12C Beam Research Articles

Influence of momentum acceptance on range monitoring of 11C and 15O ion beams using in-beam PET

In heavy-ion therapy, the stopping position of primary ions in tumours needs to be monitored for effective treatment and to prevent overdose exposure to normal tissues. Positron-emitting ion beams, such as 11C and 15O, have been suggested for range verification in heavy-ion therapy using in-beam positron emission tomography (PET) imaging, which offers the capability of visualizing the ion stopping position with a high signal-to-noise ratio. We have previously demonstrated the feasibility of in-beam PET imaging for the range verification of 11C and 15O ion beams and observed a slight shift between the beam stopping position and the dose peak position in simulations, depending on the initial beam energy spread. In this study, we focused on the experimental confirmation of the shift between the Bragg peak position and the position of the maximum detected positron-emitting fragments via a PET system for positron-emitting ion beams of 11C (210 MeV u−1) and 15O (312 MeV u−1) with momentum acceptances of 5% and 0.5%. For this purpose, we measured the depth doses and performed in-beam PET imaging using a polymethyl methacrylate (PMMA) phantom for both beams with different momentum acceptances. The shifts between the Bragg peak position and the PET peak position in an irradiated PMMA phantom for the 15O ion beams were 1.8 mm and 0.3 mm for momentum acceptances of 5% and 0.5%, respectively. The shifts between the positions of two peaks for the 11C ion beam were 2.1 mm and 0.1 mm for momentum acceptances of 5% and 0.5%, respectively. We observed larger shifts between the Bragg peak and the PET peak positions for a momentum acceptance of 5% for both beams, which is consistent with the simulation results reported in our previous study. The biological doses were also estimated from the calculated relative biological effectiveness (RBE) values using a modified microdosimetric kinetic model (mMKM) and Monte Carlo simulation. Beams with a momentum acceptance of 5% should be used with caution for therapeutic applications to avoid extra dose to normal tissues beyond the tumour when the dose distal fall-off is located beyond the treatment volume.

Biological washout modelling for in-beam PET: rabbit brain irradiation by 11C and 15O ion beams

Positron emission tomography (PET) has been used for dose verification in charged particle therapy. The causes of washout of positron emitters by physiological functions should be clarified for accurate dose verification. In this study, we visualized the distribution of irradiated radioactive beams, 11C and 15O beams, in the rabbit whole-body using our original depth-of-interaction (DOI)-PET prototype to add basic data for biological washout effect correction. Time activity curves of the irradiated field and organs were measured immediately after the irradiations. All data were corrected for physical decay before further analysis. We also collected expired gas of the rabbit during beam irradiation and the energy spectrum was measured with a germanium detector. Irradiated radioactive beams into the brain were distributed to the whole body due to the biological washout process, and the implanted 11C and 15O ions were concentrated in the regions which had high blood volume. The 11C-labelled 11CO2 was detected in expired gas under the 11C beam irradiation, while no significant signal was detected under the 15O beam irradiation as a form of C15O2. Results suggested that the implanted 11C ions form molecules that diffuse out to the whole body by undergoing perfusion, then, they are incorporated into the blood-gas exchange in the respiratory system. This study provides basic data for modelling of the biological washout effect.

Prompt gamma spectroscopy for absolute range verification of 12C ions at synchrotron-based facilities

The physical range uncertainty limits the exploitation of the full potential of charged particle therapy. In this work, we face this issue aiming to measure the absolute Bragg peak position in the target. We investigate p, 4He, 12C and 16O beams accelerated at the Heidelberg Ion-Beam Therapy Center. The residual range of the primary 12C ions is correlated to the energy spectrum of the prompt gamma radiation. The prompt gamma spectroscopy method was demonstrated for proton beams accelerated by cyclotrons and is developed here for the first time for heavier ions accelerated by a synchrotron. We develop a detector system that includes (i) a spectroscopic unit based on cerium(III) bromide and bismuth germanium oxide scintillating crystals, (ii) a beam trigger based on an array of scintillating fibers and (iii) a data acquisition system based on a FlashADC. We test the system in two different scenarios. In the first series of experiments, we detect and identify 19 independent spectral lines over a wide gamma energy spectrum in the presence of the four ion species for different targets, including a water target with a titanium insert. In the second series of experiments, we introduce a collimator aiming to relate the spectral information to the range of the primary particles. We perform extensive measurements for a 12C beam and demonstrate submillimetric precision for the measurement of its Bragg peak position in the experimental setup. The features of the energy and time spectra for gamma radiation induced by p, 4He and 16O are investigated upstream and downstream from the Bragg peak position. We conclude the analysis by extrapolating the required future developments, which would be needed to achieve range verification with a 2 mm accuracy during a single fraction delivery of physical dose.

