Cancer Risk Assessment for Space Radiation

NASA Technical Reports Server (NTRS)

Richmond, Robert C.; Cruz, Angela; Bors, Karen; Curreri, Peter A. (Technical Monitor)

2001-01-01

Predicting the occurrence of human cancer following exposure to any agent causing genetic damage is a difficult task. This is because the uncertainty of uniform exposure to the damaging agent, and the uncertainty of uniform processing of that damage within a complex set of biological variables, degrade the confidence of predicting the delayed expression of cancer as a relatively rare event within any given clinically normal individual. The radiation health research priorities for enabling long-duration human exploration of space were established in the 1996 NRC Report entitled 'Radiation Hazards to Crews of Interplanetary Missions: Biological Issues and Research Strategies'. This report emphasized that a 15-fold uncertainty in predicting radiation-induced cancer incidence must be reduced before NASA can commit humans to extended interplanetary missions. That report concluded that the great majority of this uncertainty is biologically based, while a minority is physically based due to uncertainties in radiation dosimetry and radiation transport codes. Since that report, the biologically based uncertainty has remained large, and the relatively small uncertainty associated with radiation dosimetry has increased due to the considerations raised by concepts of microdosimetry. In a practical sense, however, the additional uncertainties introduced by microdosimetry are encouraging since they are in a direction of lowered effective dose absorbed through infrequent interactions of any given cell with the high energy particle component of space radiation. Additional information is contained in the original extended abstract.

Microdosimetry of DNA conformations: relation between direct effect of (60)Co gamma rays and topology of DNA geometrical models in the calculation of A-, B- and Z-DNA radiation-induced damage yields.

PubMed

Semsarha, Farid; Raisali, Gholamreza; Goliaei, Bahram; Khalafi, Hossein

2016-05-01

In order to obtain the energy deposition pattern of ionizing radiation in the nanometric scale of genetic material and to investigate the different sensitivities of the DNA conformations, direct effects of (60)Co gamma rays on the three A, B and Z conformations of DNA have been studied. For this purpose, single-strand breaks (SSB), double-strand breaks (DSB), base damage (BD), hit probabilities and three microdosimetry quantities (imparted energy, mean chord length and lineal energy) in the mentioned DNA conformations have been calculated and compared by using GEometry ANd Tracking 4 (Geant4) toolkit. The results show that A-, B- and Z-DNA conformations have the highest yields of DSB (1.2 Gy(-1) Gbp(-1)), SSB (25.2 Gy(-1) Gbp(-1)) and BD (4.81 Gy(-1) Gbp(-1)), respectively. Based on the investigation of direct effects of radiation, it can be concluded that the DSB yield is largely correlated to the topological characteristics of DNA models, although the SSB yield is not. Moreover, according to the comparative results of the present study, a reliable candidate parameter for describing the relationship between DNA damage yields and geometry of DNA models in the theoretical radiation biology research studies would be the mean chord length (4 V/S) of the models.

Quantitative luminescence imaging system

DOEpatents

Erwin, D.N.; Kiel, J.L.; Batishko, C.R.; Stahl, K.A.

1990-08-14

The QLIS images and quantifies low-level chemiluminescent reactions in an electromagnetic field. It is capable of real time nonperturbing measurement and simultaneous recording of many biochemical and chemical reactions such as luminescent immunoassays or enzyme assays. The system comprises image transfer optics, a low-light level digitizing camera with image intensifying microchannel plates, an image process or, and a control computer. The image transfer optics may be a fiber image guide with a bend, or a microscope, to take the light outside of the RF field. Output of the camera is transformed into a localized rate of cumulative digitalized data or enhanced video display or hard-copy images. The system may be used as a luminescent microdosimetry device for radiofrequency or microwave radiation, as a thermal dosimeter, or in the dosimetry of ultra-sound (sonoluminescence) or ionizing radiation. It provides a near-real-time system capable of measuring the extremely low light levels from luminescent reactions in electromagnetic fields in the areas of chemiluminescence assays and thermal microdosimetry, and is capable of near-real-time imaging of the sample to allow spatial distribution analysis of the reaction. It can be used to instrument three distinctly different irradiation configurations, comprising (1) RF waveguide irradiation of a small Petri-dish-shaped sample cell, (2) RF irradiation of samples in a microscope for the microscopic imaging and measurement, and (3) RF irradiation of small to human body-sized samples in an anechoic chamber. 22 figs.

Quantitative luminescence imaging system

DOEpatents

Erwin, David N.; Kiel, Johnathan L.; Batishko, Charles R.; Stahl, Kurt A.

1990-01-01

The QLIS images and quantifies low-level chemiluminescent reactions in an electromagnetic field. It is capable of real time nonperturbing measurement and simultaneous recording of many biochemical and chemical reactions such as luminescent immunoassays or enzyme assays. The system comprises image transfer optics, a low-light level digitizing camera with image intensifying microchannel plates, an image process or, and a control computer. The image transfer optics may be a fiber image guide with a bend, or a microscope, to take the light outside of the RF field. Output of the camera is transformed into a localized rate of cumulative digitalized data or enhanced video display or hard-copy images. The system may be used as a luminescent microdosimetry device for radiofrequency or microwave radiation, as a thermal dosimeter, or in the dosimetry of ultra-sound (sonoluminescence) or ionizing radiation. It provides a near-real-time system capable of measuring the extremely low light levels from luminescent reactions in electromagnetic fields in the areas of chemiluminescence assays and thermal microdosimetry, and is capable of near-real-time imaging of the sample to allow spatial distribution analysis of the reaction. It can be used to instrument three distinctly different irradiation configurations, comprising (1) RF waveguide irradiation of a small Petri-dish-shaped sample cell, (2) RF irradiation of samples in a microscope for the microscopie imaging and measurement, and (3) RF irradiation of small to human body-sized samples in an anechoic chamber.

Dosimetry and microdosimetry using COTS ICs: A comparative study

NASA Technical Reports Server (NTRS)

Scheick, L.; Swift, G.; Guertin, S.; Roth, D.; McNulty, P.; Nguyen, D.

2002-01-01

A new method using an array of MOS transistors formeasuring dose absorbed from ionizing radiation is compared to previous dosimetric methods., The accuracy and precision of dosimetry based on COTS SRAMs, DRAMs, and WPROMs are compared and contrasted. Applications of these devices in various space missions will be discussed. TID results are presented for this summary and microdosimetricresults will be added to the full paper. Finally, an analysis of the optimal condition for a digital dosimeter will be presented.

Microdosimetry of low-energy electrons.

PubMed

Liamsuwan, Thiansin; Emfietzoglou, Dimitris; Uehara, Shuzo; Nikjoo, Hooshang

2012-12-01

To investigate differences in energy depositions and microdosimetric parameters of low-energy electrons in liquid and gaseous water using Monte Carlo track structure simulations. KURBUC-liq (Kyushu University and Radiobiology Unit Code for liquid water) was used for simulating electron tracks in liquid water. The inelastic scattering cross sections of liquid water were obtained from the dielectric response model of Emfietzoglou et al. (Radiation Research 2005;164:202-211). Frequencies of energy deposited in nanometre-size cylindrical targets per unit absorbed dose and associated lineal energies were calculated for 100-5000 eV monoenergetic electrons and the electron spectrum of carbon K edge X-rays. The results for liquid water were compared with those for water vapour. Regardless of electron energy, there is a limit how much energy electron tracks can deposit in a target. Phase effects on the frequencies of energy depositions are largely visible for the targets with diameters and heights smaller than 30 nm. For the target of 2.3 nm by 2.3 nm (similar to dimension of DNA segments), the calculated frequency- and dose-mean lineal energies for liquid water are up to 40% smaller than those for water vapour. The corresponding difference is less than 12% for the targets with diameters ≥ 30 nm. Condensed-phase effects are non-negligible for microdosimetry of low-energy electrons for targets with sizes smaller than a few tens of nanometres, similar to dimensions of DNA molecular structures and nucleosomes.

Comparison of particle tracking algorithms in commercial CFD packages: sedimentation and diffusion.

PubMed

Robinson, Risa J; Snyder, Pam; Oldham, Michael J

2007-05-01

Computational fluid dynamic modeling software has enabled microdosimetry patterns of inhaled toxins and toxicants to be predicted and visualized, and is being used in inhalation toxicology and risk assessment. These predicted microdosimetry patterns in airway structures are derived from predicted airflow patterns within these airways and particle tracking algorithms used in computational fluid dynamics (CFD) software packages. Although these commercial CFD codes have been tested for accuracy under various conditions, they have not been well tested for respiratory flows in general. Nor has their particle tracking algorithm accuracy been well studied. In this study, three software packages, Fluent Discrete Phase Model (DPM), Fluent Fine Particle Model (FPM), and ANSYS CFX, were evaluated. Sedimentation and diffusion were each isolated in a straight tube geometry and tested for accuracy. A range of flow rates corresponding to adult low activity (minute ventilation = 10 L/min) and to heavy exertion (minute ventilation = 60 L/min) were tested by varying the range of dimensionless diffusion and sedimentation parameters found using the Weibel symmetric 23 generation lung morphology. Numerical results for fully developed parabolic and uniform (slip) profiles were compared respectively, to Pich (1972) and Yu (1977) analytical sedimentation solutions. Schum and Yeh (1980) equations for sedimentation were also compared. Numerical results for diffusional deposition were compared to analytical solutions of Ingham (1975) for parabolic and uniform profiles. Significant differences were found among the various CFD software packages and between numerical and analytical solutions. Therefore, it is prudent to validate CFD predictions against analytical solutions in idealized geometry before tackling the complex geometries of the respiratory tract.

Comparison of microdosimetry-based absorbed doses to control tumours and clinically obtained tumour absorbed doses in treatments with ²²³Ra.

PubMed

Minguez Gabina, Pablo; Roeske, John C; Mínguez, Ricardo; Gomez de Iturriaga, Alfonso; Rodeño, Emilia

2018-06-20

We performed Monte Carlo simulations in order to determine by means of microdosimetry calculations the average number of hits to the cell nucleus required to reach a tumour control probability (TCP) of 0.9, 〈n_0.9 〉, for the source geometry of a nucleus embedded in a homogeneous distribution of ²²³Ra atoms. From the results obtained and following the MIRD methodology, we determined the values of lesion absorbed doses needed to reach a TCP of 0.9, D_0.9, for different values of mass density, cell radiosensitivity, nucleus radius and lesion volume. The greatest variation of those absorbed doses occurred with cell radiosensitivity and no dependence was found on mass density. The source geometry used was chosen because we aimed to compare the values of D_0.9 with the lesion absorbed doses obtained from image-based macrodosimetry in treatments of metastatic castration-resistant prostate cancer with ²²³Ra which were obtained assuming a homogeneous distribution of ²²³Ra atoms within the lesion. In a comparison with a study including 29 lesions, results showed that even for the case of the most radiosensitive cells simulated, 45% of the lesions treated following a schedule of two cycles of 110 kBq/kg body mass would receive absorbed doses below the values of D_0.9 determined in this study. © 2018 Institute of Physics and Engineering in Medicine.

Recent Re-Measurement of Neutron and Gamma-Ray Spectra 1080 Meters from the APRD (Army Pulse Radiation Division) Critical Facility,

DTIC Science & Technology

1984-01-01

TISSUE-EQUIVALENT ION CHAMBER GM - GEIGER-MUELLER COUNTER TE-GM - DIFFERENCE BETWEEN TE AND GM DATA MICRODOSE - MICRODOSIMETRY USING 0.5" ROSSI COUNTER...KERMA 4.26+8 1979 APRO NE-213+PR NEUTRON KERMA 4.26+8 1979 WWD NE-213 NEUTRON KERMA 3.10+8 > 550 KEV 1980 DREO MICRODOSE NEUTRON KERMA 4.32+8 1979...APRD GM GAMMA KERMA 3.86+7 1979 WWD NE-213 GAMMA KERMA 4.34+7 > 450 KEV 1980 DREO MICRODOSE GAMMA KERMA 3.90+7 76 1979 APRD TE TOTAL KERMA 4.50+8 50 c.c

Correction factors to convert microdosimetry measurements in silicon to tissue in 12C ion therapy

NASA Astrophysics Data System (ADS)

Bolst, David; Guatelli, Susanna; Tran, Linh T.; Chartier, Lachlan; Lerch, Michael L. F.; Matsufuji, Naruhiro; Rosenfeld, Anatoly B.

2017-03-01

Silicon microdosimetry is a promising technology for heavy ion therapy (HIT) quality assurance, because of its sub-mm spatial resolution and capability to determine radiation effects at a cellular level in a mixed radiation field. A drawback of silicon is not being tissue-equivalent, thus the need to convert the detector response obtained in silicon to tissue. This paper presents a method for converting silicon microdosimetric spectra to tissue for a therapeutic 12C beam, based on Monte Carlo simulations. The energy deposition spectra in a 10 μm sized silicon cylindrical sensitive volume (SV) were found to be equivalent to those measured in a tissue SV, with the same shape, but with dimensions scaled by a factor κ equal to 0.57 and 0.54 for muscle and water, respectively. A low energy correction factor was determined to account for the enhanced response in silicon at low energy depositions, produced by electrons. The concept of the mean path length < {{l}\\text{Path}}> to calculate the lineal energy was introduced as an alternative to the mean chord length < l> because it was found that adopting Cauchy’s formula for the < l> was not appropriate for the radiation field typical of HIT as it is very directional. < {{l}\\text{Path}}> can be determined based on the peak of the lineal energy distribution produced by the incident carbon beam. Furthermore it was demonstrated that the thickness of the SV along the direction of the incident 12C ion beam can be adopted as < {{l}\\text{Path}}> . The tissue equivalence conversion method and < {{l}\\text{Path}}> were adopted to determine the RBE10, calculated using a modified microdosimetric kinetic model, applied to the microdosimetric spectra resulting from the simulation study. Comparison of the RBE10 along the Bragg peak to experimental TEPC measurements at HIMAC, NIRS, showed good agreement. Such agreement demonstrates the validity of the developed tissue equivalence correction factors and of the determination of < {{l}\\text{Path}}> .

SU-E-T-771: Two Dimensional Raman Mapping of Carbon Bonds of Radiochromic Films: An Approach to Micro-Dosimetry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Heo, T; Ye, S

2015-06-15

Purpose: To study a feasibility of micro-dosimetry with high dose-sensitivity and resolution using two-dimensional Raman mapping on the basis of carbon bonds concentration of radiochromic films Methods: Unlaminated EBT3 films with the purpose of maximal Raman data acquisition were irradiated by 6 MV beam from 5 MU to 1000 MU at the reference condition. Each film was irradiated with shielding material of lead blocking on the half of film as well as the jaw open in half for distinct dose contrast. Raman peaks of 2070 cm-1, 2095 cm-1, and 2115 cm-1 were major subjects to study, which are assumed tomore » be the spectroscopy of carbon triple bonds of monomers, carbon double bonds of polymers, and carbon triple bonds of polymers, respectively. Laser exposure for Raman spectroscopy generated peak’s trend due to polymerization by laser output and this trend was utilized to find out basic peaks related to polymerization process. The relative dose contrast in each one film was detected by Raman spectroscopy with the aid of an auto-scanning stage, comparing the dose contrast between non-irradiated area and irradiated area. Raman spatial resolution was enhanced up to 20 micrometers, assuming the spatial uniformity of radio¬active rod-shaped LiPCDA crystals. An optical scanner with 9600 dpi was used to scan the red-channel intensity to read the dose contrast for 5 MU delivered film. Results: The peak intensity for Raman wavenumber of 2070 cm-1 was used for mapping since it reflected the different peak intensities based on polymerization degree by irradiation. Dose contrast from 1000MU to 5 MU was distinguished by Raman mapping analysis, whereas optical intensity of red-channel didn’t show any difference. Conclusion: In consideration of laser effect, the quantitative analysis based on raw data of Raman mapping could provide more statistically reliable dosimetry than point measurements.« less

The USNA MIDN Microdosimeter Instrument

NASA Technical Reports Server (NTRS)

Pisacane, V. L.; Ziegler, J. F.; Nelson, M. E.; Dolecek, Q.; Heyne, J.; Veade, T.; Rosenfeld, A. B.; Cucinotta, F. A.; Zaider, M.; Dicello, J. F.

2006-01-01

This paper describes the MIcroDosimetry iNstrument (MIDN) mission now under development at the United States Naval Academy. The instrument is manifested to fly on the MidSTAR-1 spacecraft, which is the second spacecraft to be developed and launched by the Academy s faculty and midshipmen. Launch is scheduled for 1 September 2006 on an ATLAS-5 launch vehicle. MIDN is a rugged, portable, low power, low mass, solid-state microdosimeter designed to measure in real time the energy distributions of energy deposited by radiation in microscopic volumes. The MIDN microdosimeter sensor is a reverse-biased silicon p-n junction array in a Silicon-On-Insulator (SOI) configuration. Microdosimetric frequency distributions as a function of lineal energies determine the radiation quality factors in support of radiation risk estimation to humans.

TEPC Response Functions

NASA Technical Reports Server (NTRS)

Shinn, J. L.; Wilson, J. W.

