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Stephen J Mcmahon - One of the best experts on this subject based on the ideXlab platform.

  • gold nanoparticle induced vasculature damage in radiotherapy comparing protons megavoltage Photons and kilovoltage Photons
    Medical Physics, 2015
    Co-Authors: H Paganetti, Stephen J Mcmahon, J Schuemann
    Abstract:

    Purpose: The purpose of this work is to investigate the radiosensitizing effect of gold nanoparticle (GNP) induced vasculature damage for proton, megavoltage (MV) Photon, and kilovoltage (kV) Photon irradiation. Methods: Monte Carlo simulations were carried out using tool for particle simulation (TOPAS) to obtain the spatial dose distribution in close proximity up to 20 μm from the GNPs. The spatial dose distribution from GNPs was used as an input to calculate the dose deposited to the blood vessels. GNP induced vasculature damage was evaluated for three particle sources (a clinical spread out Bragg peak proton beam, a 6 MV Photon beam, and two kV Photon beams). For each particle source, various depths in tissue, GNP sizes (2, 10, and 20 nm diameter), and vessel diameters (8, 14, and 20 μm) were investigated. Two GNP distributions in lumen were considered, either homogeneously distributed in the vessel or attached to the inner wall of the vessel. Doses of 30 Gy and 2 Gy were considered, representing typical in vivo enhancement studies and conventional clinical fractionation, respectively. Results: These simulations showed that for 20 Au-mg/g GNP blood concentration homogeneously distributed in the vessel, the additional dose at the inner vascular wall encircling the lumen was 43% of the prescribed dose at the depth of treatment for the 250 kVp Photon source, 1% for the 6 MV Photon source, and 0.1% for the proton beam. For kV Photons, GNPs caused 15% more dose in the vascular wall for 150 kVp source than for 250 kVp. For 6 MV Photons, GNPs caused 0.2% more dose in the vascular wall at 20 cm depth in water as compared to at depth of maximum dose (Dmax). For proton therapy, GNPs caused the same dose in the vascular wall for all depths across the spread out Bragg peak with 12.7 cm range and 7 cm modulation. For the same weight of GNPs in the vessel, 2 nm diameter GNPs caused three times more damage to the vessel than 20 nm diameter GNPs. When the GNPs were attached to the inner vascular wall, the damage to the inner vascular wall can be up to 207% of the prescribed dose for the 250 kVp Photon source, 4% for the 6 MV Photon source, and 2% for the proton beam. Even though the average dose increase from the proton beam and MV Photon beam was not large, there were high dose spikes that elevate the local dose of the parts of the blood vessel to be higher than 15 Gy even for 2 Gy prescribed dose, especially when the GNPs can be actively targeted to the endothelial cells. Conclusions: GNPs can potentially be used to enhance radiation therapy by causing vasculature damage through high dose spikes caused by the addition of GNPs especially for hypofractionated treatment. If GNPs are designed to actively accumulate at the tumor vasculature walls, vasculature damage can be increased significantly. The largest enhancement is seen using kilovoltage Photons due to the photoelectric effect. Although no significant average dose enhancement was observed for the whole vasculature structure for both MV Photons and protons, they can cause high local dose escalation (>15 Gy) to areas of the blood vessel that can potentially contribute to the disruption of the functionality of the blood vessels in the tumor.

  • biological modeling of gold nanoparticle enhanced radiotherapy for proton therapy
    Physics in Medicine and Biology, 2015
    Co-Authors: Stephen J Mcmahon, H Paganetti, J Schuemann
    Abstract:

