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Microdosimetry for Boron Neutron Capture Therapy

Description: The specific aims of the research proposal were as follows: (1) To design and construct small volume tissue equivalent proportional counters for the dosimetry and microdosimetry of high intensity thermal and epithermal neutron beams used in BNCT, and of modified fast neutron beams designed for boron neutron capture enhanced fast neutron therapy (BNCEFNT). (2) To develop analytical methods for estimating the biological effectiveness of the absorbed dose in BNCT and BNCEFNT based on the measured microdosimetric spectra. (3) To develop an analytical framework for comparing the biological effectiveness of different epithermal neutron beams used in BNCT and BNCEFNT, based on correlated sets of measured microdosimetric spectra and radiobiological data. Specific aims (1) and (2) were achieved in their entirety and are comprehensively documented in Jay Burmeister's Ph.D. dissertation entitled ''Specification of physical and biologically effective absorbed dose in radiation therapies utilizing the boron neutron capture reaction'' (Wayne State University, 1999). Specific aim (3) proved difficult to accomplish because of a lack of sufficient radiobiological data.
Date: September 5, 2000
Creator: Maughan, R.L. & Kota, C.
Partner: UNT Libraries Government Documents Department

The use of microdosimetric techniques in radiation protection measurements

Description: A major objective of radiation protection is to determine the dose equivalent for routine radiation protection applications. As microdosimetry has developed over approximately three decades, its most important application has been in measuring radiation quality, especially in radiation fields of unknown or inadequately known energy spectra. In these radiation fields, determination of dose equivalent is not straightforward; however, the use of microdosimetric principles and techniques could solve this problem. In this paper, the authors discuss the measurement of lineal energy, a microscopic analog to linear energy transfer, and demonstrate the development and implementation of the variance-covariance method, a novel method in experimental microdosimetry. This method permits the determination of dose mean lineal energy, an essential parameter of radiation quality, in a radiation field of unknown spectrum, time-varying dose rate, and high dose rate. Real-time monitoring of changes in radiation quality can also be achieved by using microdosimetric techniques.
Date: January 1, 1997
Creator: Chen, J.; Hsu, H.H.; Casson, W.H. & Vasilik, D.G.
Partner: UNT Libraries Government Documents Department

An HSEF for murine myeloid leukemia

Description: In the past decade, a large amount of effort has gone into the development of hit size effectiveness functions (HSEFs), with the ultimate aim of replacing the present absorbed dose-RBE-Q system. However, the absorbed dose determined at the tissue level is incapable of providing information on single hits on (doses to) the single cell. As a result, it is necessary to resort to microdosimetry, which is capable of providing not only the number of hits on cells, but the distribution of hit sizes as well. From this information, an HSEF can be derived. However, to date there have been no sets of data available on animals exposed to radiations of several qualities, and for which microdosimetric data were available. The objective of the present set of experiments was to remedy this situation. Large numbers of mice were exposed to radiations of several different qualities, and were observed throughout their entire lifespan for the appearance of myeloid leukemia. The HSEF developed for this neoplasm is presented and discussed.
Date: October 1, 1996
Creator: Bond, V.P.; Cronkite, E.P.; Bullis, J.E.; Wuu, C.S.; Marino, S.A. & Zaider, M.
Partner: UNT Libraries Government Documents Department

Microdosimetry of monoenergetic neutrons

Description: Tissue spheres 0.25, 0.5, 1.0, 2.0, 4.0, and 8.0 {mu}m in diameter were simulated using a wall-less spherical counter filled with a propane-based tissue-equivalent gas. Microdosimetric spectra corresponding to these site sizes were measured for five neutron energies (0.22, 0.44, 1.5, 6, and 14 MeV) and the related mean values {bar Y}{sub F} and {bar Y}{sub D} were calculated for several site sizes and neutron energies. An elaborate calibration technique combining soft x-rays, a {sup 55}Fe photon source, and a {sup 244}Cm collimated source of alpha particles was used throughout the measurement. The spectra and their mean values are compared with theoretically calculated values for ICRU tissue. The agreement between the calculated and the measured data is good in spite of a systematic discrepancy, which could be attributed, in part, to the difference in elemental composition between the tissue-equivalent gas and plastic used in the counter, and the ICRU standard tissue used in the calculations.
Date: December 31, 1993
Creator: Srdoc, D. & Marino, S. A.
Partner: UNT Libraries Government Documents Department

