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At least 19 records
All sourcesNASA NTRSDOE OSTI
NASA NTRS2006

Bragg Curve, Biological Bragg Curve and Biological Issues in Space Radiation Protection with Shielding

The space environment consists of a varying field of radiation particles including high-energy ions, with spacecraft shielding material providing the major protection to astronauts from harmful exposure. Unlike low-LET gamma or X-rays, the presence of shielding does not always reduce the radiation risks for energetic charged particle exposure. Since the dose delivered by the charged particle increases sharply as the particle approaches the end of its range, a position known as the Bragg peak, the Bragg curve does not necessarily represent the biological damage along the particle traversal since biological effects are influenced by the track structure of both primary and secondary particles. Therefore, the biological Bragg curve is dependent on the energy and the type of the primary particle, and may vary for different biological endpoints. To achieve a Bragg curve distribution, we exposed cells to energetic heavy ions with the beam geometry parallel to a monolayer of fibroblasts. Qualitative analyses of gamma-H2AX fluorescence, a known marker of DSBs, indicated increased clustering of DNA damage before the Bragg peak, enhanced homogenous distribution at the peak, and provided visual evidence of high linear energy transfer (LET) particle traversal of cells beyond the Bragg peak. A quantitative biological response curve generated for micronuclei (MN) induction across the Bragg curve did not reveal an increased yield of MN at the location of the Bragg peak. However, the ratio of mono-to bi-nucleated cells, which indicates inhibition in cell progression, increased at the Bragg peak location. These results, along with other biological concerns, show that space radiation protection with shielding can be a complicated issue.

Honglu, Wu↗
NASA NTRS2005

In Vitro Experimental Model to Investigate the Biological Effects across the Bragg Curve of High-LET Radiation

The space environment consists of a varying field of radiation particles including high energy ions, with a spacecrafts shielding material providing the only major protection to astronauts from harmful exposure. Unlike lowLET gamma or Xrays, the presence of shielding does not always reduce the radiation risks for energetic charged particle exposure since the dose delivered by the charged particle increases sharply as the particle approaches the end of its range, a position known as the Bragg peak and the correlating spatial dose distribution identified as the Bragg curve. The Bragg curve does not necessarily represent the biological damage along the particle traversal since biological effects are influenced by the track structure of both primary and secondary particles. Therefore, the biological Bragg curve is dependent of the energy and the type of the primary particle, and may vary for different biological endpoints. Here we describe a unique irradiation geometry and experimental system to measure the biological response across the Bragg curve in one consistent biological sample. Polyethylene shielding was used to achieve a Bragg curve distribution with the beam geometry parallel to a monolayer of fibroblast cells. We present data that highlights the differential formation of DNA double strand breaks (DSBs) and chromosomal deletions across the Bragg curve in human fibroblasts irradiated with 600 MeV/nucleon iron ion beams. Qualitative analyses of gammaH2AX fluorescence, a known marker of DSBs, indicated potentially increased clustering of DNA damage before the Bragg peak, enhanced homogenous distribution at the peak, and provided visual evidence of high linear energy transfer (LET) particle traversal of cells beyond the Bragg peak in agreement with one-dimensional transport approximations. A biological response curve generated for micronuclei induction across the Bragg curve for 600 MeV/n Fe ions did not reveal an increase in the yield of micronuclei at the Bragg peak location. Assessment of such biological parameters employing the described in vitro experimental system may provide improved platforms to measure a number of biological consequences of shielding materials across the Bragg curve for high charge and energy (HZE) ions.