    Gold nanoparticles (GNPs) have shown potential as a radiosensitizer for radiation therapy using Photon beams. Recently, experimental studies have been carried out using proton beams showing the GNP enhanced responses in proton therapy. In this work, we established a biological model to investigate the change in survival of irradiated cells due to the radiosensitizing effect of gold nanoparticles. Results for proton, megavoltage (MV) Photon and kilovoltage (kV) Photon beams are compared. For each particle source, we assessed various treatment depths, GNP cellular uptakes and sizes. We showed that kilovoltage Photons caused the highest enhancement due to the high interaction probability between GNPs and kV Photons. The cell survival fraction can be significantly reduced for both proton and MV Photon irradiations if GNPs accumulate in the cell. For instance, the sensitizer enhancement ratio (SER) is 1.33 for protons in the middle of a spread out Bragg peak for 1 µM of internalized 50 nm GNPs. If the GNPs can all be internalized into the cell nucleus, the SER for proton therapy increases from 1.33 to 1.81. The results also show that for the same mass of GNPs in the cells, one can expect the greatest sensitization by smaller GNPs, i.e. a SER of 1.33 for 1 µM of internalized 50 nm GNPs and a SER of 3.98 for the same mass of 2 nm GNPs. We concluded that if the GNPs cannot be internalized into the cytoplasm, no GNP enhancement will be observed for proton treatment. Meanwhile, proton radiotherapy can potentially be enhanced with GNPs if they can be internalized into cells, and especially the cell nucleus.

  • comparing gold nano particle enhanced radiotherapy with protons megavoltage Photons and kilovoltage Photons a monte carlo simulation
    Physics in Medicine and Biology, 2014
    Co-Authors: Stephen J Mcmahon, Matthew Scarpelli, H Paganetti, J Schuemann
    Abstract:

    Gold nanoparticles (GNPs) have shown potential to be used as a radiosensitizer for radiation therapy. Despite extensive research activity to study GNP radiosensitization using Photon beams, only a few studies have been carried out using proton beams. In this work Monte Carlo simulations were used to assess the dose enhancement of GNPs for proton therapy. The enhancement effect was compared between a clinical proton spectrum, a clinical 6 MV Photon spectrum, and a kilovoltage Photon source similar to those used in many radiobiology lab settings. We showed that the mechanism by which GNPs can lead to dose enhancements in radiation therapy differs when comparing Photon and proton radiation. The GNP dose enhancement using protons can be up to 14 and is independent of proton energy, while the dose enhancement is highly dependent on the Photon energy used. For the same amount of energy absorbed in the GNP, interactions with protons, kVp Photons and MV Photons produce similar doses within several nanometers of the GNP surface, and differences are below 15% for the first 10 nm. However, secondary electrons produced by kilovoltage Photons have the longest range in water as compared to protons and MV Photons, e.g. they cause a dose enhancement 20 times higher than the one caused by protons 10 μm away from the GNP surface. We conclude that GNPs have the potential to enhance radiation therapy depending on the type of radiation source. Proton therapy can be enhanced significantly only if the GNPs are in close proximity to the biological target.

J Schuemann - One of the best experts on this subject based on the ideXlab platform.

  • gold nanoparticle induced vasculature damage in radiotherapy comparing protons megavoltage Photons and kilovoltage Photons
    Medical Physics, 2015
    Co-Authors: H Paganetti, Stephen J Mcmahon, J Schuemann
    Abstract:

