Fragmentation Of Carbon Ions Research Articles

The contribution of high-LET track to DNA damage formation and cell death for Monoenergy and SOBP carbon ion irradiation

Carbon ion radiotherapy (CIRT) is a heavy ion charge particle therapy with 29 years of prominent use. Despite advantages like high relative biological effectiveness (RBE), improved quality of life, and reduced treatment time, challenges persist, especially regarding heavy nuclear fragments. Our research addresses these challenges in horizontal irradiation, aiming to comprehend Monoenergetic and Spread-Out Bragg peak (SOBP) carbon ion beam trajectories using cell survival analysis and visualizing biological effects through DNA damage (γ-H2AX). This reveals repair-related protein foci near the Bragg peak. CR-39, a plastic nuclear track detector, was explored to understand high-linear energy transfer (LET) tracks and radiation quality near the Bragg peak. Findings unveil high-LET DNA damage signatures through aligned γ-H2AX foci, correlating with LET values in SOBP. CR-39 visualized high-LET particle exposure, indicating comet-type etch-pits at the Bragg peak and suggesting carbon ion fragmentation. Unexpectedly, dot-type etch-pits in irradiated and post-Bragg peak regions indicated high-LET neutron production. This investigation highlights the intricate interplay of carbon ion beams, stressing the importance of understanding LET variations, DNA damage patterns, and undesired secondary exposure.

Charge Exchange upon the Fragmentation of Carbon Ions at an Energy of 300 MeV/Nucleon: Comparing Models of Ion–Ion Interaction

Charge Exchange upon the Fragmentation of Carbon Ions at an Energy of 300 MeV/Nucleon: Comparing Models of Ion–Ion Interaction

Charge exchange processes during carbon ion fragmentation at an energy of 300 MeV/nucleon: comparison with models of ion-ion interactions

Experimental data are presented on the differential cross sections to produce 11Be, 12Be, and 12B isotopes at the carbon beam fragmentation with an energy of 300 MeV/nucleon in the FRAGM experiment conducted based on the ITEP-TWAС multipurpose accelerator complex. The obtained experimental data are compared with the predictions of the models of ion-ion interactions: binary cascade and quantum molecular dynamics model.

Search for Nucleon Charge-Exchange Processes in the Fragmentation of Carbon Ions at an Energy of 300 MeV per Nucleon

Search for Nucleon Charge-Exchange Processes in the Fragmentation of Carbon Ions at an Energy of 300 MeV per Nucleon

A Data-Driven Fragmentation Model for Carbon Therapy GPU-Accelerated Monte-Carlo Dose Recalculation.

The advent of Graphics Processing Units (GPU) has prompted the development of Monte Carlo (MC) algorithms that can significantly reduce the simulation time with respect to standard MC algorithms based on Central Processing Unit (CPU) hardware. The possibility to evaluate a complete treatment plan within minutes, instead of hours, paves the way for many clinical applications where the time-factor is important. FRED (Fast paRticle thErapy Dose evaluator) is a software that exploits the GPU power to recalculate and optimise ion beam treatment plans. The main goal when developing the FRED physics model was to balance accuracy, calculation time and GPU execution guidelines. Nowadays, FRED is already used as a quality assurance tool in Maastricht and Krakow proton clinical centers and as a research tool in several clinical and research centers across Europe. Lately the core software has been updated including a model of carbon ions interactions with matter. The implementation is phenomenological and based on carbon fragmentation data currently available. The model has been tested against the MC FLUKA software, commonly used in particle therapy, and a good agreement was found. In this paper, the new FRED data-driven model for carbon ion fragmentation will be presented together with the validation tests against the FLUKA MC software. The results will be discussed in the context of FRED clinical applications to 12C ions treatment planning.

Biological Effects of Monoenergetic Carbon Ions and Their Associated Secondary Particles.

DNA double-strand breaks (DSBs) are the main factor behind carbon-ion radiation therapy (CIRT)-induced cell death. Nuclear interactions along the beam path between the primary carbon ions and targets result in nuclear fragmentation of carbon ions and recoiled particles. These secondary particles travel further distances past the Bragg peak to the tail region, leading to unwanted biological effects that may result in cytotoxicity in critical organs and secondary induced tumors following CIRT. Here, we confirmed that the density of the DSB distributions increases as the cell survival decreases at the Bragg peak and demonstrated that by visualizing DSBs, the various LET fragmentation ions and recoiled particles produced differences in their biological effects in the post-Bragg peak tail regions. This suggests that the density of the DSBs within the high-LET track structures, rather than only their presence, is important for inducing cell death. These results are essential for CIRT treatment planning to limit the amount of healthy cell damage and reducing both the late effect and the secondary tumor-associated risk.

