Heavy Ion Medical Accelerator In Chiba Research Articles

Heavy-ion cancer therapy

The HIMAC Heavy-Ion Medical Accelerator in Chiba was completed in 1993, and clinical trials of particle radiotherapy for cancer were started using carbon beams accelerated by HIMAC in 1994. Since then, about 2200 patients have been treated in the carbon radiotherapy up to the end of February 2005. A heavy-ion beam generates a Bragg peak in a medium, and it provides biological effects of high RBE and low OER in the Bragg peak region. In heavy-ion radiotherapy, therefore, the beam delivers a high radiation dose to a target volume highly locally. These are excellent advantages for radiotherapy over the case of X-rays. The clinical trials have proved that carbon radiotherapy brings various good results.

A method of tagging the nuclear fragmentation event induced by /sup 11/C for cancer therapy

Heavy ion cancer therapy using energetic /sup 12/C ions has been carried out successfully at the Heavy Ion Medical Accelerator in Chiba (HIMAC), Japan. The method has advantages over traditional radiation therapy using an energetic photon beam in two respects: the dose concentration owing to the Bragg peak and high biological effects. The development of a cancer therapy using /sup 11/C ions is also currently underway at HIMAC, however, there remains the problem of beam attenuation due to nuclear fragmentation reactions in the body of the patient; this requires modification of the dose calculation for the therapy. To the best of our knowledge, no research on /sup 11/C-induced nuclear fragmentation reactions has yet been published. We propose a method of identifying the nuclear fragmentation reaction event induced by the carbon beams using a total-absorption-type target detector, that plays the role of a human phantom, and a system of plastic scintillation counters surrounding the phantom. We have carried out measurements for the carbon beams with the detector system. A portion of the beam energy is lost as escaping fragment particles from the phantom, leading to a decrease in beam intensity. We were able to successfully detect nuclear reaction events on an event-by-event basis.

Measurements of the response functions of a large size NE213 organic liquid scintillator for neutrons up to 800 MeV

The response functions of 25.4 cm (length) x 25.4 cm (diameter) NE213 organic liquid scintillator have been measured for neutrons in the energy range from 20 to 800 MeV at the Heavy-Ion Medical Accelerator in Chiba (HIMAC) and at the Research Center for Nuclear Physics (RCNP) of Osaka University. At HIMAC, white (continuous) energy spectrum neutrons were produced by the 400 MeV per nucleon carbon ion bombardment on a thick graphite target, whose energy spectrum has already been measured by Kurosawa et al., [Nucl. Sci. Eng. 132, 30 (1999)] and the response functions of the time-of-flight-gated monoenergetic neutrons in a wide energy range from 20 to 800 MeV were simultaneously measured. At RCNP, the quasi-monoenergetic neutrons were produced via 7Li(p,n)7Be reaction by 250 MeV proton beam bombardment on a thin 7Li target, and the TOF-gated 245 MeV peak neutrons were measured. The absolute peak neutron yield was obtained by the measurement of 478 keV gamma rays from the 7Be nuclei produced in a Li target. The measured results show that the response functions for monoenergetic neutrons < 250 MeV have a recoil proton plateau and an edge around the maximum light output, which increases with increasing incident neutron energy, on the other hand > 250 MeV, the plateau and the edge become unclear because the proton range becomes longer than the detector size and the escaping protons increase. It can be found that the efficiency of the 24.5 cm (diameter) x 25.4 cm (length) NE213 for the 250 MeV neutrons is -10 times larger than the 12.7 cm (length) x 12.7 cm (diameter) NE213, which is widely used as a neutron spectrometer.

Reduction in Life Span of Normal Human Fibroblasts Exposed to Very Low-Dose-Rate Charged Particles

We studied the effect of chronic low-dose irradiation with heavy ions on the life span of normal human fibroblasts in vitro. Cells were cultured in a CO2 incubator that was placed in the irradiation room for biological studies of heavy ions in the Heavy Ion Medical Accelerator in Chiba (HIMAC) at National Institute of Radiological Sciences (NIRS) and were exposed to scattered radiations produced by heavy-ion beams for the life span of the cell population. The absorbed dose, which was measured using a thermoluminescence dosimeter (TLD) and a silicon semiconductor detector, was 1.4 mGy per day when the HIMAC was operated for biological experiments. The total number of population doublings of the exposed cells as reduced to 79-93% of that of nonexposed control cells. However, the life span of cells exposed to low-dose 137Cs gamma rays (approximately 1 mGy/day) in the CO2 incubator in the gamma-irradiation room in NIRS was prolonged to 104-106% of that of nonexposed control cells. Thus there is evidence that exposure to chronic low-dose heavy-ion radiation reduces the life span of cells.