2003-01-01

The tissue equivalent proportional counter had the purpose of providing the energy absorbed from a radiation field and an estimate of the corresponding linear energy transfer (LET) for evaluation of radiation quality to convert to dose equivalent. It was the recognition of the limitations in estimating LET which lead to a new approach to dosimetry, microdosimetry, and the corresponding emphasis on energy deposit in a small tissue volume as the driver of biological response with the defined quantity of lineal energy. In many circumstances, the average of the lineal energy and LET are closely related and has provided a basis for estimating dose equivalent. Still in many cases the lineal is poorly related to LET and brings into question the usefulness as a general purpose device. These relationships are examined in this paper.

1986 Annual Conference on Nuclear and Space Radiation Effects, 23rd, Providence, RI, July 21-23, 1986, Proceedings

NASA Technical Reports Server (NTRS)

Ellis, Thomas D. (Editor)

1986-01-01

The present conference on the effects of nuclear and space radiation on electronic hardware gives attention to topics in the basic mechanisms of radiation effects, dosimetry and energy-dependent effects, electronic device radiation hardness assurance, SOI/SOS radiation effects, spacecraft charging and space radiation, IC radiation effects and hardening, single-event upset (SEU) phenomena and hardening, and EMP/SGEMP/IEMP phenomena. Specific treatments encompass the generation of interface states by ionizing radiation in very thin MOS oxides, the microdosimetry of meson energy deposited on 1-micron sites in Si, total dose radiation and engineering studies, plasma interactions with biased concentrator solar cells, the transient imprint memory effect in MOS memories, mechanisms leading to SEU, and the vaporization and breakdown of thin columns of water.

Particle tracking with a Timepix based triple GEM detector

NASA Astrophysics Data System (ADS)

George, S. P.; Murtas, F.; Alozy, J.; Curioni, A.; Rosenfeld, A. B.; Silari, M.

2015-11-01

This paper details the response of a triple GEM detector with a 55 μmetre pitch pixelated ASIC for readout. The detector is operated as a micro TPC with 9.5 cm3 sensitive volume and characterized with a mixed beam of 120 GeV protons and positive pions. A process for reconstruction of incident particle tracks from individual ionization clusters is described and scans of the gain and drift fields are performed. The angular resolution of the measured tracks is characterized. Also, the readout was operated in a mixed mode where some pixels measure drift time and others charge. This was used to measure the energy deposition in the detector and the charge cloud size as a function of interaction depth. The future uses of the device, including in microdosimetry are discussed.

Correction factors to convert microdosimetry measurements in silicon to tissue in 12C ion therapy.

PubMed

Bolst, David; Guatelli, Susanna; Tran, Linh T; Chartier, Lachlan; Lerch, Michael L F; Matsufuji, Naruhiro; Rosenfeld, Anatoly B

2017-03-21

Silicon microdosimetry is a promising technology for heavy ion therapy (HIT) quality assurance, because of its sub-mm spatial resolution and capability to determine radiation effects at a cellular level in a mixed radiation field. A drawback of silicon is not being tissue-equivalent, thus the need to convert the detector response obtained in silicon to tissue. This paper presents a method for converting silicon microdosimetric spectra to tissue for a therapeutic 12 C beam, based on Monte Carlo simulations. The energy deposition spectra in a 10 μm sized silicon cylindrical sensitive volume (SV) were found to be equivalent to those measured in a tissue SV, with the same shape, but with dimensions scaled by a factor κ equal to 0.57 and 0.54 for muscle and water, respectively. A low energy correction factor was determined to account for the enhanced response in silicon at low energy depositions, produced by electrons. The concept of the mean path length [Formula: see text] to calculate the lineal energy was introduced as an alternative to the mean chord length [Formula: see text] because it was found that adopting Cauchy's formula for the [Formula: see text] was not appropriate for the radiation field typical of HIT as it is very directional. [Formula: see text] can be determined based on the peak of the lineal energy distribution produced by the incident carbon beam. Furthermore it was demonstrated that the thickness of the SV along the direction of the incident 12 C ion beam can be adopted as [Formula: see text]. The tissue equivalence conversion method and [Formula: see text] were adopted to determine the RBE 10 , calculated using a modified microdosimetric kinetic model, applied to the microdosimetric spectra resulting from the simulation study. Comparison of the RBE 10 along the Bragg peak to experimental TEPC measurements at HIMAC, NIRS, showed good agreement. Such agreement demonstrates the validity of the developed tissue equivalence correction factors and of the determination of [Formula: see text].

Microdosimetry measurements characterizing the radiation fields of 300 MeV/u 12C and 185 MeV/u 7Li pencil beams stopping in water

NASA Astrophysics Data System (ADS)

Martino, G.; Durante, M.; Schardt, D.

2010-06-01

In order to characterize the complex radiation field produced by heavy-ion beams in water, in particular the lateral dose fall-off and the radiation quality, microdosimetry measurements were performed at GSI Darmstadt using pencil-like beams of 300 MeV/u 12C and 185 MeV/u 7Li ions delivered by the heavy-ion synchrotron SIS-18. The ion beams (range in water about 17 cm) were stopped in the center of a 30 × 30 × 30 cm3 water phantom and their radiation field was investigated by in-phantom measurements using a tissue-equivalent proportional chamber (TEPC). The chamber was placed at 35 different positions in the central plane at various depths along the beam axis and at radial distances of 0, 1, 2, 5 and 10 cm. The off-axis measurements for both 12C and 7Li ions show very similar distributions of the lineal energy, all peaking between 1 and 10 \\rm keV\\,\\mu m^{-1} which is a typical range covered by secondary hydrogen fragments and neutrons. The radiation quality given by the dose-mean lineal energy \\overline{y}_D was found to be at a constant level of 1-2 \\rm keV\\,\\mu m^{-1} at radial distances larger than 2 cm. The relative absorbed dose at each position was obtained by integration of the measured spectra normalized to the number of incident primary beam particles. The results confirm that the lateral dose profile of heavy ions shows an extremely steep fall-off, with relative values of about 10-3, 10-4 and 10-5 at the 2, 5 and 10 cm distance from the beam axis, respectively. The depth-dose curves at a fixed distance from the beam axis slowly rise until they reach the depth of the Bragg peak, reflecting the build-up of secondary fragments with increasing penetration depth. The measured 12C dose profiles were found to be in good agreement with a similar experimental study at HIMAC (Japan).

Microdosimetry and Katz's track structure theory. I. One-hit detectors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zaider, M.

1990-10-01

A microdosimetric treatment of the response of one-hit detectors to radiation is formulated and compared with the model proposed by R. Katz, S. C. Sharma, and M. Homayoonfar within the framework of their track-structure theory. It is shown that radial dose distributions (on which the track structure theory is based) are generally poor substitutes for the exact microdosimetric distributions except when (a) the target is much larger than the radial extent of the track or (b) the effective specific energy in the target (alpha z) is negligibly small. Since neither one of these conditions is generally satisfied, it is suggestedmore » that a meaningful search for one-hit detectors be based on a microdosimetric description of the stochastics of energy deposition. An analysis of the phi x-174 bacteriophage inactivation data is presented.« less

Effects of 1.9 MeV monoenergetic neutrons on Vicia faba chromosomes: microdosimetric considerations.

PubMed

Geard, C R

1980-01-01

Aerated Vicia faba root meristems were irradiated with 1.9 MeV monoenergetic neutrons. This source of neutrons optimally provides one class of particles (recoil protons) with ranges able to traverse cell nuclei at moderate to high-LET. The volumes of the Vicia faba nuclei were log-normally distributed with a mean of 1100 micrometer3. The yield of chromatid-type aberrations was linear against absorbed dose and near-constant over 5 collection periods (2-12 h), after irradiation. Energy deposition events (recoil protons) determined by microdosimetry were related to cytological changes with the finding that 19% of incident recoil protons initiate visible changes in Vicia faba chromosomes. It is probable that a substantial fraction of recoil proton track length and deposited energy is in insensitive (non-DNA containing) portions of the nuclear volume.

Cancer Risk Assessment for Space Radiation

NASA Technical Reports Server (NTRS)

Richmond, Robert C.; Curreri, Peter A. (Technical Monitor)

2002-01-01

Predicting the occurrence of human cancer following exposure to any agent causing genetic damage is a difficult task. This is because the uncertainty of uniform exposure to the damaging agent, and the uncertainty of uniform processing of that damage within a complex set of biological variables, degrade the confidence of predicting the delayed expression of cancer as a relatively rare event within any given clinically normal individual. The radiation health research priorities for enabling long-duration human exploration of space were established in the 1996 NRC Report entitled "Radiation Hazards to Crews of Interplanetary Missions: Biological Issues and Research Strategies". This report emphasized that a 15-fold uncertainty in predicting radiation-induced cancer incidence must be reduced before NASA can commit humans to extended interplanetary missions. That report concluded that the great majority of this uncertainty is biologically based, while a minority is physically based due to uncertainties in radiation dosimetry and radiation transport codes. Since that report, the biologically based uncertainty has remained large, and the relatively small uncertainty associated with radiation dosimetry has increased due to the considerations raised by concepts of microdosimetry. In a practical sense, however, the additional uncertainties introduced by microdosimetry are encouraging since they are in a direction of lowered effective dose absorbed through infrequent interactions of any given cell with the high energy particle component of space radiation. The biological uncertainty in predicting cancer risk for space radiation derives from two primary facts. 1) One animal tumor study has been reported that includes a relevant spectrum of particle radiation energies, and that is the Harderian gland model in mice. Fact #1: Extension of cancer risk from animal models, and especially from a single study in an animal model, to humans is inherently uncertain. 2) One human database is predominantly used for assessing cancer risk caused by space radiation, and that is the Japanese atomic bomb survivors. Fact #2: The atomic-bomb-survivor database, itself a remarkable achievement, contains uncertainties. These include the actual exposure to each individual, the radiation quality of that exposure, and the fact that the exposure was to acute doses of predominantly low-LET radiation, not to chronic exposures of high-LET radiation expected on long-duration interplanetary manned missions.

Auger-electron cascades, charge potential and microdosimetry of iodine-125.

PubMed

Booz, J; Paretzke, H G; Pomplun, E; Olko, P

1987-01-01

This paper is a contribution to the microdosimetry of I-125. It shows microdosimetric spectra of individual and average disintegrations of I-125 for various target sizes and gives evidence for the relative contributions of energy-deposition events of low and high LET. It further presents information on the relative efficiencies of Auger-electrons and multiple charges in terms of local energy deposition, e.g. to model targets of DNA, and discusses their radiobiological implications, e.g. the microdosimetric understanding of the different efficiencies of specific and random incorporations of I-125. When I-125 is specifically incorporated into DNA, most of the energy deposition events are very large, e.g. above 40 keV/micron for a simulated target volume of 20 nm diameter, regardless of the number and energy of Auger electrons emitted. Therefore it is not necessary, for the discussion of the radiobiological implications, to distinguish between different classes of disintegrations. For unspecific, homogeneous incorporation of I-125 somewhere into tissue, about 20% of the dose to critical targets of 25 nm diameter is made up by disintegrations that happen to occur within these targets. When assuming that other critical targets and target structures can be neglected, this part of the dose will be equally effective as in the case of specific incorporation of I-125 into such target models. In addition, there are the normal, low-LET radiation effects from the other, 80% large fraction of the dose. With this information, for the biological systems and end points for which a short section of the elemental chromatine fiber can be taken as the relevant critical target, it is shown that the expected D37 value for homogeneous unspecific incorporation of I-125 can be estimated when the D37 for specific incorporation in DNA is known. For an example calculation, the estimated D37-value for nonspecific, homogeneous incorporation of I-125 would be about half as effective as specifically incorporated I-125. Thus, the microdosimetric data of the present work show that a high efficiency of homogeneous incorporation of I-125 into the cell nucleus is not necessarily in contradiction with the idea of I-125 disintegrations inside the DNA being the main cause of radiation action.

DNA Repair Domain Modeling Can Predict Cell Death and Mutation Frequency for Wide Range Spectrum of Radiation

NASA Technical Reports Server (NTRS)

Viger, Louise; Ponomarev, Artem L.; Plante, Ianik; Evain, Trevor; Penninckx, Sebastien; Blattnig, Steve R.; Costes, Sylvain V.

2017-01-01

Exploration missions to Mars and other destinations raise many questions about the health of astronauts. The continuous exposure of astronauts to galactic cosmic rays is one of the main concerns for long-term missions. Cosmic ionizing radiations are composed of different ions of various charges and energies notably, highly charged energy (HZE) particles. The HZE particles have been shown to be more carcinogenic than low-LET radiation, suggesting the severity of chromosomal aberrations induced by HZE particles is one possible explanation. However, most mathematical models predicting cell death and mutation frequency are based on directly fitting various HZE dose response and are in essence empirical approaches. In this work, we assume a simple biological mechanism to model DNA repair and use it to simultaneously explain the low- and high-LET response using the exact same fitting parameters. Our work shows that the geometrical position of DNA repair along tracks of heavy ions are sufficient to explain why high-LET particles can induce more death and mutations. Our model is based on assuming DNA double strand breaks (DSBs) are repaired within repair domain, and that any DSBs located within the same repair domain cluster into one repair unit, facilitating chromosomal rearrangements and increasing the probability of cell death. We introduced this model in 2014 using simplified microdosimetry profiles to predict cell death. In this work, we collaborated with NASA Johnson Space Center to generate more accurate microdosimetry profiles derived by Monte Carlo techniques, taking into account track structure of HZE particles and simulating DSBs in realistic cell geometry. We simulated 224 data points (D, A, Z, E) with the BDSTRACKS model, leading to a large coverage of LET from 10 to 2,400 keV/µm. This model was used to generate theoretical RBE for various particles and energies for both cell death and mutation frequencies. The RBE LET dependence is in agreement with experimental data known in human and murine cells. It suggests that cell shape and its orientation with respect to the HZE particle beam can modify the biological response to radiation. Such discovery will be tested experimentally and, if proven accurate, will be another strong supporting evidence for DNA repair domains and their critical role in interpreting cosmic radiation sensitivity.

A Radiation Chemistry Code Based on the Green's Function of the Diffusion Equation

NASA Technical Reports Server (NTRS)

Plante, Ianik; Wu, Honglu

2014-01-01

Stochastic radiation track structure codes are of great interest for space radiation studies and hadron therapy in medicine. These codes are used for a many purposes, notably for microdosimetry and DNA damage studies. In the last two decades, they were also used with the Independent Reaction Times (IRT) method in the simulation of chemical reactions, to calculate the yield of various radiolytic species produced during the radiolysis of water and in chemical dosimeters. Recently, we have developed a Green's function based code to simulate reversible chemical reactions with an intermediate state, which yielded results in excellent agreement with those obtained by using the IRT method. This code was also used to simulate and the interaction of particles with membrane receptors. We are in the process of including this program for use with the Monte-Carlo track structure code Relativistic Ion Tracks (RITRACKS). This recent addition should greatly expand the capabilities of RITRACKS, notably to simulate DNA damage by both the direct and indirect effect.

Etude microdosimetrique de l'influence des materiaux sur l'efficacite biologique d'une source d'iode-125

NASA Astrophysics Data System (ADS)

Taschereau, Richard

Cette these concerne les implants permanents pour la prostate. Les isotopes employes, le 103Pd et l'125I, semblent produire les memes resultats cliniques: le premier a cause d'une radiation plus efficace et le second a cause de sa demi-vie plus longue. La recherche utilise le cadre theorique de la microdosimetrie et des simulations Monte Carlo. Elle propose d'employer le spectre d'ejection dans le calcul de l'efficacite; ce changement fait passer l'efficacite relative du 103Pd de 10% a 5%. Elle montre ensuite qu'il est possible d'ameliorer l'efficacite de la radiation de 125I par l'exploitation des rayons X caracteristiques de la capsule. Une source amelioree faite de molybdene et d'yttrium est donnee en exemple. Elle procure une radiation de 5--7% plus efficace, ce qui surclasse les deux sources existantes. Les applications ne se limitent pas au traitement de la prostate; le traitement du melanome oculaire et la curietherapie endovasculaire pourraient en beneficier.

UVPROM dosimetry, microdosimetry and applications to SEU and extreme value theory

NASA Astrophysics Data System (ADS)

Scheick, Leif Zebediah

A new method is described for characterizing a device in terms of the statistical distribution of first failures. The method is based on the erasure of a commercial Ultra- Violet erasable Programmable Read Only Memory (UVPROM). The method of readout would be used on a spacecraft or in other restrictive radiation environments. The measurement of the charge remaining on the floating gate is used to determine absorbed dose. The method of determining dose does not require the detector to be destroyed or erased nor does it effect the ability for taking further measurements. This is compared to extreme value theory applied to the statistical distributions that apply to this device. This technique predicts the threshold of Single Event Effects (SEE), like anomalous changes in erasure time in programmable devices due to high microdose energy-deposition events. This technique also allows for advanced non-destructive, screening of a single microelectronic devices for predictable response in a stressful, i.e. radiation, environments.

Determination of quality factors by microdosimetry

NASA Astrophysics Data System (ADS)

Al-Affan, I. A. M.; Watt, D. E.