Desai, N.↗
NASA NTRS2007

Distribution of Micronuclei in Human Fibroblasts across the Bragg Curve of Light and Heavy Ions

The space environment consists of energetic particles of varying mass and energy, and understanding the :biological Bragg curve" is essential in optimizing shielding effectiveness against space radiation induced biological impacts. The "biological Bragg curve" is dependent on the energy and the type of the primary particle, and may vary for different biological endpoints. Previously, we studied the induction of micronuclei (MN) across the Bragg curve of energetic Fe and Si ions, and observed no increased yield of MN at the location of the Bragg peak. However, the ratio of mono- to bi-nucleated cells, which indicates inhibition of cell progression, was found higher at the Bragg peak location in comparison to the plateau region of the Bragg curve. Here, we report the induction of MN in normal human fibroblast cells across the Bragg curve of incident protons generated at Loma Linda University. Similar to Si and Fe ions, the ratio of mono- to bi-nucleated cells showed a clear spike as the protons reached the Bragg peak. Unlike the two heavy ions, however, the MN yield also increased at the Bragg peak location. These results confirm the hypothesis that severely damaged cells at the Bragg peak of heavy, but not light ions are more likely to go through reproductive death and not be evaluated for micronuclei.

Hada, M.↗
NASA NTRS2006

Induction of micronuclei in human fibroblasts across the Bragg curve of energetic heavy ions

The space environment consists of a varying field of radiation particles including high energy ions, with spacecraft shielding material providing the major protection to astronauts from harmful exposure. Unlike low-L or X-rays, the presence of shielding does not always reduce the radiation risks for energetic charged particle exposure. Although the dose delivered by the charged particle increases sharply as the particle approaches the Bragg peak, the Bragg curve does not necessarily represent the biological damage along the particle traversal. The "biological Bragg curve" is dependent on the energy and the type of the primary particle, and may vary for different biological endpoints. To investigate "biological Bragg curves", we analyzed micronuclei (MN) induction along the particle traversal of Si and Fe ions at incident energies of 300 MeV/nucleon and 1 GeV/nucleon. A quantitative biological response curve did not reveal an increased yield of MN at the location of the Bragg peak. However, the ratio of mono-to bi-nucleated cells, which indicates inhibition in cell progression, increased at the Bragg peak location. These results confirm the hypothesis that "over kill" at the Bragg peak will affect the outcome of other biological endpoints.

Hada, Megumi↗
NASA NTRS2006

Induction of Micronuclei in Human Fibroblasts across the Bragg Curve of Energetic Si and Fe Ions

The space environment consists of a varying field of radiation particles including high-energy ions, with spacecraft shielding material providing the major protection to astronauts from harmful exposure. Unlike low-LET gamma or X-rays, the presence of shielding does not always reduce the radiation risks for energetic charged particle exposure. Since the dose delivered by the charged particle increases sharply as the particle approaches the end of its range, a position known as the Bragg peak, the Bragg curve does not necessarily represent the biological damage along the particle traversal since biological effects are influenced by the track structure of both primary and secondary particles. Therefore, the biological Bragg curve is dependent on the energy and the type of the primary particle, and may vary for different biological endpoints. We studied micronuclei (MN) induction across the Bragg curve of Si and Fe ions at incident energies of 300 MeV/nucleon and 1 GeV/nucleon. A quantitative biological response curve did not reveal an increased yield of MN at the location of the Bragg peak. However, the ratio of mono- to bi-nucleated cells, which indicates inhibition in cell progression, increased at the Bragg peak location. These results confirm the hypothesis that severely damaged cells at the Bragg peak are likely to go through reproduction death.

Wu, H.↗
DOE OSTI2020

Bragg curve spectroscopy for improved fission fragment identification

We report on the development of Bragg curve spectroscopy techniques to improve fission fragment identification in the measurement of independent fission product yields. The NIFFTE collaboration’s fissionTPC detector provides ionization energy and particle tracking information from neutroninduced fission targets. A joint effort between PNNL, LLNL, LANL, and the Colorado School of Mines is investigating the ionization profiles deposited by U-235, U-238, and Pu-239 fission products in this detector, with the goal of including additional stopping power information beyond a standard 2E analysis. The aim is to improve the determination of fragment atomic and mass numbers with this information, via methods such as parametric fits and machine learning techniques.