Nuclear track detector response to energetic heavy ions: study case

Nuclear track methodology (NTM), is employed to analyze PADC detectors response to different energetic ion beams. Due to the passive device linearity response to heavy ions with LET-value > 30 keV μm−1, they are employed in several fields e.g. nuclear industry, medical, environmental radiation and aircraft dosimetry. To further improve application, PADC-detectors were irradiated by beams of 4He (150 MeV nucleon−1), 12C (390 MeV nucleon−1) and 56Fe (465 MeV nucleon−1), in relatively low-dose range ≤ 1 mGy. Results provided, through etched track analysis, valuable information of interest for NTM when high LET ionizing radiation is involved.

Timing performances of a Time-Of-Flight detection system for the FRACAS large acceptance mass spectrometer

In this work, we report on the timing performances of the Time-Of-Flight (TOF) apparatus of the FRACAS large acceptance mass spectrometer designed to measure the fragmentation cross sections of a 12C beam in hadrontherapy. The TOF system is composed of a Parallel Plate Avalanche Counter and scintillating detectors to create so-called ΔE—TOF maps used in the fragment charge identification process. From tests with an alpha source and a 12C beam experiment, we measured a coincidence resolving time for the apparatus below 300 ps. Those results should lead in the final design to the identification of all the fragments produced by the interaction of 12C ions with thin targets for energies up to 400 MeV/nucleon.

Kinetic energy of secondary fragments of 12C at varying incident energies in different biological media – A Monte Carlo study

This is a Monte Carlo study in GATE V8.0 investigating the nuclear fragmentation when 12C beams were incident at varying energies on different biological media. The researchers used one million monoenergetic pencil beam primary carbons irradiated to water, adipose tissue, skeletal muscle and cortical bone phantoms. The target was a box with dimensions of 20 cm × 20 cm × 20 cm to approximate the size of a human head. The energy was varied at 186.7 MeV/u, 241.7 MeV/u and 308.3 MeV/u. We obtained the number of the secondary particles produced in the fragmentation. We then chose the ten most abundant fragments and determined their kinetic energy distributions. 12C was most abundant in the fragmentation followed by proton. Either 3He or 11B had the least entries. The kinetic energy was inversely proportional to particles atomic number. In most cases proton and deuteron had the largest kinetic energy. The number of secondary particles increased with increasing incident energy. The kinetic energy had maximum increase at the stopping range, whose depth varied directly with incident energy and inversely with density of each material. The results were in agreement with the Bethe-Bloch formula.

Heavy Ion RBS Characterization of Multilayer Coatings Deposited on Glass Through the Sol-Gel Technique

Multilayer reflecting thin films of the systems TiO2-SiO2 and ZrO2-SiO2 were deposited on glass surface using the sol-gel technique. A 12C beam was utilized in RBS analysis to investigate the inner structure of these multilayer stacks. No evidence for defects or diffusion between the layers were found. Optical Spectroscopy showed wavelength selectivity in the reflection of an 8-layer TiO2-SiO2 sample.

Long-term exposure of a polycrystalline diamond detector irradiated by 62 MeV/nucleon carbon beams

The present work reports on a long-term irradiation test performed on a 0.3-mm thick polycrystalline diamond detector prototype. The device, biased at 300 V, was continuously irradiated for about 60 h by using a 12C beam at 62 MeV/nucl. at the LNS-INFN Cyclotron facility in Catania. An ionization chamber, calibrated using a single crystal diamond detector, was used to evaluate the total absorbed dose in the diamond detector under study. Data analysis carried out on recorded oscilloscope waveforms shows no significant variation of the signal properties in terms of amplitude, slope and charge after exposure to an integrated flux of 6.2⋅ 1013 ions/cm2. The results indicate that a polycrystalline diamond detector can be used for calibrating intensity monitors at the future superconducting fragment separator Super-FRS at FAIR (Darmstadt).

