Human Fibroblasts

We studied the LET and ion species dependence of the induction of chromatin breaks measured immediately after irradiation as initially measured breaks and after 24 h postirradiation incubation (37 degrees C) as non-rejoined breaks in normal human fibroblasts with different heavy ions, such as carbon, neon, silicon and iron, generated by the Heavy Ion Medical Accelerator in Chiba (HIMAC) at the National Institute of Radiological Science (NIRS). Chromatin breaks were measured as an excess number of fragments of prematurely condensed chromosomes using premature chromosome condensation (PCC). The results showed that the number of excess fragments per cell per Gy for initially measured chromatin breaks was dependent on LET in the range from 13.3 to 113.1 keV/mum but was not dependent on ion species. On the other hand, the number of non-rejoined chromatin breaks detected after 24 h postirradiation incubation was clearly dependent on both LET and ion species. No significant difference was observed in the cross section for initially measured breaks, but a statistically significant difference was observed in the cross section for non-rejoined breaks among carbon, neon, silicon and iron ions. This suggests that the LET-dependent structure in the biological effects is reflected in biological consequences of repair processes.

Light Output Characteristic of Inorganic Scintillators to Intermediate-energy Charged Particles

In order to convert the light output of an inorganic scintillator to the deposited energy, the study of light output curves is very important due to its non linearity. We carried out experiments to investigate the light output response of Nal(Tl), CsI(Tl), GSO(Ce) and LYSO(Ce) crystals to intermediate-energy 4He and 12C beams from HIMAC at National Institute of Radiological Sciences. Scintillation efficiency was obtained in the wide energy range. It was found that a light output curve is represented using the peculiar scintillation efficiency despite it greatly changes its shape with different particles. In addition, it was found that scintillation efficiency was a function of the stopping power. Using the measured scintillation efficiency, the light output curves of the crystals were systematically reproduced

Water radiolysis with heavy ions of energies up to 28 GeV—2: Extension of primary yield measurements to very high LET values

Measurements of primary g-values (at ∼10 −7 s after the initial ionizing event) of e aq - , OH and H 2O 2 were extended to the very high linear energy transfer (LET) region (∼700 eV/nm) near the Bragg peak. Heavy ions ( 4He 2+, 12C 6+, 20Ne 10+, 28Si 14+, 40Ar 18+ and 56Fe 26+) of energies up to 28 GeV were provided by the Heavy Ion Medical Accelerator in Chiba (HIMAC) of the National Institute of Radiological Sciences (NIRS) in Chiba, Japan. Energies of the ions were decreased down to about 10 MeV/u for 4He 2+ using an energy absorber made of polymethylmethacrylate (PMMA) plates in order to vary the LET values. Beam was visualized after passing through the energy absorber using agarose gel of aqueous solution containing methyl viologen and sodium formate in order to determine how long ions can penetrate into water. Based on the information of the penetration depth of ions in samples, much attention was paid to dose correction and LET evaluation. The obtained data were plotted as a function of ( Z eff/ β) 2 also instead of LET in order to discuss effects of physical track structures on product yields, resulted in better universality.

Discrimination of heavy ions using copolymers of CR-39 and DAP

Mixtures of allyl diglycol carbonate (CR-39) and diallyl phthalate (DAP) were cast into resin plates under same polymerizing conditions. The copolymer plates were irradiated with many kinds of ions at the medium energy beam irradiation room or biological irradiation room of National Institute of Radiological Sciences (NIRS)-Heavy Ion Medical Accelerator in Chiba (HIMAC). After etching in an aqueous solution of KOH, whether enlarged ion tracks exist or not was determined by using an optical microscope. It was found that every plate has a characteristic value in LET as threshold for track formation. The threshold increases with the concentration of DAP. It has been shown that the threshold is adjustable by changing the ratio of CR-39 and DAP. It is expected that the copolymers can be used for the discrimination of heavy ions in cosmic rays.