Bragg Peak Region Research Articles

Liquid water radiolysis induced by secondary electrons generated from MeV-energy carbon ions.

Fast ion beams induce damage to deoxyribonucleic acid (DNA) by chemical products, including secondary electrons, produced from interaction with liquid water in living cells. However, the production process of these chemical products in the Bragg peak region used in particle therapy is not fully understood. To investigate this process, we conducted experiments to evaluate the radiolytic yields produced when a liquid water jet in vacuum is irradiated with MeV-energy carbon beams. We used secondary ion mass spectrometry to measure the products, such as hydronium cations (H3O+) and hydroxyl anions (OH-), produced along with ·OH radicals, which are significant inducers of DNA damage formation. In addition, we simulated the ionization process in liquid water by incident ions and secondary electrons using a Monte Carlo code for radiation transport. Our results showed that secondary electrons, rather than incident ions, are the primary cause of ionization in water. We found that the production yield of H3O+ or OH- was linked to the frequency of ionization by secondary electrons in water, with these electrons having energies between 10.9 and 550eV. These electrons are responsible for ionizing the outer-shell electrons of water molecules. Finally, we present that the elementary processes contribute to advancing radiation biophysics and biochemistry, which study the formation mechanism of DNA damage.

First independent validation of the proton-boron capture therapy concept

Boron has been suggested to enhance the biological effectiveness of proton beams in the Bragg peak region via the p + 11B → 3α nuclear capture reaction. However, a number of groups have observed no such enhancement in vitro or questioned its proposed mechanism recently. To help elucidate this phenomenon, we irradiated DU145 prostate cancer or U-87 MG glioblastoma cells by clinical 190 MeV proton beams in plateau or Bragg peak regions with or without 10B or 11B isotopes added as sodium mercaptododecaborate (BSH). The results demonstrate that 11B but not 10B or other components of the BSH molecule enhance cell killing by proton beams. The enhancement occurs selectively in the Bragg peak region, is present for boron concentrations as low as 40 ppm, and is not due to secondary neutrons. The enhancement is likely initiated by proton-boron capture reactions producing three alpha particles, which are rare events occurring in a few cells only, and their effects are amplified by intercellular communication to a population-level response. The observed up to 2–3-fold reductions in survival levels upon the presence of boron for the studied prostate cancer or glioblastoma cells suggest promising clinical applications for these tumour types.

Proton relative biological effectiveness for the induction of DNA double strand breaks based on Geant4

Uncertainties in the relative biological effectiveness (RBE) of proton remains a major barrier to the biological optimization of proton therapy. A large amount of experimental data suggest that proton RBE is variable. As an evolving Monte Carlo code toolkit, Geant4-DNA is able to simulate the initial DNA damage caused by particle beams through physical and chemical interactions at the nanometer scale over a short period of time. This contributes to evaluating the radiobiological effects induced by ionizing radiation. Based on the Geant4-DNA toolkit, this study constructed a DNA geometric model containing 6.32Gbp, simulated the relationship between radiochemical yields (G-values) and their corresponding chemical constructors, and calculated a detailed calculation of the sources of damage and the complexity of damage in DNA strand breaks. The damage model constructed in this study can simulate the relative biological effectiveness (RBE) in the proton Bragg peak region. The results indicate that: (1) When the electron energy is below 400 keV, the yield of OH· account for 18.1% to 25.3% of the total water radiolysis yields. (2) Under the influence of histone clearance function, the yield of indirect damage account for over 72.93% of the yield of DNA strand breaks (SBs). When linear energy transfer (LET) increased from 29.79 (keV/μm) to 64.29 (keV/μm), the yield of double strand breaks (DSB) increased from 17.27% to 32.65%. (3) By investigating the effect of proton Bragg peak depth on the yield of direct DSB (DSBdirect) and total DSB (DSBtotal), the RBEDSBtot and RBEDSBdir levels of cells show that the RBE value of protons reaches 2.2 in the Bragg peak region.