Interaction of therapeutic 12C ions with bone-like targets: physical characterization and dosimetric effect at material interfaces

Carbon therapy is a promising treatment option for cancer. The physical and biological properties of carbon ions can theoretically allow for the delivery of curative doses to the tumor, while simultaneously limiting risks of toxicity to adjacent healthy structures. The treatment effectiveness can be further improved by decreasing the uncertainties stemming from several sources, including the modeling of tissue heterogeneity. Current treatment plans employ density-based conversion methods to translate patient-specific anatomy into a water system, where dose distribution is calculated. This approach neglects differences in nuclear interactions stemming from the elemental composition of each tissue. In this work, we investigated the interaction of therapeutic carbon ions with bone-like materials. The study concentrated on nuclear interactions and included attenuation curves of 200 and 400 AMeV beams in different types of bones, as well as kinetic energy spectra of all charged fragments produced up to 29 degrees from the beam direction. The comparison between measurements and calculations of the treatment planning system TRiP98 indicated that bone tissue causes less fragmentation of carbon ions than water. Overall, hydrogen and helium particles were found to be the most abundant species, while heavier fragments were mostly detected within 5 degrees from the beam direction. We also investigated how the presence of a soft tissue-bone interface could affect the depth-dose profile. The results revealed a dose spike in the transition region, that extended from the entry channel to the target volume. The findings of this work indicated that the tissue-to-water conversion method based only on density considerations can result in dose inaccuracies. Tissue heterogeneity regions containing bones can potentially produce dose spikes, whose magnitude will depend on the patient anatomy. Dose uncertainties can be decreased by modeling nuclear interactions directly in bones, without applying the tissue-to-water conversion.

Nuclear Fragmentation Imaging for Carbon-Ion Radiation Therapy Monitoring: an In Silico Study.

PurposeThis article presents an in vivo imaging technique based on nuclear fragmentation of carbon ions in irradiated tissues for potential real-time monitoring of carbon-ion radiation therapy (CIRT) treatment delivery and quality assurance purposes in clinical settings.Materials and MethodsA proof-of-concept imaging and monitoring system (IMS) was devised to implement the technique. Monte Carlo simulations were performed for a prospective pencil-beam scanning CIRT nozzle. The development IMS benchmark considered a 5×5-cm2 pixelated charged-particle detector stack positioned downstream from a target phantom and list-mode data acquisition. The abundance and production origins, that is, vertices, of the detected fragments were studied. Fragment trajectories were approximated by straight lines and a beam back-projection algorithm was built to reconstruct the vertices. The spatial distribution of the vertices was then used to determine plan relevant markers.ResultsThe IMS technique was applied for a simulated CIRT case, a primary brain tumor. Four treatment plan monitoring markers were conclusively recovered: a depth dose distribution correlated profile, ion beam range, treatment target boundaries, and the beam spot position. Promising millimeter-scale (3-mm, ≤10% uncertainty) beam range and submillimeter (≤0.6-mm precision for shifts <3 cm) beam spot position verification accuracies were obtained for typical therapeutic energies between 150 and 290 MeV/u.ConclusionsThis work demonstrated a viable online monitoring technique for CIRT treatment delivery. The method's strong advantage is that it requires few signal inputs (position and timing), which can be simultaneously acquired with readily available technology. Future investigations will probe the technique's applicability to motion-sensitive organ sites and patient tissue heterogeneities. In-beam measurements with candidate detector-acquisition systems are ultimately essential to validate the IMS benchmark performance and subsequent deployment in the clinic.

Cumulative {pi}-Mesons in {}^{{12}}{C}{+}{}^{{9}}Be-Interactions at 3.2 GeV/Nucleon

In the FRAGM experiment at the heavy-ion accelerator-accumulator complex ITEP-TWA, yields of cumulative charged pi mesons have been measured in a fragmentation of carbon ions with the energy of 3.2 GeV/nucleon on a beryllium target. The momentum spectra of pi mesons cover four orders of the invariant cross section magnitude. They demonstrate the exponential fall with increasing energy. The measured inverse slope parameter is compared with similar measurements in nucleon–nucleus interactions and ion–ion collisions at lower energies. The energy dependence of the ratio of the yields of negative to positive pi mesons is presented. This dependence is discussed in a connection with Coulomb and isotopic effects. The obtained data are compared with predictions of several ion–ion interaction models.

