Microdosimetry of diagnostic X rays: applications of the variance-covariance method.

Microdosimetric measurements in beams of diagnostic X rays (between 30 and 125 kV) have been performed. In these pulsed radiation fields, microdosimetric measurements are possible only by application of the variance-covariance technique. The dose mean lineal energy, yD, is determined for various simulated diameters, at different depths in the absorber, and at different points within the pulse intervals. From the measured temporal dependences one can also obtain values of yD for different X-ray pulse generators. The results demonstrate the potential of the variance-covariance method for a diversity of microdosimetric measurements in radiation protection and in the quality control of radiation beams.     

Dosimetric uncertainties impact on cell survival curve with low energy proton

There is an increasing number of radiobiological experiments being conducted with low energy protons (less than 5 MeV) for radiobiological studies due to availability of sub-millimetre focused beam. However, low energy proton has broad microdosimetric spectra which can introduce dosimetric uncertainty. In this work, we quantify the impact of this dosimetric uncertainties on the cell survival curve and how it affects the estimation of the alpha and beta parameters in the LQ formalism. Monte Carlo simulation is used to generate the microdosimetric spectra in a micrometer-sized water sphere under proton irradiation. This is modelled using radiobiological experiment set-up at the Centre of Ion Beam Application (CIBA) in National University of Singapore. Our results show that the microdosimetric spectra can introduce both systematic and random shifts in dose and cell survival; this effect is most pronounced with low energy protons. The alpha and beta uncertainties can be up to 10% and above 30%, respectively for low energy protons passing through thin cell target (about 10 microns). These uncertainties are non-negligible and show that care must be taken in using the cell survival curve and its derived parameters for radiobiological models.     

Derivation of radiation quality average parameters in neutron-gamma radiation fields with the high-pressure ionization chamber: theory and practice

The established radiation quality parameters in mixed neutron-gamma radiation fields may be measured by applying the initial (columnar) recombination of ions in tissue-equivalent (TE) high-pressure ionization chambers (recombination chambers). The mean quality factor can be determined to within 10-15% for mixed fields with neutrons ranging from thermal to 10 MeV, and the dose mean LET of the proton component can be determined to within 10-15% if the gamma-ray absorbed dose fraction is known. These average parameters are derived by measuring the ratio of the ionization currents collected at two high-field strengths and constant gas pressure applied to the ionization chamber. By utilizing approximate correlations between physical parameters in the neutron energy region from thermal to 10 MeV, the dose mean LET of the heavy ion component, the overall dose mean LET, and the microdosimetric parameter y0,D of the mixed field can also be derived. Experimental verification of the method is presented for various neutron-gamma radiation spectra in air and in water by comparison to theoretical calculations and results from low-pressure proportional counter measurements. Good agreement is shown. The TE high-pressure ionization chamber appears to have wide potential for use as a dose-equivalent meter in radiation protection or as a beam characterization device in radiobiology.     

Comparison of microdosimetric simulations using PENELOPE and PITS for a 25 keV electron microbeam in water

The calculations presented compared the performances of two Monte Carlo codes used for the estimation of microdosimetric quantities: Positive Ion Track Structure code (PITS) and a main user code based on the PENetration and Energy Loss of Positrons and Electrons code (PENELOPE-2000). Event-by-event track structure codes like PITS are believed to be superior for microdosimetric applications, and they are written for this purpose. PITS tracks electrons in water down to 10 eV. PENELOPE is one of the few general-purpose codes that can simulate random electron-photon showers in any material for energies from 100 eV to 1 GeV. The model used in the comparison is a water cylinder with an internal scoring geometry made of spheres 1 microm in diameter where the scoring quantities are calculated. The source is a 25 keV electron pencil beam impinging normally on the sphere surface. This work shows only the lineal energy y and spectra graphical presentation as a function of y since for microdosimetry and biology applications, and for discussion of radiation quality in general, these results are more appropriate. The computed PENELOPE results are in agreement with those obtained with the PITS code and published previously in this journal. This paper demonstrates PENELOPE's usefulness at low energies and for small geometries. What is still needed are experimental results to confirm these analyses.     