Fulsom, Bryan G.↗
DOE OSTI2016

SU-F-T-144: Analytical Closed Form Approximation for Carbon Ion Bragg Curves in Water

Purpose: Semi-empirical modeling is a powerful computational method in radiation dosimetry. A set of approximations exist for proton ion depth dose distribution (DDD) in water. However, the modeling is more complicated for carbon ions due to fragmentation. This study addresses this by providing and evaluating a new methodology for DDD modeling of carbon ions in water. Methods: The FLUKA, Monte Carlo (MC) general-purpose transport code was used for simulation of carbon DDDs for energies of 100–400 MeV in water as reference data model benchmarking. Based on Thomas Bortfeld’s closed form equation approximating proton Bragg Curves as a basis, we derived the critical constants for a beam of Carbon ions by applying models of radiation transport by Lee et. al. and Geiger to our simulated Carbon curves. We hypothesized that including a new exponential (κ) residual distance parameter to Bortfeld’s fluence reduction relation would improve DDD modeling for carbon ions. We are introducing an additional term to be added to Bortfeld’s equation to describe fragmentation tail. This term accounts for the pre-peak dose from nuclear fragments (NF). In the post peak region, the NF transport will be treated as new beams utilizing the Glauber model for interaction cross sections and the Abrasion- Ablation fragmentation model. Results: The carbon beam specific constants in the developed model were determined to be : p= 1.75, β=0.008 cm-1, γ=0.6, α=0.0007 cm MeV, σmono=0.08, and the new exponential parameter κ=0.55. This produced a close match for the plateau part of the curve (max deviation 6.37%). Conclusion: The derived semi-empirical model provides an accurate approximation of the MC simulated clinical carbon DDDs. This is the first direct semi-empirical simulation for the dosimetry of therapeutic carbon ions. The accurate modeling of the NF tail in the carbon DDD will provide key insight into distal edge dose deposition formation.

07 ISOTOPE AND RADIATION SOURCES↗
DOE OSTI2023

Machine learning methods for fission product identification from Bragg curves

A fission time projection chamber (fission-TPC) was developed to provide precise neutron-induced fission measurements for several major actinides. As fission fragments lose energy in one of the gas volumes of the fission-TPC, energy loss information is captured and may be used to determine fission product yields as the stopping power of an ion is dependent on the atomic number. The work presented here demonstrates the ability to apply machine learning techniques for Bragg curve classification. A set of one million energy loss curves for 24 different fission-fragment elements was generated using common stopping power software. A ResNet architecture optimized for 1D data was used to train, test, and validate a model for light and heavy fission fragments using the simulated data. The resultant classification accuracy for the light and heavy fragments indicates that this could be a viable method for elemental classification of data from the fission-TPC.

73 NUCLEAR PHYSICS AND RADIATION PHYSICS↗
NASA NTRS1981

Laboratory studies on a spherically curved Bragg spectrometer for cosmic X-ray spectroscopy

A spherical array of twenty LiF 200 crystals was built to test the performances of a freestanding, self-focussing spherical crystal cosmic X-ray spectrometer. Measurements presently available show that the size of the image for a point source at infinite distance would be 3 mm (FWHM) along the focalisation axis and 2.1 mm (FWHM) along the dispersion axis. The mosaic spread on individual crystals is less than 0.1 degree. A slightly systematic deviation from the ideal bending (0.1 degree) is observed at the edges of most crystals and this appears to be the major limitation to spectrometer performance.

Cantin, M.↗
DOE OSTI2016

TH-CD-209-12: Spatial Mapping of Scanned Proton Biologic Effect Using the High-Throughput Technique, Continued