Monte Carlo-based Investigation of Absorbed-dose Energy Dependence of Thermoluminescent Dosimeters in Therapeutic Proton and Carbon Ion Beams.

The present study is aimed at calculating relative absorbed-dose energy response correction (R) of commonly used thermoluminescent dosimeters (TLDs) such as LiF, Li2B4O7, and Al2O3 as a function of depth in water for protons (50-250 MeV/n) and carbon ion (80-480 MeV/n) beams using Monte Carlo-based FLUKA code. On-axis depth-dose profiles in water are calculated for protons (50-250 MeV/n) and carbon ion (80-480 MeV/n) beams using FLUKA code. For the calculation of R, selective depths are chosen based on the depth-dose profiles. In the simulations, the TLDs of dimensions 1 mm × 1 mm × 1 mm are positioned at the flat, dose gradient, and Bragg peak regions of the depth-dose profile. Absorbed dose to detector was calculated within the TLD material. In the second step, TLD voxels were replaced by water voxel of similar dimension and absorbed dose to water was scored. The study reveals that for both proton and carbon ion beams, the value of R differs from unity significantly at the Bragg peak position and is close to unity at the flat region for the investigated TLDs. The calculated R value is sensitive to depth in water, beam energy, type of ion beam, and type of TLD. For accurate dosimetry of protons and carbon ion beams using TLDs, the response of the TLD should be corrected to account for its absorbed-dose energy dependence.

Internal structural changes in crystals induced by GeV heavy ion beam irradiation of LiF

<sec>When an incident high-energy heavy ion beam enters into solid material, the energy deposition density along the ion flight path can change the temperature and pressure of macroscopic target, and new material defects can be created under the high-pressure and high-density conditions. To accurately control the extreme state in material generated by heavy ion beam, it is necessary to conduct in-depth research on the energy deposition density of ions and ascertain the new potential defects in matter. Reported in this work is the new experiment conducted on the HIRFL-CSR at Lanzhou, with the extracted 264 MeV/u Xe<sup>36+</sup> ion beams irradiating an LiF crystal target. The emission spectrum of the LiF is measured <i>in-situ</i>. Moreover, the crystal color is observed to vary along the ion path, and X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS) are used to observe the potential new phases at different positions of crystal through the target dissociation method.</sec><sec>It is apparent that in No. 3-front a new phase around 52.6° is found in XRD result, which is believed to be LiF<sub>3</sub> (LiF+F<sub>2</sub>) structural phase and appears in the Bragg peak region of Xe ions in LiF. Furthermore, to verify this result, a similar experiment is done by using a 430 MeV/u <sup>84</sup>Kr<sup>26+</sup> ion beam, and the stacked layered LiF target is analyzed after the irradiation. The XPS result shows more complex defects aggregating in the Bragg peak region of Kr ions in LiF at room temperature. In previous study, such complex defects were all created under high temperature conditions. We find that these complex defects can be produced around the Bragg peak region of ions in LiF at room temperature, resulting in a temporally high temperature and high pressure condition. This paper can provide some experimental evidences and references for the target material modification in heavy ion beam driven high-energy density physics research.</sec>

Technical note: Determination of proton linear energy transfer from the integral depth dose.

