The Experts below are selected from a list of 1992 Experts worldwide ranked by ideXlab platform
F.a. Cucinotta - One of the best experts on this subject based on the ideXlab platform.
-
Comparison of Model Calculations of Biological Damage from Exposure to Heavy Ions with Measurements
2014Co-Authors: Myung-hee Y. Kim, Megumi Hada, F.a. CucinottaAbstract:NASA Johnson Space Center, Houston, TX 77058, USA 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 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
-
Distribution of Micronuclei in Human Fibroblasts across the Bragg Curve of Light and Heavy Ions
2007Co-Authors: Megumi Hada, A. Rusek, S. Lacy, Daila S. Gridley, F.a. CucinottaAbstract: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.
-
In vitro H2AX phosphorylation and micronuclei induction in human fibroblasts across the Bragg Curve of a 577 MeV/nucleon Fe incident beam
Radiation Measurements, 2006Co-Authors: N. Desai, M. Durante, A. Rusek, Zi-wei Lin, John Sodolak, Brad Gersey, F.a. CucinottaAbstract:Abstract The space environment consists of a varying field of radiation particles including high-energy ions, with spacecraft shielding material providing the only major protection to astronauts from harmful exposure. Unlike low-linear energy transfer (LET) γ 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, and the “biological Bragg Curve” is dependent on the energy and the type of the primary particle, and may vary for different biological endpoints. Here we used a unique irradiation geometry to measure the biological response across the Bragg Curve in human fibroblasts exposed to 577 MeV/nucleon incident Fe ions in vitro. Polyethylene shielding was used to achieve a Bragg Curve distribution with the beam geometry parallel to a monolayer of fibroblast cells. Qualitative analyses of γ -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-LET particle traversal of cells beyond the Bragg peak in agreement with one-dimensional transport approximations. A quantitative biological response Curve generated for micronuclei induction across the Bragg Curve did not reveal an increased yield of micronuclei at the location of the Bragg peak. However, the percentage of mononucleated cells, which indicates inhibition in cell progression, increased at the location of the peak. These results confirm the argument that severely damaged cells at the Bragg peak, as observed by increased γ -H2AX formation, are likely to go through reproduction death. Depending on the LET value of the primary particles, the yield of the biological endpoint of interest (micronuclei formation in the present study) may or may not increase at the location of the Bragg peak.
-
in vitro h2ax phosphorylation and micronuclei induction in human fibroblasts across the Bragg Curve of a 577 mev nucleon fe incident beam
Radiation Measurements, 2006Co-Authors: N. Desai, M. Durante, A. Rusek, Zi-wei Lin, John Sodolak, Brad Gersey, F.a. CucinottaAbstract:Abstract The space environment consists of a varying field of radiation particles including high-energy ions, with spacecraft shielding material providing the only major protection to astronauts from harmful exposure. Unlike low-linear energy transfer (LET) γ 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, and the “biological Bragg Curve” is dependent on the energy and the type of the primary particle, and may vary for different biological endpoints. Here we used a unique irradiation geometry to measure the biological response across the Bragg Curve in human fibroblasts exposed to 577 MeV/nucleon incident Fe ions in vitro. Polyethylene shielding was used to achieve a Bragg Curve distribution with the beam geometry parallel to a monolayer of fibroblast cells. Qualitative analyses of γ -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-LET particle traversal of cells beyond the Bragg peak in agreement with one-dimensional transport approximations. A quantitative biological response Curve generated for micronuclei induction across the Bragg Curve did not reveal an increased yield of micronuclei at the location of the Bragg peak. However, the percentage of mononucleated cells, which indicates inhibition in cell progression, increased at the location of the peak. These results confirm the argument that severely damaged cells at the Bragg peak, as observed by increased γ -H2AX formation, are likely to go through reproduction death. Depending on the LET value of the primary particles, the yield of the biological endpoint of interest (micronuclei formation in the present study) may or may not increase at the location of the Bragg peak.
-
Bragg Curve, Biological Bragg Curve and Biological Issues in Space Radiation Protection with Shielding
2006Co-Authors: Wu Honglu, F.a. Cucinotta, M. Durante, Z. Lin, A. RusekAbstract: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.
Radhe Mohan - One of the best experts on this subject based on the ideXlab platform.
