Function Of Linear Energy Transfer Research Articles

Relative biological effectiveness of oxygen ion beams in the rat spinal cord: Dependence on linear energy transfer and dose and comparison with model predictions

Background and purposeIon beams exhibit an increased relative biological effectiveness (RBE) with respect to photons. This study determined the RBE of oxygen ion beams as a function of linear energy transfer (LET) and dose in the rat spinal cord. Materials and methodsThe spinal cord of rats was irradiated at four different positions of a 6 cm spread-out Bragg-peak (LET: 26, 66, 98 and 141 keV/µm) using increasing levels of single and split oxygen ion doses. Dose-response curves were established for the endpoint paresis grade II and based on ED50 (dose at 50 % effect probability), the RBE was determined and compared to model predictions. ResultsWhen LET increased from 26 to 98 keV/µm, ED50 decreased from 17.2 ± 0.3 Gy to 13.5 ± 0.4 Gy for single and from 21.7 ± 0.4 Gy to 15.5 ± 0.5 Gy for split doses, however, at 141 keV/µm, ED50 rose again to 15.8 ± 0.4 Gy and 17.2 ± 0.4 Gy, respectively. As a result, the RBE increased from 1.43 ± 0.05 to 1.82 ± 0.08 (single dose) and from 1.58 ± 0.04 to 2.21 ± 0.08 (split dose), respectively, before declining again to 1.56 ± 0.06 for single and 1.99 ± 0.06 for split doses at the highest LET. Deviations from RBE-predictions were model-dependent. ConclusionThis study established first RBE data for the late reacting central nervous system after single and split doses of oxygen ions. The data was used to validate the RBE-dependence on LET and dose of three RBE-models. This study extends the existing data base for protons, helium and carbon ions and provides important information for future patient treatments with oxygen ions.

Geant4-DNA simulation of human cancer cells irradiation with helium ion beams

Purpose:This study aimed to develop a computational environment for the accurate simulation of human cancer cell irradiation using Geant4-DNA. New cell geometrical models were developed and irradiated by alpha particle beams to induce DNA damage. The proposed approach may help further investigation of the benefits of external alpha irradiation therapy. Methods:The Geant4-DNA Monte Carlo (MC) toolkit allows the simulation of cancer cell geometries that can be combined with accurate modelling of physical, physicochemical and chemical stages of liquid water irradiation, including radiolytic processes. Geant4-DNA is used to calculate direct and non-direct DNA damage yields, such as single and double strand breaks, produced by the deposition of energy or by the interaction of DNA with free radicals. Results:In this study, the “molecularDNA” example application of Geant4-DNA was used to quantify early DNA damage in human cancer cells upon irradiation with alpha particle beams, as a function of linear energy transfer (LET). The MC simulation results are compared to experimental data, as well as previously published simulation data. The simulation results agree well with the experimental data on DSB yields in the lower LET range, while the experimental data on DSB yields are lower than the results obtained with the “molecularDNA” example in the higher LET range. Conclusion:This study explored and demonstrated the possibilities of the Geant4-DNA toolkit together with the “molecularDNA” example to simulate the helium beam irradiation of cancer cell lines, to quantify the early DNA damage, or even the following DNA damage response.

Relative efficiency of radiophotoluminescent glass detectors in low energy ion beams

In heavy charged particle dosimetry, the luminescence efficiency strongly depends on linear energy transfer (LET) and characterization of the detectors' efficiency as a function of the particle LET is very important. Available literature data for the efficiency of radiophotoluminescent (RPL) glass detectors are scarce and especially for low energy range no data was found. In this study, detectors made of the most widely known RPL material (silver activated phosphate glass) were exposed to various low energy ion beams (1H, 7Li, and 12C). For every ion beam, the linear dose (fluence) response of the RPL glass detectors was confirmed for the investigated dose (fluence) range and the RPL efficiency relative to 60Co gamma rays was evaluated. The relative efficiency decreased as LET increased but not as a unique function of LET, where the relative efficiency (expressed for doses in RPL glass) decreased from 0.85 ± 0.06 for the 5 MeV 1H ion beam (LETw = 8.1 keV/μm) to 0.017 ± 0.001 for the 15 MeV 12C ion beam (LETw = 673.8 keV/μm). More experimental data are still needed but results obtained in this study may motivate the application and testing of microdosimetric models for RPL glass detectors.