Slow beam-extraction method using a fast Q-magnet assisted by RF-knockout

A new method for slow beam-extraction from a synchrotron ring is proposed, based on controlling a quadrupole field with a fast response (FQ), assisted by a transverse RF-field (RF-knockout). This method works as follows: (1) particles of a circulating beam are diffused by RF-knockout to just inside the boundary of a separatrix produced under a resonant condition, (2) exciting the FQ shrinks the separatrix to a certain size, and the particles outside the separatrix can be extracted, (3) the fast Q-field is turned off, and (4) the above process is repeated until all of the circulating beam is completely extracted. This method can extract prescribed particles at required timings quickly and precisely, because it is controlled with only the fast Q-field. A proof-of-principle experiment was carried out at the Heavy Ion Medical Accelerator in Chiba (HIMAC) synchrotron. As a result, it was verified that the beam was extracted only with exciting the FQ, but not with turning the RF-knockout on.

A multi-harmonic RF system using a MA cavity

A magnetic alloy (MA)-loaded cavity has been installed in Heavy Ion Medical Accelerator in Chiba (HIMAC). A beam study with a new Direct Digital Synthesis (DDS) system has been performed. The DDS system can generate multi-harmonic RF that includes up to 3 different RF frequencies. The multi-harmonic RF is amplified by a solid state and final amplifiers. These harmonic frequencies are in the band width of the MA RF system. Beam acceleration was performed by the system, and the acceleration efficiency was improved by both dual and triple harmonic RF.

LET and Ion Species Dependence for Cell Killing in Normal Human Skin Fibroblasts

We studied the LET and ion species dependence of the RBE for cell killing to clarify the differences in the biological effects caused by the differences in the track structure that result from the different energy depositions for different ions. Normal human skin fibroblasts were irradiated with heavy-ion beams such as carbon, neon, silicon and iron ions that were generated by the Heavy Ion Medical Accelerator in Chiba (HIMAC) at the National Institute of Radiological Science (NIRS) in Japan. Cell killing was measured as reproductive cell death using a colony formation assay. The RBE-LET curves were different for carbon ions and for the other ions. The curve for carbon ions increased steeply up to around 98 keV/microm. The RBE of carbon ions at 98 keV/microm was 4.07. In contrast, the curves for neon, silicon and iron ions had maximum peaks around 180 keV/microm, and the RBEs at the peak position ranged from 3.03 to 3.39. When the RBEs were plotted as a function of Z*2/beta2 (where Z* is the effective charge and beta is the relative velocity of the ion) instead of LET, the discrepancies between the RBE-LET curves for the different ion beams were reduced, but branching of the RBE-Z*2/beta2 curves still remained. When the inactivation cross section was plotted as a function of either LET or Z*2/beta2, it increased with increasing LET. However, the inactivation cross section was always smaller than the geometrical cross section. These results suggest that the differences in the energy deposition track structures of the different ion sources have an effect on cell killing.

Biological effects of radioactive 9C-ion beams on cells

The distinguishing feature and current technique progress of tumor treatment with heavy-ion beams is introduced in the paper. Additional superiority to tumor treatment from a radioactive ion beam (RIB) is emphatically discussed. The experimental research of the radioactive 9C-ion beams aimed at tumor treatment at Heavy Ion Medical Accelerator in Chiba (HIMAC), National Institute of Radiological Sciences (NIRS), Japan is described in detail, including production of the beams, optimization of parameters, distribution of depth dose, survival effect of cell and comparison of RBE between 9C- and 12C-beams. Results show that under 40 mm thick Beryllium target and 10 mm thick aluminum degrader at full (5%) momentum acceptance, the production rate and purity of the produced 9C-beams are 9.07×l06 and 82.88% respectively with the primary 12Cbeams of 430 MeV/u and 1.8×l09 pps. A uniform irradiation field with homogeneity up to 89.6% inside central area 10 mm in diameter is obtained by using spot scanning. In this case, the dose rate at the entrance is 0.5 Gy/h. In survival experiment of cells, the average relative biological effectiveness (RBE) of 9C-beams is 5.28 and 2.93 for 12C-beams in the region around Bragg peak. The RBE of 9C-beams is 1.8 times higher than that of 12C-beams. It indicates that cell-killing efficiency of 9C-beams is stronger than that of {u12}C-beams. 9C-beams are more efficacious for tumor treatment than 12C-beams.