Proton linear energy transfer (LET) is associated with the relative biological effectiveness of radiation on tissues. Monte Carlo (MC) simulations have been known to be the preferred method to calculate LET. Detectors have also been built to measure LET, but they need to be calibrated with MC simulations. To propose and test a MC-free method for determining LET from the measured integral depth dose (LFI) of the protons of interest. LFI consists of three steps: (1) IDD measurements, (2) extraction of energy spectrum (ES) from the IDD, and (3) LET determination from the extracted ES and the stopping power of each energy. To validate the accuracy of the extraction of ES, we use Gaussian ES to synthesize IDD, extract ES from the synthesized IDD, and then compare the original (ground truth) and extracted ES. LETs calculated from the original and extracted ES are also compared. To obtain the LET of protons of interest, we measure IDDs by a large-area plane-parallel ionization chamber in water. Finally, TOPAS MC is employed to simulate IDDs, ES, and LETs. From the simulated IDD, the extracted ES and LET are compared with the simulations from TOPAS MC. From the synthesized IDDs, the LETs agreed excellently when the peak energies ≥10 and 1.25 MeV with depth resolutions 0.1and 0.01mm, respectively. For energy<1.25 MeV, even higher depth resolution than 0.01mm is required. From the MC simulated IDDs, our track-averaged LET excellently agreed with MC simulation, but not the LETd. Our LETd was smaller than MC simulated LETd in the shallow region but larger in the distal Bragg peak region. LET can be accurately determined from the IDD. This method can be used in the clinic to commission or validate LETs from other measurement methods or a treatment planning system.

Development of a model for evaluating the luminescence intensity of phosphors based on the PHITS track-structure simulation

Radiation-induced phosphors are frequently used as radiation detectors to measure dose distributions of swift ions. However, the luminescence intensity per dose of the phosphor at the Bragg peak regions decreases because of the quenching effects. To precisely measure the dose distribution for various radiation types using phosphor detectors, understanding the mechanism of quenching effects, induced by the electrons at the atomic scale, is crucial. In this study, we developed a new microdosimetric model for evaluating the luminescence intensity of phosphors based on the track-structure (TS) modes applicable to arbitrary materials implemented in the Particle and Heavy Ion Transport code System (PHITS). Herein, the two dominant factors for determining the luminescence intensity, such as (1) the energy required to generate an electron-hole pair and (2) their transfer efficiency to the luminescence center, are estimated from the TS mode in PHITS by calculating the number of stopped electrons and their spatial distributions. Using the developed model, we calculated the energy required to generate an electron-hole pair in various phosphors, which revealed a complex dependency on the bandgap energy, the composition, and the density of the material. Furthermore, we simulated the quenching effects of the BaFBr detector by calculating its transfer efficiencies for swift-ion irradiation and compared the simulation results with the corresponding experimental data. The comparison suggested that the density of luminescence centers is an essential parameter of the phosphors to reproduce the experimental quenching effects. The developed model is based on the first-principles calculation without any empirical correction; therefore, it is expected to contribute widely to developing phosphor detectors.

Quality Control for Ocean Current Measurement Using High-Frequency Direction-Finding Radar

High-frequency radars (HFRs) are important for remote sensing of the marine environment due to their ability to provide real-time, wide-coverage, and high-resolution measurements of the ocean surface current, wave height, and wind speed. However, due to the intricate multidimensional processing demands (e.g., time, Doppler, and space) for internal data and effective suppression of external noise, conducting quality control (QC) on radar-measured data is of great importance. In this paper, we first present a comprehensive quality evaluation model for both radial current and synthesized vector current obtained by direction-finding (DF) HFRs. In the proposed model, the quality factor (QF) is calculated for each current cell to evaluate its reliability. The QF for the radial current depends on the signal-to-noise ratio (SNR) and DF factor of the first-order Bragg peak region in the range–Doppler (RD) spectrum, and the QF for the synthesized vector current can be calculated using an error propagation model based on geometric dilution of precision (GDOP). A QC method is then proposed for processing HFR-derived surface current data via the following steps: (1) signal preprocessing is performed to minimize the effect of unwanted external signals such as radio frequency interference and ionospheric clutter; (2) radial currents with low QFs and outliers are removed; (3) the vector currents with low QFs are also removed before spatial smoothing and interpolation. The proposed QC method is validated using a one-month-long dataset collected by the Ocean State Monitoring and Analyzing Radar, model S (OSMAR-S). The improvement in the current quality is proven to be significant. Using the buoy data as ground truth, after applying QC, the correlation coefficients (CCs) of the radial current, synthesized current speed, and synthesized current direction are increased by 4.33~102.91%, 1.04~90.74%, and 1.20~62.67%, respectively, and the root mean square errors (RMSEs) are decreased by 2.51~49.65%, 7.86~27.22%, and 1.68~28.99%, respectively. The proposed QC method has now been incorporated into the operational software (RemoteSiteConsole v1.0.0.65) of OSMAR-S.