Purpose: To investigate the biologic effects of scanned protons by evenly sampling dose-averaged LET (LETd) values. Methods: Our previous high-throughput clonogenic study demonstrated a distinct relationship between RBE and LETd. However, our initial experimental design resulted in over-sampling the low LETd values in the plateau region of the Bragg curve while under-sampling in the region proximal to the Bragg peak as well as the high LETd values in the distal edge of the Bragg curve. To further examine the relationship between RBE and LETd, we refined the experimental design to more evenly sample proton LETd values from 1 to 20 keV/µm by optimizing the thicknesses of the irradiation jig steps. We used the clonogenic survival as the biological endpoint for the H460 lung cancer cell line cultured in 96-well plates (12 columns by 8 rows). In the irradiation, the 8 wells in each column received a uniform dose-LETd pair. The dose-LETd pairs of the 12 different columns were sampled along the Bragg curve of 81.4 MeV scanned protons. Five peak dose levels from 1.5 Gy to 7.5 Gy were delivered with an increment of 1.5 Gy in the preliminary test. Two 96-well plates were irradiated simultaneously to decrease the statistical uncertainties. Results: In the proximal region, for LETd = 5 keV/µm and 8 keV/µm, we did not observe any distinct differential biologic effects between the survival curves. At the Bragg peak (LETd = 9.5 keV/µm) and in the distal edge, irradiation with increasing LET values resulted in decreasing cell survival. Conclusion: The survival curves from the new experimental design support our previous findings that below 10 keV/µm, the LET effect in cell kill is obscured, but above 10 keV/µm, the biologic effects increase with LETd. Funding Support: U19 CA021239-35 and R21 CA187484-01.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗
DOE OSTI2015

Degradation of proton depth dose distributions attributable to microstructures in lung-equivalent material

Purpose: The purpose of the work reported here was to investigate the influence of sub-millimeter size heterogeneities on the degradation of the distal edges of proton beams and to validate Monte Carlo (MC) methods’ ability to correctly predict such degradation. Methods: A custom-designed high-resolution plastic phantom approximating highly heterogeneous, lung-like structures was employed in measurements and in Monte Carlo simulations to evaluate the degradation of proton Bragg curves penetrating heterogeneous media. Results: Significant differences in distal falloff widths and in peak dose values were observed in the measured and the Monte Carlo simulated curves compared to pristine proton Bragg curves. Furthermore, differences between simulations of beams penetrating CT images of the phantom did not agree well with the corresponding experimental differences. The distal falloff widths in CT image-based geometries were underestimated by up to 0.2 cm in water (corresponding to 0.8–1.4 cm in lung tissue), and the peak dose values of pristine proton beams were overestimated by as much as ~35% compared to measured curves or depth-dose curves simulated on the basis of true geometry. The authors demonstrate that these discrepancies were caused by the limited spatial resolution of CT images that served as a basis for dose calculations and lead to underestimation of the impact of the fine structure of tissue heterogeneities. A convolution model was successfully applied to mitigate the underestimation. Conclusions: The results of this study justify further development of models to better represent heterogeneity effects in soft-tissue geometries, such as lung, and to correct systematic underestimation of the degradation of the distal edge of proton doses.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2014

TH-A-19A-05: Modeling Physics Properties and Biologic Effects Induced by Proton and Helium Ions

Purpose: Currently, proton and carbon ions are used for cancer treatment. More recently, other light ions including helium ions have shown interesting physical and biological properties. The purpose of this work is to study the biological and physical properties of helium ions (He-3) in comparison to protons. Methods: Monte Carlo simulations with FLUKA, GEANT4 and MCNPX were used to calculate proton and He-3 dose distributions in water phantoms. The energy spectra of proton and He-3 beams were calculated with high resolution for use in biological models. The repair-misrepairfixation (RMF) model was subsequently used to calculate the RBE. Results: The proton Bragg curve calculations show good agreement between the three general purpose Monte Carlo codes. In contrast, the He-3 Bragg curve calculations show disagreement (for the magnitude of the Bragg peak) between FLUKA and the other two Monte Carlo codes. The differences in the magnitude of the Bragg peak are mainly due to the discrepancy in the secondary fragmentation cross sections used by the codes. The RBE for V79 cell lines is about 0.96 and 0.98 at the entrance of proton and He-3 ions depth dose respectively. The RBE increases to 1.06 and 1.59 at the Bragg peak of proton and He-3 ions. The results demonstrated that LET, microdosimetric parameters (such as dose-mean lineal energy) and RBE are nearly constant along the plateau region of Bragg curve, while all parameters increase within the Bragg peak and at the distal edge for both proton and He-3 ions. Conclusion: The Monte Carlo codes should revise the fragmentation cross sections to more accurately simulate the physical properties of He-3 ions. The increase in RBE for He-3 ions is higher than for proton beams at the Bragg peak.