Comparative study of alternative Geant4 hadronic ion inelastic physics models for prediction of positron-emitting radionuclide production in carbon and oxygen ion therapy

The distribution of fragmentation products predicted by Monte Carlo simulations of heavy ion therapy depend on the hadronic physics model chosen in the simulation. This work aims to evaluate three alternative hadronic inelastic fragmentation physics options available in the Geant4 Monte Carlo radiation physics simulation framework to determine which model most accurately predicts the production of positron-emitting fragmentation products observable using in-beam PET imaging. Fragment distributions obtained with the BIC, QMD, and INCL + + physics models in Geant4 version 10.2.p03 are compared to experimental data obtained at the HIMAC heavy-ion treatment facility at NIRS in Chiba, Japan. For both simulations and experiments, monoenergetic beams are applied to three different block phantoms composed of gelatin, poly(methyl methacrylate) and polyethylene. The yields of the positron-emitting nuclei 11C, 10C and 15O obtained from simulations conducted with each model are compared to the experimental yields estimated by fitting a multi-exponential radioactive decay model to dynamic PET images using the normalised mean square error metric in the entrance, build up/Bragg peak and tail regions. Significant differences in positron-emitting fragment yield are observed among the three physics models with the best overall fit to experimental 12C and 16O beam measurements obtained with the BIC physics model.

Effect of Beam Transmission of Stable Isotopes on Online δ13C for SSAMS

ABSTRACTIt is known that 12C beam transmission through the accelerator decreases at high beam currents. This effect depends on machine design and varies across different types of AMS instruments. For beam currents of about 100 μA, the effect is small on the 500 kV tandem CAMS unit, whereas beam saturation is observed for similar high beam currents on the 250 kV SSAMS unit. While this effect is very evident for high 12C beam currents, we have also observed that even the 13C beam is found to suffer modest transmission loss with beam current. As a result, the 13C/12C ratio does not remain constant with beam current. By correcting for the effects of 12C beam saturation and decreased 13C transmission, we have obtained online δ13C values that are more accurate and precise at moderately high beam currents for SSAMS.

Range verification of radioactive ion beams of 11C and 15O using in-beam PET imaging

In advanced ion therapy, the visualization of the range of incident ions in a patient’s body is important for exploiting the advantages of this type of therapy. It is ideal to use radioactive ion beams for in-beam positron emission tomography (PET) imaging in particle therapy due to the high quality of PET images caused by the high signal-to-noise ratio. We have shown the feasibility of this idea through an in-beam PET study for 11C and 15O ion beams using the dedicated OpenPET system. In this work, we investigate the potential difference between the Bragg peak position and the position of the maximum detected positron-emitting fragments by a PET system for the radioactive beams of 11C and 15O. For this purpose, we measured the depth dose in a water phantom and performed PET scans of an irradiated PMMA phantom for the available beams of 11C and 15O at the Heavy Ion Medical Accelerator in Chiba (HIMAC). Then, we simulated the depth dose profiles in the water phantom and the yield of the positron-emitting fragments in a PMMA phantom for both available beams using the Monte Carlo code PHITS. The positions of the Bragg peak and maximum positron-emitting fragments from the measurements were well reproduced by simulation. The effect of beam energy broadening on the positional differences between two peaks was studied by simulating an irradiated PMMA phantom. The differences in position between the Bragg peak and the maximum positron-emitting fragments increased when the beam energy spread was broadened, although the differences were zero for the ideal mono-energetic beams. Greater differences were observed for 11C ion beams compared to 15O ion beams, although both beams had the same range in water, and the higher energy corresponded to a larger difference. For the known energy spread of the beams, the predicted differences between two peaks from the simulation were consistent with the measured data within submillimetre agreement.