    Purpose: The purpose of this work is to investigate the radiosensitizing effect of gold nanoparticle (GNP) induced vasculature damage for proton, megavoltage (MV) Photon, and kilovoltage (kV) Photon irradiation. Methods: Monte Carlo simulations were carried out using tool for particle simulation (TOPAS) to obtain the spatial dose distribution in close proximity up to 20 μm from the GNPs. The spatial dose distribution from GNPs was used as an input to calculate the dose deposited to the blood vessels. GNP induced vasculature damage was evaluated for three particle sources (a clinical spread out Bragg peak proton beam, a 6 MV Photon beam, and two kV Photon beams). For each particle source, various depths in tissue, GNP sizes (2, 10, and 20 nm diameter), and vessel diameters (8, 14, and 20 μm) were investigated. Two GNP distributions in lumen were considered, either homogeneously distributed in the vessel or attached to the inner wall of the vessel. Doses of 30 Gy and 2 Gy were considered, representing typical in vivo enhancement studies and conventional clinical fractionation, respectively. Results: These simulations showed that for 20 Au-mg/g GNP blood concentration homogeneously distributed in the vessel, the additional dose at the inner vascular wall encircling the lumen was 43% of the prescribed dose at the depth of treatment for the 250 kVp Photon source, 1% for the 6 MV Photon source, and 0.1% for the proton beam. For kV Photons, GNPs caused 15% more dose in the vascular wall for 150 kVp source than for 250 kVp. For 6 MV Photons, GNPs caused 0.2% more dose in the vascular wall at 20 cm depth in water as compared to at depth of maximum dose (Dmax). For proton therapy, GNPs caused the same dose in the vascular wall for all depths across the spread out Bragg peak with 12.7 cm range and 7 cm modulation. For the same weight of GNPs in the vessel, 2 nm diameter GNPs caused three times more damage to the vessel than 20 nm diameter GNPs. When the GNPs were attached to the inner vascular wall, the damage to the inner vascular wall can be up to 207% of the prescribed dose for the 250 kVp Photon source, 4% for the 6 MV Photon source, and 2% for the proton beam. Even though the average dose increase from the proton beam and MV Photon beam was not large, there were high dose spikes that elevate the local dose of the parts of the blood vessel to be higher than 15 Gy even for 2 Gy prescribed dose, especially when the GNPs can be actively targeted to the endothelial cells. Conclusions: GNPs can potentially be used to enhance radiation therapy by causing vasculature damage through high dose spikes caused by the addition of GNPs especially for hypofractionated treatment. If GNPs are designed to actively accumulate at the tumor vasculature walls, vasculature damage can be increased significantly. The largest enhancement is seen using kilovoltage Photons due to the photoelectric effect. Although no significant average dose enhancement was observed for the whole vasculature structure for both MV Photons and protons, they can cause high local dose escalation (>15 Gy) to areas of the blood vessel that can potentially contribute to the disruption of the functionality of the blood vessels in the tumor.

  • biological modeling of gold nanoparticle enhanced radiotherapy for proton therapy
    Physics in Medicine and Biology, 2015
    Co-Authors: Stephen J Mcmahon, H Paganetti, J Schuemann
    Abstract:

    Gold nanoparticles (GNPs) have shown potential as a radiosensitizer for radiation therapy using Photon beams. Recently, experimental studies have been carried out using proton beams showing the GNP enhanced responses in proton therapy. In this work, we established a biological model to investigate the change in survival of irradiated cells due to the radiosensitizing effect of gold nanoparticles. Results for proton, megavoltage (MV) Photon and kilovoltage (kV) Photon beams are compared. For each particle source, we assessed various treatment depths, GNP cellular uptakes and sizes. We showed that kilovoltage Photons caused the highest enhancement due to the high interaction probability between GNPs and kV Photons. The cell survival fraction can be significantly reduced for both proton and MV Photon irradiations if GNPs accumulate in the cell. For instance, the sensitizer enhancement ratio (SER) is 1.33 for protons in the middle of a spread out Bragg peak for 1 µM of internalized 50 nm GNPs. If the GNPs can all be internalized into the cell nucleus, the SER for proton therapy increases from 1.33 to 1.81. The results also show that for the same mass of GNPs in the cells, one can expect the greatest sensitization by smaller GNPs, i.e. a SER of 1.33 for 1 µM of internalized 50 nm GNPs and a SER of 3.98 for the same mass of 2 nm GNPs. We concluded that if the GNPs cannot be internalized into the cytoplasm, no GNP enhancement will be observed for proton treatment. Meanwhile, proton radiotherapy can potentially be enhanced with GNPs if they can be internalized into cells, and especially the cell nucleus.

  • comparing gold nano particle enhanced radiotherapy with protons megavoltage Photons and kilovoltage Photons a monte carlo simulation
    Physics in Medicine and Biology, 2014
    Co-Authors: Stephen J Mcmahon, Matthew Scarpelli, H Paganetti, J Schuemann
    Abstract:

    Gold nanoparticles (GNPs) have shown potential to be used as a radiosensitizer for radiation therapy. Despite extensive research activity to study GNP radiosensitization using Photon beams, only a few studies have been carried out using proton beams. In this work Monte Carlo simulations were used to assess the dose enhancement of GNPs for proton therapy. The enhancement effect was compared between a clinical proton spectrum, a clinical 6 MV Photon spectrum, and a kilovoltage Photon source similar to those used in many radiobiology lab settings. We showed that the mechanism by which GNPs can lead to dose enhancements in radiation therapy differs when comparing Photon and proton radiation. The GNP dose enhancement using protons can be up to 14 and is independent of proton energy, while the dose enhancement is highly dependent on the Photon energy used. For the same amount of energy absorbed in the GNP, interactions with protons, kVp Photons and MV Photons produce similar doses within several nanometers of the GNP surface, and differences are below 15% for the first 10 nm. However, secondary electrons produced by kilovoltage Photons have the longest range in water as compared to protons and MV Photons, e.g. they cause a dose enhancement 20 times higher than the one caused by protons 10 μm away from the GNP surface. We conclude that GNPs have the potential to enhance radiation therapy depending on the type of radiation source. Proton therapy can be enhanced significantly only if the GNPs are in close proximity to the biological target.

H Paganetti - One of the best experts on this subject based on the ideXlab platform.

  • gold nanoparticle induced vasculature damage in radiotherapy comparing protons megavoltage Photons and kilovoltage Photons
    Medical Physics, 2015
    Co-Authors: H Paganetti, Stephen J Mcmahon, J Schuemann
    Abstract:

    Purpose: The purpose of this work is to investigate the radiosensitizing effect of gold nanoparticle (GNP) induced vasculature damage for proton, megavoltage (MV) Photon, and kilovoltage (kV) Photon irradiation. Methods: Monte Carlo simulations were carried out using tool for particle simulation (TOPAS) to obtain the spatial dose distribution in close proximity up to 20 μm from the GNPs. The spatial dose distribution from GNPs was used as an input to calculate the dose deposited to the blood vessels. GNP induced vasculature damage was evaluated for three particle sources (a clinical spread out Bragg peak proton beam, a 6 MV Photon beam, and two kV Photon beams). For each particle source, various depths in tissue, GNP sizes (2, 10, and 20 nm diameter), and vessel diameters (8, 14, and 20 μm) were investigated. Two GNP distributions in lumen were considered, either homogeneously distributed in the vessel or attached to the inner wall of the vessel. Doses of 30 Gy and 2 Gy were considered, representing typical in vivo enhancement studies and conventional clinical fractionation, respectively. Results: These simulations showed that for 20 Au-mg/g GNP blood concentration homogeneously distributed in the vessel, the additional dose at the inner vascular wall encircling the lumen was 43% of the prescribed dose at the depth of treatment for the 250 kVp Photon source, 1% for the 6 MV Photon source, and 0.1% for the proton beam. For kV Photons, GNPs caused 15% more dose in the vascular wall for 150 kVp source than for 250 kVp. For 6 MV Photons, GNPs caused 0.2% more dose in the vascular wall at 20 cm depth in water as compared to at depth of maximum dose (Dmax). For proton therapy, GNPs caused the same dose in the vascular wall for all depths across the spread out Bragg peak with 12.7 cm range and 7 cm modulation. For the same weight of GNPs in the vessel, 2 nm diameter GNPs caused three times more damage to the vessel than 20 nm diameter GNPs. When the GNPs were attached to the inner vascular wall, the damage to the inner vascular wall can be up to 207% of the prescribed dose for the 250 kVp Photon source, 4% for the 6 MV Photon source, and 2% for the proton beam. Even though the average dose increase from the proton beam and MV Photon beam was not large, there were high dose spikes that elevate the local dose of the parts of the blood vessel to be higher than 15 Gy even for 2 Gy prescribed dose, especially when the GNPs can be actively targeted to the endothelial cells. Conclusions: GNPs can potentially be used to enhance radiation therapy by causing vasculature damage through high dose spikes caused by the addition of GNPs especially for hypofractionated treatment. If GNPs are designed to actively accumulate at the tumor vasculature walls, vasculature damage can be increased significantly. The largest enhancement is seen using kilovoltage Photons due to the photoelectric effect. Although no significant average dose enhancement was observed for the whole vasculature structure for both MV Photons and protons, they can cause high local dose escalation (>15 Gy) to areas of the blood vessel that can potentially contribute to the disruption of the functionality of the blood vessels in the tumor.