Microdosimetric investigations at the fast neutron therapy facility at Fermilab

Description: Microdosimetry was used to investigate three issues at the neutron therapy facility (NTF) at Fermilab. Firstly, the conversion factor from absorbed dose in A-150 tissue equivalent plastic to absorbed dose in ICRU tissue was determined. For this, the effective neutron kerma factor ratios, i.e., oxygen tissue equivalent plastic and carbon to A-150 tissue equivalent plastic, were measured in the neutron beam. An A-150 tissue equivalent plastic to ICRU tissue absorbed dose conversion factor of 0.92 {+-} 0.04 was determined. Secondly, variations in the radiobiological effectiveness (RBE) in the beam were mapped by determining variations in two related quantities, e{sup *} and R, with field size and depth in tissue. Maximal variation in e{sup *} and R of 9% and 15% respectively were determined. Lastly, the feasibility of utilizing the boron neutron capture reaction on boron-10 to selectively enhance the tumor dose in the NTF beam was investigated.
Date: December 1, 1997
Creator: Langen, K.M.
Partner: UNT Libraries Government Documents Department

Comparative Dosimetric Estimates of a 25 keV Electron Micro-beam with three Monte Carlo Codes

Description: The calculations presented compare the different performances of the three Monte Carlo codes PENELOPE-1999, MCNP-4C and PITS, for the evaluation of Dose profiles from a 25 keV electron micro-beam traversing individual cells. The overall model of a cell is a water cylinder equivalent for the three codes but with a different internal scoring geometry: hollow cylinders for PENELOPE and MCNP, whereas spheres are used for the PITS code. A cylindrical cell geometry with scoring volumes with the shape of hollow cylinders was initially selected for PENELOPE and MCNP because of its superior simulation of the actual shape and dimensions of a cell and for its improved computer-time efficiency if compared to spherical internal volumes. Some of the transfer points and energy transfer that constitute a radiation track may actually fall in the space between spheres, that would be outside the spherical scoring volume. This internal geometry, along with the PENELOPE algorithm, drastically reduced the computer time when using this code if comparing with event-by-event Monte Carlo codes like PITS. This preliminary work has been important to address dosimetric estimates at low electron energies. It demonstrates that codes like PENELOPE can be used for Dose evaluation, even with such small geometries and energies involved, which are far below the normal use for which the code was created. Further work (initiated in Summer 2002) is still needed however, to create a user-code for PENELOPE that allows uniform comparison of exact cell geometries, integral volumes and also microdosimetric scoring quantities, a field where track-structure codes like PITS, written for this purpose, are believed to be superior.
Date: September 11, 2002
Creator: Mainardi, Enrico; Donahue, Richard J. & Blakely, Eleanor A.
Partner: UNT Libraries Government Documents Department

Nanodosimetry and nanodosimetric-based models of radiation action for radon alpha particles. Progress report, July 1990--June 1992

Description: We report on a theory for describing the biological effects of ionizing radiation in particular radon {alpha} particles. Behind this approach is the recognition that biological effects such as chromosome aberrations, cellular transformation, cellular inactivation, etc, are the result of a hierarchic sequence of radiation effects. We indicate how to treat each of the individual processes in this sequence, and also how to relate one effect to the hierarchically superior one.
Date: December 31, 1992
Creator: Zaider, M.
Partner: UNT Libraries Government Documents Department

Digital characterization of particle tracks for microdosimetry

Description: Work is in progress to develop a digital approach to microdosimetry and to construct a prototype instrument to obtain digital information about charged-particle tracks. The objective of such a device is to measure the numbers of electrons produced in various subvolumes of a chamber gas along a particle's path. This paper describes results of Monte Carlo calculations of charged-particle tracks in a cubical time-projection ionization chamber containing methane. Results are presented to show the effects of electron diffusion during charge collection. The calculations indicate that the optimum ratio of field strength and pressure is about 0.6 volts cm/sup -1/ torr/sup -1/. Examples of proton, carbon-ion, and electron tracks are shown. 2 refs., 6 figs.
Date: January 1, 1985
Creator: Turner, J.E.; Hamm, R.N.; Hurst, G.S.; Wright, H.A. & Chiles, M.M.
Partner: UNT Libraries Government Documents Department

Low doses of ionizing radiation to mammalian cells may rather control than cause DNA damage