-
A model for relative biological effectiveness of therapeutic proton beams based on a global fit of cell survival data
Scientific Reports, 2017Co-Authors: Ramin Abolfath, Lawrence Bronk, Christopher R. Peeler, Mark Newpower, David Grosshans, Radhe MohanAbstract:We introduce an approach for global fitting of the recently published high-throughput and high accuracy clonogenic cell-survival data for therapeutic scanned proton beams. Our fitting procedure accounts for the correlation between the cell-survival, the absorbed (physical) dose and the proton linear energy transfer (LET). The fitting polynomials and constraints have been constructed upon generalization of the microdosimetric kinetic model (gMKM) adapted to account for the low energy and high lineal-energy spectrum of the beam where the current radiobiological models may underestimate the reported relative biological effectiveness (RBE). The parameters ( α , β ) of the linear-quadratic (LQ) model calculated by the presented method reveal a smooth transition from low to high LETs which is an advantage of the current method over methods previously employed to fit the same clonogenic data. Finally, the presented approach provides insight into underlying microscopic mechanisms which, with future study, may help to elucidate radiobiological responses along the Bragg Curve and resolve discrepancies between experimental data and current RBE models.
-
TH-A-19A-05: Modeling Physics Properties and Biologic Effects Induced by Proton and Helium Ions
Medical Physics, 2014Co-Authors: Reza Taleei, Fada Guan, C Peeler, Uwe Titt, Dragan Mirkovic, David R. Grosshans, Radhe MohanAbstract: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.
Ramin Abolfath - One of the best experts on this subject based on the ideXlab platform.
-
A model for relative biological effectiveness of therapeutic proton beams based on a global fit of cell survival data
Scientific Reports, 2017Co-Authors: Ramin Abolfath, Lawrence Bronk, Christopher R. Peeler, Mark Newpower, David Grosshans, Radhe MohanAbstract:We introduce an approach for global fitting of the recently published high-throughput and high accuracy clonogenic cell-survival data for therapeutic scanned proton beams. Our fitting procedure accounts for the correlation between the cell-survival, the absorbed (physical) dose and the proton linear energy transfer (LET). The fitting polynomials and constraints have been constructed upon generalization of the microdosimetric kinetic model (gMKM) adapted to account for the low energy and high lineal-energy spectrum of the beam where the current radiobiological models may underestimate the reported relative biological effectiveness (RBE). The parameters ( α , β ) of the linear-quadratic (LQ) model calculated by the presented method reveal a smooth transition from low to high LETs which is an advantage of the current method over methods previously employed to fit the same clonogenic data. Finally, the presented approach provides insight into underlying microscopic mechanisms which, with future study, may help to elucidate radiobiological responses along the Bragg Curve and resolve discrepancies between experimental data and current RBE models.
Hajime Kawashima - One of the best experts on this subject based on the ideXlab platform.
-
Contribution to dose in healthy tissue from secondary target fragments in therapeutic proton, He and C beams measured with CR-39 plastic nuclear track detectors
Scientific Reports, 2019Co-Authors: Satoshi Kodaira, Mieko Kurano, Hisashi Kitamura, Hajime KawashimaAbstract:The linear energy transfer (LET) spectrum, absorbed dose and dose equivalent from secondary particles of LET_∞H_2O ≥15 keV/μm deposited within the plateau of the Bragg Curve in primary particle-induced nuclear target fragmentation reactions in tissue during proton and heavy ion radiotherapy were measured using CR-39 plastic nuclear track detectors and analyzed by means of atomic force microscopy. It was found that secondary target fragments contributed 20% to dose equivalent for primary protons (157 MeV), 13% for primary helium ions (145 MeV/n) and 4% for primary carbon ions (383 MeV/n), respectively. Little research has been done on the contribution from these particles to primary given dose. The smaller contribution measured for energetic carbon ion beams compared to proton beams can be considered an advantage of carbon ion radiotherapy over proton radiotherapy.