A Molecular Approach to Characterize the Effects of Fluence, Fluence Rate and LET on Radiation Damage

Effects of fluence, fluence rate and LET on radiation damage are not resolved using traditional methods of measuring energy deposited by ionization events. The deficiency led to the use of empirical RBE factors in the clinical applications of particle therapy. The use of ionization dosimetry is similarly challenged when applied to development of radiation treatment at ultrahigh (FLASH) dose rate. This study reports a molecular method using plasmid DNA as a more comprehensive model for radiation dosimetry than ionization measurements. Aqueous solutions of purified supercoiled plasmid DNA, pUC19 (2686 bp), were prepared at different scavenging conditions and injected into 5x5x1 mm3 wells as detector elements. Irradiated samples were analyzed using base excision repair enzymes (Nth and Fpg) and gel electrophoresis to measure yields for DNA single and double strand breaks (SSB and DSB), and clustered lesions. The low LET characteristics of conventional radiation treatment was modeled using orthovoltage 150 kVp x-rays to deliver 2-110 Gy at 90 and 0.5 Gy/s. Higher LET irradiations in the range of 2 - 14 keV/μm were facilitated by measurements in the pristine Bragg peak region using synchrotron-produced 142.2 MeV protons to deliver dose at 2 - 160 Gy at 600 and 1 Gy/s. The DNA wells were inserted into a solid water equivalent phantom for proton irradiation. Only 4 wells could be positioned in the short Bragg peak region in water (∼ 2 cm). To alleviate the uncertainties due to rapidly varying dose and LET distributions, we innovated the use of a 3% water density (i.e., Styrofoam) medium to extend the Bragg peak region from 2 cm to 20 cm, enabling the placement of 20 well containers. Quantity and quality of molecular damage in the plasmid DNA model varies with fluence, fluence rate and LET of radiation. At high fluence (> 30 Gy) of low-LET radiations, the yields of DNA SSB and non-DSB clustered lesions depend on the fluence rate. These yields decrease by two times between ultrahigh and conventional dose rate irradiation. At a given fluence and fluence rate, the yields for the formation of DNA DSB and non-DSB clustered lesions increase linearly with LET. The low-density phantom allows significant (∼ 10 folds) increase in the number of sampling points and more accurate sample positioning at specific LET compared to water-equivalent phantom. Monte-Carlo track structure simulation of yields for different DNA lesions is being developed to model the molecular damage. In parallel, approaches to improve the sensitivity of the measurements to dose are being investigated. Our results suggest that a molecular-based approach can be used to differentiate the effects of fluence, fluence rate, and LET on radiation damage. The approach demonstrates the potential to improve on the modeling of radiation effects in biological systems than using measured ionization energy. Correlation of the molecular changes to biological outcome for in vitro and in vivo systems are under investigation.

Modeling ultra-high dose rate electron and proton FLASH effect with the physicochemical approach