Probabilistic approach to obtain hit-size effectiveness functions which relate microdosimetry and radiobiology

A probabilistic approach has been developed to relate microdosimetry, biological effects, and radiation quality. It is used to derive, and subsequently apply, microdosimetry-based cellular response functions for different biological end points of relevance for radiological protection. The approach makes use of measurable microdosimetry spectra and avoids assumptions concerning the course of mechanisms of radiation action. Instead, it postulates a response function that is, and behaves like, the cumulative probability that a subcellular target structure will respond to a specific target-averaged ionization density. Statistical distributions are applied and their parameters are evaluated to characterize the randomness involved in the localization of sensitive sites and in the reactivity of the whole sensitive structure. The resulting response functions can be used for prediction of the effects of low-level radiation. Such predictions for some selected effects of a stochastic nature (mutagenesis, chromosome abnormalities, etc.) are presented as relative biological effectiveness values based on low doses of radiations with a wide range of linear energy transfer and compared with various quality factor specifications. Cellular response relationships, termed hit-size effectiveness functions, can also be applied directly in radiation protection metrology by incorporating them into the software used to process the readings of microdosimetric spectrometers. The derivation of the functions, rather than their uses in radiation protection, is the principal subject of this report.     

Radiation quality of tritium beta-rays: microdosimetric distributions for nanometer-size targets in a medium containing tritiated water

To elucidate the characteristics of the action of tritium beta-rays, the following parameters are derived: electron slowing down spectra of primary electrons (beta-rays) and delta-rays in a medium containing tritiated water; and frequency distributions for the microdosimetric quantity j (number of effective primary events per track per target), fj, for nanometer-size targets exposed to tritiated water. Features of the radiation quality of tritium beta-rays are discussed by comparing the present results with those for 60Co gamma-rays and 7 MeV electrons. It is concluded that, although tritium beta-rays, 60Co gamma-rays, and 7 MeV electrons are classified as the same low l.e.t. radiation, the radiation quality of tritium beta-rays is considerably different from those of 60Co gamma-rays and 7 MeV electrons, and has specific features such as a high average l.e.t., a small total electron fluence per unit absorbed dose, and a different microdosimetric distribution, fj, for nanometer-size targets.     

Energy deposition spectra of negative pions and their application to radiation therapy

Summary Treatment planning for pion radiation therapy must take into account changes in radiation quality within the patient. At the biomedical channelE3 of SIN (Swiss Institute for Nuclear Research) microdosimetric measurements have been performed to investigate radiation quality within pion irradiated phantoms. Results are presented in terms of microdosimetric spectra and derived quantities. As expected marked differences are observed between dose peak and plateau for narrow pion beams. The influence of simulated site diameter on measured spectra has been found to be more pronounced in the plateau region than in the peak. Investigation of the influence of peak width on radiation quality revealed a dilution of the high-LET dose fraction for broader peaks.     

Microdosimetric calculation of absorption fraction and the resulting dose conversion factor for radon progeny

It is an established fact that radon progeny can induce lung cancers. However, there is a well-known discrepancy between the epidemiologically derived dose conversion factor for radon progeny (4 mSv/WLM) and the dosimetrically derived value (15 mSv/WLM) (mSv is a unit of the dose while WLM is a unit of exposure to radon progeny). Up to now there is no satisfactory explanation to this. In the present study we propose that microdosimetry will help reduce the discrepancy significantly. The ICRP Human Respiratory Tract Model (HRTM) has been applied to calculate the effective dose conversion factor. All parameters have been kept at their best estimates. Modifications were made in the calculation of the absorbed fractions of alpha particles. In contrast to the ICRP approach where the energy has been considered to be deposited in the layer containing the sensitive cells, we used a microdosimetric approach in which the alpha particles deposit their energy only in the nuclei of sensitive cells. This modification alone has lowered the dose conversion factor by about one-third (from 15 mSv/WLM down to approximately 10 mSv/ WLM). Received: 19 February 2001 / Accepted: 10 July 2001     

Estimated yield of double-strand breaks from internal exposure to tritium

Internal exposure to tritium may result in DNA lesions. Of those, DNA double-strand breaks (DSBs) are believed to be important. However, experimental and computational data of DSBs induction by tritium are very limited. In this study, microdosimetric characteristics of uniformly distributed tritium were determined in dimensions of critical significance in DNA DSBs. Those characteristics were used to identify other particles comparable to tritium in terms of microscopic energy deposition. The yield of DSBs could be strongly dependent on biological systems and cellular environments. After reviewing theoretically predicted and experimentally determined DSB yields available in the literature for low-energy electrons and high-energy protons of comparable microdosimetric characteristics to tritium in the dimensions relevant to DSBs, it is estimated that the average DSB yields of 2.7 × 10(-11), 0.93 × 10(-11), 2.4 × 10(-11) and 1.6 × 10(-11) DSBs Gy(-1) Da(-1) could be reasonable estimates for tritium in plasmid DNAs, yeast cells, Chinese hamster V79 cells and human fibroblasts, respectively. If a biological system is not specified, the DSB yield from tritium exposure can be estimated as (2.3 ± 0.7) × 10(-11) DSBs Gy(-1) Da(-1), which is a simple average over experimentally determined yields of DSBs for low-energy electrons in various biological systems without considerations of variations caused by different techniques used and obvious differences among different biological systems where the DSB yield was measured.     