Space radiation quality factor for Galactic Cosmic Rays and typical space mission scenarios using a microdosimetric approach

Space radiation exposure from omnipresent Galactic Cosmic Rays (GCRs) in interplanetary space poses a serious carcinogenic risk to astronauts due to the—limited or absent—protective effect of the Earth’s magnetosphere and, in particular, the terrestrial atmosphere. The radiation risk is directly influenced by the quality of the radiation, i.e., its pattern of energy deposition at the micron/DNA scale. For stochastic biological effects, radiation quality is described by the quality factor, Q, which can be defined as a function of Linear Energy Transfer (LET) or the microdosimetric lineal energy (y). In the present work, the average Q of GCR for different mission scenarios was calculated using a modified version of the microdosimetric Theory of Dual Radiation Action (TDRA). NASA’s OLTARIS platform was utilized to generate the radiation environment behind different aluminum shielding (0–30 g/cm2) for a typical mission scenario in low-earth orbit (LEO) and in deep space. The microdosimetric lineal energy spectra of ions (Zge 1) in 1 μm liquid water spheres were calculated by a generalized analytical model which considers energy-loss fluctuations and δ-ray transport inside the irradiated medium. The present TDRA-based Q-values for the LEO and deep space missions were found to differ by up to 10% and 14% from the corresponding ICRP-based Q-values and up to 3% and 6% from NASA’s Q-model. In addition, they were found to be in good agreement with the Q-values measured in the International Space Station (ISS) and by the Mars Science Laboratory (MSL) Radiation Assessment Detector (RAD) which represent, respectively, a LEO and deep space orbit.

Characterisation and Quenching Correction for an Al2O3:C Optical Fibre Real Time System in Therapeutic Proton, Helium, and Carbon-Charged Beams

Real time radioluminescence fibre-based detectors were investigated for application in proton, helium, and carbon therapy dosimetry. The Al2O3:C probes are made of one single crystal (1 mm) and two droplets of micro powder in two sizes (38 μm and 4 μm) mixed with a water-equivalent binder. The fibres were irradiated behind different thicknesses of solid slabs, and the Bragg curves presented a quenching effect attributed to the nonlinear response of the radioluminescence (RL) signal as a function of linear energy transfer (LET). Experimental data and Monte Carlo simulations were utilised to acquire a quenching correction method, adapted from Birks' formulation, to restore the linear dose-response for particle therapy beams. The method for quenching correction was applied and yielded the best results for the '4 μm' optical fibre probe, with an agreement at the Bragg peak of 1.4% (160 MeV), and 1.5% (230 MeV) for proton-charged particles; 2.4% (150 MeV/u) for helium-charged particles and of 4.8% (290 MeV/u) and 2.9% (400 MeV/u) for the carbon-charged particles. The most substantial deviations for the '4 μm' optical fibre probe were found at the falloff regions, with ~3% (protons), ~5% (helium) and 6% (carbon).

Investigation and Simulation of SEL Cross Sections at Different Temperatures

The single-event latchup (SEL) cross sections as functions of linear energy transfer (LET) in different CMOS circuits were experimentally investigated at different temperatures. A simplified simulation method for the SEL cross section temperature dependence is proposed and validated.

Biological effectiveness and relative biological effectiveness of ion beams for in-vitro cell irradiation.

Biological effectiveness and relative biological effectiveness are critical for proton and ion beam radiotherapy. However, the relationship between the two quantities and physical character of ion beams is not well established. By analyzing 1188 sets of in‐vitro cell irradiation experiments using ion beams ranging from protons to 238U, compiled by the Particle Irradiation Data Ensemble (PIDE) project, the biological effectiveness of the ion beams, with cell survival fractionation (SF) as the endpoint, was found to be dependent on the fluence and linear energy transfer (LET) of the ion beam. Consequently, the relative biological effectiveness of the ion beam to photon beam was also established as a function of LET. A common form of relationship among SF, fluence, and LET was found to be valid for all ion beam experiments. The close form relationship could be used for proton and ion beam radiotherapy applications.