1987-03-01

The application of microdose parameters for the specification of a revised scale of quality factors which would be applicable at low doses and dose rates is examined in terms of an original proposal by Rossi. Two important modifications are suggested to enable an absolute scale of quality factors to be constructed. Allowance should be made to allow for the dependence of the saturation threshold of lineal energy on the type of heavy charged particle. Also, an artificial saturation threshold should be introduced for electron tracks as a mean of modifying the measurements made in the microdosimeter to the more realistic site sizes of nanometer dimensions. The proposed absolute scale of quality factors nicely encompasses the high RBEs of around 3 observed at low doses for tritium β rays and is consistent with the recent recommendation of the ICRP that the quality factor for fast neutrons be increased by a factor of two, assuming that there is no biological repair for the reference radiation.

An easy-to-operate portable pulse-height analysis system for area monitoring with TEPC in radiation protection

NASA Astrophysics Data System (ADS)

Kunz, A.; Pihet, P.; Arend, E.; Menzel, H. G.

1990-12-01

A portable area monitor for the measurement of dose-equivalent quantities in practical radiation-protection work has been developed. The detector applied is a low-pressure proportional counter (TEPC) used in microdosimetry. The complex analysis system required has been optimized with regard to low power consumption and small size to achieve a real operational survey meter. The newly designed electronic includes complete analog, digital and microprocessor boards. It presents the characteristic of fast pulse-height processing over a large (5 decades) dynamic range. Three original circuits have been specifically developed, consisting of: (1) a miniaturized adjustable high-voltage power supply with low ripple and high stability; (2) a double spectroscopy amplifier with constant gain ratio and common pole-zero stage; and (3) an analog-to-digital converter with quasi-logarithmic characteristics based on a flash converter using fast comparators associated in parallel. With the incorporated single-board computer, the maximal total power consumption is 5 W, enabling 40 hours operation time with batteries. With minor adaptations the equipment is proposed as a low-cost solution for various measuring problems in environmental studies.

Neutron dose estimation via LET spectrometry using CR-39 detector for the reaction 9Be (p, n)

PubMed Central

Sahoo, G. S.; Tripathy, S. P.; Paul, S.; Sharma, S. D.; Sharma, S. C.; Joshi, D. S.; Bandyopadhyay, T.

2014-01-01

CR-39 detectors, widely used for neutron dosimetry in accelerator radiation environment, have also been applied in tissue microdosimetry by generating the linear energy transfer (LET) spectrum. In this work, the neutron dose has been estimated via LET spectrometry for 9Be (p, n) reaction which is useful for personnel monitoring around particle accelerators and accelerator based therapy facilities. Neutrons were generated by the interaction of protons of 6 different energies from 4–24 MeV with a thick Be target. The LET spectra were obtained from the major and minor radii of each track and the thickness of removed surface. From the LET spectra, the absorbed dose (DLET) and the dose equivalent (HLET) were estimated using Q-L relationship as given by International Commission on Radiological Protection (ICRP) 60. The track density in CR-39 detector and hence the neutron yield was found to be increasing with the increase in projectile (proton) energy. Similar observations were also obtained for absorbed dose (DLET) and dose equivalents (HLET). PMID:25525310

Radiation Damage to Nervous System: Designing Optimal Models for Realistic Neuron Morphology in Hippocampus

NASA Astrophysics Data System (ADS)

Batmunkh, Munkhbaatar; Bugay, Alexander; Bayarchimeg, Lkhagvaa; Lkhagva, Oidov

2018-02-01

The present study is focused on the development of optimal models of neuron morphology for Monte Carlo microdosimetry simulations of initial radiation-induced events of heavy charged particles in the specific types of cells of the hippocampus, which is the most radiation-sensitive structure of the central nervous system. The neuron geometry and particles track structures were simulated by the Geant4/Geant4-DNA Monte Carlo toolkits. The calculations were made for beams of protons and heavy ions with different energies and doses corresponding to real fluxes of galactic cosmic rays. A simple compartmental model and a complex model with realistic morphology extracted from experimental data were constructed and compared. We estimated the distribution of the energy deposition events and the production of reactive chemical species within the developed models of CA3/CA1 pyramidal neurons and DG granule cells of the rat hippocampus under exposure to different particles with the same dose. Similar distributions of the energy deposition events and concentration of some oxidative radical species were obtained in both the simplified and realistic neuron models.

Microdosimetry of the full slowing down of protons using Monte Carlo track structure simulations.

PubMed

Liamsuwan, T; Uehara, S; Nikjoo, H

2015-09-01

The article investigates two approaches in microdosimetric calculations based on Monte Carlo track structure (MCTS) simulations of a 160-MeV proton beam. In the first approach, microdosimetric parameters of the proton beam were obtained using the weighted sum of proton energy distributions and microdosimetric parameters of proton track segments (TSMs). In the second approach, phase spaces of energy depositions obtained using MCTS simulations in the full slowing down (FSD) mode were used for the microdosimetric calculations. Targets of interest were water cylinders of 2.3-100 nm in diameters and heights. Frequency-averaged lineal energies ([Formula: see text]) obtained using both approaches agreed within the statistical uncertainties. Discrepancies beyond this level were observed for dose-averaged lineal energies ([Formula: see text]) towards the Bragg peak region due to the small number of proton energies used in the TSM approach and different energy deposition patterns in the TSM and FSD of protons. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Fission neutron source in Rome

NASA Astrophysics Data System (ADS)

Coppola, Mario; Di Majo, V.; Ingrao, G.; Rebessi, S.; Testa, A.

1997-02-01

A fission neutron source is operating in Rome at the ENEA Casaccia Research Center since 1971, consisting of a low power fast reactor named RSV-Tapiro. it is employed for a variety of experiments, including dosimetry, material testing, radiation protection and biology. In particular, application to experimental radiobiology includes studies of the biological action of neutrons in the whole-body irradiated animal, or in specialized systems in vivo or in vitro. For his purpose a vertical irradiation facility was originally constructed. Recently, a new horizontal irradiation facility has been designed to allow the exposure of larger samples or larger sample batches at one time. Dosimetry at the sample irradiation positions is routinely carried out by the conventional method of using two ion chambers. This physical dosimetry has recently been compared with the results of biological dosimetry based on the detection of chromosomal aberrations in peripheral blood human lymphocytes irradiated in vitro. A characterization of the radiation quality in the two configurations has been carried out by tissue equivalent proportional counter microdosimetry measurements. Information about the main characteristics of the reactor and the two irradiation facilities is provided and relevant results of the various measurements are summarized. Radiobiological results obtained using this neutron source are also briefly outlined.

Monte Carlo track structure for radiation biology and space applications

NASA Technical Reports Server (NTRS)

Nikjoo, H.; Uehara, S.; Khvostunov, I. G.; Cucinotta, F. A.; Wilson, W. E.; Goodhead, D. T.

2001-01-01

Over the past two decades event by event Monte Carlo track structure codes have increasingly been used for biophysical modelling and radiotherapy. Advent of these codes has helped to shed light on many aspects of microdosimetry and mechanism of damage by ionising radiation in the cell. These codes have continuously been modified to include new improved cross sections and computational techniques. This paper provides a summary of input data for ionizations, excitations and elastic scattering cross sections for event by event Monte Carlo track structure simulations for electrons and ions in the form of parametric equations, which makes it easy to reproduce the data. Stopping power and radial distribution of dose are presented for ions and compared with experimental data. A model is described for simulation of full slowing down of proton tracks in water in the range 1 keV to 1 MeV. Modelling and calculations are presented for the response of a TEPC proportional counter irradiated with 5 MeV alpha-particles. Distributions are presented for the wall and wall-less counters. Data shows contribution of indirect effects to the lineal energy distribution for the wall counters responses even at such a low ion energy.

Toxicokinetic and Dosimetry Modeling Tools for Exposure ...

EPA Pesticide Factsheets

New technologies and in vitro testing approaches have been valuable additions to risk assessments that have historically relied solely on in vivo test results. Compared to in vivo methods, in vitro high throughput screening (HTS) assays are less expensive, faster and can provide mechanistic insights on chemical action. However, extrapolating from in vitro chemical concentrations to target tissue or blood concentrations in vivo is fraught with uncertainties, and modeling is dependent upon pharmacokinetic variables not measured in in vitro assays. To address this need, new tools have been created for characterizing, simulating, and evaluating chemical toxicokinetics. Physiologically-based pharmacokinetic (PBPK) models provide estimates of chemical exposures that produce potentially hazardous tissue concentrations, while tissue microdosimetry PK models relate whole-body chemical exposures to cell-scale concentrations. These tools rely on high-throughput in vitro measurements, and successful methods exist for pharmaceutical compounds that determine PK from limited in vitro measurements and chemical structure-derived property predictions. These high throughput (HT) methods provide a more rapid and less resource–intensive alternative to traditional PK model development. We have augmented these in vitro data with chemical structure-based descriptors and mechanistic tissue partitioning models to construct HTPBPK models for over three hundred environmental and pharmace

Space radiation research in the new millenium--from where we come and where we go.

PubMed

Kiefer, J

2001-01-01

Space radiation research had a significant impact in the past. The physical interaction of heavy charged particles with living matter and the development of models, including microdosimetry, were stimulated by problems encountered in space. New phenomena were discovered. Advanced dosimetric techniques had to be developed and computational methods to describe the radiation field in space. The understanding of the radiobiology of heavy ions, necessary for a well-founded risk assessment and prompted by space radiation research, constitutes also the basis for heavy ion radiotherapy. So far unknown areas like the interaction of microgravity and radiation were opened. The space station will give even more opportunities. For the first time it will be possible to investigate animals for a longer time under the influence of both microgravity and radiation. Living systems can be exposed under well defined conditions with parallel physical measurements. Solar particle events are still an unsolved problem. Significant improvement in their predictability and quantitative description can be expected. All this will not only give exciting opportunities for research but will also translate into immediate benefit for human beings. This paper will attempt to give an overview of the past achievements and glance into the future.

Nanodosimetry of (125)I Auger electrons.

PubMed

Bantsar, Aliaksandr; Pszona, Stanislaw

2012-12-01

The nanodosimetric description of the radiation action of Auger electrons on nitrogen targets of nanometric size is presented. Experimental microdosimetry at nanometer scale for Auger electrons has been accomplished with the set-up called Jet Counter. This consists of a pulse-operated valve which injects an expanding nitrogen jet into an interaction chamber where a gaseous sensitive volume of cylindrical shape is created. The ionization cluster size distributions (ICSD) created by Auger electrons emitted by (125)I while crossing a nanometer-sized volume have been measured. The ICSD for the sensitive volumes corresponding to 3 and 12 nm in diameter (in unit density 1 g/cm(3)) irradiated by electrons emitted by a (125)I source were collected and compared with the corresponding Monte Carlo (MC) simulation. The preliminary results of the experiments with Auger electrons of (125)I interacting with a nitrogen jet having nanometric size comparable to a deoxyribonucleic acid (DNA) and nucleosome, showing the discrete spectrum of ICSD with extended cluster size, are described. The presented paper describes for the first time the nanodosimetric experiments with Auger electrons emitted by (125)I. A set of the new descriptors of the radiation quality describing the radiation effect at nanometer level is proposed. The ICSD were determined for the first time for an Auger emitter of (125)I.

COMPARISON STUDY OF VARIOUS PLASTICS AS THE WALL MATERIAL OF THGEM-BASED MICRODOSEMETERS FOR FAST NEUTRON MEASUREMENTS.

PubMed

Moslehi, A; Raisali, G; Lamehi, M

2017-04-15

To find appropriate substitutions for the expensive plastics of A-150 and rexolite used in the construction of thick gas electron multiplier (THGEM)-based tissue-equivalent proportional counters, in the present work, the responses of a THGEM-based microdosimetric detector made of A-150 and rexolite and three others composed of plexiglas (PMMA), polyethylene and polystyrene plastics as the wall materials have been compared. Lineal energy distribution, frequency-averaged lineal energy, dose-averaged lineal energy, mean quality factor and dose-equivalent for 0.1, 1 and 10 MeV neutrons and also for 241Am-Be neutrons are calculated using Geant4 simulation toolkit. Frequency-averaged lineal energy, dose-averaged lineal energy, mean quality factor and dose-equivalent values for all plastics are found similar. In addition, the response of an indigenously constructed microdosemeter with PMMA walls is also measured for 241Am-Be neutrons. The experimental results are in good agreement with the simulation predictions. Conclusively, it was found that the three considered plastics can be used as good candidates instead of A-150 and rexolite plastics in fast neutron microdosimetry. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Next generation radiotherapy biomaterials loaded with high-Z nanoparticles

NASA Astrophysics Data System (ADS)

Cifter, Gizem

This research investigates the dosimetric feasibility of using high-Z nanoparticles as localized radiosensitizers to boost the dose to the residual tumor cells during accelerated partial breast irradiation while minimizing the dose to surrounding healthy tissue. Analytical microdosimetry calculations were carried out to calculate dose enhancement (DEF) in the presence of high-Z nanoparticles. It has been proposed that routinely used inert radiotherapy (RT) biomaterials (e.g. fiducials, spacers) can be upgraded to smarter ones by coating/loading them with radiosensitizing gold nanoparticles (GNPs), for sustained in-situ release after implantation to enhance RT. Prototype smart biomaterials were produced by incorporating the GNPs in poly (D,L-lactide-co-glycolide) (PLGA) polymer millirods during the gel phase of production. In vitro release of GNPs was monitored over time by optical/spectroscopy methods as a function of various design parameters. The prototype smart biomaterials displayed sustained customizable release of NPs in-vitro, reaching a burst release profile approximately after 25 days. The results also show that customizable release profiles can be achievable by varying GNP concentrations that are embedded within smart biomaterials, as well as other design parameters. This would potentially allow customizable local dose boost resulting in diverse treatment planning opportunities for individual cases. Considered together, the results provide preliminary data for development of next generation of RT biomaterials, which can be employed at no additional inconvenience to RT patients.

Implementation of new physics models for low energy electrons in liquid water in Geant4-DNA.

PubMed

Bordage, M C; Bordes, J; Edel, S; Terrissol, M; Franceries, X; Bardiès, M; Lampe, N; Incerti, S

2016-12-01

A new alternative set of elastic and inelastic cross sections has been added to the very low energy extension of the Geant4 Monte Carlo simulation toolkit, Geant4-DNA, for the simulation of electron interactions in liquid water. These cross sections have been obtained from the CPA100 Monte Carlo track structure code, which has been a reference in the microdosimetry community for many years. They are compared to the default Geant4-DNA cross sections and show better agreement with published data. In order to verify the correct implementation of the CPA100 cross section models in Geant4-DNA, simulations of the number of interactions and ranges were performed using Geant4-DNA with this new set of models, and the results were compared with corresponding results from the original CPA100 code. Good agreement is observed between the implementations, with relative differences lower than 1% regardless of the incident electron energy. Useful quantities related to the deposited energy at the scale of the cell or the organ of interest for internal dosimetry, like dose point kernels, are also calculated using these new physics models. They are compared with results obtained using the well-known Penelope Monte Carlo code. Copyright © 2016 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

SU-F-T-193: Evaluation of a GPU-Based Fast Monte Carlo Code for Proton Therapy Biological Optimization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Taleei, R; Qin, N; Jiang, S

2016-06-15

Purpose: Biological treatment plan optimization is of great interest for proton therapy. It requires extensive Monte Carlo (MC) simulations to compute physical dose and biological quantities. Recently, a gPMC package was developed for rapid MC dose calculations on a GPU platform. This work investigated its suitability for proton therapy biological optimization in terms of accuracy and efficiency. Methods: We performed simulations of a proton pencil beam with energies of 75, 150 and 225 MeV in a homogeneous water phantom using gPMC and FLUKA. Physical dose and energy spectra for each ion type on the central beam axis were scored. Relativemore » Biological Effectiveness (RBE) was calculated using repair-misrepair-fixation model. Microdosimetry calculations were performed using Monte Carlo Damage Simulation (MCDS). Results: Ranges computed by the two codes agreed within 1 mm. Physical dose difference was less than 2.5 % at the Bragg peak. RBE-weighted dose agreed within 5 % at the Bragg peak. Differences in microdosimetric quantities such as dose average lineal energy transfer and specific energy were < 10%. The simulation time per source particle with FLUKA was 0.0018 sec, while gPMC was ∼ 600 times faster. Conclusion: Physical dose computed by FLUKA and gPMC were in a good agreement. The RBE differences along the central axis were small, and RBE-weighted dose difference was found to be acceptable. The combined accuracy and efficiency makes gPMC suitable for proton therapy biological optimization.« less

Simulated Response of a Tissue-equivalent Proportional Counter on the Surface of Mars.