Description: This report examines the origin of tissue effects that may follow from different cellular responses to low-dose irradiation, using published data. Two principal categories of cellular responses are considered. One response category relates to the probability of radiation-induced DNA damage. The other category consists of low-dose induced metabolic changes that induce mechanisms of DNA damage mitigation, which do not operate at high levels of exposure. Modeled in this way, tissue is treated as a complex adaptive system. The interaction of the various cellular responses results in a net tissue dose-effect relation that is likely to deviate from linearity in the low-dose region. This suggests that the LNT hypothesis should be reexamined. This paper aims at demonstrating tissue effects as an expression of cellular responses, both damaging and defensive, in relation to the energy deposited in cell mass, by use of microdosimetric concepts.
Date: December 31, 1998
Creator: Feinendegen, L.E.; Bond, V.P.; Sondhaus, C.A. & Altman, K.I.
Partner: UNT Libraries Government Documents Department

A microdosimetric study of {sup 10}B(n,{alpha}){sup 7}Li and {sup 157}Gd(n,{gamma}) reactions for neutron capture therapy

Description: This paper presents the microdosimetric analysis for the most interesting cell survival experiment recently performed at the Brookhaven National Laboratory (BNL). In this experiment, the cells were first treated with a gadolinium (Gd) labeled tumor-seeking boronated porphyrin (Gd-BOPP) or with BOPP alone, and then irradiated with thermal neutrons. The resulting cell survival curves indicate that the {sup 157}Gd(n,{gamma}) reactions is very effective in cell killing. The death of a cell treated with GD-BOPP were attributed to either the {sup 10}B(n,{alpha}) {sup 7}Li reactions or the {sup 157}Gd(n,{gamma}) reactions (or both). However, the quantitative relationship between the two types of reaction and the cell survival fraction was not clear. This paper presents the microdosimetric analysis for the BNL experiment based on the measured experimental parameters, and the results clearly suggest a quantitative relationship between the two types of reaction and the cell survival fraction. The results also suggest new research in Gadolinium neutron capture therapy (GDNCT) which may lead to a more practical modality than the boron neutron capture therapy (BNCT) for treating cancers.
Date: December 31, 1996
Creator: Wang, C.K.C.; Sutton, M.; Evans, T.M. & Laster, B.H.
Partner: UNT Libraries Government Documents Department

Microdosimetric investigations at the Fast Neutron Therapy Facility at Fermilab

Description: Microdosimetry was used to investigate three issues at the neutron therapy facility (NTF) at Fermilab. Firstly, the conversion factor from absorbed dose in A-150 tissue equivalent plastic to absorbed dose in ICRU tissue was determined. For this, the effective neutron kerma factor ratios, i.e. oxygen tissue equivalent plastic and carbon to A-150 tissue equivalent plastic, were measured in the neutron beam. An A-150 tissue equivalent plastic to ICRU tissue absorbed dose conversion factor of 0.92 {+-} 0.04 determined. Secondly, variations in the radiobiological effectiveness (RBE) in the beam were mapped by determining variations in two related quantities, e{sup *} and R, with field size and depth in tissue. Maximal variation in e{sup *} and R of 9% and 15% respectively were determined. Lastly, the feasibility of utilizing the boron neutron capture reaction on boron-10 to selectively enhance the tumor dose in the NTF beam was investigated. In the unmodified beam, a negligible enhancement for a 50 ppm boron loading was measured. To boost the boron dose enhancement to 3% it was necessary to change the primary proton energy from 66 MeV and to filter the beam by 90 mm of tungsten.
Date: December 31, 1997
Creator: Langen, K.M.
Partner: UNT Libraries Government Documents Department

Protecting effects specifically from low doses of ionizing radiation to mammalian cells challenge the concept of linearity

Description: This report examines the origin of tissue effects that may follow from different cellular responses to low-dose irradiation, using published data. Two principal categories of cellular responses are considered. One response category relates to the probability of radiation-induced DNA damage. The other category consists of low-dose induced changes in intracellular signaling that induce mechanisms of DNA damage control different from those operating at high levels of exposure. Modeled in this way, tissue is treated as a complex adaptive system. The interaction of the various cellular responses results in a net tissue dose-effect relation that is likely to deviate from linearity in the low-dose region. This suggests that the LNT hypothesis should be reexamined. The aim of this paper is to demonstrate that by use of microdosimetric concepts, the energy deposited in cell mass can be related to the occurrence of cellular responses, both damaging and defensive.
Date: December 31, 1998
Creator: Feinendegen, L.E.; Bond, V.P.; Sondhaus, C.A. & Altman, K.I.
Partner: UNT Libraries Government Documents Department

Time-specific measurements of energy deposition from radiation fields in simulated sub-micron tissue volumes