Relative biological effectiveness of single and split helium ion doses in the rat spinal cord increases strongly with linear energy transfer

Background and purposeDetermination of the relative biological effectiveness (RBE) of helium ions as a function of linear energy transfer (LET) for single and split doses using the rat cervical spinal cord as model system for late-responding normal tissue. Material and methodsThe rat cervical spinal cord was irradiated at four different positions within a 6 cm spread-out Bragg-peak (SOBP) (LET 2.9, 9.4, 14.4 and 20.7 keV/µm) using increasing levels of single or split doses of helium ions. Dose-response curves were determined and based on TD50-values (dose at 50% effect probability using paresis II as endpoint), RBE-values were derived for the endpoint of radiation-induced myelopathy. ResultsWith increasing LET, RBE-values increased from 1.13 ± 0.04 to 1.42 ± 0.05 (single dose) and 1.12 ± 0.03 to 1.50 ± 0.04 (split doses) as TD50-values decreased from 21.7 ± 0.3 Gy to 17.3 ± 0.3 Gy (single dose) and 30.6 ± 0.3 Gy to 22.9 ± 0.3 Gy (split doses), respectively. RBE-models (LEM I and IV, mMKM) deviated differently for single and split doses but described the RBE variation in the high-LET region sufficiently accurate. ConclusionThis study established the LET-dependence of the RBE for late effects in the central nervous system after single and split doses of helium ions. The results extend the existing database for protons and carbon ions and allow systematic testing of RBE-models. While the RBE-values of helium were generally lower than for carbon ions, the increase at the distal edge of the Bragg-peak was larger than for protons, making detailed RBE-modeling necessary.

An SRAM SEU Cross Section Curve Physics Model

Static random access memories (SRAMs) are prone to a single-event upset (SEU), also known as soft errors, due to transient noise caused by a single strike of radiation. Beam testing has been extensively used to measure the SEU cross section of SRAMs as a function of the linear energy transfer (LET) of charged particle radiation. The evolution of the cross section as a function of LET is called the cross section curve, which plays a vital role in upset rate analysis for hardness assurance. Various analytical models have been developed to describe SRAM SEU cross-section curves, and they have proven to be useful in reducing the cost of beam testing as well as revealing the physics behind test results. However, they involve arbitrary parameters, which make it challenging to predict cross-section curves without any beam results. Moreover, the current method of analyzing cross-section curves or the LET dependence of cross sections relies on a model different from that is used in the analysis of power-supply-voltage dependence, which is becoming increasingly important because of the demand for low-power operation. To overcome these problems, this paper proposes a unified equation that describes both LET and the power-supply-voltage dependence of SRAM SEU cross sections. It comprises only parameters that are physically clear and familiar to SEU researchers. As well as giving possible constraints, comparisons with data from the literature suggest it can be applied to SRAMs fabricated in bulk and silicon-on-insulator (SOI) processes across generations from the early 1000-nm-scale to the current 10-nm-scale technology nodes.

Demonstration of an optically stimulated luminescence (OSL) material with reduced quenching for proton therapy dosimetry: MgB4O7:Ce,Li

The objective of this work is to demonstrate that MgB4O7:Ce,Li, a new optically stimulated luminescence (OSL) dosimetric material, shows improved response for proton therapy dosimetry, with less reduction in luminescence detector efficiency with the particle linear energy transfer (LET). MgB4O7:Ce,Li was synthesized and its luminescence efficiency as a function of LET was characterized for dose-averaged LET values from 0.73 keV/μm up to 74.9 keV/μm using proton, 4He, and 12C ion beams. Commercial Al2O3:C OSLDs were also used for comparison. Monte Carlo simulations were used to predict the material's response in pristine and spread-out Bragg peaks (SOBP), suggesting the MgB4O7:Ce,Li would offer minimum quenching in proton beams of energies relevant to radiotherapy. This prediction was confirmed by irradiations of MgB4O7:Ce,Li and Al2O3:C along SOBPs from proton beams. The results demonstrate that new OSL materials optimized for proton dosimetry can be developed using their dose response to low-LET radiation as a guide during material development.