PubMed

Northum, Jeremy D; Guetersloh, Stephen B; Braby, Leslie A; Ford, John R

2015-10-01

Uncertainties persist regarding the assessment of the carcinogenic risk associated with galactic cosmic ray (GCR) exposure during a mission to Mars. The GCR spectrum peaks in the range of 300(-1) MeV n to 700 MeV n(-1) and is comprised of elemental ions from H to Ni. While Fe ions represent only 0.03% of the GCR spectrum in terms of particle abundance, they are responsible for nearly 30% of the dose equivalent in free space. Because of this, radiation biology studies focusing on understanding the biological effects of GCR exposure generally use Fe ions. Acting as a thin shield, the Martian atmosphere alters the GCR spectrum in a manner that significantly reduces the importance of Fe ions. Additionally, albedo particles emanating from the regolith complicate the radiation environment. The present study uses the Monte Carlo code FLUKA to simulate the response of a tissue-equivalent proportional counter on the surface of Mars to produce dosimetry quantities and microdosimetry distributions. The dose equivalent rate on the surface of Mars was found to be 0.18 Sv y(-1) with an average quality factor of 2.9 and a dose mean lineal energy of 18.4 keV μm(-1). Additionally, albedo neutrons were found to account for 25% of the dose equivalent. It is anticipated that these data will provide relevant starting points for use in future risk assessment and mission planning studies.

A journey into medical physics as viewed by a physicist

NASA Astrophysics Data System (ADS)

Gueye, Paul

2007-03-01

The world of physics is usually linked to a large variety of subjects spanning from astrophysics, nuclear/high energy physics, materials and optical sciences, plasma physics etc. Lesser is known about the exciting world of medical physics that includes radiation therapy physics, medical diagnostic and imaging physics, nuclear medicine physics, and medical radiation safety. These physicists are typically based in hospital departments of radiation oncology or radiology, and provide technical support for patient diagnosis and treatment in a clinical environment. This talk will focus on providing a bridge between selected areas of physics and their medical applications. The journey will first start from our understanding of high energy beam production and transport beamlines for external beam treatment of diseases (e.g., electron, gamma, X-ray and proton machines) as they relate to accelerator physics. We will then embrace the world of nuclear/high energy physics where detectors development provide a unique tool for understanding low energy beam distribution emitted from radioactive sources used in Brachytherapy treatment modality. Because the ultimate goal of radiation based therapy is its killing power on tumor cells, the next topic will be microdosimetry where responses of biological systems can be studied via electromagnetic systems. Finally, the impact on the imaging world will be embraced using tools heavily used in plasma physics, fluid mechanics and Monte Carlo simulations. These various scientific areas provide unique opportunities for faculty and students at universities, as well as for staff from research centers and laboratories to contribute in this field. We will conclude with the educational training related to medical physics programs.

Design study of beam transport lines for BioLEIR facility at CERN

NASA Astrophysics Data System (ADS)

Ghithan, S.; Roy, G.; Schuh, S.

2017-09-01

The biomedical community has asked CERN to investigate the possibility to transform the Low Energy Ion Ring (LEIR) accelerator into a multidisciplinary, biomedical research facility (BioLEIR) that could provide ample, high-quality beams of a range of light ions suitable for clinically oriented, fundamental research on cell cultures and for radiation instrumentation development. The present LEIR machine uses fast beam extraction to the next accelerator in the chain, eventually leading to the Large Hadron Collider (LHC) . To provide beam for a biomedical research facility, a new slow extraction system must be installed. Two horizontal and one vertical experimental beamlines were designed for transporting the extracted beam to three experimental end-stations. The vertical beamline (pencil beam) was designed for a maximum energy of 75 MeV/u for low-energy radiobiological research, while the two horizontal beamlines could deliver up to 440 MeV/u. One horizontal beamline shall be used preferentially for biomedical experiments and shall provide pencil beam and a homogeneous broad beam, covering an area of 5 × 5 cm2 with a beam homogeneity of ±5%. The second horizontal beamline will have pencil beam only and is intended for hardware developments in the fields of (micro-)dosimetry and detector development. The minimum full aperture of the beamlines is approximately 100 mm at all magnetic elements, to accommodate the expected beam envelopes. Seven dipoles and twenty quadrupoles are needed for a total of 65 m of beamlines to provide the specified beams. In this paper we present the optical design for the three beamlines.

“Protective Bystander Effects Simulated with the State-Vector Model”—HeLa x Skin Exposure to 137Cs Not Protective Bystander Response But Mammogram and Diagnostic X-Rays Are

PubMed Central

Leonard, Bobby E.

2008-01-01

The recent Dose Response journal article “Protective Bystander Effects Simulated with the State-Vector Model” (Schollnberger and Eckl 2007) identified the suppressive (below natural occurring, zero primer dose, spontaneous level) dose response for HeLa x skin exposure to 137Cs gamma rays (Redpath et al 2001) as a protective Bystander Effect (BE) behavior. I had previously analyzed the Redpath et al (2001) data with a Microdose Model and conclusively showed that the suppressive response was from Adaptive Response (AR) radio-protection (Leonard 2005, 2007a). The significance of my microdose analysis has been that low LET radiation induced single (i.e. only one) charged particle traversals through a cell can initiate a Poisson distributed activation of AR radio-protection. The purpose of this correspondence is to clarify the distinctions relative to the BE and the AR behaviors for the Redpath groups 137Cs data, show conversely however that the Redpath group data for mammography (Ko et al 2004) and diagnostic (Redpath et al 2003) X-rays do conclusively reflect protective bystander behavior and also herein emphasize the need for radio-biologist to apply microdosimetry in planning and analyzing their experiments for BE and AR. Whether we are adamantly pro-LNT, adamantly anti-LNT or, like most of us, just simple scientists searching for the truth in radio-biology, it is important that we accurately identify our results, especially when related to the LNT hypothesis controversy. PMID:18846260

Gold nanoparticle enhancement of stereotactic radiosurgery for neovascular age-related macular degeneration

NASA Astrophysics Data System (ADS)

Ngwa, Wilfred; Makrigiorgos, G. Mike; Berbeco, Ross I.

2012-10-01

Age-related macular degeneration (AMD) is the leading cause of blindness in developed countries for people over the age of 50. In this work, the dosimetric feasibility of using gold nanoparticles (AuNP) as radiosensitizers to enhance kilovoltage stereotactic radiosurgery for neovascular AMD is investigated. Microdosimetry calculations at the sub-cellular level were carried out to estimate the radiation dose enhancement to individual nuclei in neovascular AMD endothelial cells (nDEF) due to photon-induced photo-/Auger electrons from x-ray-irradiated AuNP. The nDEF represents the ratio of radiation doses to the endothelial cell nuclei with and without AuNP. The calculations were carried out for a range of feasible AuNP local concentrations using the clinically applicable 100 kVp x-ray beam parameters employed by a commercially available x-ray therapy system. The results revealed nDEF values of 1.30-3.26 for the investigated concentration range of 1-7 mg g-1, respectively. In comparison, for the same concentration range, nDEF values of 1.32-3.40, 1.31-3.33, 1.29-3.19, 1.28-3.12 were calculated for 80, 90, 110 and 120 kVp x-rays, respectively. Meanwhile, calculations as a function of distance from the AuNP showed that the dose enhancement, for 100 kVp, is markedly confined to the targeted neovascular AMD endothelial cells where AuNP are localized. These findings provide impetus for considering the application of AuNP to enhance therapeutic efficacy during stereotactic radiosurgery for neovascular AMD.

Cellular studies and interaction mechanisms of extremely low frequency fields

NASA Astrophysics Data System (ADS)

Liburdy, Robert P.

1995-01-01

Worldwide interest in the biological effects of ELF (extremely low frequency, <1 kHz) electromagnetic fields has grown significantly. Health professionals and government administrators and regulators, scientists and engineers, and, importantly, an increasing number of individuals in the general public are interested in this health issue. The goal of research at the cellular level is to identify cellular responses to ELF fields, to develop a dose threshold for such interactions, and with such information to formulate and test appropriate interaction mechanisms. This review is selective and will discuss the most recent cellular studies directed at these goals which relate to power line, sinusoidal ELF fields. In these studies an interaction site at the cell membrane is by consensus a likely candidate, since changes in ion transport, ligand-receptor events such as antibody binding, and G protein activation have been reported. These changes strongly indicate that signal transduction (ST) can be influenced. Also, ELF fields are reported to influence enzyme activation, gene expression, protein synthesis, and cell proliferation, which are triggered by earlier ST events at the cell membrane. The concept of ELF fields altering early cell membrane events and thereby influencing intracellular cell function via the ST cascade is perhaps the most plausible biological framework currently being investigated for understanding ELF effects on cells. For example, the consequence of an increase due to ELF fields in mitogenesis, the final endpoint of the ST cascade, is an overall increase in the probability of mutagenesis and consequently cancer, according to the Ames epigenetic model of carcinogenesis. Consistent with this epigenetic mechanism and the ST pathway to carcinogenesis is recent evidence that ELF fields can alter breast cancer cell proliferation and can act as a copromoter in vitro. The most important dosimetric question being addressed currently is whether the electric (E) or the magnetic (B) field, or if combinations of static B and time-varying B fields represent an exposure metric for the cell. This question relates directly to understanding fundamental interaction mechanisms and to the development of a rationale for ELF dose threshold guidelines. The weight of experimental evidence indicates that an induced E field according to Faraday's law of induction during magnetic field exposures elicits cellular effects. An E-field-mediated interaction has interesting consequences for microdosimetry at the cellular level and is mechanistically consistent with an interaction at the cell surface, since the E field does not penetrate beyond the cell membrane. Recently, several studies have suggested that an ELF B field by itself or in combination with a static B field may elicit cellular effects. Thus in addition to E-field-mediated effects, other interaction mechanisms as yet not fully understood may operate at the cellular level; this complexity is in contrast to the case for ionizing radiation. In addition to the question of an exposure field metric, the biological state of the target cell is important in ELF interactions. Biological factors such as cell type, cell cycle, cell activation, age of donor animal, passage number of cell line, presence of specific growth/mitogenic factors, temperature, shape, and cell density/packing during exposures have been shown to play a role in mediating ELF interactions with cells. Most recently, reports of single-cell studies usher in a new direction for research that can be termed microbioelectromagnetics. Single-cell digital microscopy introduces a new approach to answer the above questions with potential for real-time microdosimetry and bioeffects limited only by the spatial resolution of state-of-the-art microscopy, which is approximately 0.1 /μm. Digital imaging microscopy should therefore permit the quantitative assessment of spatial and temporal features of ELF field interactions within living single cells.

Chasing Ghosts in Space Radiobiology Research: The Lost Focus on Non-Targeted Effects

NASA Astrophysics Data System (ADS)

Cucinotta, Francis; Saganti, Premkumar; Cacao, Eliedonna

2016-07-01

The doses and dose-rates of astronaut exposures to galactic cosmic rays (GCR) are accurately known, and lead to particle hits per cell nucleus from high charge and energy (HZE) particles of much less than one hit per cell per week. A large number of experiments have shown that additivity of biological effects is a valid assumption for space radiation exposures, while experiments at higher doses and dose-rates than occur in space continue to be a focus of the majority of space radiobiology research. Furthermore HZE particle exposures with mono-energetic particles manifest themselves as a mixed-radiation field due to the contributions of delta-rays and the random impact parameter of a particles track core to DNA and non-DNA targets in cells and tissues. The mixed-field manifestation of mono-energetic HZE particle exposures is well known from theoretical studies of microdosimetry and track structure. Additional mixed-field effects occur for single species experiments due to nuclear fragmentation in particle accelerator beam-lines and biological samples along with energy straggling. In contrast to these well known aspects of space radiobiology there are many open questions on the contribution of non-targeted effects to low dose and dose-rate exposures. Non-targeted effects (NTEs) include bystander effects and genomic instability, and have been shown to be the most important outstanding question for reducing uncertainties in space radiation cancer risk assessment. The dose-rate and radiation quality dependence of NTE's has not been established, while there is an over-arching need to develop 21st century experimental models of human cancer risk. We review possible mechanisms of NTE's and how new experiments to address these issues could be designed.

Weanling piglet cerebellum: a surrogate for tolerance to MRT (microbeam radiation therapy) in pediatric neuro-oncology

NASA Astrophysics Data System (ADS)

Laissue, Jean A.; Blattmann, Hans; Di Michiel, Marco; Slatkin, Daniel N.; Lyubimova, Nadia; Guzman, Raphael; Zimmermann, Werner; Birrer, Stephan; Bley, Tim; Kircher, Patrick; Stettler, Regina; Fatzer, Rosmarie; Jaggy, Andre; Smilowitz, Henry; Brauer, Elke; Bravin, Alberto; Le Duc, Geraldine; Nemoz, Christian; Renier, Michel; Thomlinson, William C.; Stepanek, Jiri; Wagner, Hans-Peter

2001-12-01

The cerebellum of the weanling piglet (Yorkshire) was used as a surrogate for the radiosensitive human infant cerebellum in a Swiss-led program of experimental microbeam radiation therapy (MRT) at the ESRF. Five weanlings in a 47 day old litter of seven, and eight weanlings in a 40 day old litter of eleven were irradiated in November, 1999 and June, 2000, respectively. A 1.5 cm-wide x 1.5 xm-high array of equally space approximately equals 20-30 micrometers wide, upright microbeams spaced at 210 micrometers intervals was propagated horizontally, left to right, through the cerebella of the prone, anesthetized piglets. Skin-entrance intra-microbeam peak adsorbed doses were uniform, either 150, 300, 425, or 600 gray (Gy). Peak and inter-microbeam (valley) absorbed doses in the cerebellum were computed with the PSI version of the Monte Carlo code GEANT and benchmarked using Gafchromic and radiochromic film microdosimetry. For approximately equals 66 weeks [first litter; until euthanasia], or approximately equals 57 weeks [second litter; until July 30, 2001] after irradiation, the littermates were developmentally, behaviorally, neurologically and radiologically normal as observed and tested by experienced farmers and veterinary scientists unaware of which piglets were irradiated or sham-irradiated. Morever, MRT implemented at the ESRF with a similar array of microbeams and a uniform skin-entrance peak dose of 625 Gy, followed by immunoprophylaxis, was shown to be palliative or curative in young adult rats bearing intracerebral gliosarcomas. These observations give further credence to MRT's potential as an adjunct therapy for brain tumors in infancy, when seamless therapeutic irradiation of the brain is hazardous.

Dosimetric and microdosimetric analyses for blood exposed to reactor-derived thermal neutrons.

PubMed

Ali, F; Atanackovic, J; Boyer, C; Festarini, A; Kildea, J; Paterson, L C; Rogge, R; Stuart, M; Richardson, R B

2018-06-06

Thermal neutrons are found in reactor, radiotherapy, aircraft, and space environments. The purpose of this study was to characterise the dosimetry and microdosimetry of thermal neutron exposures, using three simulation codes, as a precursor to quantitative radiobiological studies using blood samples. An irradiation line was designed employing a pyrolytic graphite crystal or-alternatively-a super mirror to expose blood samples to thermal neutrons from the National Research Universal reactor to determine radiobiological parameters. The crystal was used when assessing the relative biological effectiveness for dicentric chromosome aberrations, and other biomarkers, in lymphocytes over a low absorbed dose range of 1.2-14 mGy. Higher exposures using a super mirror will allow the additional quantification of mitochondrial responses. The physical size of the thermal neutron fields and their respective wavelength distribution was determined using the McStas Monte Carlo code. Spinning the blood samples produced a spatially uniform absorbed dose as determined from Monte Carlo N-Particle version 6 simulations. The major part (71%) of the total absorbed dose to blood was determined to be from the 14 N(n,p) 14 C reaction and the remainder from the 1 H(n,γ) 2 H reaction. Previous radiobiological experiments at Canadian Nuclear Laboratories involving thermal neutron irradiation of blood yielded a relative biological effectiveness of 26 ± 7. Using the Particle and Heavy Ion Transport Code System, a similar value of ∼19 for the quality factor of thermal neutrons initiating the 14 N(n,p) 14 C reaction in soft tissue was determined by microdosimetric simulations. This calculated quality factor is of similar high value to the experimentally-derived relative biological effectiveness, and indicates the potential of thermal neutrons to induce deleterious health effects in superficial organs such as cataracts of the eye lens.

Testing portable luminescence reader signals against late Pleistocene to modern OSL ages of coastal and desert dunefield sand in Israel

NASA Astrophysics Data System (ADS)

Roskin, Joel; Sivan, Dorit; Bookman, Revital; Porat, Naomi; López, Gloria I.

2017-04-01

Rapid assessment of luminescence signals of poly-mineral samples by a pulsed-photon portable OSL reader (PPSL) is useful for interpreting sedimentary sections during fieldwork, and can assist with targeted field sampling for later full OSL dating and prioritize laboratory work. This study investigates PPSL signal intensities in order to assess its usefulness in obtaining relative OSL ages from linear regressions created by interpolating newly generated PPSL values of samples with existing OSL ages from two extensive Nilotic-sourced dunefields. Eighteen OSL-dated sand samples from two quartz-dominated sand systems in Israel were studied:(1) the Mediterranean littoral-sourced coastal dunefields that formed since the middle Holocene; and (2) the inland north-western Negev desert dunefield that rapidly formed between the Last Glacial Maximum and the Holocene. Samples from three coastal dune profiles were also measured. Results show that the PPSL signals differ by several orders of magnitude between modern and late Pleistocene sediments. The coastal and desert sand have different OSL age - PPSL signal ratios. Coastal sand show better correlations between PPSL values and OSL ages. However, using regression curves for each dunefield to interpolate ages is less useful than expected as samples with different ages exhibit similar PPSL signals. The coastal dune profiles yielded low luminescence signal values depicting a modern profile chronology. This study demonstrates that a rapid assessment of the relative OSL ages across different and extensive dunefields is useful and may be achieved. However, the OSL ages obtained by linear regression are only a very rough age estimate. The reasons for not obtaining more reliable ages need to be better understood, as several variables can affect the PPSL signal such as mineral provenance, intrinsic grain properties, micro-dosimetry and moisture content.