  • biological modeling of gold nanoparticle enhanced radiotherapy for proton therapy
    Physics in Medicine and Biology, 2015
    Co-Authors: Stephen J Mcmahon, H Paganetti, J Schuemann
    Abstract:

    Gold nanoparticles (GNPs) have shown potential as a radiosensitizer for radiation therapy using Photon beams. Recently, experimental studies have been carried out using proton beams showing the GNP enhanced responses in proton therapy. In this work, we established a biological model to investigate the change in survival of irradiated cells due to the radiosensitizing effect of gold nanoparticles. Results for proton, megavoltage (MV) Photon and kilovoltage (kV) Photon beams are compared. For each particle source, we assessed various treatment depths, GNP cellular uptakes and sizes. We showed that kilovoltage Photons caused the highest enhancement due to the high interaction probability between GNPs and kV Photons. The cell survival fraction can be significantly reduced for both proton and MV Photon irradiations if GNPs accumulate in the cell. For instance, the sensitizer enhancement ratio (SER) is 1.33 for protons in the middle of a spread out Bragg peak for 1 µM of internalized 50 nm GNPs. If the GNPs can all be internalized into the cell nucleus, the SER for proton therapy increases from 1.33 to 1.81. The results also show that for the same mass of GNPs in the cells, one can expect the greatest sensitization by smaller GNPs, i.e. a SER of 1.33 for 1 µM of internalized 50 nm GNPs and a SER of 3.98 for the same mass of 2 nm GNPs. We concluded that if the GNPs cannot be internalized into the cytoplasm, no GNP enhancement will be observed for proton treatment. Meanwhile, proton radiotherapy can potentially be enhanced with GNPs if they can be internalized into cells, and especially the cell nucleus.

  • comparing gold nano particle enhanced radiotherapy with protons megavoltage Photons and kilovoltage Photons a monte carlo simulation
    Physics in Medicine and Biology, 2014
    Co-Authors: Stephen J Mcmahon, Matthew Scarpelli, H Paganetti, J Schuemann
    Abstract:

    Gold nanoparticles (GNPs) have shown potential to be used as a radiosensitizer for radiation therapy. Despite extensive research activity to study GNP radiosensitization using Photon beams, only a few studies have been carried out using proton beams. In this work Monte Carlo simulations were used to assess the dose enhancement of GNPs for proton therapy. The enhancement effect was compared between a clinical proton spectrum, a clinical 6 MV Photon spectrum, and a kilovoltage Photon source similar to those used in many radiobiology lab settings. We showed that the mechanism by which GNPs can lead to dose enhancements in radiation therapy differs when comparing Photon and proton radiation. The GNP dose enhancement using protons can be up to 14 and is independent of proton energy, while the dose enhancement is highly dependent on the Photon energy used. For the same amount of energy absorbed in the GNP, interactions with protons, kVp Photons and MV Photons produce similar doses within several nanometers of the GNP surface, and differences are below 15% for the first 10 nm. However, secondary electrons produced by kilovoltage Photons have the longest range in water as compared to protons and MV Photons, e.g. they cause a dose enhancement 20 times higher than the one caused by protons 10 μm away from the GNP surface. We conclude that GNPs have the potential to enhance radiation therapy depending on the type of radiation source. Proton therapy can be enhanced significantly only if the GNPs are in close proximity to the biological target.

  • biological considerations when comparing proton therapy with Photon therapy
    Seminars in Radiation Oncology, 2013
    Co-Authors: H Paganetti, Peter Van Luijk
    Abstract:

    Owing to the limited availability of data on the outcome of proton therapy, treatments are generally optimized based on broadly available data on Photon-based treatments. However, the microscopic pattern of energy deposition of protons differs from that of Photons, leading to a different biological effect. Consequently, proton therapy needs a correction factor (relative biological effectiveness) to relate proton doses to Photon doses, and currently, a generic value is used. Moreover, the macroscopic distribution of dose in proton therapy differs compared with Photon treatments. Although this may offer new opportunities to reduce dose to normal tissues, it raises the question whether data obtained from Photon-based treatments offer sufficient information on dose–volume effects to optimally use unique features of protons. In addition, there are potential differences in late effects due to low doses of secondary radiation outside the volume irradiated by the primary beam. This article discusses the controversies associated with these 3 issues when comparing proton and Photon therapy.