Monte Carlo simulation of base damage as a function of linear energy transfer for applications in radiation biophysics

Monte Carlo simulation of base damage as a function of linear energy transfer for applications in radiation biophysics

Response of the GAGG(Ce) scintillator to charged particles compared with the CsI(Tl) scintillator

GAGG(Ce) is a novel scintillator with a fast response and high light output without a hygroscopic nature. It is expected to be a useful detector for charged particles at high-counting rates. However, the response of the GAGG(Ce) scintillator to charged particles has not been fully examined. In the present work, the light output and energy resolution of the GAGG(Ce) scintillator were measured for protons and alpha particles at E p=5–68 MeV and E α=8–54 MeV as well as gamma rays at E γ=662 keV from a 137Cs source. The results were compared with those of the CsI(Tl) scintillator. The scintillation efficiencies dL/dE of the GAGG(Ce) and CsI(Tl) scintillators were obtained and parametrized as a function of linear energy transfer dE/dx.

A Geant4-DNA Evaluation of Radiation-Induced DNA Damage on a Human Fibroblast.

Simple SummaryDNA damage caused by ionizing radiation in a human fibroblast cell evaluated by the Geant4-DNA Monte Carlo toolkit is presented. A validation study using a computational geometric human DNA model was then carried out, and the calculated DNA damage as a function of particle type and energy is presented. The results of this work showed a significant improvement on past work and were consistent with recent radiobiological experimental data, such as damage yields. This work and the developed methodology could impact a broad number of research fields in which the understanding of radiation effects is crucial, such as cancer radiotherapy, space science, and medical physics.Accurately modeling the radiobiological mechanisms responsible for the induction of DNA damage remains a major scientific challenge, particularly for understanding the effects of low doses of ionizing radiation on living beings, such as the induction of carcinogenesis. A computational approach based on the Monte Carlo technique to simulate track structures in a biological medium is currently the most reliable method for calculating the early effects induced by ionizing radiation on DNA, the primary cellular target of such effects. The Geant4-DNA Monte Carlo toolkit can simulate not only the physical, but also the physico-chemical and chemical stages of water radiolysis. These stages can be combined with simplified geometric models of biological targets, such as DNA, to assess direct and indirect early DNA damage. In this study, DNA damage induced in a human fibroblast cell was evaluated using Geant4-DNA as a function of incident particle type (gammas, protons, and alphas) and energy. The resulting double-strand break yields as a function of linear energy transfer closely reproduced recent experimental data. Other quantities, such as fragment length distribution, scavengeable damage fraction, and time evolution of damage within an analytical repair model also supported the plausibility of predicting DNA damage using Geant4-DNA.The complete simulation chain application “molecularDNA”, an example for users of Geant4-DNA, will soon be distributed through Geant4.

Evaluation of radiophotoluminescent glass dosimeter response for therapeutic spot scanning proton beam: suggestion of linear energy transfer-based correction.

A radiophotoluminescent glass dosimeter (RGD) is used for a postal audit of a photon beam because of its various excellent characteristics. However, it has not been used for scanning proton beams because its response characteristics have not been verified. In this study, the response of RGD to scanning protons was investigated to develop a dosimetry protocol using the linear energy transfer (LET)‐based correction factor. The responses of RGD to four maximum‐range‐energy‐pattern proton beams were verified by comparing it with ionization chamber (IC) dosimetry. The LET at each measurement depth was calculated via Monte Carlo (MC) simulation. The LET correction factor (kLETRGD) was the ratio between the uncorrected RGD dose (DrawRGD) and the IC dose at each measurement depth. kLETRGD can be represented as a function of LET using the following equation: kLETRGDLET=‐0.035LET+1.090. DrawRGD showed a linear under‐response with increasing LET, and the maximum dose difference between the IC dose and DrawRGD was 15.2% at an LET of 6.07 keV/μm. The LET‐based correction dose (DLETRGD) conformed within 3.6% of the IC dose. The mean dose difference (±SD) of DrawRGD and DLETRGD was –2.5 ± 6.9% and 0.0 ± 1.6%, respectively. To achieve accurate dose verification for scanning proton beams using RGD, we derived a linear regression equation based on LET. The results show that with appropriate LET correction, RGD can be used for dose verification of scanning proton beams.