High spatial resolution microdosimetry with monolithic ΔE-E detector on 12C beam: Monte Carlo simulations and experiment

NASA Astrophysics Data System (ADS)

Tran, Linh T.; Bolst, David; Guatelli, Susanna; Biasi, Giordano; Fazzi, Alberto; Sagia, Eleni; Prokopovich, Dale A.; Reinhard, Mark I.; Keat, Ying C.; Petasecca, Marco; Lerch, Michael L. F.; Pola, Andrea; Agosteo, Stefano; Matsufuji, Naruhiro; Jackson, Michael; Rosenfeld, Anatoly B.

2018-04-01

Nuclear fragmentation produced in 12C ion therapeutic beams contributes significantly to the Relative Biological Effectiveness (RBE)-weighted dose in the distal edge of the Spread out Bragg Peak (SOBP) and surrounding tissues in out-of-field. Complex mixed radiation field originated by the therapeutic 12C ion beam in a phantom is difficult to measure. This study presents a new method to characterise the radiation field produced in a 12C ion beam using a monolithic ΔE-E telescope which provides the capability to identify the particle components of the mixed radiation field as well as the microdosimetric spectra that allows derivation of the RBE based on a radiobiological model. The response of the monolithic ΔE-E telescope to a 290 MeV/u 12C ion beam at defined positions along the pristine Bragg Peak was studied using the Geant4 Monte Carlo toolkit. The microdosimetric spectra derived from the ΔE stage and the two-dimensional scatter plots of energy deposition in ΔE and E stages of the device in coincidence are presented, as calculated in-field and out-of-field. Partial dose weighted contribution to the microdosimetric spectra from nuclear fragments and recoils, such as 1H, 4He, 3He, 7Li, 9Be and 11B, have been analysed for each position. Comparison of simulation and experimental results are presented and demonstrates that the microdosimetric spectra changes dramatically within 0.5 mm depth increments close to and at the distal edge of the Bragg Peak which is impossible to identify using conventional Tissue Equivalent Proportional Counter (TEPC).

A Compact Soft X-Ray Microscope using an Electrode-less Z-Pinch Source.

PubMed

Horne, S F; Silterra, J; Holber, W

2009-01-01

Soft X-rays (< 1Kev) are of medical interest both for imaging and microdosimetry applications. X-ray sources at this low energy present a technological challenge. Synchrotrons, while very powerful and flexible, are enormously expensive national research facilities. Conventional X-ray sources based on electron bombardment can be compact and inexpensive, but low x-ray production efficiencies at low electron energies restrict this approach to very low power applications. Laser-based sources tend to be expensive and unreliable. Energetiq Technology, Inc. (Woburn, MA, USA) markets a 92 eV, 10W(2pi sr) electrode-less Z-pinch source developed for advanced semiconductor lithography. A modified version of this commercial product has produced 400 mW at 430 eV (2pi sr), appropriate for water window soft X-ray microscopy. The US NIH has funded Energetiq to design and construct a demonstration microscope using this source, coupled to a condenser optic, as the illumination system. The design of the condenser optic matches the unique characteristics of the source to the illumination requirements of the microscope, which is otherwise a conventional design. A separate program is underway to develop a microbeam system, in conjunction with the RARAF facility at Columbia University, NY, USA. The objective is to develop a focused, sub-micron beam capable of delivering > 1 Gy/second to the nucleus of a living cell. While most facilities of this type are coupled to a large and expensive particle accelerator, the Z-pinch X-ray source enables a compact, stand-alone design suitable to a small laboratory. The major technical issues in this system involve development of suitable focusing X-ray optics. Current status of these programs will be reported.

A Compact Soft X-Ray Microscope using an Electrode-less Z-Pinch Source

PubMed Central

Silterra, J; Holber, W

2009-01-01

Soft X-rays (< 1Kev) are of medical interest both for imaging and microdosimetry applications. X-ray sources at this low energy present a technological challenge. Synchrotrons, while very powerful and flexible, are enormously expensive national research facilities. Conventional X-ray sources based on electron bombardment can be compact and inexpensive, but low x-ray production efficiencies at low electron energies restrict this approach to very low power applications. Laser-based sources tend to be expensive and unreliable. Energetiq Technology, Inc. (Woburn, MA, USA) markets a 92 eV, 10W(2pi sr) electrode-less Z-pinch source developed for advanced semiconductor lithography. A modified version of this commercial product has produced 400 mW at 430 eV (2pi sr), appropriate for water window soft X-ray microscopy. The US NIH has funded Energetiq to design and construct a demonstration microscope using this source, coupled to a condenser optic, as the illumination system. The design of the condenser optic matches the unique characteristics of the source to the illumination requirements of the microscope, which is otherwise a conventional design. A separate program is underway to develop a microbeam system, in conjunction with the RARAF facility at Columbia University, NY, USA. The objective is to develop a focused, sub-micron beam capable of delivering > 1 Gy/second to the nucleus of a living cell. While most facilities of this type are coupled to a large and expensive particle accelerator, the Z-pinch X-ray source enables a compact, stand-alone design suitable to a small laboratory. The major technical issues in this system involve development of suitable focusing X-ray optics. Current status of these programs will be reported. PMID:20198115

Radiation track, DNA damage and response—a review

NASA Astrophysics Data System (ADS)

Nikjoo, H.; Emfietzoglou, D.; Liamsuwan, T.; Taleei, R.; Liljequist, D.; Uehara, S.

2016-11-01

The purpose of this paper has been to review the current status and progress of the field of radiation biophysics, and draw attention to the fact that physics, in general, and radiation physics in particular, with the aid of mathematical modeling, can help elucidate biological mechanisms and cancer therapies. We hypothesize that concepts of condensed-matter physics along with the new genomic knowledge and technologies and mechanistic mathematical modeling in conjunction with advances in experimental DNA (Deoxyrinonucleic acid molecule) repair and cell signaling have now provided us with unprecedented opportunities in radiation biophysics to address problems in targeted cancer therapy, and genetic risk estimation in humans. Obviously, one is not dealing with ‘low-hanging fruit’, but it will be a major scientific achievement if it becomes possible to state, in another decade or so, that we can link mechanistically the stages between the initial radiation-induced DNA damage; in particular, at doses of radiation less than 2 Gy and with structural changes in genomic DNA as a precursor to cell inactivation and/or mutations leading to genetic diseases. The paper presents recent development in the physics of radiation track structure contained in the computer code system KURBUC, in particular for low-energy electrons in the condensed phase of water for which we provide a comprehensive discussion of the dielectric response function approach. The state-of-the-art in the simulation of proton and carbon ion tracks in the Bragg peak region is also presented. The paper presents a critical discussion of the models used for elastic scattering, and the validity of the trajectory approach in low-electron transport. Brief discussions of mechanistic and quantitative aspects of microdosimetry, DNA damage and DNA repair are also included as developed by the authors’ work.

Spaceflight-relevant types of ionizing radiation and cortical bone: Potential LET effect?

NASA Astrophysics Data System (ADS)

Lloyd, Shane A. J.; Bandstra, Eric R.; Travis, Neil D.; Nelson, Gregory A.; Bourland, J. Daniel; Pecaut, Michael J.; Gridley, Daila S.; Willey, Jeffrey S.; Bateman, Ted A.

2008-12-01

Extended exposure to microgravity conditions results in significant bone loss. Coupled with radiation exposure, this phenomenon may place astronauts at a greater risk for mission-critical fractures. In a previous study, we identified a profound and prolonged loss of trabecular bone (29-39%) in mice following exposure to an acute, 2 Gy dose of radiation simulating both solar and cosmic sources. However, because skeletal strength depends on trabecular and cortical bone, accurate assessment of strength requires analysis of both bone compartments. The objective of the present study was to examine various properties of cortical bone in mice following exposure to multiple types of spaceflight-relevant radiation. Nine-week old, female C57BL/6 mice were sacrificed 110 days after exposure to a single, whole body, 2 Gy dose of gamma, proton, carbon, or iron radiation. Femora were evaluated with biomechanical testing, microcomputed tomography, quantitative histomorphometry, percent mineral content, and micro-hardness analysis. Compared to non-irradiated controls, there were significant differences compared to carbon or iron radiation for only fracture force, medullary area and mineral content. A greater differential effect based on linear energy transfer (LET) level may be present: high-LET (carbon or iron) particle irradiation was associated with a decline in structural properties (maximum force, fracture force, medullary area, and cortical porosity) and mineral composition compared to low-LET radiation (gamma and proton). Bone loss following irradiation appears to be largely specific to trabecular bone and may indicate unique biological microenvironments and microdosimetry conditions. However, the limited time points examined and non-haversian skeletal structure of the mice employed highlight the need for further investigation.

WE-G-BRE-03: Dose Painting by Numbers Using Targeted Gold Nanoparticles

DOE Office of Scientific and Technical Information (OSTI.GOV)

Altundal, Y; Sajo, E; Korideck, H

Purpose: Homogeneous dose enhancement in tumor cells of lung cancer patients treated with conventional dose of 60–66 Gy in five fractions is limited due to increased risk of toxicity to normal structures. Dose painting by numbers (DPBN) is the prescription of a non-uniform radiation dose distribution in the tumor for each voxel based on the intensity level of that voxel obtained from the tumor image. The purpose of this study is to show that DPBN using targeted gold nanoparticles (GNPs) could enhance conventional doses in the more resistant tumor areas. Methods: Cone beam computed tomography (CBCT) images of GNPs aftermore » intratumoral injection into human tumor were taken at 0, 48, 144 and 160 hours. The dose enhancement in the tumor voxels by secondary electrons from the GNPs was calculated based on analytical microdosimetry methods. The dose enhancement factor (DEF) is the ratio of the doses to the tumor with and without the presence of GNPs. The DEF was calculated for each voxel of the images based on the GNP concentration in the tumor sub-volumes using 6-MV photon spectra obtained using Monte Carlo simulations at 5 cm depth (10×10 cm2 field). Results: The results revealed DEF values of 1.05–2.38 for GNPs concentrations of 1–30 mg/g which corresponds to 12.60 – 28.56 Gy per fraction for delivering 12 Gy per fraction homogenously to lung tumor region. Conclusion: Our preliminary results verify that DPBN could be achieved using GNPs to enhance conventional doses to high risk tumor sub-volumes. In practice, DPBN using GNPs could be achieved due to diffusion of targeted GNPs sustainably released in-situ from radiotherapy biomaterials (e.g. fiducials) coated with polymer film containing the GNPs.« less

SU-E-T-98: Towards Cell Nucleus Microdosimetry: Construction of a Confocal Laser-Scanning Fluorescence Microscope to Readout Fluorescence Nuclear Track Detectors (FNTDs).

PubMed

McFadden, C; Bartz, J; Akselrod, M; Sawakuchi, G

2012-06-01

To construct a custom confocal laser scanning microscope (CLSM) capable of resolving individual proton tracks in the volume of an Al 2 O 3 :C,Mg fluorescent nuclear track detector (FNTD). The spatial resolution of the FNTD technique is at the sub-micrometer scale. Therefore the FNTD technique has the potential to perform radiation measurements at the cell nucleus scale. The crystal volume of an FNTD contains defects which become fluorescent F 2 + centers after trapping delta electrons from ionizing radiation. These centers have an absorption band centered at 620 nm and an emission band in the near infrared. Events of energy deposition in the crystal are read-out using a CLSM with sub-micrometer spatial resolution. Excitation light from a 635 nm laser is focused in the crystal volume by an objective lens. Fluorescence is collected back through the same path, filtered through a dichroic mirror, and focused through a small pinhole onto an avalanche photodiode. Lateral scanning of the focal point is performed with a scanning mirror galvanometer, and axial scanning is performed using a stepper-motor stage. Control of electronics and image acquisition was performed using a custom built LabVIEW VI and further image processing was done using Java. The system was used to scan FNTDs exposed to a 6 MV x-ray beam and an unexposed FNTD. Fluorescence images above the unexposed background were obtained at scan depths ranging from 5 - 10 micrometer below the crystal surface using a 100 micrometer pinhole size. Further work needs to be done to increase the resolution and the signal to noise ratio of the images so that energy deposition events may be identified more easily. Natural Sciences and Engineering Research Council of Canada. © 2012 American Association of Physicists in Medicine.

Microdosimetry calculations for monoenergetic electrons using Geant4-DNA combined with a weighted track sampling algorithm.

PubMed

Famulari, Gabriel; Pater, Piotr; Enger, Shirin A

2017-07-07

The aim of this study was to calculate microdosimetric distributions for low energy electrons simulated using the Monte Carlo track structure code Geant4-DNA. Tracks for monoenergetic electrons with kinetic energies ranging from 100 eV to 1 MeV were simulated in an infinite spherical water phantom using the Geant4-DNA extension included in Geant4 toolkit version 10.2 (patch 02). The microdosimetric distributions were obtained through random sampling of transfer points and overlaying scoring volumes within the associated volume of the tracks. Relative frequency distributions of energy deposition f(>E)/f(>0) and dose mean lineal energy ([Formula: see text]) values were calculated in nanometer-sized spherical and cylindrical targets. The effects of scoring volume and scoring techniques were examined. The results were compared with published data generated using MOCA8B and KURBUC. Geant4-DNA produces a lower frequency of higher energy deposits than MOCA8B. The [Formula: see text] values calculated with Geant4-DNA are smaller than those calculated using MOCA8B and KURBUC. The differences are mainly due to the lower ionization and excitation cross sections of Geant4-DNA for low energy electrons. To a lesser extent, discrepancies can also be attributed to the implementation in this study of a new and fast scoring technique that differs from that used in previous studies. For the same mean chord length ([Formula: see text]), the [Formula: see text] calculated in cylindrical volumes are larger than those calculated in spherical volumes. The discrepancies due to cross sections and scoring geometries increase with decreasing scoring site dimensions. A new set of [Formula: see text] values has been presented for monoenergetic electrons using a fast track sampling algorithm and the most recent physics models implemented in Geant4-DNA. This dataset can be combined with primary electron spectra to predict the radiation quality of photon and electron beams.

Comparisons of Integrated Radiation Transport Models with Microdosimetry Data in Spaceflight

NASA Technical Reports Server (NTRS)

Cucinotta, Francis A.; Nikjoo, H.; Kim, M. Y.; Hu, X.; Dicello, J. F.; Pisacane, V. L.

2006-01-01

Astronauts are exposed to galactic cosmic rays (GCR), trapped protons, and possible solar particle events (SPE) during spaceflight. For such complicated mixtures of radiation types and kinetic energies, tissue equivalent proportional counters (TEPC's) represent a simple time-dependent approach for radiation monitoring. Of interest in radiation protection is the average quality factor of a radiation field defined as a function of linear energy transfer, LET, Q(sub ave)(LET). However TEPC's measure the average quality factors as a function of lineal energy (y), Q(sub ave)(y) defined as the average energy deposition in a volume divided by the average chord length of the volume. Lineal energy, y deviates from LET due to energy straggling, delta-ray escape or entry, and nuclear fragments produced in the detector. Using integrated space radiation models that includes the transport code HZETRN/BRYNTRN, the quantum nuclear interaction model, QMSFRG, and results from Monte-Carlo track simulations of TEPC's response to ions, we consider comparisons of model calculations to TEPC results from NASA missions in low Earth orbit and make predictions for lunar and Mars missions. Good agreement between the model and measured spectra from past NASA missions is found. A finding of this work is that TEPC's values for trapped or solar protons of Q(sub ave)(y) range from 1.9-2.5, overestimating Q(sub ave)(LET), which ranges from 1.4-1.6 with both quantities increasing with shielding depth due to nuclear secondaries Comparisons for the complete GCR spectra show that Q(sub ave)(LET) for GCR is approximately 3.5-4.5, while TEPC's measure 2.9-3.4 for Q(sub ave)(y) with the GCR values decreasing with depth as heavy ions are absorbed in shielding material. Our results support the use of TEPC's for space radiation environmental monitoring when computational analysis is used for proper data interpretation.

Radon induced hyperplasia: effective adaptation reducing the local doses in the bronchial epithelium.