Overview of clinical experiences on carbon ion radiotherapy at NIRS

Carbon ion beams provide physical and biological advantages over photons. This study summarizes the experiences of carbon ion radiotherapy at the Heavy Ion Medical Accelerator in Chiba (HIMAC) at the National Institute of Radiological Sciences. Between June 1994 and August 2003, a total of 1601 patients with various types of malignant tumors were enrolled in phase I/II dose-escalation studies and clinical phase II studies. All but malignant glioma patients received carbon ion radiotherapy alone with a fraction number and overall treatment time being fixed for each tumor site, given to one field per day and 3 or 4 days per week. In dose-escalation studies, the total dose was escalated by 5 or 10% increments to ensure a safe patient treatment and to determine appropriate dose levels. In the initial dose-escalation studies, severe late complications of the recto-sigmoid colon and esophagus were observed in those patients who received high dose levels for prostate, uterine cervix and esophageal cancer. Such adverse effects, however, did shortly disappear as a result of determining safe dose levels and because of improvements in the irradiation method. Carbon ion radiotherapy has shown improvement of outcome for tumor entities: (a) locally advanced head and neck tumors, in particular those with non-squamous cell histology including adenocarcinoma, adenoid cystic carcinoma, and malignant melanoma; (b) early stage NSCLC and locally advanced NSCLC; (c) locally advanced bone and soft tissue sarcomas not suited for surgical resection; (d) locally advanced hepatocellular carcinomas; (e) locally advanced prostate carcinomas, in particular for high-risk patients; (f) chordoma and chondrosarcoma of the skull base and cervical spine, and (g) post-operative pelvic recurrence of rectal cancer. Treatment of malignant gliomas, pancreatic, uterine cervix, and esophageal cancer is being investigated within dose-escalation studies. There is a rationale for the use of short-course RT regimen due to the superior dose localization and the unique biological properties of high-LET beams. This has been proven in treatment of NSCLC and hepatoma, where the fraction number has been successfully reduced to 4-12 fractions delivered within 1-3 weeks. Even for other types of tumors including prostate cancer, bone/soft tissue sarcoma and head/neck tumors, it was equally possible to apply the therapy in much shorter treatment times as compared to conventional RT regimen. Carbon ion radiotherapy, due to its physical and biologic advantages over photons, has provided improved outcome in terms of minimized toxicity and high local control rates for locally advanced tumors and pathologically non-squamous cell type of tumors. Using carbon ion radiotherapy, hypofractionated radiotherapy with application of larger doses per fraction and a reduction of overall treatment times as compared to conventional radiotherapy was enabled.

Contribution of synchrotron oscillation to spill ripple in RF-knockout slow-extraction

We have studied the effect of synchrotron oscillations on the spill ripple in RF-knockout extraction, in order to investigate the ripple component of the synchrotron-oscillation frequency and to suppress this component. By using a simplified model of RF-knockout extraction and the simulation, it was found that the following conditions are essential for suppressing the spill ripple including the component of the synchrotron-oscillation frequency: (1) sufficient amplitude of the synchrotron oscillation and (2) uniform distribution in longitudinal phase-space. In the experiment at the Heavy Ion Medical Accelerator in Chiba (HIMAC) synchrotron, the debunch–recapture was carried out before the extraction to obtain the larger oscillation amplitude and the uniform distribution in the longitudinal phase-space. In this article, the contribution of the synchrotron oscillation to the spill ripple is described in detail.

Double-side silicon strip detector (DSSD) with VA32TA applied for medium energy particle detector in high-count rate environment

We are developing a medium energy particle detector in a high-count rate environment, in order to solve the acceleration mechanism and the process of high-energy particles in the collision less plasma shock region in the space. The key observation is to measure the maximum energy of accelerated particles correctly. It is important to reduce the pile-up events, in order to measure the correct maximum energy. The new developed detector for the high-count rate environment consists of the double-sided silicon strip detector (DSSD) and the readout Application Specific Integrated Circuit (ASIC) chips VA32TA, made by IDEA. The performance of the new DSSD system for charged particles was tested using proton beams with an energy of 6 MeV from the medium-energy accelerator in the Heavy Ion Medical Accelerator in Chiba (HIMAC) of the National Institute for Radiological Science. The result is that the new DSSD system works well and has high performance in detecting not only X-rays, but also charged particles. It is certain that this new DSSD system can measure the correct energy of incident particles in high-count rate environments using the accelerator.