07 ISOTOPE AND RADIATION SOURCES↗
DOE OSTI2015

SU-E-T-526: Irradiation of Human Cell Lines Using Carbon Ions: Real Time Dosimetry Using Gaf-Chromic Film

Purpose: The purpose of this study is to investigate and quantify several factors affecting biological effects of carbon ions such as cell type, dose, energy and position where the cells are irradiated along the pristine Bragg curve. Methods: Experiments to quantify clonogenic cell survival in three human lung cancer cell lines and a fibroblast cell line were performed at the NASA Space Radiation Laboratory, BNL, Upton, USA. A system of water or media-filled T25 flasks lined up along the beam axis was designed so that the cell-containing surfaces of the flasks were placed at specific depths along the Bragg curve. Gaf-chromic films were placed between the flasks to monitor the dose distribution in the sample as soon as the irradiation was finished. Additional studies were conducted at four selected depths along the Bragg curve to obtain full cell survival dose response curves for the four cell lines. Results: The percent depth dose of the beams was determined using an ionization chamber and showed that the physical Bragg peak is at 22.5 cm water depth. However, the clonogenic cell survival data indicated that the maximum cell killing occurred at 21.5 cm. Gaf-chromic films revealed some inhomogeneity in the dose distribution on the flasks near the peak, presumably due to lack of scattering from the sides of the flasks, which might account for the differences. Depending on the cell line and radiation dose, the maximum cell killing (i.e., the greatest RBE) is at the 21.5 (the peak) or 24 cm (distal fall off) depth. Conclusion: There is a difference in biological effect along the Bragg curve of a carbon ion beam, indicating an elevated RBE at or beyond the end of the range. Gaf-chromic films are proven to be effective in monitoring the 2D irradiation pattern to the flasks. Research supported by NIH/NCI through grant no. R21 CA182259.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Ultra low background time projection alpha particle detector ( Phase II Final Scientific/Technical Report)

When alpha particles are emitted into a gas they create an ionization track of gas ions and electrons. In our commercial UltraLo instrument we apply a voltage between a planar sample and an anode, integrate the anode signal as it collects the electrons, and distinguish between alphas emitted from the sample and elsewhere (anode, sidewalls) by the duration and shape of the resultant signal. The major contributors limiting the instrument’s lower detection limit are cosmic rays that pass through the detector close to the sample and Rn decays that produce charge tracks the originate in the gas and end on the sample. In this work we proposed to identify and reject these events by converting the anode into a multi-pixel array and operating in time projection mode. Cosmic rays would be eliminated by generating charge on many pixels, while charge collection asymmetry would distinguish between sample events (Bragg curve up) and Rn events (Bragg curve down). We therefore proposed to modify an UltraLo by pixilating its anode, developing low noise, low power multiplexed electronics to track each pixel’s signal individually, and develop analysis software to make the required discriminations.

46 INSTRUMENTATION RELATED TO NUCLEAR SCIENCE AND ↗
NASA NTRS2014

Comparison of Model Calculations of Biological Damage from Exposure to Heavy Ions with Measurements