Objective. A physicochemical model built on the radiochemical kinetic theory was recently proposed in (Labarbe et al ) to explain the FLASH effect. We performed extensive simulations to scrutinize its applicability for oxygen depletion studies and FLASH-related experiments involving both proton and electron beams. Approach. Using the dose and beam delivery parameters for each FLASH experiment, we numerically solved the radiochemical rate equations comprised of a set of coupled nonlinear ordinary differential equations to obtain the area under the curve (AUC) of radical concentrations. Main results. The modeled differences in AUC induced by ultra-high dose rates appeared to correlate well with the FLASH effect. (i) For the whole brain irradiation of mice performed in (Montay-Gruel et al ), the threshold dose rate values for memory preservation coincided with those at which AUC started to decrease much less rapidly. (ii) For the proton pencil beam scanning FLASH of (Cunningham et al ), we found linear correlations between radicals’ AUC and the biological endpoints: TGF-β1, leg contracture and plasma level of cytokine IL-6. (iii) Compatible with the findings of the proton FLASH experiment in (Kim et al ), we found that radicals’ AUC at the entrance and mid-Spread-Out Bragg peak regions were highly similar. In addition, our model also predicted ratios of oxygen depletion G-values between normal and UHDR irradiation similar to those observed in (Cao et al ) and (El Khatib et al ). Significance. Collectively, our results suggest that the normal tissue sparing conferred by UHDR irradiation may be due to the lower degree of exposure to peroxyl and superoxide radicals. We also found that the differential effect of dose rate on the radicals’ AUC was less pronounced at lower initial oxygen levels, a trait that appears to align with the FLASH differential effect on normal versus tumor tissues.

Characterization of a Gd-based color CMOS detector for proton dosimetry

A color scintillation detector for relative dose distribution measurement was developed at PSI. The system consists of a gadolinium-based scintillating screen mounted perpendicularly to the beam axis and coupled with a color CMOS camera in a light-tight box. The camera is equipped with an iris (aperture) controller to remotely adjust the number of photons reaching the image sensor. To improve the measurement accuracy and decrease the image artifacts, we investigated different methods for spatial calibration and optimized the internal light reflection by adjusting the detector structure. The response dependence on camera working distance, iris setting, and color channels was assessed. The depth-dose curves of the gadolinium-based scintillator in three RGB channels were compared with reference curves measured by an Advanced Markus plane-parallel ion chamber. The quenching effect of the ▪ screen measured with this system amounts to about 10% in the Bragg peak region of a 150 MeV proton beams. The shape of the emission spectrum was observed to be independent of the ionization density. Preliminary investigations showed that it is possible to correlate the ratio of the detector response in different color channels with the proton ionization density.

Calculating dose‐averaged linear energy transfer in an analytical treatment planning system for carbon‐ion radiotherapy

Compelling evidence shows the association between the relative biological effectiveness (RBE) of carbon-ion radiotherapy (CIRT) and the dose averaged linear energy transfer (LETd). However, the ability to calculate the LETd in commercially available treatment planning systems (TPS) is lacking. This study aims to develop a method of calculating the LETd of CIRT plans that could be robustly carried out in RayStation (V10B, Raysearch, Sweden). The calculation used the fragment spectra in RayStation for the CIRT treatment planning. The dose-weighted averaging procedure was supported by the microdosimetric kinetic model (MKM). The MKM-based pencil beam dose engine (PBA, v4.2) for calculating RBE-weighted doses was reformulated to become a LET-weighted calculating engine. A separate module was then configured to inversely calculate the LETd from the absorbed dose of a plan and the associated fragment spectra. In this study, the ion and energy-specific LET table in the LETd module was further matched with the values decoded from the baseline data of the Syngo TPS (V13C, Siemens, Germany). The LETd distributions of several monoenergetic and modulated beams were calculated and validated against the values derived from the Syngo TPS and the published data. The differences in LETds of the monoenergetic beams between the new method and the traditional method were within 3% in the entrance and Bragg-peak regions. However, a larger difference was observed in the distal region. The results of the modulated beams were in good agreement with the works from the published literature. The method presented herein reformulates the MKM dose engine in the RayStation TPS to inversely calculate LETds. The robustness and accuracy were demonstrated.

A phenomenological model of proton FLASH oxygen depletion effects depending on tissue vasculature and oxygen supply.