PubMed

Madas, Balázs G

2016-09-01

There is experimental and histological evidence that chronic irritation and cell death may cause hyperplasia in the exposed tissue. As the heterogeneous deposition of inhaled radon progeny results in high local doses at the peak of the bronchial bifurcations, it was proposed earlier that hyperplasia occurs in these deposition hot spots upon chronic radon exposure. The objective of the present study is to quantify how the induction of basal cell hyperplasia modulates the microdosimetric consequences of a given radon exposure. For this purpose, computational epithelium models were constructed with spherical cell nuclei of six different cell types based on histological data. Basal cell hyperplasia was modelled by epithelium models with additional basal cells and increased epithelium thickness. Microdosimetry for alpha-particles was performed by an own-developed Monte-Carlo code. Results show that the average tissue dose, and the average hit number and dose of basal cells decrease by the increase of the measure of hyperplasia. Hit and dose distribution reveal that the induction of hyperplasia may result in a basal cell pool which is shielded from alpha-radiation. It highlights that the exposure history affects the microdosimetric consequences of a present exposure, while the biological and health effects may also depend on previous exposures. The induction of hyperplasia can be considered as a radioadaptive response at the tissue level. Such an adaptation of the tissue challenges the validity of the application of the dose and dose rate effectiveness factor from a mechanistic point of view. As the location of radiosensitive target cells may change due to previous exposures, dosimetry models considering the tissue geometry characteristic of normal conditions may be inappropriate for dose estimation in case of protracted exposures. As internal exposures are frequently chronic, such changes in tissue geometry may be highly relevant for other incorporated radionuclides.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wroe, A; Slater, J; McAuley, G

Purpose: To design, implement and evaluate a shielding system that will reduce out-of-field dose experienced by the patient and associated electronic systems in passively scattered proton therapy treatment. Methods: A multi-stage neutron shielding system was retrofitted to the Gantry 1 treatment nozzle at Loma Linda University Medical Center. The system uses multiple borated polyethylene plates staged after the primary beam modifying devices to attenuate and absorb neutrons produced by such devices. This arrangement locates increasing levels of shielding between the sources of secondary particles in the nozzle and the patient. Additionally, the design of this shielding structure allows it tomore » be easily retrofitted to an existing proton nozzle system without impacting design or treatment beam characteristics. The effectiveness of the shielding was evaluated both through experimental measurements and Geant4 Monte Carlo simulations. Results: Measurements were completed with Landauer Luxel+ dosimeters that use optically stimulated luminescence and CR-39 to detect fast neutrons, thermal neutrons, protons, photons and beta particles. Measurements of a 250 MeV proton beam indicated that the shielding system reduced out-of-field dose to the patient by almost half with dose equivalent values at 50 and 40 cm from the field edge decreasing from 0.965 and 1.262 mSv/Gy to 0.596 and 0.777 mSv/Gy respectively. The installation of the multi-stage shielding system also reduced dose equivalent experienced by electronic systems installed in the treatment room by up to 80%. Geant4 simulations were also used to evaluate the neutron fluence at various positions in the treatment room as well as provide information on microdosimetry spectra within the patient and treatment room. Conclusion: The shielding system described above proved to be an effective an inexpensive method of reducing out-of-field doses to the patient and electronic systems and can be easily retrofitted to existing passive scattering nozzles.« less

TU-H-CAMPUS-TeP2-03: High Sensitivity and High Resolution Fiber Based Micro-Detector for Sub-Millimeter Preclinical Dosimetry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Izaguirre, E; Pokhrel, S; Knewtson, T

2016-06-15

Purpose: Current precision of small animal and cell micro-irradiators has continuously increased during the past years. Currently, preclinical irradiators can deliver sub-millimeter fields with micrometric precision but there are no water equivalent dosimeters to determine small field profiles and dose in the orthovoltage range of energies with micrometric resolution and precision. We have developed a fiber based micro-dosimeter with the resolution and dosimetric accuracy required for radiobiological research. Methods: We constructed two prototypes of micro-dosimeters based on different compositions of fiber scintillators to study the spatial resolution and dosimetric precision of small animal and cell micro-irradiators. The first has greenmore » output and the second has blue output. The blue output dosimeter has the highest sensitivity because it matches the spectral sensitivity of silicon photomultipliers. A blue detector with 500um cross section was built and tested respect to a CC01 ion chamber, film, and the 1500um green output detector. Orthovoltage fields from 1×1mm2 to 5×5mm2 were used for detector characteristics comparison. Results: The blue fiber dosimeter shows great agreement with films and matches dose measurements with the gold-standard ion chamber for 5×5mm2 fields. The detector has the appropriate sensitivity to measure fields from 1×1mm2 to larger sizes with a 1% dosimetric accuracy. The spatial resolution is in the sub-millimeter range and the spectral matching with the photomultiplier allows reducing the sensor cross section even further than the presented prototype. These results suggest that scintillating fibers combined with silicon photomultipliers is the appropriate technology to pursue micro-dosimetry for small animals and disperse cell samples. Conclusion: The constructed detectors establish a new landmark for the resolution and sensitivity of fiber based microdetectors. The validation of the detector in our small animal and cell irradiator shows that they are appropriate for preclinical and micro single cell irradiation quality assurance and dosimetry.« less

SU-E-T-26: A Study On the Influence of Photonuclear Reactions On the Biological Effectiveness of Therapeutic High Energy X-Ray Beam

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wakita, A; National Cancer Center Hospital, Chuo-ku, Tokyo; Matsufuji, N

2014-06-01

Purpose: Photons from a modern high-energy therapeutic linear accelerator used in X-ray radiotherapy causes photonuclear reactions in an accelerator or patient's body. The aim of this study is to evaluate the biological effectiveness including these particles by Microdosimetric Kinetic Model (MKM) based on microdosimetry. Methods: A linear accelerator operating at 15 MV was used. CR-39 was used to obtain LET spectra of secondary ions selectively, as CR-39 is regarded insensitive to photons. CR-39 was put on the central axis of the X-ray beam at depths of 0, 5 and 10 cm in plastic phantom at a source to detector distancemore » of 100 cm. Pits formed by the traversal of ions were etched then analyzed to obtain restricted LET distribution. Frequency-mean and dose-mean lineal energy was evaluated from the relationship between the restricted LET and the lineal energy required to evaluate the biological effectiveness by MKM. The relationship was calculated by Monte Carlo simulations with GEANT4. Results: Restricted LET distributions of secondary particles showed broad distributions that decreases exponentially with increasing LET. Frequency-mean and dose-mean lineal energy were determined uniquely within the scope of the energies of secondary particles generated from photons of 15 MeV. The frequency-mean lineal energies at the depth of 0, 5 and 10 cm were 15.1, 16.0 and 19.7 keV/μm respectively, and the dose-mean lineal energies were 18.6, 20.5 and 19.6 keV/μm, respectively. RBE of secondary particles for HSG cell evaluated by MKM was about 2.0 at all depths, and RBE of all particles including photons was evaluated 1.0. Conclusion: We investigated the biological effectiveness of secondary particles by photonuclear reactions. The method to evaluate RBE by MKM was established with measurements and simulations. However, the influence of these secondary ions on RBE was found negligible in the entire biological effectiveness of the high-energy X-ray. This study has been supported by JSPS KAKENHI Grant Number 25861144.« less

SU-E-T-565: RAdiation Resistance of Cancer CElls Using GEANT4 DNA: RACE

DOE Office of Scientific and Technical Information (OSTI.GOV)

Perrot, Y; Payno, H; Delage, E

2014-06-01

Purpose: The objective of the RACE project is to develop a comparison between Monte Carlo simulation using the Geant4-DNA toolkit and measurements of radiation damage on 3D melanoma and chondrosarcoma culture cells coupled with gadolinium nanoparticles. We currently expose the status of the developments regarding simulations. Methods: Monte Carlo studies are driven using the Geant4 toolkit and the Geant4-DNA extension. In order to model the geometry of a cell population, the opensource CPOP++ program is being developed for the geometrical representation of 3D cell populations including a specific cell mesh coupled with a multi-agent system. Each cell includes cytoplasm andmore » nucleus. The correct modeling of the cell population has been validated with confocal microscopy images of spheroids. The Geant4 Livermore physics models are used to simulate the interactions of a 250 keV X-ray beam and the production of secondaries from gadolinium nanoparticles supposed to be fixed on the cell membranes. Geant4-DNA processes are used to simulate the interactions of charged particles with the cells. An atomistic description of the DNA molecule, from PDB (Protein Data Bank) files, is provided by the so-called PDB4DNA Geant4 user application we developed to score energy depositions in DNA base pairs and sugar-phosphate groups. Results: At the microscopic level, our simulations enable assessing microscopic energy distribution in each cell compartment of a realistic 3D cell population. Dose enhancement factors due to the presence of gadolinium nanoparticles can be estimated. At the nanometer scale, direct damages on nuclear DNA are also estimated. Conclusion: We successfully simulated the impact of direct radiations on a realistic 3D cell population model compatible with microdosimetry calculations using the Geant4-DNA toolkit. Upcoming validation and the future integration of the radiochemistry module of Geant4-DNA will propose to correlate clusters of ionizations with in vitro experiments. All those developments will be released publicly. This work was supported by grants from Plan Cancer 2009-2013 French national initiative managed by INSERM (Institut National de la Sante et de la Recherche Medicale)« less

Use of radiochromic film as a high-spatial resolution dosimeter by Raman spectroscopy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mirza, Jamal Ahmad; Park, Hyeonsuk

Purpose: Due to increasing demand for high-spatial resolution dosimetry, radiochromic films have been investigated as potential candidates but are often limited by the scanning system, e.g., flatbed optical scanner. In this study, Raman spectroscopy in conjunction with a microscope was selected as an alternative method for high-spatial resolution dosimetry of radiochromic film. Methods: Unlaminated Gafchromic™ EBT3 films were irradiated with doses between 0 and 50 Gy using 6 MV x-rays of a clinical linear accelerator. Depth profiling from the surface of unlaminated film was performed to acquire the maximum Raman intensity peaks of C≡C and C=C stretching bands of diacetylenemore » polymer. The Raman mapping technique for a region of interest (200 × 200, 30 × 30 μm{sup 2}) was developed to reduce a large variation in a Raman spectrum produced with a sampling resolution of a few μm. The preprocessing of Raman spectra was carried out to determine a dosimetric relationship with the amount of diacetylene polymerization. Results: Due to partial diacetylene polymerization upon irradiation, two Raman peaks of C=C and C≡C stretching bands were observed around 1447 and 2060 cm{sup −1}, respectively. The maximum intensities of the two peaks were obtained by positioning a focused laser spot on the surface of unlaminated film. For the dose range of 0–50 Gy, the band heights of both C≡C and C=C peaks increase asymptotically with increasing doses and can be fit with an exponential function of two components. The relative standard deviation in Raman mapping was found to be less than ±5%. By using this technique, dose uniformity was found to be within ±2%. Conclusions: The Raman intensity for C=C and C≡C peaks increases with an increase in the amount of diacetylene polymerization due to an increase in dose. This study shows the potential of Raman spectroscopy as an alternative for absolute dosimetry verifications with a high-spatial resolution of a few μm, but these findings need to be further validated for the purpose of microdosimetry.« less

Particle radiation transport and effects models from research to space weather operations

NASA Astrophysics Data System (ADS)

Santin, Giovanni; Nieminen, Petteri; Rivera, Angela; Ibarmia, Sergio; Truscott, Pete; Lei, Fan; Desorgher, Laurent; Ivanchenko, Vladimir; Kruglanski, Michel; Messios, Neophytos

Assessment of risk from potential radiation-induced effects to space systems requires knowledge of both the conditions of the radiation environment and of the impact of radiation on sensi-tive spacecraft elements. During sensitivity analyses, test data are complemented by models to predict how external radiation fields are transported and modified in spacecraft materials. Radiation transport is still itself a subject of research and models are continuously improved to describe the physical interactions that take place when particles pass through shielding materi-als or hit electronic systems or astronauts, sometimes down to nanometre-scale interactions of single particles with deep sub-micron technologies or DNA structures. In recent years, though, such radiation transport models are transitioning from being a research subject by itself, to being widely used in the space engineering domain and finally being directly applied in the context of operation of space weather services. A significant "research to operations" (R2O) case is offered by Geant4, an open source toolkit initially developed and used in the context of fundamental research in high energy physics. Geant4 is also being used in the space domain, e.g. for modelling detector responses in science payloads, but also for studying the radiation environment itself, with subjects ranging from cosmic rays, to solar energetic particles in the heliosphere, to geomagnetic shielding. Geant4-based tools are now becoming more and more integrated in spacecraft design procedures, also through user friendly interfaces such as SPEN-VIS. Some examples are given by MULASSIS, offering multi-layered shielding analysis capa-bilities in realistic spacecraft materials, or GEMAT, focused on micro-dosimetry in electronics, or PLANETOCOSMICS, describing the interaction of the space environment with planetary magneto-and atmospheres, or GRAS, providing a modular and easy to use interface to various analysis types in simple or complex and realistic 3D geometry models. GRAS will also be part of the space weather SEISOP system for supplying near-real-time detailed information on the interaction of the space radiation environment with selected spacecraft elements.

Gold nanoparticle-aided brachytherapy with vascular dose painting: estimation of dose enhancement to the tumor endothelial cell nucleus.

PubMed

Ngwa, Wilfred; Makrigiorgos, G Mike; Berbeco, Ross I

2012-01-01

Theoretical microdosimetry at the subcellular level is employed in this study to estimate the dose enhancement to tumor endothelial cell nuclei, caused by radiation-induced photo/Auger electrons originating from gold nanoparticles (AuNPs) targeting the tumor endothelium, during brachytherapy. A tumor vascular endothelial cell (EC) is modeled as a slab of 2 μm (thickness) × 10 μm (length) × 10 μm (width). The EC contains a nucleus of 5 μm diameter and thickness of 0.5-1 μm, corresponding to nucleus size 5%-10% of cellular volume, respectively. Analytic calculations based on the electron energy loss formula of Cole were carried out to estimate the dose enhancement to the nucleus caused by photo/Auger electrons from AuNPs attached to the exterior surface of the EC. The nucleus dose enhancement factor (nDEF), representing the ratio of the dose to the nucleus with and without the presence of gold nanoparticles was calculated for different AuNP local concentrations. The investigated concentration range considers the potential for significantly higher local concentration near the EC due to preferential accumulation of AuNP in the tumor vasculature. Four brachytherapy sources: I-125, Pd-103, Yb-169, and 50 kVp x-rays were investigated. For nucleus size of 10% of the cellular volume and AuNP concentrations ranging from 7 to 140 mg/g, brachytherapy sources Pd-103, I-125, 50 kVp, and Yb-169 yielded nDEF values of 5.6-73, 4.8-58.3, 4.7-56.6, and 3.2-25.8, respectively. Meanwhile, for nucleus size 5% of the cellular volume in the same concentration range, Pd-103, I-125, 50 kVp, and Yb-169 yielded nDEF values of 6.9-79.2, 5.1-63.2, 5.0-61.5, and 3.3-28.3, respectively. The results predict that a substantial dose boost to the nucleus of endothelial cells can be achieved by applying tumor vasculature-targeted AuNPs in combination with brachytherapy. Such vascular dose boosts could induce tumor vascular shutdown, prompting extensive tumor cell death.

Spectroscopic properties and radiation damage investigation of a diamond based Schottky diode for ion-beam therapy microdosimetry

NASA Astrophysics Data System (ADS)

Verona, C.; Magrin, G.; Solevi, P.; Grilj, V.; Jakšić, M.; Mayer, R.; Marinelli, Marco; Verona-Rinati, G.

2015-11-01

In this work, a detailed analysis of the properties of a novel microdosimeter based on a synthetic single crystal diamond is reported. Focused ion microbeams were used to investigate the device spectropscopic properties as well as the induced radiation damage effects. A diamond based Schottky diode was fabricated by chemical vapor deposition with a very thin detecting region, about 400 nm thick (approximately 1.4 μm water equivalent thickness), corresponding to the typical size in microdosimetric measurements. A 200 × 200 μm2 square metallic contact was patterned on the diamond surface by standard photolithography to define the sensitive area. Experimental measurements were carried out at the Ruder Bo\\vskovic' Institute microbeam facility using 4 MeV carbon and 5 MeV silicon ions. Ion beam induced charge maps were employed to characterize the microdosimeter response in terms of its charge collection properties. A stable response with no evidence of polarization or memory effects was observed up to the maximum investigated ion beam flux of about 1.7 × 109 ions.cm-2.s-1. A homogeneity of the response about 6% was found over the sensitive region with a well-defined confinement of the response within the active area. Tests of the radiation damage effect were performed by selectively irradiating small areas of the device with different ion fluences, up to about 1012 ions/cm2. An exponential decrease of the charge collection efficiency was observed with a characteristic decay constant of about 4.8 MGy and 1 MGy for C and Si ions, respectively. The experimental data were analyzed by means of GEANT4 Monte Carlo simulations. A direct correlation between the diamond damaging effect and the Non Ionizing Energy Loss (NIEL) fraction was found. In particular, an exponential decay of the charge collection efficiency with an exponential decay as a function of NIEL is observed, with a characteristic constant of about 9.3 kGy-NIEL for both carbon and silicon ions.

Interpretation of TEPC Measurements in Space Flights for Radiation Monitoring

NASA Technical Reports Server (NTRS)

Kim, Myung-Hee Y.; Nikjoo, Hooshang; Dicello, John F.; Pisacane, Vincent; Cucinotta, Francis A.