DNA double-strand breaks in cancer cells as a function of proton linear energy transfer and its variation in time

Purpose The complex relationship between linear energy transfer (LET) and cellular response to radiation is not yet fully elucidated. To better characterize DNA damage after irradiations with therapeutic protons, we monitored formation and disappearance of DNA double-strand breaks (DNA DSB) as a function of LET and time. Comparisons with conventional γ-rays and high LET carbon ions were also performed. Materials and Methods In the present work, we performed immunofluorescence-based assay to determine the amount of DNA DSB induced by different LET values along the 62 MeV therapeutic proton Spread out Bragg peak (SOBP) in three cancer cell lines, i.e. HTB140 melanoma, MCF-7 breast adenocarcinoma and HTB177 non-small lung cancer cells. Time dependence of foci formation was followed as well. To determine irradiation positions, corresponding to the desired LET values, numerical simulations were carried out using Geant4 toolkit. We compared γ-H2AX foci persistence after irradiations with protons to that of γ-rays and carbon ions. Results With the rise of LET values along the therapeutic proton SOBP, the increase of γ-H2AX foci number is detected in the three cell lines up to the distal end of the SOBP, while there is a decrease on its distal fall-off part. With the prolonged incubation time, the number of foci gradually drops tending to attain the residual level. For the maximum number of DNA DSB, irradiation with protons attain higher level than that of γ-rays. Carbon ions produce more DNA DSB than protons but not substantially. The number of residual foci produced by γ-rays is significantly lower than that of protons and particularly carbon ions. Carbon ions do not produce considerably higher number of foci than protons, as it could be expected due to their physical properties. Conclusions In situ visualization of γ-H2AX foci reveal creation of more lesions in the three cell lines by clinically relevant proton SOBP than γ-rays. The lack of significant differences in the number of γ-H2AX foci between the proton and carbon ion-irradiated samples suggests an increased complexity of DNA lesions and slower repair kinetics after carbon ions compared to protons. For all three irradiation types, there is no major difference between the three cell lines shortly after irradiations, while later on, the formation of residual foci starts to express the inherent nature of tested cells, therefore increasing discrepancy between them.

Double-strand breaks measured along a 160 MeV proton Bragg curve using a novel FIESTA-DNA probe in a cell-free environment

Proton radiotherapy treatment planning systems use a constant relative biological effectiveness (RBE) = 1.1 to convert proton absorbed dose into biologically equivalent high-energy photon dose. This method ignores linear energy transfer (LET) distributions, and RBE is known to change as a function of LET. Variable RBE approaches have been proposed for proton planning optimization. Experimental validation of models underlying these approaches is a pre-requisite for their clinical implementation. This validation has to probe every level in the evolution of radiation-induced biological damage leading to cell death, starting from DNA double-strand breaks (DSB). Using a novel FIESTA-DNA probe, we measured the probability of double-strand break (P DSB) along a 160 MeV proton Bragg curve at two dose levels (30 and 60 Gy (RBE)) and compared it to measurements in a 6 MV photon beam. A machined setup that held an Advanced Markus parallel plate chamber for proton dose verification alongside the probes was fabricated. Each sample set consisted of five 10 μl probes suspended inside plastic microcapillary tubes. These were irradiated with protons to 30 Gy (RBE) at depths of 5–17.5 cm and 60 Gy (RBE) at depths of 10–17.2 cm with 1 mm resolution around Bragg peak. Sample sets were also irradiated using 6MV photons to 20, 40, 60, and 80 Gy. For the 30 Gy (RBE) measurements, increases in P DSB/Gy were observed at 17.0 cm followed by decreases at larger depth. For the 60 Gy (RBE) measurements, no increase in P DSB/Gy was observed, but there was a decrease after 17.0 cm. Dose-response for P DSB between 30 and 60 Gy (RBE) showed less than doubling of P DSB when dose was doubled. Proton RBE effect from DSB, RBEP,DSB, was <1 except at the Bragg peak. The experiment showed that the novel probe can be used to perform DNA DSB measurements in a proton beam. To establish relevance to clinical environment, further investigation of the probe’s chemical scavenging needs to be performed.