A comparative study of microdosimetric properties of x-rays, γ-rays,and β-rays

The objective of this study was the computation of microdosimetric functions and quantities for sparsely ionizing radiations. The calculations are performed on simulated electron tracks generated by Monte-Carlo techniques. Ten different radiations of biomedical interest are considered. The comparison of radiation qualities shows marked differences between these sparsely ionizing radiations. The microdosimetric data are represented graphically for use in radiation biology and in clinical applications.     

Theory of survival of bacteria exposed to ionizing radiation. I. X and gamma rays

A new model for the survival of bacteria exposed to ionizing radiation is constructed in the framework of a target theory based on microdosimetric concepts, where single- and double-strand breaks of DNA and their repair in vivo can be described consistently in terms of the microdosimetric quantity j (number of effective primary events per track per target). In this model, the ability of cells to repair DNA damage is taken into consideration in terms of the repair capacities for single- and double-strand breaks of DNA, xi 1 and xi 2 (0 less than or equal to xi 1, xi 2 less than or equal to 1). To apply this model to Escherichia coli K-12 strains with different repair abilities, values of the repair capacity for single-strand breaks, xi 1, were derived from experimental survival curves. The theoretical survival curves for 60Co gamma rays were found to be effectively insensitive to the value of xi 2. Experimental survival curves for the wild-type, uvr, and rec strains of E. coli K-12 were well reproduced in this model. From these results, it is concluded that the theoretical formulation for the survival fraction of bacteria can afford a quantitative method for analysis of the repair process for radiation-induced single-strand breaks in DNA in vivo.     

Radiobiological effectiveness (RBE) of megavoltage X-ray and electron beams in radiotherapy

Recent experiments indicate that significant differences exist in the microdosimetric properties (i.e., lineal energy distributions) of megavoltage X-ray and electron beams used in radiation therapy. In particular, dose averaged values of lineal energy for 18 MeV electrons are 10-30% lower than for 10 MeV bremsstrahlung X rays, which in turn are 30-60% lower than for 250 kVp X rays. Differences of this magnitude may manifest themselves in observable radiobiological effectiveness (RBE) differences between these radiations. Cell survival data have been obtained for line DLD-1 human tumor cells on all three of the above radiation sources. Results clearly demonstrate an RBE difference between orthovoltage and megavoltage radiation (P = 0.001). A small difference is also measured in RBE between megavoltage photons and megavoltage electrons, but the difference is not statistically significant (P = 0.25). All biological, dosimetric, and microdosimetric data were obtained under nearly identical geometric conditions. These data raise interesting questions vis à vis the applicability of microdosimetric theories in the interpretation of biological effects.     

Microdosimetric measurements in the secondary radiation field produced in 12C-therapy irradiations

The ambient dose equivalent from the secondary radiation produced during irradiation of a cylindrical water phantom with 200 MeV/u ¹²C-ions was investigated at the biophysics cave at GSI Helmholtzzentrum für Schwerionenforschung in Darmstadt, Germany. Pencil-like ion beams were delivered by the heavy-ion synchrotron SIS18 using the slow extraction mode. Since the secondary radiation field outside the phantom is complex in its particle composition and particle energy distribution, microdosimetric methods developed for the dosimetry of the cosmic radiation field at flight altitudes, which is similar in terms of complexity, were applied. Lineal energy distributions and the ambient dose equivalent were measured with a tissue-equivalent proportional counter at different particle emission angles. An additional veto counter allowed the identification of the different contributions of charged and neutral particles. A significant increase in the mean quality factor was observed at large emission angles which could be attributed to the decreasing contributions of charged particles compared to the (relative) contributions from neutrons.     

Interaction distance of primary lesions in the formation of dicentric chromosomes after irradiation of human lymphocytes with 3-MeV electrons in vitro

The rejoining distance for the formation of dicentric chromosomes in human lymphocytes is derived on the basis of microdosimetric concepts. For the formation of a dicentric chromosome, primary lesions produced by absorption events can interact within the nucleus over a distance of between 0.5 and 1.0 μ. The intercellular distribution of dicentric chromosomes is consistent with a Poisson distribution.     