2007-01-01

For the proper interpretation of radiation data measured in space, the results of integrated radiation transport models were compared with the tissue equivalent proportional counter (TEPC) measurements. TEPC is a simple, time-dependent approach to radiation monitoring for astronauts on board the International Space Station. Another and a newer approach to microdosimetry is the use of silicon-on-insulator (SOI) technology launched on the MidSTAR-1 mission in low Earth orbit (LEO). In the radiation protection practice, the average quality factor of a radiation field is defined as a function of linear energy transfer (LET), Qave(LET). However, TEPC measures the average quality factor as a function of the lineal energy y, Qave(y), defined as the average energy deposition in a volume divided by the average chord length of the volume. The deviation of y from LET is caused by energy straggling, delta-ray escape or entry, and nuclear fragments produced in the detector volume. The response distribution functions of the wall-less and walled TEPCs were calculated from Monte-Carlo track simulations. Using an integrated space radiation model (which includes the transport codes HZETRN and BRYNTRN, and the quantum nuclear interaction model QMSFRG) and the resultant response distribution functions from Monte-Carlo track simulations, we compared model calculations with the walled-TEPC measurements from NASA missions in LEO and made predictions for the lunar and the Mars missions. Good agreement was found for Qave(y) between the model and measured spectra from past NASA missions. The Qave(y) values for the trapped or the solar protons ranged from 1.9-2.5. This over-estimates the Qave(LET) values which ranged from 1.4-1.6. Both quantities increase with shield thickness due to nuclear fragmentation. The Qave(LET) for the complete GCR spectra was found to be 3.5-4.5, while flight TEPCs measured 2.9-3.4 for Qave(y). The GCR values are decreasing with the shield thickness. Our analysis of the measurements of TEPCs can be used for a proper interpretation of observed data of monitoring the space radiation environment.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Miller, Brian W.; Frost, Sophia; Frayo, Shani

Abstract Alpha emitting radionuclides exhibit a potential advantage for cancer treatments because they release large amounts of ionizing energy over a few cell diameters (50–80 μm) causing localized, irreparable double-strand DNA breaks that lead to cell death. Radioimmunotherapy (RIT) approaches using monoclonal antibodies labeled with alpha emitters may inactivate targeted cells with minimal radiation damage to surrounding tissues. For accurate dosimetry in alpha-RIT, tools are needed to visualize and quantify the radioactivity distribution and absorbed dose to targeted and non-targeted cells, especially for organs and tumors with heterogeneous radionuclide distributions. The aim of this study was to evaluate and characterizemore » a novel single-particle digital autoradiography imager, iQID (ionizing-radiation Quantum Imaging Detector), for use in alpha-RIT experiments. Methods: The iQID camera is a scintillator-based radiation detection technology that images and identifies charged-particle and gamma-ray/X-ray emissions spatially and temporally on an event-by-event basis. It employs recent advances in CCD/CMOS cameras and computing hardware for real-time imaging and activity quantification of tissue sections, approaching cellular resolutions. In this work, we evaluated this system’s characteristics for alpha particle imaging including measurements of spatial resolution and background count rates at various detector configurations and quantification of activity distributions. The technique was assessed for quantitative imaging of astatine-211 (211At) activity distributions in cryosections of murine and canine tissue samples. Results: The highest spatial resolution was measured at ~20 μm full width at half maximum (FWHM) and the alpha particle background was measured at a rate of (2.6 ± 0.5) × 10–4 cpm/cm2 (40 mm diameter detector area). Simultaneous imaging of multiple tissue sections was performed using a large-area iQID configuration (ø 11.5 cm). Estimation of the 211At activity distribution was demonstrated at mBq/μg levels. Conclusion: Single-particle digital autoradiography of alpha emitters has advantages over traditional autoradiographic techniques in terms of spatial resolution, sensitivity, and activity quantification capability. The system features and characterization results presented in this study show that iQID is a promising technology for microdosimetry, because it provides necessary information for interpreting alpha-RIT outcomes and for predicting the therapeutic efficacy of cell-targeted approaches using alpha emitters.« less

Customizable radiotherapy enhancement (CuRE) for prostate cancer using platinum based nanoparticles

NASA Astrophysics Data System (ADS)

Cifter, Gizem

New approach to prostate cancer (PCa) therapy titled "Customizable Radiotherapy Enhancement (CuRE)" employs cisplatin (C), carboplatin (Ca) and oxaliplatin (O) nanoparticles (CNPs, CaNPs and ONPs) as adjuvants to brachytherapy and external beam radiation therapy (EBRT), with the CNPs/CaNPs/ONPs released in situ from either brachytherapy spacers or fudicials loaded with the nanoparticles. The chemotherapy dose from the nanoparticles released in situ from within the prostate capsule, is enhanced by the physical dose due to photon interactions with the nanoparticles. The physical dose enhancement is due to low energy photons from the brachytherapy and EBRT sources interacting with the high-Z platinum component of the nanoparticles, causing emission of short-range photoelectrons to boost dose to the tumor. By varying the nanoparticle parameters, such as size, initial concentration, functionalization, location of spacer or fiducial, and intra-tumor biodistribution, the dose enhancement can be customized to maximize dose to tumor cells while minimizing toxicity to healthy cells. The hypothesis is that the CuRE approach will be a more efficacious method for concomitant cisplatin/carboplatin/oxaliplatin and radiotherapy treatment of localized prostate cancer due to significant dose boost to the PCa cells with minimal toxicity to healthy tissue. To investigate this hypothesis, microdosimetry calculations employing the energy loss formula of Cole were used to calculate the dose enhancement to the PCa cells from the CNPs/CaNPs/OPNs. The dose enhancement ratio (DEF) representing the ratio of the overall dose in the presence of CNPs/CaNPs/ONPs to the dose without CNPs/CaNPs/ONPs was determined for a range of CNP/CaNP/OPN concentrations up to their FDA approved limits. The dose enhancement to endothelial cells with (EDEF) with single concentration of cisplatin (42.8 mg/g) was found 2.6 with Pd-103. When EBRT source was used with single concentration of cisplatin, with 10cm x 10cm field size, at 10 cm depth with standard setting, EDEF was found 2.4. Dose enhancement to tumor cells (DEF) with single concentration of cisplatin was found 5.9 with I-125 while it was found 3.1 when EBRT source was used. The results predict that major localized dose enhancement to PCa cells can be achieved using targeted CNP/CaNP/OPN.

Quantitative single-particle digital autoradiography with α-particle emitters for targeted radionuclide therapy using the iQID camera

DOE Office of Scientific and Technical Information (OSTI.GOV)

Miller, Brian W., E-mail: brian.miller@pnnl.gov; Frost, Sofia H. L.; Frayo, Shani L.

2015-07-15

Purpose: Alpha-emitting radionuclides exhibit a potential advantage for cancer treatments because they release large amounts of ionizing energy over a few cell diameters (50–80 μm), causing localized, irreparable double-strand DNA breaks that lead to cell death. Radioimmunotherapy (RIT) approaches using monoclonal antibodies labeled with α emitters may thus inactivate targeted cells with minimal radiation damage to surrounding tissues. Tools are needed to visualize and quantify the radioactivity distribution and absorbed doses to targeted and nontargeted cells for accurate dosimetry of all treatment regimens utilizing α particles, including RIT and others (e.g., Ra-223), especially for organs and tumors with heterogeneous radionuclidemore » distributions. The aim of this study was to evaluate and characterize a novel single-particle digital autoradiography imager, the ionizing-radiation quantum imaging detector (iQID) camera, for use in α-RIT experiments. Methods: The iQID camera is a scintillator-based radiation detection system that images and identifies charged-particle and gamma-ray/x-ray emissions spatially and temporally on an event-by-event basis. It employs CCD-CMOS cameras and high-performance computing hardware for real-time imaging and activity quantification of tissue sections, approaching cellular resolutions. In this work, the authors evaluated its characteristics for α-particle imaging, including measurements of intrinsic detector spatial resolutions and background count rates at various detector configurations and quantification of activity distributions. The technique was assessed for quantitative imaging of astatine-211 ({sup 211}At) activity distributions in cryosections of murine and canine tissue samples. Results: The highest spatial resolution was measured at ∼20 μm full width at half maximum and the α-particle background was measured at a rate as low as (2.6 ± 0.5) × 10{sup −4} cpm/cm{sup 2} (40 mm diameter detector area). Simultaneous imaging of multiple tissue sections was performed using a large-area iQID configuration (ø 11.5 cm). Estimation of the {sup 211}At activity distribution was demonstrated at mBq/μg-levels. Conclusions: Single-particle digital autoradiography of α emitters has advantages over traditional film-based autoradiographic techniques that use phosphor screens, in terms of spatial resolution, sensitivity, and activity quantification capability. The system features and characterization results presented in this study show that the iQID is a promising technology for microdosimetry, because it provides necessary information for interpreting alpha-RIT outcomes and for predicting the therapeutic efficacy of cell-targeted approaches using α emitters.« less

Quantitative single-particle digital autoradiography with α-particle emitters for targeted radionuclide therapy using the iQID camera.

PubMed

Miller, Brian W; Frost, Sofia H L; Frayo, Shani L; Kenoyer, Aimee L; Santos, Erlinda; Jones, Jon C; Green, Damian J; Hamlin, Donald K; Wilbur, D Scott; Fisher, Darrell R; Orozco, Johnnie J; Press, Oliver W; Pagel, John M; Sandmaier, Brenda M

2015-07-01

Alpha-emitting radionuclides exhibit a potential advantage for cancer treatments because they release large amounts of ionizing energy over a few cell diameters (50-80 μm), causing localized, irreparable double-strand DNA breaks that lead to cell death. Radioimmunotherapy (RIT) approaches using monoclonal antibodies labeled with α emitters may thus inactivate targeted cells with minimal radiation damage to surrounding tissues. Tools are needed to visualize and quantify the radioactivity distribution and absorbed doses to targeted and nontargeted cells for accurate dosimetry of all treatment regimens utilizing α particles, including RIT and others (e.g., Ra-223), especially for organs and tumors with heterogeneous radionuclide distributions. The aim of this study was to evaluate and characterize a novel single-particle digital autoradiography imager, the ionizing-radiation quantum imaging detector (iQID) camera, for use in α-RIT experiments. The iQID camera is a scintillator-based radiation detection system that images and identifies charged-particle and gamma-ray/x-ray emissions spatially and temporally on an event-by-event basis. It employs CCD-CMOS cameras and high-performance computing hardware for real-time imaging and activity quantification of tissue sections, approaching cellular resolutions. In this work, the authors evaluated its characteristics for α-particle imaging, including measurements of intrinsic detector spatial resolutions and background count rates at various detector configurations and quantification of activity distributions. The technique was assessed for quantitative imaging of astatine-211 ((211)At) activity distributions in cryosections of murine and canine tissue samples. The highest spatial resolution was measured at ∼20 μm full width at half maximum and the α-particle background was measured at a rate as low as (2.6 ± 0.5) × 10(-4) cpm/cm(2) (40 mm diameter detector area). Simultaneous imaging of multiple tissue sections was performed using a large-area iQID configuration (ø 11.5 cm). Estimation of the (211)At activity distribution was demonstrated at mBq/μg-levels. Single-particle digital autoradiography of α emitters has advantages over traditional film-based autoradiographic techniques that use phosphor screens, in terms of spatial resolution, sensitivity, and activity quantification capability. The system features and characterization results presented in this study show that the iQID is a promising technology for microdosimetry, because it provides necessary information for interpreting alpha-RIT outcomes and for predicting the therapeutic efficacy of cell-targeted approaches using α emitters.

A review: Development of a microdose model for analysis of adaptive response and bystander dose response behavior.

PubMed

Leonard, Bobby E

2008-02-27

Prior work has provided incremental phases to a microdosimetry modeling program to describe the dose response behavior of the radio-protective adaptive response effect. We have here consolidated these prior works (Leonard 2000, 2005, 2007a, 2007b, 2007c) to provide a composite, comprehensive Microdose Model that is also herein modified to include the bystander effect. The nomenclature for the model is also standardized for the benefit of the experimental cellular radio-biologist. It extends the prior work to explicitly encompass separately the analysis of experimental data that is 1.) only dose dependent and reflecting only adaptive response radio-protection, 2.) both dose and dose-rate dependent data and reflecting only adaptive response radio-protection for spontaneous and challenge dose damage, 3.) only dose dependent data and reflecting both bystander deleterious damage and adaptive response radio-protection (AR-BE model). The Appendix cites the various applications of the model. Here we have used the Microdose Model to analyze the, much more human risk significant, Elmore et al (2006) data for the dose and dose rate influence on the adaptive response radio-protective behavior of HeLa x Skin cells for naturally occurring, spontaneous chromosome damage from a Brachytherapy type (125)I photon radiation source. We have also applied the AR-BE Microdose Model to the Chromosome inversion data of Hooker et al (2004) reflecting both low LET bystander and adaptive response effects. The micro-beam facility data of Miller et al (1999), Nagasawa and Little (1999) and Zhou et al (2003) is also examined. For the Zhou et al (2003) data, we use the AR-BE model to estimate the threshold for adaptive response reduction of the bystander effect. The mammogram and diagnostic X-ray induction of AR and protective BE are observed. We show that bystander damage is reduced in the similar manner as spontaneous and challenge dose damage as shown by the Azzam et al (1996) data. We cite primary unresolved questions regarding adaptive response behavior and bystander behavior. The five features of major significance provided by the Microdose Model so far are 1. Single Specific Energy Hits initiate Adaptive Response. 2. Mammogram and diagnostic X-rays induce a protective Bystander Effect as well as Adaptive Response radio-protection. 3. For mammogram X-rays the Adaptive Response protection is retained at high primer dose levels. 4. The dose range of the AR protection depends on the value of the Specific Energy per Hit, 1 >. 5. Alpha particle induced deleterious Bystander damage is modulated by low LET radiation.

A Review: Development of a Microdose Model for Analysis of Adaptive Response and Bystander Dose Response Behavior

PubMed Central

Leonard, Bobby E.

2008-01-01

Prior work has provided incremental phases to a microdosimetry modeling program to describe the dose response behavior of the radio-protective adaptive response effect. We have here consolidated these prior works (Leonard 2000, 2005, 2007a, 2007b, 2007c) to provide a composite, comprehensive Microdose Model that is also herein modified to include the bystander effect. The nomenclature for the model is also standardized for the benefit of the experimental cellular radio-biologist. It extends the prior work to explicitly encompass separately the analysis of experimental data that is 1.) only dose dependent and reflecting only adaptive response radio-protection, 2.) both dose and dose-rate dependent data and reflecting only adaptive response radio-protection for spontaneous and challenge dose damage, 3.) only dose dependent data and reflecting both bystander deleterious damage and adaptive response radio-protection (AR-BE model). The Appendix cites the various applications of the model. Here we have used the Microdose Model to analyze the, much more human risk significant, Elmore et al (2006) data for the dose and dose rate influence on the adaptive response radio-protective behavior of HeLa x Skin cells for naturally occurring, spontaneous chromosome damage from a Brachytherapy type 125I photon radiation source. We have also applied the AR-BE Microdose Model to the Chromosome inversion data of Hooker et al (2004) reflecting both low LET bystander and adaptive response effects. The micro-beam facility data of Miller et al (1999), Nagasawa and Little (1999) and Zhou et al (2003) is also examined. For the Zhou et al (2003) data, we use the AR-BE model to estimate the threshold for adaptive response reduction of the bystander effect. The mammogram and diagnostic X-ray induction of AR and protective BE are observed. We show that bystander damage is reduced in the similar manner as spontaneous and challenge dose damage as shown by the Azzam et al (1996) data. We cite primary unresolved questions regarding adaptive response behavior and bystander behavior. The five features of major significance provided by the Microdose Model so far are 1.) Single Specific Energy Hits initiate Adaptive Response, 2.) Mammogram and diagnostic X-rays induce a protective Bystander Effect as well as Adaptive Response radio-protection. 3.) For mammogram X-rays the Adaptive Response protection is retained at high primer dose levels. 4.) The dose range of the AR protection depends on the value of the Specific Energy per Hit, . 5.) Alpha particle induced deleterious Bystander damage is modulated by low LET radiation. PMID:18648579

Boron neutron capture therapy applied to advanced breast cancers: Engineering simulation and feasibility study of the radiation treatment protocol

NASA Astrophysics Data System (ADS)

Sztejnberg Goncalves-Carralves, Manuel Leonardo

This dissertation describes a novel Boron Neutron Capture Therapy (BNCT) application for the treatment of human epidermal growth factor receptor type 2 positive (HER2+) breast cancers. The original contribution of the dissertation is the development of the engineering simulation and the feasibility study of the radiation treatment protocol for this novel combination of BNCT and HER2+ breast cancer treatment. This new concept of BNCT, representing a radiation binary targeted treatment, consists of the combination of two approaches never used in a synergism before. This combination may offer realistic hope for relapsed and/or metastasized breast cancers. This treatment assumes that the boronated anti-HER2 monoclonal antibodies (MABs) are administrated to the patient and accumulate preferentially in the tumor. Then the tumor is destroyed when is exposed to neutron irradiation. Since the use of anti-HER2 MABs yields good and promising results, the proposed concept is expected to amplify the known effect and be considered as a possible additional treatment approach to the most severe breast cancers for patients with metastasized cancer for which the current protocol is not successful and for patients refusing to have the standard treatment protocol. This dissertation makes an original contribution with an integral numerical approach and proves feasible the combination of the aforementioned therapy and disease. With these goals, the dissertation describes the theoretical analysis of the proposed concept providing an integral engineering simulation study of the treatment protocol. An extensive analysis of the potential limitations, capabilities and optimization factors are well studied using simplified models, models based on real CT patients' images, cellular models, and Monte Carlo (MCNP5/X) transport codes. One of the outcomes of the integral dosimetry assessment originally developed for the proposed treatment of advanced breast cancers is the implementation of BNCT for HER2+ breast cancers for deep seated tumors using MITRII-FCB facility with an 8 cm diameter beam (port closest-to-tumor position), with boron concentrations in the tumor higher than 32 mug/g, and for a tumor-to-healthy tissue boron concentration ratio of 8:1. The therapeutic ratios for the proposed treatment would be higher than five for skin and adipose tissue and higher than three for tumor surrounding fibroglandular tissue. The microdosimetry study shows potential improvements in the therapeutic ratios based on the expected sub-cellular boron biodistributions. The engineering simulation study of clinical cases shows the advantages of using BNCT for HER+ breast cancers. Assuming an assured high efficiency of the boron agent delivery, the proposed concept can be considered for stage IV HER2+ breast cancers in treating the metastasized tumors in brain, head and neck, and lungs.