Radiation-induced oxygen depletion in tissue is assumed as a contributor to the FLASH sparing effects. In this study, we simulated the heterogeneous oxygen depletion in the tissue surrounding the vessels and calculated the proton FLASH effective-dose-modifying factor (FEDMF), which could be used for biology-based treatment planning. The dose and dose-weighted linear energy transfer (LET) of a small animal proton irradiator was simulated with Monte Carlo simulation. We deployed a parabolic partial differential equation to account for the generalized radiation oxygen depletion, tissue oxygen diffusion, and metabolic processes to investigate oxygen distribution in 1D, 2D, and 3D solution space. Dose and dose rates, particle LET, vasculature spacing, and blood oxygen supplies were considered. Using a similar framework for the hypoxic reduction factor (HRF) developed previously, the FEDMF was derived as the ratio of the cumulative normoxic-equivalent dose (CNED) between CONV and UHDR deliveries. Dynamic equilibrium between oxygen diffusion and tissue metabolism can result in tissue hypoxia. The hypoxic region displayed enhanced radio-resistance and resulted in lower CNED under UHDR deliveries. In 1D solution, comparing 15 Gy proton dose delivered at CONV 0.5 and UHDR 125 Gy/s, 61.5% of the tissue exhibited ≥20% FEDMF at 175 μm vasculature spacing and 18.9 μM boundary condition. This percentage reduced to 34.5% and 0% for 8 and 2 Gy deliveries, respectively. Similar trends were observed in the 3D solution space. The FLASH versus CONV differential effect remained at larger vasculature spacings. A higher FLASH dose rate showed an increased region with ≥20% FEDMF. A higher LET near the proton Bragg peak region did not appear to alter the FLASH effect. We developed 1D, 2D, and 3D oxygen depletion simulation process to obtain the dynamic HRF and derive the proton FEDMF related to the dose delivery parameters and the local tissue vasculature information. The phenomenological model can be used to simulate or predict FLASH effects based on tissue vasculature and oxygen concentration data obtained from other experiments.

Distribution of radial dose in water at nanometer scale for ions of the same linear energy transfer: benefits of the concept of annular dose

Annular-dose AD is a new conception , based on the radial dose distribution, RDD, introduced by the present work. AD is the integrated dose for many shells around the ions and it is defined as the dose deposited in the shell volume perpendicular to the ion path of width length equal and thickness equal unity (1 nm). Thus, it integrates and maps the deposited dose due to ion in any medium at nanometer scale better than the ordinary radial dose. Katz and Awad radial dose formulae plus Butts-Katz and Tabata electron range-energy relations are composing three different approaches. These approaches were used for studying the AD for 30 ions forming 4 different equal LET groups and have energy at Bragg peak region from 1.5 to 24 MeV n−1. The annular dose, AD as a function of the shell width for the ions under investigation showed that dose distributions around the ions of same LET are not the same and a clear peak at certain shell width called the ion’s maximum annular dose width, r MADW was determined for the first time. The r MADW is the position where the maximum reachable dose is delivered by secondary electrons around the ion. The ion’s r MADW showed an increasing function with Z*β within the same LET group. Interestingly, it was found that r MADW behaves as an increasing monotonic function of the relative ion velocity, β using the three approaches considered in this work.

Depth dose measurements in water for 11C and 10C beams with therapy relevant energies