A. Rusek - One of the best experts on this subject based on the ideXlab platform.
-
DNA damage intensity in fibroblasts in a 3-dimensional collagen matrix correlates with the Bragg Curve energy distribution of a high LET particle
International Journal of Radiation Biology, 2010Co-Authors: Andres I. Roig, A. Rusek, Suzie K. Hight, John D. Minna, Jerry W. Shay, Michael D. StoryAbstract:Purpose: The DNA double-strand break (DSB) damage response induced by high energy charged particles on lung fibroblast cells embedded in a 3-dimensional (3-D) collagen tissue equivalents was investigated using antibodies to the DNA damage response proteins gamma-histone 2AX (γ-H2AX) and phosphorylated DNA-PKcs (p-DNA-PKcs).Materials and methods: 3-D tissue equivalents were irradiated in positions across the linear distribution of the Bragg Curve profiles of 307.7 MeV/nucleon, 556.9 MeV/nucleon, or 967.0 MeV/nucleon 56Fe ions at a dose of 0.30 Gy.Results: Patterns of discrete DNA damage streaks across nuclei or saturated nuclear damage were observed, with saturated nuclear damage being more predominant as samples were positioned closer to the physical Bragg peak. Quantification of the DNA damage signal intensities at each distance for each of the examined energies revealed a biological Bragg Curve profile with a pattern of DNA damage intensity similar to the physical Bragg Curve for the particular energy. ...
-
Distribution of Micronuclei in Human Fibroblasts across the Bragg Curve of Light and Heavy Ions
2007Co-Authors: Megumi Hada, A. Rusek, S. Lacy, Daila S. Gridley, F.a. CucinottaAbstract: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.
-
In vitro H2AX phosphorylation and micronuclei induction in human fibroblasts across the Bragg Curve of a 577 MeV/nucleon Fe incident beam
Radiation Measurements, 2006Co-Authors: N. Desai, M. Durante, A. Rusek, Zi-wei Lin, John Sodolak, Brad Gersey, F.a. CucinottaAbstract:Abstract The space environment consists of a varying field of radiation particles including high-energy ions, with spacecraft shielding material providing the only major protection to astronauts from harmful exposure. Unlike low-linear energy transfer (LET) γ 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, and the “biological Bragg Curve” is dependent on the energy and the type of the primary particle, and may vary for different biological endpoints. Here we used a unique irradiation geometry to measure the biological response across the Bragg Curve in human fibroblasts exposed to 577 MeV/nucleon incident Fe ions in vitro. Polyethylene shielding was used to achieve a Bragg Curve distribution with the beam geometry parallel to a monolayer of fibroblast cells. Qualitative analyses of γ -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-LET particle traversal of cells beyond the Bragg peak in agreement with one-dimensional transport approximations. A quantitative biological response Curve generated for micronuclei induction across the Bragg Curve did not reveal an increased yield of micronuclei at the location of the Bragg peak. However, the percentage of mononucleated cells, which indicates inhibition in cell progression, increased at the location of the peak. These results confirm the argument that severely damaged cells at the Bragg peak, as observed by increased γ -H2AX formation, are likely to go through reproduction death. Depending on the LET value of the primary particles, the yield of the biological endpoint of interest (micronuclei formation in the present study) may or may not increase at the location of the Bragg peak.
-
in vitro h2ax phosphorylation and micronuclei induction in human fibroblasts across the Bragg Curve of a 577 mev nucleon fe incident beam
Radiation Measurements, 2006Co-Authors: N. Desai, M. Durante, A. Rusek, Zi-wei Lin, John Sodolak, Brad Gersey, F.a. CucinottaAbstract:Abstract The space environment consists of a varying field of radiation particles including high-energy ions, with spacecraft shielding material providing the only major protection to astronauts from harmful exposure. Unlike low-linear energy transfer (LET) γ 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, and the “biological Bragg Curve” is dependent on the energy and the type of the primary particle, and may vary for different biological endpoints. Here we used a unique irradiation geometry to measure the biological response across the Bragg Curve in human fibroblasts exposed to 577 MeV/nucleon incident Fe ions in vitro. Polyethylene shielding was used to achieve a Bragg Curve distribution with the beam geometry parallel to a monolayer of fibroblast cells. Qualitative analyses of γ -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-LET particle traversal of cells beyond the Bragg peak in agreement with one-dimensional transport approximations. A quantitative biological response Curve generated for micronuclei induction across the Bragg Curve did not reveal an increased yield of micronuclei at the location of the Bragg peak. However, the percentage of mononucleated cells, which indicates inhibition in cell progression, increased at the location of the peak. These results confirm the argument that severely damaged cells at the Bragg peak, as observed by increased γ -H2AX formation, are likely to go through reproduction death. Depending on the LET value of the primary particles, the yield of the biological endpoint of interest (micronuclei formation in the present study) may or may not increase at the location of the Bragg peak.
-
Bragg Curve, Biological Bragg Curve and Biological Issues in Space Radiation Protection with Shielding
2006Co-Authors: Wu Honglu, F.a. Cucinotta, M. Durante, Z. Lin, A. RusekAbstract: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.