Physical and biological studies with protons and HZE particles in a NASA supported research center in radiation health.

PubMed

Chatterjee, A; Borak, T H

2001-01-01

NASA has established and supports a specialized center for research and training (NSCORT) to specifically address the potential deleterious effects of HZE particles on human health. The NSCORT in radiation health is a joint effort between Lawrence Berkeley National Laboratory (LBNL) and Colorado State University (CSU). The overall scope of research encompasses a broad range of subjects from microdosimetric studies to cellular and tissue responses to initial damage produced by highly energetic protons and heavy charged particles of the type found in galactic cosmic rays (GCR) spectrum. The objectives of the microdosimetry studies are to determine the response of Tissue Equivalent Proportional Counter (TEPC) to cosmic rays using ground based accelerators. This includes evaluation of energy loss due to the escape of high-energy delta rays and increased energy deposition due to the enhanced delta ray production in the wall of the detector. In this report major results are presented for 56Fe at 1000, 740, 600 and 400 MeV/nucleon. An assessment of DNA repair and early development of related chromosomal changes is extremely important to our overall understanding of enhanced biological effectiveness of high LET particle radiation. Results are presented with respect to the fidelity of the rejoining of double strand breaks and the implications of misrejoining. The relationship between molecular and cytogenetic measurements is presented by studying damage processing in highly heterochromatic supernumerary (correction of sypernumerary) X chromosomes and the active X-chromosome. One of the important consequences of cell's inability to handle DNA damage can be evaluated through mutation studies. Part of our goal is the assessment of potential radioprotectors to reduce the mutation yield following HZE exposures, and some promising results are presented on one compound. A second goal is the integration of DNA repair and mutation studies. Results are presented on a direct comparison of initial double strand breaks induction, the time course and fidelity of double strand break rejoining, cell killing and mutation induction in the same human model system. In order to understand the carcinogenic potential of protons and HZE particles, the role of damaged microenvironment in this process must be understood. In this project it has been postulated that radiation affects the microenvironment, which then modifies cell interactions in a manner conducive to neoplastic progression. Both TGF-beta and FGF-2 are important components of microenvironment. A recent result on the assessment of the role of FGF-2 and its cross-talk with TGF-beta as a function of radiation quality is presented. Theoretical modeling has so far played a central role in analyzing and integrating experimental data on repair and mutation studies and predicting new phenomena. The integrated NSCORT program also provides a broad training experience for students and postdoctoral fellows in space radiation health.

Physical and biological studies with protons and HZE particles in a NASA supported research center in radiation health

NASA Technical Reports Server (NTRS)

Chatterjee, A.; Borak, T. H.

2001-01-01

NASA has established and supports a specialized center for research and training (NSCORT) to specifically address the potential deleterious effects of HZE particles on human health. The NSCORT in radiation health is a joint effort between Lawrence Berkeley National Laboratory (LBNL) and Colorado State University (CSU). The overall scope of research encompasses a broad range of subjects from microdosimetric studies to cellular and tissue responses to initial damage produced by highly energetic protons and heavy charged particles of the type found in galactic cosmic rays (GCR) spectrum. The objectives of the microdosimetry studies are to determine the response of Tissue Equivalent Proportional Counter (TEPC) to cosmic rays using ground based accelerators. This includes evaluation of energy loss due to the escape of high-energy delta rays and increased energy deposition due to the enhanced delta ray production in the wall of the detector. In this report major results are presented for 56Fe at 1000, 740, 600 and 400 MeV/nucleon. An assessment of DNA repair and early development of related chromosomal changes is extremely important to our overall understanding of enhanced biological effectiveness of high LET particle radiation. Results are presented with respect to the fidelity of the rejoining of double strand breaks and the implications of misrejoining. The relationship between molecular and cytogenetic measurements is presented by studying damage processing in highly heterochromatic supernumerary (correction of sypernumerary) X chromosomes and the active X-chromosome. One of the important consequences of cell's inability to handle DNA damage can be evaluated through mutation studies. Part of our goal is the assessment of potential radioprotectors to reduce the mutation yield following HZE exposures, and some promising results are presented on one compound. A second goal is the integration of DNA repair and mutation studies. Results are presented on a direct comparison of initial double strand breaks induction, the time course and fidelity of double strand break rejoining, cell killing and mutation induction in the same human model system. In order to understand the carcinogenic potential of protons and HZE particles, the role of damaged microenvironment in this process must be understood. In this project it has been postulated that radiation affects the microenvironment, which then modifies cell interactions in a manner conducive to neoplastic progression. Both TGF-beta and FGF-2 are important components of microenvironment. A recent result on the assessment of the role of FGF-2 and its cross-talk with TGF-beta as a function of radiation quality is presented. Theoretical modeling has so far played a central role in analyzing and integrating experimental data on repair and mutation studies and predicting new phenomena. The integrated NSCORT program also provides a broad training experience for students and postdoctoral fellows in space radiation health.

Comparison of Integrated Radiation Transport Models with TEPC Measurements for the Average Quality Factors in Spaceflights

NASA Technical Reports Server (NTRS)

Kim, Myung-Hee Y.; Nikjoo, Hooshang; Dicello, John F.; Pisacane, Vincent; Cucinotta, Francis A.

2007-01-01

The purpose of this work is to test our theoretical model for the interpretation of radiation data measured in space. During the space missions astronauts are exposed to the complex field of radiation type and kinetic energies from galactic cosmic rays (GCR), trapped protons, and sometimes solar particle events (SPEs). The tissue equivalent proportional counter (TEPC) is a simple time-dependent approach for radiation monitoring for astronauts on board the International Space Station. Another and a newer approach to Microdosimetry is the use of silicon-on-insulator (SOI) technology launched on the MidSTAR-1 mission in low Earth orbit (LEO). In the radiation protection practice, the average quality factor of a radiation field is defined as a function of linear energy transfer (LET), Q(sub ave)(LET). However, TEPC measures the average quality factor as a function of the lineal energy y, Q(sub ave)(y), defined as the average energy deposition in a volume divided by the average chord length of the volume. Lineal energy, y, deviates from LET due to energy straggling, delta-ray escape or entry, and nuclear fragments produced in the detector volume. Monte Carlo track structure simulation was employed to obtain the response of a TEPC irradiated with charged particle for an equivalent site diameter of 1 micron of wall-less counter. The calculated data of the energy absorption in the wall-less counter were compiled for various y values for several ion types at various discrete projectile energy levels. For the simulation of TEPC response from the mixed radiation environments inside a spacecraft, such as, Space Shuttle and International Space Station, the complete microdosimetric TEPC response, f( y, E, Z), were calculated with the Monte Carlo theoretical results by using the first order Lagrangian interpolation for a monovariate function at a given y value (y = 0.1 keV/micron 5000 keV/micron) at any projectile energy level (E = 0.01 MeV/u to 50,000 MeV/u) of each specific radiation type (Z = 1 to 28). Because the anomalous response has been observed at large event sizes in the experiment due to the escape of energy out of sensitive volume by delta-rays and the entry of delta-rays from the high-density wall into the low-density gas-volume cavity, Monte Carlo simulation was also made for the response of a walled-TEPC with wall thickness 2 mm and density 1 g/cm(exp 3). The radius of cavity was set to 6.35 mm and a gas density 7.874 x 10(exp -5) g/cm(exp 3). The response of the walled- and the wall-less counters were compared. The average quality factor Q(sub ave)(y) for trapped protons on STS-89 demonstrated the good agreement between the model calculations and flight TEPC data as shown. Using an integrated space radiation model (this includes the transport codes HZETRN and BRYNTRN, the quantum nuclear interaction model QMSFRG) and the resultant response distribution functions of walled-TEPC from Monte-Carlo track simulations, we compared model calculations with walled-TEPC measurements from NASA missions in LEO and made predictions for the lunar and the Mars missions. The Q(sub ave)(y) values for the trapped or the solar protons ranged from 1.9-2.5. This over-estimates the Qave(LET) values which ranged from 1.4-1.6. Both quantities increase with shield thickness due to nuclear fragmentation. The Q(sub ave)(LET) for the complete GCR spectra was found to be 3.5-4.5, while flight TEPCs measured 2.9-3.4 for Q(sub ave)(y). The GCR values are decreasing with the shield thickness. Our analysis for a proper interpretation of data supports the use of TEPCs for monitoring space radiation environment.

Microdosimetric measurements of a clinical proton beam with micrometer-sized solid-state detector.

PubMed

Anderson, Sarah E; Furutani, Keith M; Tran, Linh T; Chartier, Lachlan; Petasecca, Marco; Lerch, Michael; Prokopovich, Dale A; Reinhard, Mark; Perevertaylo, Vladimir L; Rosenfeld, Anatoly B; Herman, Michael G; Beltran, Chris

2017-11-01

Microdosimetry is a vital tool for assessing the microscopic patterns of energy deposition by radiation, which ultimately govern biological effect. Solid-state, silicon-on-insulator microdosimeters offer an approach for making microdosimetric measurements with high spatial resolution (on the order of tens of micrometers). These high-resolution, solid-state microdosimeters may therefore play a useful role in characterizing proton radiotherapy fields, particularly for making highly resolved measurements within the Bragg peak region. In this work, we obtain microdosimetric measurements with a solid-state microdosimeter (MicroPlus probe) in a clinical, spot-scanning proton beam of small spot size. The MicroPlus probe had a 3D single sensitive volume on top of silicon oxide. The sensitive volume had an active cross-sectional area of 250 μm × 10 μm and thickness of 10 μm. The proton facility was a synchrotron-based, spot-scanning system with small spot size (σ ≈ 2 mm). We performed measurements with the clinical beam current (≈1 nA) and had no detected pulse pile-up. Measurements were made in a water-equivalent phantom in water-equivalent depth (WED) increments of 0.25 mm or 1.0 mm along pristine Bragg peaks of energies 71.3 MeV and 159.9 MeV, respectively. For each depth, we measured lineal energy distributions and then calculated the dose-weighted mean lineal energy, y¯D. The measurements were repeated for two field sizes: 4 × 4 cm 2 and 20 × 20 cm 2 . For both 71.3 MeV and 159.9 MeV and for both field sizes, y¯D increased with depth toward the distal edge of the Bragg peak, a result consistent with Monte Carlo calculations and measurements performed elsewhere. For the 71.3 MeV, 4 × 4 cm 2 beam (range at 80% distal falloff, R 80  = 3.99 cm), we measured y¯D=1.96±0.08 keV/μm at WED = 2 cm, and y¯D=10.6±0.32 keV/μm at WED = 3.95 cm. For the 71.3 MeV, 20 × 20 cm 2 beam, we measured y¯D=2.46±0.12 keV/μm at WED = 2.6 cm, and y¯D=11.0±0.24 keV/μm at WED = 3 cm. For the 159.9 MeV, 4 × 4 cm 2 beam (R 80  = 17.7 cm), y¯D=2.24±0.15 keV/μm at WED = 5 cm, and y¯D=8.99±0.71 keV/μm at WED = 17.6 cm. For the 159.9 MeV, 20 × 20 cm 2 beam, y¯D=2.56±0.10 keV/μm at WED = 5 cm, and y¯D=9.24±0.73 keV/μm at WED = 17.6 cm. We performed microdosimetric measurements with a novel solid-state, silicon-on-insulator microdosimeter in a clinical spot-scanning proton beam of small spot size and unmodified beam current. For all of the proton field sizes and energies considered, the measurements of y¯D were in agreement with expected trends. Furthermore, we obtained measurements with a spatial resolution of 10 μm in the beam direction. This spatial resolution greatly exceeded that possible with a conventional gaseous tissue-equivalent proportional counter and allowed us to perform a high-resolution investigation within the Bragg peak region. The MicroPlus probe is therefore suitable for applications in proton radiotherapy. © 2017 American Association of Physicists in Medicine.

Nanomaterials in Space: is the Future Granted?

NASA Astrophysics Data System (ADS)

Mircea, Chipara

The quantum effects of this confinement resulted in new or modified physical properties. Actually, these studies are extended from confined and patterned materials at the nanometer scale, to metamaterials (a new class of engineered nanocomposites) in which the role of interfaces, at nanometer scale, has a particular relevance. These researches resulted not only in new materials, but also in new devices and technologies. Smaller, lighter, better, and more efficient, are the blueprints of these new devices and technologies. Such features are of particular importance for space applications. patterned at nanometer scale and metamaterials) in space environments, by identifying several groups of problems: a). Dosimetry. The models for the range and deposited energy in a target assume that the target is infinite. The effect of the confinement at the nanometer scale is not considered. Accordingly, microdosimetry concepts have to be developed and tested at such scales. Physicists faced analogous problems at the transition from macroscopic to microscopic properties, as for example in the case of magnetic calculations. The usual macroscopic approaches failed to give an accurate representation of magnetic properties in the case of nanowires, magnetic nanoclusters, ultrathin films and multilayers, and patterned magnetic materials at nanometer scale, resulting in the development of a new theoretical approach (micromagnetic calculations and modeling [1, 2]). The linear approximation (single event), frequently used to explain and model the effect of ionizing radiation on materials would become obsolete. There are several factors that would enhance the contribution of higher order effects. The first is due to the fact that the energy released by the incident particle within the target is delocalised over an area of 102 to 104 nm2. This is actually the size of the latent track within the target. For a nanopatterned structure this area is larger than the size of the feature. As a result, the energy deposited by the incident particle may be spreaded over several features, resulting in a cooperative irradiation effect. Analogous effects including significant departures from linearity were noticed in the degradation of polymers [3]. b). Radiation induced defects in nanomaterials. The effects of ionizing radiation on nanometer sized crystalline structures may be dramatic. This behavior is extremely simple taking into account that the incident particle may displace the target's nuclei, by producing lattice defects. For a macroscopic crystal consisting of a huge number of nuclei, such defects have usually a reduced weight and accordingly the structure of the target is not significantly affected. At nanometer scale, the number of nuclei is fairly low 102 to 106 and the relative weight of these processes in dramatically enhanced. It is possible to speculate that in space, the future nanomaterial is not a nanocrystal but rather a nano amorphous structure. In metamaterials or nanocomposites the nanometer sized interface is affected by several contributions as the displacement of the atoms from one side of the interface into the other side of the interface, the enhancement of the diffusion process within the interface due to the energy released as heat in the nanointerface by the incident particle, and even the appearance of new interfaces represented by cooperative nanometer sized defects, induced by the impinging particle. Such effects have been already reported in the case of irradiated copolymers and block copolymers [3]. c). Competition between several degradation processes. The space environment is not only a cocktail of ionizing particles. Several factors as temperature, thermal cycling, pressure, presence of atomic oxygen, UV-Vis or IR radiation compete with the ionizing radiation. A proper understanding of their effect as well as a detailed analysis of possible couplings between such processes is important. develop and test a new theory for the effects of radiation on solid targets, at the nanometer scale, to extend previous calculations in order to include higher order effects, and finally to understand and if it is possible to protect these nanometer sized structures or to design nanometer sized structures that are less significantly affected by the space environment. As a final warning, a recent paper [4] mentioned that the under the effect of ion beam bombardment the nanocrystalline zirconia has been transformed in an amorphous material. References: [1]. A. Aharoni, Introduction to the Theory of Ferromagnetism, Oxford University Press, Oxford, 1996. [2]. M. Chipara, R. Skomski, D. J. Sellmyer, J. Magn. Magn. Mat. to appear. [3]. Irradiation of Polymers: Fundamentals and Technological Applications, Edited by Roger L. Clough, S. W. Shalaby, [4] A. Meldrum, L. A. Boatner, R. C. Ewing, Phys. Rev. Lett, 88, 025503-1 (2002).