Characterization of 2D Al2O3:C,Mg radiophotoluminescence films in charged particle beams

In particle-therapy, 2D dosimetry systems require high spatial resolution and linear dose response as the patient treatment show steep gradients of dose in depth. In this work we report on the characterization of the radiophotoluminescence (RPL) response from Al₂O₃:C,Mg films exposed to proton (61.3 MeV, 91.5 MeV, 155.5 MeV and 230 MeV) and carbon clinical beams (110 MeV/u). The film response is evaluated in terms of properties particularly important for relative dose measurements, as dose response, film uniformity and minimum detectable dose. The films, based on coatings with average grain sizes of ≈7 μm, demonstrate a better response than those used in our previous studies, with grain sizes of ≈47 μm. Moreover, the Linear Energy Transfer (LET) changes when penetrating through material and it is known that solid-state detectors change luminescence efficiency ηHT,γ as a function of LET. Therefore, we performed a detailed characterization of our new film to evaluate its response as function of dose and LET. The ηHT,γ curve, as a function of particle LET, obtained from discrete dose points (slabs) ηHT,γ is compared with the ηHT,γ curves from Al₂O₃:C (OSL) and Al₂O₃:C,Mg (RPL) films from our previous study. The ηHT,γ curves are consistent with Birks’ law, where we observe expected quenching for increasing LET. Additionally, we present 2D RPL images, using a wedge phantom, from Al₂O₃:C,Mg films irradiated with proton and carbon beams, which resulted in a 2D depth dose distribution of the Bragg curve and a comparable LET dependence with the data obtained with the slabs. The results confirm that the images obtained can be advantageously applied to obtain dose distribution in proton and carbon therapy without many corrections.

Dosimetric response of a glass dosimeter in proton beams: LET-dependence and correction factor.

A radiophotoluminescent glass dosimeter (RGD) is widely used in postal audit system for photon beams in Japan. However, proton dosimetry in RGDs is scarcely used owing to a lack of clarity in their response to beam quality. In this study, we investigated RGD response to beam quality for establishing a suitable linear energy transfer (LET)-corrected dosimetry protocol in a therapeutic proton beam. The RGD response was compared with ionization chamber measurement for a 100-225MeV passive proton beam. LET of the measurement points was calculated by the Monte Carlo method. An LET-correction factor, defined as a ratio between the non-corrected RGD dose and ionization chamber dose, of 1.226×(LET)-0.171 was derived for the RGD response. The magnitude of the LET-dependence of RGD increased with LET; for an LET of 8.2keV/μm, the RGD under-response was up to 16%. The coefficient of determination, mean difference±SD of non-corrected RGD dose, residual range-corrected RGD dose, and LET-corrected RGD dose to the ionization chamber are 0.923, 3.7±4.2%, -2.4±7.5%, and 0.04±2.1%, respectively. The LET-corrected RGD dose was within 5% of the corresponding ionization chamber dose at all energies until 200MeV, where it was 5.3% lower than the ionization chamber dose. A corrected LET-dependence of RGD using a correction factor based on a power function of LET and precise dosimetric verification close to the maximum LET were realized here. We further confirmed establishment of an accurate postal audit under various irradiation conditions.

Detector performance of the position-sensitive tissue-equivalent proportional chamber for space dosimetry onboard the international space station

We investigated the performance of a flight model of the position-sensitive tissue-equivalent proportional chamber (PS-TEPC) by irradiating with heavy-ion beams prior to launch to the International Space Station. The flight model operated stably with an effective gas gain of 1000 under a sealed gas. This gain was almost consistent with the effective gas gain under a gas flow. Energies of H, C, Si and Fe beams measured using the PS-TEPC flight model agreed well with calculations using the SRIM2008 code. Energy resolutions of 9.7% and 3.8% were obtained for the C and Fe beams, respectively. The uncertainties in dose equivalents were estimated to be better than 30% assuming both the theoretical model and best-fit function of linear energy transfer and referring to previously reported integrated dose fractions for an actual spacecraft. These features of the flight model satisfy the National Council on Radiation Protection and Measurements criteria for space dosimeters.

Comparison of biophysical models with experimental data for three cell lines in response to irradiation with monoenergetic ions.

The relative biological effectiveness (RBE) in particle therapy is currently estimated using biophysical models. We compared experimental measurements to the α curves as function of linear energy transfer computed by the Local Effect Model (LEM I-IV), the Microdosimetric Kinetic Model (MKM) and the NanOx model for HSG, V79 and CHO-K1 cells in response to monoenergetic irradiations. Although the LEM IV and the MKM predictions accurately reproduced the trend observed in the data, NanOx yielded a better agreement than the other models for more irradiation configurations. Its estimator was indeed the lowest for three over seven considered cases.