Measurement of 12C Fragmentation Cross Sections on C, O, and H in the Energy Range of Interest for Particle Therapy Applications

In a carbon ion treatment the nuclear fragmentation of both target and beam projectiles impacts on the dose released on the tumor and on the surrounding healthy tissues. Carbon ion fragmentation occurring inside the patient body has to be studied in order to take into account this contribution. These data are also important for the development of the range monitoring techniques with charged particles. The production of charged fragments generated by carbon ion beams of 115–353 MeV/u kinetic energy impinging on carbon, oxygen, and hydrogen targets has been measured at the CNAO particle therapy center (Pavia, Italy). The use of thin targets of graphite (C), PMMA (C2O5H8) and polyvinyl-toluene [plastic scintillator (PS), ${\text{C}}_{b}{\text{H}}_{a}$ ] allowed to measure fragments production cross sections, exploiting a time-of-flight (ToF) technique. PS detectors have been used to perform the ToF measurements, while LYSO crystals have been used for the deposited energy measurement and to perform particle identification. Cross sections have been measured at 90° and 60° with respect to the beam direction. The measured proton, deuteron, and triton differential production cross sections on C, O, and H, obtained exploiting the target subtraction strategy, are presented here as a function of the fragment kinetic energy.

Ion production in the 12C + 9Be interactions at GeV energies

Differential cross sections for nuclear fragment yields at an angle of 3.5° in the fragmentation of carbon ions with an energy of 0.95 and 2.0 GeV/nucleon on a beryllium target have been measured. The momentum spectra of the fragments were used for testing predictions of few models of ion-ion interactions.

Investigation of single carbon ion fragmentation in water and PMMA for hadron therapy

Carbon ion radiotherapy is an attractive alternative to conventional radiotherapy, especially in case of deep-seated and radio-resistant tumors. As a consequence of inelastic nuclear reactions between primary particles and patient’s tissues, the primary carbon ions may undergo nuclear fragmentation. The resulting decrease of primary ions and production of secondary fragments have to be carefully considered for accurate dose calculations in the treatment planning systems. The experimental data currently available provide only general information on carbon ion fragmentation and are not sufficient to cover the entire range of beam energies, target configurations and compositions relevant for radiotherapy.Therefore, new investigations were carried out to analyse the outcomes of the inelastic nuclear reaction processes on a single-ion-based approach. Measurements were performed at HIT, using 430 MeV/u carbon ion beams crossing water and PMMA targets. Unique in this method is the possibility of measuring number and type of fragments produced from each single carbon ion, provided that they are within the acceptance of the experimental apparatus.Concerning the amount of residual carbon ions behind water and PMMA targets with the same water equivalent thickness (WET), no significant differences were found. The experimental attenuation curve was well reproduced by the simulations. However, in the experiments, differences were observed regarding the amount of secondary fragments produced in water and in PMMA targets with the same WET. Differences were also found between experiments and simulations. These findings should be considered when dosimetric measurements are performed with PMMA instead of water phantoms. The found differences between experiments and simulations may contribute to improve the nuclear interaction and fragmentation models in Monte Carlo codes.

A Novel Method for Fragmentation Studies in Particle Therapy: Principles of Ion Identification.

In carbon ion beam radiation therapy, fragmentation processes within the patient lead to changes in the composition of the particle field with increasing depth. Consequences are alterations of the resulting dose distribution and its biological effectiveness. To enable accurate treatment planning, the characteristics of the ion spectra resulting from fragmentation processes need to be known for various ion energies and target materials. In this work, we present a novel method for ion type identification using a small and highly flexible setup based on a single detector and designed to simplify measurements and overcome current shortages in available fragmentation data. The presented approach is based on the pixelated, semiconductor detector Timepix. The large number of pixels with small pitch, all individually calibrated for energy deposition, enables detection and visualization of single particle tracks. For discrimination among different ion species, the pattern recognition analysis of the detector signal is used. Fragmentation spectra resulting from a primary carbon ion beam at various depths of tissue-equivalent material were studied to identify different ion species in mixed particle fields. The performance of the method was evaluated quantitatively using reference data from an established technique. All ion species resulting from carbon ion fragmentation in tissue-equivalent material could be separated. For measurements behind a 158-mm-thick water tank, the relative fractions of H, He, Be, and B ions detected agreed with corresponding reference data within the limits of uncertainty. For the relatively rare lithium ions, the agreement was within 2.3 Δref (uncertainty of reference). For designated configurations, the presented ion type identification method enables studies of therapeutic carbon ion beams with a simple, small, and configurable detection setup. The technique is promising to enable online fragmentation studies over a wide range of beam and target parameters in the future.

Yields of nuclear fragments in the interactions of carbon nuclei with a beryllium target at a projectile energy of 0.6 GeV per nucleon

The yields of long-lived nuclear fragments at an angle of 3.5° that originate fromthe fragmentation of carbon ions with an energy of T0 = 0.6 GeV per nucleon on a berylliumtarget were measured in the FRAGMexperiment at the ITEP TWA heavy-ion accelerator. The momentum spectra of these fragments cover both the fragmentation-maximum region and the cumulative region. The respective differential cross sections change by about five orders of magnitude. The momentum distributions of fragments in the laboratory frame and their kinetic-energy distributions in the rest frame of the fragmenting nucleus are used to test the predictions of four models of ion–ion interactions: BC, INCL++, LAQGSM03.03, and QMD.