Description: A tissue-equivalent spherical proportional counter is used with a modified amplifier system to measure specific energy deposited from a uniform radiation field for short periods of time ({approximately}1 {micro}s to seconds) in order to extrapolate to dose in sub-micron tissue volumes. The energy deposited during these time intervals is compared to biological repair processes occurring within the same intervals after the initial energy deposition. The signal is integrated over a variable collection time which is adjusted with a square-wave pulse. Charge from particle passages is collected on the anode during the period in which the integrator is triggered, and the signal decays quickly to zero after the integrator feedback switch resets; the process repeats for every triggering pulse. Measurements of energy deposited from x rays, {sup 137}Cs gamma rays, and electrons from a {sup 90}Sr/{sup 90}Y source for various time intervals are taken. Spectral characteristics as a function of charge collection time are observed and frequency plots of specific energy and collection time-interval are presented. In addition, a threshold energy flux is selected for each radiation type at which the formation of radicals (based on current measurements) in mammalian cells equals the rate at which radicals are repaired.
Date: July 7, 1997
Creator: Famiano, M.A.
Partner: UNT Libraries Government Documents Department

Gene conversion in yeast as a function of linear energy transfer (LET) for low-LET radiation

Description: The relative biological effectiveness (RBE) for low-LET radiation is known to depend on such factors as LET and dose rate. Microdosimetric calculations indicate that the biological target size could also be an important parameter, and calculations predict that the RBE for effects produced by hits in target sizes below about 100 nm should be unity for all low LET radiation. We have measured that RBE for gene conversion in yeast (a small target) for five different low LET photon sources, and the results were consistent with an RBE of unity, which agrees with microdosimetric predictions. 4 refs.
Date: May 1, 1992
Creator: Unrau, P.; Morrison, D. P. & Johnson, J. R.
Partner: UNT Libraries Government Documents Department

The biophysical stage of radiation carcinogenesis

Description: The dependence of the induction of cancer on the absorbed dose of ionizing radiations has been specified in terms of increasing complexity. The first notion of the linear hypothesis is now frequently replaced with a dependence on both the first and second powers of the dose the linear-quadratic model, which implies proportionality at low doses only. Microdosimetric considerations and in particular the theory of dual radiation action would be in accord with this relation if tumors were to arise from single cells as the result of a transformation that depends only on the radiation received by the cell. In this case it must be expected that the linear portion of the dose-effect curve is dose rate independent but that the quadratic component may decrease with decreasing dose rate because of repair. However it was shown some time ago that the dose-incidence relation of a neoplasm indicates a non-autonomous response because of departure from a linear dependence when the mean number of events in cells is much less than one in neutron irradiations. Another discrepancy is the repeated observation that reduction of dose rate, while resulting in the expected lessening of the effectiveness of low-LET radiation, increases the effectiveness of neutrons especially in the case of oncogenic cell transformation. 32 refs., 3 figs.
Date: January 1, 1986
Creator: Rossi, H.H. & Zaider, M.
Partner: UNT Libraries Government Documents Department

Low intensity configuration at NTF for microdosimetry and spectroscopy

Description: Additional circuitry has been developed to regulate beam delivery to Fermilab`s Neutron Therapy Facility. This allows the number of protons on target to be reduced to a point that makes microdosimetry and spectroscopy possible. An introduction to the problem is presented. The modifications are described and results verifying their effectiveness are reported.
Date: September 1, 1995
Creator: Kroc, T.K.
Partner: UNT Libraries Government Documents Department

Microdosimetric measurements for photons in a water phantom

Description: Microdosimetric event distributions were determined in air at three primary photon energies (60, 660 and 1250 keV) and at depths of 2, 5, and 10 cm in a water phantom (30 x 30 x 30cm) from measurements of charge produced in a walled Rossi-type proportional counter. For 660 and 1250 keV photon energies free air sources of /sup 137/Cs and /sup 60/Co, respectively, were used at the Brookhaven National Laboratory (BNL) calibration facility and for 60 keV a 300 mCi /sup 241/Am source was used. Event size spectra were taken at simulated site diameters of 0.5, 1, and 2 ..mu..m. The frequency mean (anti Y/sub F/) and dose mean (anti Y/sub D/) of lineal energy density were determined from these measurements. Our results without a phantom indicate reasonably good agreement for anti Y/sub F/ and anti Y/sub D/ with measurements reported in the literature for walled proportional counters. Ratios anti Y/sub F/(water)/anti Y/sub F/(air) and anti Y/sub D/(water)/anti Y/sub D/(air) were determined for each site diameter and depth in the phantom. For 60 keV photons the maximum increase in these ratios was approximately 8 percent for a site diameter of 2 microns at 10 cm depth in the phantom. For 660 keV photons the maximum increase in these ratios was 24 percent whereas for 1250 keV photons this maximum increase was approximately 15 percent. However, for 60 keV photons only about 8 percent increase was observed; this small increase is consistent with the fact that about half of the scattered photons are removed by photoelectric processes. Since anti Y/sub D/ in the phantom increased only by about 24 percent large changes in biological effectiveness are not expected as a function of depth in typical biological systems.
Date: January 1, 1980
Creator: Varma, M N; Baum, J W; Kliauga, P & Bond, V P
Partner: UNT Libraries Government Documents Department