Owing to the favorable depth-dose distribution and the radiobiological properties of heavy ion radiation, ion beam therapy shows an improved success/toxicity ratio compared to conventional radiotherapy. The sharp dose gradients and very high doses in the Bragg peak region, which represent the larger physical advantage of ion beam therapy, make it also extremely sensitive to range uncertainties. The use of β+-radioactive ion beams would be ideal for simultaneous treatment and accurate online range monitoring through PET imaging. Since all the unfragmented primary ions are potentially contributing to the PET signal, these beams offer an improved image quality while preserving the physical and radiobiological advantages of the stable counterparts. The challenging production of radioactive ion beams and the difficulties in reaching high intensities, have discouraged their clinical application. In this context, the project Biomedical Applications of Radioactive ion Beams (BARB) started at GSI (Helmholtzzentrum für Schwerionenforschung GmbH) with the main goal to assess the technical feasibility and investigate possible advantages of radioactive ion beams on the pre-clinical level. During the first experimental campaign 11C and 10C beams were produced and isotopically separated with the FRagment Separator (FRS) at GSI. The β+-radioactive ion beams were produced with a beam purity of 99% for all the beam investigated (except one case where it was 94%) and intensities potentially sufficient to treat a small animal tumors within few minutes of irradiation time, ∼106 particle per spill for the 10C and ∼107 particle per spill for the 11C beam, respectively. The impact of different ion optical parameters on the depth dose distribution was studied with a precision water column system. In this work, the measured depth dose distributions are presented together with results from Monte Carlo simulations using the FLUKA software.

Microdosimetry Study of Proton Quality Factor Using Analytic Model Calculations

The quality factor (Q) is formally linked to the stochastic (e.g., carcinogenic) risk of diverse ionizing radiations at low doses and/or low dose rates. Q can be a function of the non-stochastic physical quantity Linear Energy Transfer (LET) or the microdosimetric parameter lineal energy (y). These two physical quantities can be calculated either by Monte Carlo (MC) track-structure simulations or by analytic models. In this work, various generalized analytical models were utilized and combined to determine the proton lineal energy spectra in liquid water spheres of various sizes (i.e., 10–3000 nm diameter) over the proton energy range of 1–250 MeV. The calculated spectra were subsequently used within the Theory of Dual Radiation Action (TDRA) and the ICRU Report 40 microdosimetric methodologies to determine the variation of Q¯ with proton energy. The results revealed that the LET-based Q values underestimated the microdosimetric-based Q¯ values for protons with energy below ~100 MeV. At energies relevant to the Bragg peak region (&lt;20–30 MeV), the differences were larger than 20–50%, while reaching 200–500% at ~5 MeV. It was further shown that the microdosimetric-based Q¯ values for protons below ~100 MeV were sensitive to the sphere size. Finally, condensed-phase effects had a very small (&lt;5%) influence on the calculated microdosimetric-based Q¯ over the proton energy range considered here.

A primary proton integral depth dose calculation model corrected with straight scattering track approximation

PurposeProton therapy requires a highly accurate dose calculation model. The Bortfeld analytical formula (BAF) is a classical depth-dose calculation model that exhibits a dose deviation compared to the Monte Carlo simulation. This study focuses on the lateral scattering effect on depth dose deviation between model calculations and Monte Carlo simulations and provides a modified model to correct. MethodsOnly the dose contributed by the primary particles was studied in this work. The Bethe stopping power formula was applied to reduce the deviation in the flat region. The proton track lateral scattering is considered to reduce the deviation in the Bragg peak region. Lateral scattering tracks were approximated as straight lines and assumed to have a Gaussian slope distribution. The tracks were projected to the central axis to correct the depth-dose curve. The calculated dose was compared with a Geant4 simulation. Four proton beams with energies of 50 MeV, 100 MeV, 150 MeV, and 200 MeV were calculated and verified. The dose deviation between the model calculation and Monte Carlo simulation was quantified under a dose and depth tolerance of 2%/1 mm with gamma analysis. ResultsThe straight scattering track approximation significantly reduced the primary dose deviation between the model calculation and the Geant4 simulation. The gamma values of all verified cases are below 1, which means that the deviation is acceptable under a given tolerance of 2%/1 mm. ConclusionsThis study proposes a modification of the primary depth-dose calculation model involving scattering-track correction. Good dose agreement between the calculation and Geant4 simulation was obtained. The modified model shows good accuracy in primary depth dose calculation and will be helpful for clinical application together with further secondary dose models, which are still under investigation.