Measurement of fragmentation cross sections ofC12ions on a thin gold target with the FIRST apparatus

A detailed knowledge of the light ions interaction processes with matter is of great interest in basic and applied physics. As an example, particle therapy and space radioprotection require highly accurate fragmentation cross-section measurements to develop shielding materials and estimate acute and late health risks for manned missions in space and for treatment planning in particle therapy. The Fragmentation of Ions Relevant for Space and Therapy experiment at the Helmholtz Center for Heavy Ion research (GSI) was designed and built by an international collaboration from France, Germany, Italy, and Spain for studying the collisions of a C12 ion beam with thin targets. The collaboration's main purpose is to provide the double-differential cross-section measurement of carbon-ion fragmentation at energies that are relevant for both tumor therapy and space radiation protection applications. Fragmentation cross sections of light ions impinging on a wide range of thin targets are also essential to validate the nuclear models implemented in MC simulations that, in such an energy range, fail to reproduce the data with the required accuracy. This paper presents the single differential carbon-ion fragmentation cross sections on a thin gold target, measured as a function of the fragment angle and kinetic energy in the forward angular region (θ≲6∘), aiming to provide useful data for the benchmarking of the simulation softwares used in light ions fragmentation applications. The C12 ions used in the measurement were accelerated at the energy of 400 MeV/nucleon by the SIS (heavy ion synchrotron) GSI facility.

Protons from carbon ion fragmentation at 0.3–2.0 GeV/nucleon: Comparison with models of ion-ion interactions

Yields of protons at 3.5° from carbon ion fragmentation at energies of T0 = 0.3, 0.6, 0.95, and 2.0 GeV/nucleon on a Be target were measured in the FRAGM experiment at TWA-ITEP heavy-ion facility. Proton momentum spectra cover both the region of the fragmentation maximum and the cumulative region. The differential cross sections span six orders of its magnitude. The spectra are compared with the predictions of four models of ion-ion interactions: LAQGSM03.03, SHIELD-HIT, QMD, and BC.

Measurements of 12 C ion fragmentation on thin carbon target from the FIRST collaboration at GSI

The FIRST (Fragmentation of Ions Relevant for Space and Therapy) experiment at GSI laboratory took data in summer 2011, studying the collisions of a 12C ion beam with Carbon and Au thin targets. The experiment main purpose is the double differential cross section measurement of the carbon ion fragmentation at energies that are relevant both for tumor therapy and space radiation protection applications (100-1000 MeV/u). The FIRST dataset contains carbon ions collisions on a 3.43 g·Cin−2 carbon target (about 24 M events) and on a 0.96 g·cm−2 Au target (about 4.5 M events). The SIS (heavy ion synchrotron) was used to accelerate the 12C ions at the energy of 400 MeV/u. The preliminary results of differential cross sections measurements as a function of angle and energy for carbon target, in the small angle region (θ ≤ 5°), are presented.

Small-angle fragmentation of carbon ions at 0.6 GeV/n: a comparison with models of ion-ion interactions

Small-angle fragmentation of carbon ions at 0.6 GeV/n: a comparison with models of ion-ion interactions

Small-angle fragmentation of carbon ions at 0.6 GeV/n: a comparison with models of ion-ion interactions

Momentum distributions of hydrogen and helium isotopes from 12C fragmentation at 3.5° were measured at 0.6 GeV/nucleon in the FRAGM experiment at ITEP TWA heavy ion accelerator. The fragments were selected by correlated time of flight and dE/dx measurements with a magnetic spectrometer with scintillation counters. The main attention was drawn to the high momentum region where the fragment velocity exceeds the velocity of the projectile nucleus. The momentum spectra of fragments span the region of the fragmentation peak as well as the cumulative region. The differential cross sections cover six orders of magnitude. The distributions measured are compared to the predictions of three ion-ion interaction models: BC, QMD and LAQGSM03.03. The kinetic energy spectra of fragments in the projectile rest frame have an exponential shape with two temperatures, being defined by their slope parameters.

Carbon ion fragmentation effects on the nanometric level behind the Bragg peak depth

In this study, fragmentation yields of carbon therapy beams are estimated using the Geant4 simulation toolkit version 9.5. Simulations are carried out in a step-by-step mode using the Geant4-DNA processes for each of the major contributing fragments. The energy of the initial beam is taken 400 MeV amu−1 as this is the highest energy, which is used for medical accelerators and this would show the integral role of secondary contributions in radiotherapy irradiations. The obtained results showed that 64% of the global dose deposition is initiated by carbon ions, while up to 36% is initiated by the produced fragments including all their isotopes. The energy deposition clustering yields of each of the simulated fragments are then estimated using the DBSCAN clustering algorithm and they are compared to the yields of the incident primary beam.