The space environment consists of a varying field of radiation particles including high-energy ions, with spacecraft shielding material providing the major protection to astronauts from harmful exposure. Unlike low-LET gamma or X rays, the presence of shielding does not always reduce the radiation risks for energetic charged-particle exposure. Dose delivered by the charged particle increases sharply at the Bragg peak. However, the Bragg curve does not necessarily represent the biological damage along the particle path since biological effects are influenced by the track structures of both primary and secondary particles. Therefore, the ''biological Bragg curve'' is dependent on the energy and the type of the primary particle and may vary for different biological end points. Measurements of the induction of micronuclei (MN) have made across the Bragg curve in human fibroblasts exposed to energetic silicon and iron ions in vitro at two different energies, 300 MeV/nucleon and 1 GeV/nucleon. Although the data did not reveal an increased yield of MN at the location of the Bragg peak, the increased inhibition of cell progression, which is related to cell death, was found at the Bragg peak location. These results are compared to the calculations of biological damage using a stochastic Monte-Carlo track structure model, Galactic Cosmic Ray Event-based Risk Model (GERM) code (Cucinotta, et al., 2011). The GERM code estimates the basic physical properties along the passage of heavy ions in tissue and shielding materials, by which the experimental set-up can be interpreted. The code can also be used to describe the biophysical events of interest in radiobiology, cancer therapy, and space exploration. The calculation has shown that the severely damaged cells at the Bragg peak are more likely to go through reproductive death, the so called "overkill".

Kim, Myung-Hee Y.↗
NASA NTRS1972

Response of mouse epidermal cells to single doses of heavy-particles

The survival of mouse epidermal cells to heavy-particles has been studied In Vivo by the Withers clone technique. Experiments with accelerated helium, lithium and carbon ions were performed. The survival curve for the helium ion irradiations used a modified Bragg curve method with a maximum tissue penetration of 465 microns, and indicated that the dose needed to reduce the original cell number to 1 surviving cell/square centimeters was 1525 rads with a D sub o of 95 rads. The LET at the basal cell layer was 28.6 keV per micron. Preliminary experiments with lithium and carbon used treatment doses of 1250 rads with LET's at the surface of the skin of 56 and 193 keV per micron respectively. Penetration depths in skin were 350 and 530 microns for the carbon and lithium ions whose Bragg curves were unmodified. Results indicate a maximum RBE for skin of about 2 using the skin cloning technique. An attempt has been made to relate the epidermal cell survival curve to mortality of the whole animal for helium ions.

Leith, J. T.↗
DOE OSTI2014

WE-D-BRF-04: Experimental Investigations On Ion Radiography with Beam Scanning Using a Range Telescope

Purpose: Ion beams exhibit a finite range and an inverted depth-dose profile, the Bragg peak. These favorable properties allow superior tumordose conformality, but introduce sensitivity to range uncertainties. Hence, imaging techniques play an increasingly important role to support the treatment planning and the in-vivo monitoring of the actual ion beam treatment. Methods: This work presents the experimental investigations carried out to address the feasibility of ion transmission imaging at the Heidelberg Ion Therapy center using an active raster scanning beam delivery system and a prototype range telescope set-up based on a stack of 61 parallel-plate ionization chambers (PPIC) interleaved with 3 mm absorber plates of PMMA. Results: An extensive characterization of the set-up in terms of beam parameters and settings of the read-out electronics was performed and results will be presented. A data processing method to increase the range resolution (MIRR) of the PPIC stack was developed. In this approach, the position of the maximum of the Bragg curve is deduced from the ratio of measured signals in adjacent PPIC channels. MIRR evaluation is based on Bragg curves obtained from Monte Carlo simulations and validated with experimental data acquired with the PPIC stack using ion beams. MIRR was applied to the carbon ion radiography of an anthropomorphic Alderson head phantom yielding a resolution of 0.8 mm water equivalent thickness (WET) compared to the nominal value of 3.495 mm WET given by the thickness of the absorber slabs in the PPIC stack. An absolute comparison of the Alderson phantom carbon ion transmitted image with an X-ray digitally reconstructed radiography, both converted into WET, will also be shown. Conclusion: The obtained results are very promising and motivate further developments of the system towards an eventual clinical use.This work is supported by the German Research Foundation and the German Academic Exchange Service. This work is supported by the German Research Foundation (DFG) and the German Academic Exchange Service (DAAD)

07 ISOTOPE AND RADIATION SOURCES↗