Multi-centric analysis of linear energy transfer distribution from clinical proton beam based on TOPAS

Linear energy transfer (LET), a key parameter of relative biological effectiveness (RBE) in proton therapy, is not easy to measure or simulate in a standardized protocol. A multi-centric analysis of dose-averaged LET (LETd) and track-averaged LET (LETt) including individual particle contributions, scoring slab thickness, inhomogeneous medium and clinical beam configurations are investigated using the Monte Carlo code TOPAS. Primary and secondary protons are scored separately within the simulation. It is found that the primary protons are the major contribution to LET at the dose plateau and Bragg Peak (BP) regions, whilst the secondary protons have complete contribution to the tail-LET beyond the BP. The calculated LETt is always lower than LETd, nearly a factor of two lower in the region distal to the BP. Varying the scoring slab thickness shows a negligible influence on LETt, whereas, there is up to 26% discrepancy in LETd at 5-cm depth with thicknesses varying from 0.1 mm to 2 mm for 153.3 MeV proton beam. Moreover, smaller scoring thickness of 0.1 mm results in large fluctuations for tail LETd. LETd distributions with 3-cm thick bone- and lung-slab at the entrance of water phantom against primary and secondary protons' contribution are derived. A small trough appears at the position of inserted inhomogeneous material and large spikes which could account for the changes of cross section in nuclear interactions by secondary protons display on the tail of LETd curve. Regarding the modulated beams, substantial-high LET values are obtained at both-sides along the beam path which should gain more attention when calculating LET in clinical applications. In conclusion, the selection of Monte Carlo simulation schemes indeed affects the calculated LET values, more procedures should be considered when building bridges between LET and radiological effectiveness.

Neuroprotective Effects of Ultra-High Dose Rate FLASH Bragg Peak Proton Irradiation

To investigate brain tissue response to ultra-high dose rate (uHDR, FLASH) and standard dose rate (SDR) proton irradiations in the Bragg peak region. Active scanning uHDR delivery was established for proton beams for investigation of dose rate effects between clinical SDR and uHDR at ∼10 Gy in the Bragg peak region (dose-averaged linear energy transfer [LETD] ranging from 4.5 to 10.2 keV µm-1 ). Radiation- induced injury of neuronal tissue was assessed by studying the DNA double strand break repair kinetics surrogated by nuclear γH2AX staining (radiation induced foci [RIF]), microvascular density and structural integrity (MVD, CD31+ endothelium), and inflammatory microenvironmental response (CD68+ microglia/macrophages and high mobility group box protein 1[HMGB]) in healthy C57BL/6 mouse brains. Averaged dose rates achieved were 0.17 Gy/s (SDR) and 120 Gy/s (uHDR). The fraction of RIF-positive cells increased after SDR ∼10-fold, whereas a significantly lower fraction of RIF-positive cells was found after uHDR versus SDR (∼2 fold, P < .0001). Moreover, uHDR substantially preserved the microvascular architecture and reduced microglia/macrophage regulated associated inflammation as compared with SDR. The feasibility of uHDR raster scanning proton irradiation is demonstrated to elicit FLASH sparing neuroprotective effects compared to SDR in a preclinical in vivo model.

Analysis of I-V characteristics of Si diodes irradiated with short-range ions

Radiation degradation of Si ion detectors becomes critical for the experiments at new facilities giving the beam intensity increase up to 105 times. The study is focused on the impact of heavily damaged Bragg peak region (BPR) at the ion range end on the bulk current of Si sensors irradiated with 53.4 MeV 40Ar ions in the fluence range (1-4)·10^9 ion/cm2. It is shown that taking into account only the generation current component is insufficient to explain the experimental I-V curves. Simulating I-V characteristics and the electric field profiles demonstrated arising of a built-in junction in the BPR, which controls hole diffusion at voltages below full depletion voltage. Contribution of this component to the total diode current enabled the agreement between experimental and simulated I-V curves. Keywords: silicon sensors, radiation degradation, current-voltage characteristic, carrier diffusion.