Production of intense mass separated 11C beams for PET-aided hadron therapy

A novel production system based on the Isotope Separation On-Line (ISOL) method is being developed to produce intense mass separated 11C beams for PET-aided hadron therapy. In this work, we present a systematic study of the target that was developed for optimized 11C beam production. A solid boron nitride target (BN) with approximately 21% open porosity was manufactured by spark plasma sintering to provide maximized in-target production yield with enhanced isotope release properties. Operational limitations with respect to high temperatures and oxidizing atmospheres were studied, revealing that the BN target can withstand temperatures up to 1500 °C and can be operated with a controlled O2 leak, providing O2 potentials up to −300 kJ/mol, measured at 1000 °C.

Optical imaging for the characterization of radioactive carbon and oxygen ion beams

Heavy ion therapy is a promising cancer therapy technique due to the sharper Bragg peak and smaller lateral scattering characteristics of heavy ion beams as compared to a proton therapy. Recently, the potential for radioactive ion beam therapy has been investigated in combination with the OpenPET system to improve the accuracy of in vivo beam range verification. However, the characteristics of the radioactive ion beams have not been investigated thoroughly. Optical imaging has been proposed as a novel high-resolution beam range estimation method for heavy ion beams. In this study, high-resolution luminescence imaging and Cerenkov light imaging were performed for the range estimation of radioactive ion beams such as 11C and 15O in the Heavy Ion Medical Accelerator in Chiba (HIMAC) secondary beam line. A polymethyl methacrylate (PMMA) phantom (10.0 × 10.0 × 9.9 cm3) was irradiated by 11C and 15O ion beams. In order to obtain the in-beam luminescence and off-line beam Cerenkov light images, an optical system was used that consisted of a lens and a cooled CCD camera. The Bragg peaks and stopping positions of the 11C and 15O ion beams could be visualized by using the luminescence and Cerenkov light imaging, respectively. The Bragg peaks showed a good correlation with the peak of the luminescence profile with a positional discrepancy of 1 mm and 0.4 mm for the 11C and 15O ion beams, respectively. In conclusion, optical imaging using luminescence and Cerenkov light could be used for the precise range estimation of radioactive ion beams.

Challenges in 11C charge breeding

In this paper we discuss the possibilities of using a charge breeding scheme based on an Electron Beam Ion Source for beam preparation of a radioactive 11C beam for hadron therapy. Test measurements under extreme operating conditions were conducted at the REX-ISOLDE facility to explore the limitations of the charge breeder for high-intensity, low-repetition-rate, molecular CO+ beams. Based on our findings, we discuss different possible scenarios of coupling a charge breeder with either a medical synchrotron or linear accelerator. This paper is a highly condensed version of an exhaustive report on the topic [1], which we would like to refer to for further details.

Characterization of prompt gamma ray emission for in vivo range verification in particle therapy: A simulation study

In this paper we investigate the emission and detection characteristics of prompt gamma (PG) rays for in vivo range verification during hadron therapy, using Geant4 simulations. Proton, 4He and 12C beams of varying energy are incident on water phantoms. The PG production yield, energy spectral characteristics and spatial correlation with the Bragg Peak (BP) have been quantified. Further, the angular distributions for PG detection with respect to a point-of-reference on the phantom surface have been explored. The temporal properties of PG emission and time-of-flight (TOF) of PG detection have also been investigated in correlation with the changing particle beam range. Our results show that the primary PG rays from nuclear interactions of the primary beam exhibit the closest correlation to the beam range but its signal is significantly masked by the concurrent secondary PG rays, particularly for heavier ions such as carbon ion beams. The PG TOF spectroscopy encodes the essential information of the beam range but requires high time resolution measurements to retrieve it. A hybrid PG detection system to utilize the energy, timing and spatial characteristics of PG rays is desirable for BP tracking in real-time.