Chromosome aberration in human lymphocytes after X-irradiation in vitro. II. Analysis of primary processes in the formation of dicentric chromosomes

The rejoining distance for the formation of dicentric chromosomes in human lymphocytes has been derived on the basis of microdosimetric concepts. For the formation of a dicentric chromosome, primary lesions produced by absorption events can interact within the nucleus over a distance of at least 1 μm. The dispersion of dicentrics is near to 1 and corresponds to a site number between 17 and 120.     

Comparative microdosimetry of photoelectrons and Compton electrons: an analysis in terms of generalized proximity functions

A current discussion on mammography screening is focused on claims of high relative biological effectiveness (RBE) of mammography X rays compared to conventional 200 kV X rays. An earlier assessment in terms of the electron spectra of these radiations has led to the conclusion that the RBE is bound to be less than 2, regardless of specific model assumptions and the microdosimetric properties of electrons. The present study extends this result in terms of the microdosimetric proximity function, t(x), for electrons, which is essentially the spatial auto-correlation function of energy within particle tracks. If pairs of DNA lesions, e.g. chromosome breaks or deletions, bring about the observed damage, the value t(x) determines for a specified radiation the relative frequency of pairs of lesions a distance x apart. The effectiveness of the radiation is thus proportional to an average of the values of t(x) over the distances, x, for which lesions can combine. The analysis suggests that 15 keV electrons can have a low-dose relative biological effectiveness (RBE(M)) of 1.6 relative to 40 keV electrons if the interaction distances do not exceed about 1 micro m. An extension of the concept, the reduced proximity function, t(delta)(x), permits the inclusion of models with an energy threshold, such as delta = 100 eV, 500 eV or 2 keV, for the formation of each of the DNA lesions. This makes it possible to assess the potential impact of the Auger electrons which accompany most photoelectrons, but only a minority of the Compton electrons. It is found that the Auger electrons could make photoelectrons substantially more effective than Compton electrons at energies below 10 keV but not at energies above 15 keV. The conclusions obtained for the RBE of 15 keV electrons relative to 40 keV electrons will be roughly representative of the RBE of mammography X rays relative to conventional 200 kV X rays.     

Concepts of microdosimetry

This is the second part of an investigation of microdosimetric concepts relevant to numerical calculations. Two different types of distributions of the microdosimetric quantities are discussed. The sampling procedures are considered, which lead from the initial pattern of enregy transfers, the so-called inchoate distribution, to the distribution of specific energy and their mean values. The dependence of the distributions of specific energy on absorbed dose is related to the sampling procedures.     

Generalization of the variance-covariance method for microdosimetric measurements

Numerical simulations in terms of microdosimetric data for 5-MeV neutrons are utilized to test the twin detector method of microdosimetric measurements in its new, extended form. Three different conditions of measurement are considered: (I) constant dose increments per measurement, (II) fluctuating dose increments per measurement, and (III) fluctuating dose increments combined with slow changes of the dose-rate ratio for the two detectors. Under each of the conditions, large numbers of measurement series are simulated, and the estimation formulae for the mean and the two subsequent moments of the dose-weighted single-event distribution, d(y), are applied. The estimation formulae exist in three different forms: uncorrected formulae that apply to condition I, corrected formulae that are valid also for condition II, and fully corrected formulae that remain applicable under condition III. The results of the simulations indicate the acceptable ranges of doses per measurement interval. It can be seen that all three parameters are obtainable through the twin detector method, and that the fully corrected formulae for the two lower moments are generally applicable. The determination of the third moment is possible only under limited conditions, and the fully corrected formula is not useful in this case, while the corrected formula has some applicability even under condition III. Received: 10 January 1996 / Accepted in revised form: 27 May 1996     

Microdosimetric measurements and estimation of human cell survival for heavy-ion beams

The microdosimetric spectra for high-energy beams of photons and proton, helium, carbon, neon, silicon and iron ions (LET = 0.5-880 keV/microm) were measured with a spherical-walled tissue-equivalent proportional counter at various depths in a plastic phantom. Survival curves for human tumor cells were also obtained under the same conditions. Then the survival curves were compared with those estimated by a microdosimetric model based on the spectra and the biological parameters for each cell line. The estimated alpha terms of the liner-quadratic model with a fixed beta value reproduced the experimental results for cell irradiation for ion beams with LETs of less than 450 keV/microm, except in the region near the distal peak.     

Concepts of microdosimetry

This is the first part of an investigation of microdosimetric concepts relevant to numerical calculations. The definitions of the microdosimetric quantities are reviewed and formalized, and some additional conventions are adopted. The common interpretation of the quantities in terms of energy imparted to spherical sites is contrasted with their interpretation as the result of a diffusing process applied to the initial spatial pattern of energy transfers in the irradiated medium.