Cross sections for the production of residual nuclides by high-energy heavy ions

Irradiation experiments were performed at the Heavy Ion Medical Accelerator in Chiba (HIMAC) facility, National Institute of Radiological Sciences. The radioactive spallation products in a thick Cu target were obtained for Ar(230, 400 MeV/nucleon), Si(800 MeV/nucleon), Ne(100, 230, 400 MeV/nucleon), C(100, 230, 400 MeV/nucleon), He(100, 230 MeV/nucleon), p(100, 230 MeV) ions. The gamma-ray spectra from irradiated Cu, C, Al, Cr, Fe, Ni, Pb samples inserted into the composite Cu target were measured with a HPGe detector. From the gamma-ray spectra, we obtained the reaction cross section data on the Cu, C, Al, Cr, Fe, Ni and Pb samples. The measured cross sections were fitted to a modified form of Rudstam’s semi-empirical formula in order to evaluate the cross sections of unmeasured nuclides. These estimated cross sections were added to the experimental yields for each mass number and the total mass-yield and isobaric charge distributions. We also calculated the cross sections for the production of residual nuclides by high-energy heavy ions by the particle and heavy-ion transport code system (PHITS) code and compared with measured results. The PHITS code provides good results on cross section calculations.

Status report on ECR ion sources at HIMAC

The Heavy Ion Medical Accelerator in Chiba (HIMAC) at the National Institute of Radiological Sciences (NIRS) is the first heavy-ion accelerator complex dedicated to cancer therapy. Over 1600 patients have already been treated with 140–400 MeV/amu carbon beams since 1994. The production of carbon ions for medical applications has been established. It is quite obvious from our experiences that the ECR ion source is an extremely suitable type of ion source for this purpose. An 18 GHz ECR ion source is mainly operated to offer various heavy-ion beams for basic experiments of biomedical science, physics, chemistry, etc. The results of recent developments, a thermal-controlled MIVOC system, and an electron bombardment evaporator are also reported.

Improvement of the yield of highly charged ions by a gas-pulsing technique and the current status of the NIRS Penning source

The yields of highly charged ions have been improved by using a gas-pulsing technique in the pulsed Penning-ionized-gauge ion source (PIGIS) in the heavy-ion medical accelerator in Chiba. So far, this pulsed PIGIS has been operated under a low-duty factor (10−2–10−3), in which the gas flow is not being pulsed. A solenoid-type gas valve, having a simple structure compared to the piezo-electric type, was attached to the outside of the PIGIS chamber in order to control the gas flow into the PIGIS chimney. Beam tests for Ne with gas pulsing showed that the pressure response time should actually be a few tens ms, and the intensity of Ne6+ was increased by ten times, from 20 to 200 eμA. The gas pulsing also improved the average vacuum in the low energy beam transport (LEBT) line by a factor of 4. When producing H2+, H3+, and He1+ by PIGIS with gas pulsing, the beam loss of highly charged ions from electron cyclotron resonance ion sources in the LEBT was reduced to be negligible; meanwhile, it was around 30% without gas pulsing. This paper describes the gas-pulsing technique and the preliminary results, as well as some recent developments in the NIRS-PIGIS.

Beam diagnostics using a chopped beam

A new type of beam chopper has been developed and installed at HIMAC (Heavy Ion Medical Accelerator in Chiba) in NIRS (National Institute of Radiological Sciences). The chopper has only 11.6 cm length and has been set between the ion sources and the RFQ. It is similar to a beam transformer, and modulates the beam kinetic energy by 10%. The beam is successfully chopped because the RFQ has a rather small energy acceptance. A chopped beam was injected into the synchrotron and a beam study has been performed. A very short bunch was formed and accelerated to the top energy. The behavior of the short bunch shows that a dipole oscillation was excited because of an unexpected frequency error of the RF system. It was caused by noise in the B-clock (Gauss Clock) circuit. The dipole oscillation caused by the frequency error was significantly reduced and the acceleration efficiency was improved by replacing the B-clock module.

Total Energy Dependence of Angular Distributions of IMFs Produced in Proton and Heavy-Ion Induced Target Multifragmentation Reactions at around 10 GeV

We have extended our investigations on nuclear multifragmentations induced by GeV-energy light projectiles using light heavy-ion beams ( 16O, 20Ne and 28Si) provided from the Heavy-Ion Medical Accelerator in Chiba (HIMAC) at the National Institute for Radi- ological Science (NIRS). At a total beam energy of 8 GeV we found there are noticeable differences in spectrum shapes of Intermediate-Mass Fragment (IMF) and their magni- tudes depending upon the projectile mass, but all of their angular distributions clearly exhibit the existence of sideward-peaked components, indicating fragment formations are mainly governed by a total energy of the projectile, not by a incident energy per nucleon.