S. H. Aronson - One of the best experts on this subject based on the ideXlab platform.

  • Measurement of Direct Photons in Au+Au Collisions at sqrt(s_NN) = 200 GeV
    Physical Review Letters, 2012
    Co-Authors: S. Afanasiev, C. Aidala, N. N. Ajitanand, Y. Akiba, A. Al-jamel, J. Alexander, K. Aoki, Laurent Aphecetche, R. Armendariz, S. H. Aronson
    Abstract:

    We report the measurement of direct Photons at midrapidity in Au+Au collisions at sqrt{s_NN} = 200 GeV. The direct Photon signal was extracted for the transverse-momentum range of 4 GeV/c < p_T < 22 GeV/c, using a statistical method to subtract decay Photons from the inclusive-Photon sample. The direct-Photon nuclear-modification factor R_AA was calculated as a function of p_T for different Au+Au collision centralities using the measured p+p direct-Photon spectrum and compared to theoretical predictions. R_AA was found to be consistent with unity for all centralities over the entire measured p_T range. Theoretical models that account for modifications of initial-direct-Photon production due to modified-parton-distribution functions in Au and the different isospin composition of the nuclei, predict a modest change of R_AA from unity and are consistent with the data. Models with compensating effects of the quark-gluon plasma on high-energy Photons, such as suppression of jet-fragmentation Photons and induced-Photon bremsstrahlung from partons traversing the medium, are also consistent with this measurement.

R Abreu - One of the best experts on this subject based on the ideXlab platform.

  • search for nonpointing and delayed Photons in the diPhoton and missing transverse momentum final state in 8 tev pp collisions at the lhc using the atlas detector
    Physical Review D, 2014
    Co-Authors: B Abbott, J Abdallah, Abdel S Khalek, O Abdinov, R Aben, M Abolins, O S Abouzeid, H Abramowicz, H Abreu, R Abreu
    Abstract:

    A search has been performed, using the full 20.3 fb(-1) data sample of 8 TeV proton-proton collisions collected in 2012 with the ATLAS detector at the LHC, for Photons originating from a displaced vertex due to the decay of a neutral long-lived particle into a Photon and an invisible particle. The analysis investigates the diPhoton plus missing transverse momentum final state, and is therefore most sensitive to pair production of long-lived particles. The analysis technique exploits the capabilities of the ATLAS electromagnetic calorimeter to make precise measurements of the flight direction, as well as the time of flight, of Photons. No excess is observed over the Standard Model predictions for background. Exclusion limits are set within the context of gauge mediated supersymmetry breaking models, with the lightest neutralino being the next-to-lightest supersymmetric particle and decaying into a Photon and gravitino with a lifetime in the range from 250 ps to about 100 ns.

  • electron and Photon energy calibration with the atlas detector using lhc run 1 data
    European Physical Journal C, 2014
    Co-Authors: B Abbott, J Abdallah, Abdel S Khalek, O Abdinov, R Aben, M Abolins, O S Abouzeid, H Abramowicz, H Abreu, R Abreu
    Abstract:

    This paper presents the electron and Photon energy calibration achieved with the ATLAS detector using about 25 fb(-1) of LHC proton-proton collision data taken at centre-of-mass energies of root s = 7 and 8 TeV. The reconstruction of electron and Photon energies is optimised using multivariate algorithms. The response of the calorimeter layers is equalised in data and simulation, and the longitudinal profile of the electromagnetic showers is exploited to estimate the passive material in front of the calorimeter and reoptimise the detector simulation. After all corrections, the Z resonance is used to set the absolute energy scale. For electrons from Z decays, the achieved calibration is typically accurate to 0.05% in most of the detector acceptance, rising to 0.2% in regions with large amounts of passive material. The remaining inaccuracy is less than 0.2-1% for electrons with a transverse energy of 10 GeV, and is on average 0.3% for Photons. The detector resolution is determined with a relative inaccuracy of less than 10% for electrons and Photons up to 60 GeV transverse energy, rising to 40% for transverse energies above 500 GeV.