Measurement of energy deposition near high energy, heavy ion tracks. Progress report, December 1982-April 1985

Description: The microscopic spatial distribution of energy deposition in irradiated tissue plays a significant role in the final biological effect produced. Therefore, it is important to have accurate microdosimetric spectra of radiation fields used for radiobiology and radiotherapy. The experiments desribed here were designed to measure the distributions of energy deposition around high energy heavy ion tracks generated at Lawrence Berkeley Laboratory's Bevalac Biomedical Facility. A small proportional counter mounted in a large (0.6 by 2.5 m) vacuum chamber was used to measure energy deposition distributions as a function of the distance between detector and primary ion track. The microdosimetric distributions for a homogeneous radiation field were then calculated by integrating over radial distance. This thesis discusses the rationale of the experimental design and the analysis of measurements on 600 MeV/amu iron tracks. 53 refs., 19 figs.
Date: August 1, 1986
Creator: Metting, N.F.; Braby, L.A.; Rossi, H.H.; Kliauga, P.J.; Howard, J.; Schimmerling, W. et al.
Partner: UNT Libraries Government Documents Department

Alternatives to dose, quality factor and dose equivalent for low level irradiation

Description: Randomly occurring energy deposition events produced by low levels of ionizing radiation interacting with tissue deliver variable amounts of energy to the sensitive target volumes within a small fraction of the cell population. A model is described in which an experimentally derived function relating event size to cell response probability operates mathematically on the microdosimetric event size distribution characterizing a given irradiation and thus determines the total fractional number of responding cells; this fraction measures the effectiveness of the given radiation. Normalizing to equal numbers of events produced by different radiations and applying this cell response or hit size effectiveness function (HSEF) should define radiation quality, or relative effectiveness, on a more nearly absolute basis than do the absorbed dose and dose evaluation, which are confounded when applied to low level irradiations. Examples using both calculation and experimental data are presented. 15 refs., 18 figs.
Date: January 1, 1988
Creator: Sondhaus, C.A.; Bond, V.P. & Feinendegen, L.E.
Partner: UNT Libraries Government Documents Department

Nanodosimetry and nanodosimetric-based models of radiation action for radon alpha particles

Description: We report on a theory for describing the biological effects of ionizing radiation in particular radon [alpha] particles. Behind this approach is the recognition that biological effects such as chromosome aberrations, cellular transformation, cellular inactivation, etc, are the result of a hierarchic sequence of radiation effects. We indicate how to treat each of the individual processes in this sequence, and also how to relate one effect to the hierarchically superior one.
Date: January 1, 1992
Creator: Zaider, M.
Partner: UNT Libraries Government Documents Department

Microdosimetry of plutonium in beagle dog lung

Description: A better understanding of the microdosimetry of internally-deposited radionuclides should provide new clues to the complex relationships between organ dose distribution and early or late biological effects. Our current interest is the microdosimetry of plutonium and other alpha emitters in the lung. Since the lung is an inhomogeneous tissue, it was necessary to characterize the microscopic distributions of alveolar tissue, air space, and epithelial cell nuclei to define source-target parameters. A statistical representation of the microstructure of beagle dog lung was developed from automated image analysis of specimens from three healthy adult male dogs. The statistical distributions obtained constituted a data base from which it was possible to calculate both the energy dissipation of an alpha particle as it traversed a straight line path through pulmonary tissue, and the probability of intersecting a potentially sensitive biological site in the cell. Computer methods were modified to accomodate tissues with air space regions such as one finds in lung tissue. With the lung model description, these methods were used to determine probability density curves in specific energy for inhaled plutonium aerosols. It was assumed that the activity was randomly distributed on alveolar walls. Calculated examples are given for various activities of inhaled plutonium point sources deposited in lung tissue.
Date: August 1, 1980
Creator: Fisher, D.R. & Roesch, W.C.
Partner: UNT Libraries Government Documents Department