Measurement and calculation of radioactivities of spallation products by high-energy heavy ions

Abstract Irradiation experiments were performed at the HIMAC (Heavy Ion Medical Accelerator in Chiba) facility, National Institute of Radiological Sciences, Japan. The radioactivity distributions of spallation products in a thick Cu target were obtained by irradiating 230 and 100MeV/nucleon Ne, C, He, p and 230MeV/nucleon Ar ions. The gamma-ray spectra from thin irradiated samples of C, Al and Cu inserted into a Cu target were measured with a HPGe detector. From the gamma-ray spectra, we obtained the spatial distribution of radioactive yields of spallation products of about 40 nuclides in Cu sample in the Cu target. Our results agree with other experimental data. We also calculated the spatial distribution of residual radioactivities in the Cu target by the PHITS (Particle and Heavy-Ion Transport code System) code and compared with measured results. The PHITS code provides good results on residual activity calculations.

Shielding experiment of heavy-ion produced neutrons using a tissue-equivalent proportional counter.

A shielding experiment was performed at the HIMAC (Heavy Ion Medical Accelerator in Chiba), of National Institute of Radiological Sciences (NIRS), to measure neutron dose using a spherical TEPC (tissue-equivalent proportional counter) of 12.55 cm inner diameter. Neutrons are produced from a 5 cm thick stopping length Cu target bombarded by 400 MeV/nucleon C6+ ions and penetrate concrete or iron shields of various thicknesses at 0 degree to the beam direction. From this shielding experiment. y-distribution, mean lineal energy, absorbed dose, dose equivalent and mean-quality factor were obtained behind the shield as a function of shield thickness. The neutron dose attenuation lengths were also obtained as 126 g cm(-2) for concrete and 211 g cm(-2) for iron. The measured results were compared with the calculated results using the MARS Monte Carlo code.

The Effects of Heavy Ion Particles on the Developing Murine Cerebellum, with Special Reference to Cell Death

We report here the effects of heavy ion beams on postnatal mouse cerebellar development, with reference to cell death. Eight-day-old B6C3F1 mice were irradiated with single doses of 0.1, 0.25, 0.5, 1.0, and 2.0 Gy, using a carbon beam of 290 MeV delivered from a heavy ion medical accelerator in Chiba (HIMAC). To compare the effects of X-rays with those of accelerated carbon ions, 8-day-old mice were exposed to X-rays single doses of 0.1, 0.25, 0.5, 1.0, and 2.0 Gy, respectively. Pups were fixed at 1, 6, 12 and 24 hr after exposure to HIMAC beams or X-rays. Four-μm-thick parasagittal sections of the cerebella were processed for hematoxylin-eosin staining as well as for staining with the TUNEL (terminal dUTP nick-end labeling) technique. The density of fragmented nuclei in the external granular layer increased with time, peaking at 6 hr after exposure, in both the HIMAC and X-irradiated groups. In the HIMAC groups, the density was significantly higher in those animals exposed to 0.25 Gy or more compared to 0 Gy, whereas in the X-irradiated groups it was significantly higher in those mice exposed to 0.5 Gy or more. Electron microscopic examinations revealed chromatin condensation in the cell nuclei in the HIMAC groups. This is the first in vivo evidence that apoptotic cell death is induced in developing mouse cerebellum after exposure to heavy ion particles. The difference in the frequency of dying cells between exposure to heavy ion particles and to X-rays may reflect the high linear energy transfer (LET) associated with a heavy ion beam.

LET and Ion-species Dependence for Cell Killing and Mutation Induction in Normal Human Fibroblasts.

We have been studying LET and ion species dependence of RBE values in cell killing and mutation induction. Normal human skin fibroblasts were irradiated with heavy-ion beams such as carbon (290 Mev/u and 135 Mev/u), neon (230 Mev/u and 400 Mev/u), silicon (490 Mev/u) and iron (500 Mev/u) ion beams, generated by Heavy Ion Medical Accelerator in Chiba (HIMAC) at National Institute of Radiological Sciences (NIRS). Cell killing effect was detected as reproductive cell death using a colony formation assay. Mutation induction in hprt locus was detected to measure 6-thioguanine resistant colonies. The RBE-LET curves of cell killing and mutation induction were different each ion beam. So, we plotted RBE for cell killing and mutation induction as function of Z*2/beta2 instead of LET. RBE-Z*2/beta2 curves of cell killing indicated that the discrepancy of RBE-LET curves was reconciled each ion species. But RBE-Z*2/beta2 curves of mutation induction didn't corresponded between carbon- and silicon-ion beams. These results suggested that different biological endpoints may be suitable for different physical parameter, which represent the track structure of energy deposition of ion beams.