δ13C correction to AMS data: Values derived from AMS vs IRMS values

14C data from AMS measurements need to be corrected for isotopic fractionation using the δ13C values. Whether to use the δ13C values obtained from the AMS stable isotope measurements as they reflect any additional isotopic fractionation or to use Isotope Ratio Mass Spectrometry (IRMS) δ13C values due to their high precision and accuracy is the question that finds supporting arguments on either side. In this article, we present our observations by examining the data from the two AMS units at CAIS: a 500 kV CAMS and a 250 kV SSAMS. Offline δ13C values resulted in the fraction modern values of standards that are in excellent agreement with the consensus values for both machines. In the case of SSAMS, beyond a certain value, the high energy 12C beam current is found suppressed and skewed the δ13C. In general, the 13C+/12C+ ratio on SSAMS is more susceptible to beam current variation than it is on CAMS. But 14C+/13C+ ratios are nearly independent of beam current variations on both machines. Our analysis shows that online δ13C works well for CAMS, but results are not satisfactory for SSAMS. But we have found that using pre-acceleration 12C− instead of post-acceleration 12C+ for stable isotope ratio calculation substantially improves the online δ13C for SSAMS.

Modelling the Biological Beamline at HIMAC using Geant4

A Geant4 simulation modelling the passive Biological beamline at the Heavy Ion Medical Accelerator Chiba (HIMAC) is described and validated against experimental measurements for a mono-energetic and spread out Bragg peak (SOBP) 12C beam. Comparisons to experimental data showed good agreement for both lateral and depth dose profiles. It was found that simplifying the simulation model by generating a cone beam instead of using the wobbler magnets provided a good approximation for both lateral and depth dose measurements.

Characterization of prompt gamma rays for in-vivo range verification in hadron therapy: A Geant4 simulation study

Prompt gamma (PG) rays have been proposed for in-vivo beam range verification during treatment delivery. As a secondary by-product emitted almost instantaneously upon ion-nuclear interaction, PG rays offer real-time tracking of the Bragg peak (BP). However their detection is challenging since they have a broad energy spectrum with interference from neutrons and stray gamma rays. Numerous approaches have been proposed to utilise PG for in-vivo beam range verification. In this work, Geant4 Monte Carlo (MC) simulations have been used to study the spectral, spatial, temporal and angular distribution characteristics of PG emission and detection from hadron radiation fields of varying energy. Proton, 12C and 4He beams irradiated homogeneous water phantoms. These studies will provide valuable information for the development of clinically suitable and reliable PG detector systems.

Improved C− efficiency and ion beam currents by modifying SNICS cathode material

We investigated the possibility of increasing the 14C AMS efficiency and maximizing C− beam currents by modifying sample cathode geometry and material. Previously, we reported results which showed an increase in C− beam current and improved ionization efficiency when reducing the cathode sample well diameter from 1 mm to 0.75 mm and using zinc inserts, pressed into the aluminum cathode holder [4]. In this study we expand that effort by using cathodes with inserts made of Fe, Mo, Ni, Ti, Cu, and Zn. We pressed cathodes with 100 μg of Oxalic Acid I (OX-I) and ran them to exhaustion. 12C beam currents, 14C counts, and graphite weight were used to determine ion source efficiency.

Potential lethal damage repair in glioblastoma cells irradiated with ion beams of various types and levels of linear energy transfer.

Glioblastoma (GBM), a Grade IV brain tumour, is a well-known radioresistant cancer. To investigate one of the causes of radioresistance, we studied the capacity for potential lethal damage repair (PLDR) of three altered strains of GBM: T98G, U87 and LN18, irradiated with various ions and various levels of linear energy transfer (LET). The GBM cells were exposed to 12C and 28Si ion beams with LETs of 55, 100 and 200 keV/μm, and with X-ray beams of 1.7 keV/μm. Mono-energetic 12C ions and 28Si ions were generated by the Heavy Ion Medical Accelerator at the National Institute of Radiological Science, Chiba, Japan. Clonogenic assays were used to determine cell inactivation. The ability of the cells to repair potential lethal damage was demonstrated by allowing one identical set of irradiated cells to repair for 24 h before subplating. The results show there is definite PLDR with X-rays, some evidence of PLDR at 55 keV/μm, and minimal PLDR at 100 keV/μm. There is no observable PLDR at 200 keV/μm. This is the first study, to the authors’ knowledge, demonstrating the capability of GBM cells to repair potential lethal damage following charged ion irradiations. It is concluded that a GBM’s PLDR is dependent on LET, dose and GBM strain; and the more radioresistant the cell strain, the greater the PLDR.