3D simulations for evaluation of location factors in an urban environment: application of a novel methodology to calculate external exposure doses for evacuees from Pripyat.

This article presents a methodology for assessing the radiation doses in an urban environment due to external irradiation from radionuclides deposited on the ground and other surfaces as well as from a passing radioactive cloud. The approach was developed and applied to assess individual doses of residents of the town of Pripyat who were evacuated shortly after the Chernobyl accident. Typically, the so-called location factor is defined as the ratio of the dose rate at a point of exposure and the dose rate at an undisturbed lawn far from any buildings. The present study used a new definition of the location factor as a regular four-dimensional grid of ratios of air kerma rates indoors and outdoors distributed in space and time. The location factors were calculated for two scenarios: outdoor and indoor values for typical apartments and buildings in Pripyat. Indoor location factors varied within two orders of magnitude depending on the floor of residence and place of staying inside the apartment. Values of the indoor location factor differed during the daytime and night by a factor of 30-40 depending on the behaviour of an individual within the apartment. Both, outdoor and indoor location factors decreased with decreasing distances between buildings. It was shown that during the first 4 days after the accident, air kerma rates in Pripyat were governed by the radionuclides deposited on the ground surface, and not by radionuclides in the cloud. Specifically, the contribution of the radioactive cloud to air kerma rate was maximal (i.e., 2.3%) on the morning of 28 April 1986. The methodology and results of this study are currently being used to reconstruct the radiation gonadal dose for the subjects of the American-Ukrainian study of parental irradiation in Chernobyl cleanup workers and evacuees for investigating germline mutations in their offspring.

Simulation of bronchial mucociliary clearance of insoluble particles by computational fluid and particle dynamics methods.

For a correct assessment of health consequences of inhaled aerosols as a function of dose, whether for environmental, occupational or therapeutic agents, knowledge of their deposition distribution in the respiratory tract and subsequent clearance is important. The objective of this study is to model particle clearance at bronchial airway bifurcation level and to analyze the combined effect of deposition and clearance. For this purpose, a numerical model has been implemented. Air and mucus flow fields were computed in a model bronchial airway bifurcation. Inhaled particles with 1 and 10 µm aerodynamic diameters were tracked to determine deposition and clearance patterns. Simulation results revealed the existence of a slow clearance zone around the peak of the airway bifurcation causing delayed clearance of the particles depositing or entering here. Particles clearing up from the deeper airways and crossing the studied bifurcation do not accumulate in this zone, because of their tendency to avoid it. The average residence time of these particles was around 20 min independently of particle size (whether it is 1 or 10 µm). However, as a result of the superposition of deposition and clearance mechanisms, the final spatial distribution of particles deposited primarily in the target bifurcation is size dependent, because deposition is size specific. Although deposition density of particles deposited in the slow clearance area is one-two orders of magnitude higher than the average deposition density, these values are reduced by clearance by the factors of 4-7, depending on the particle size and the surface area of the selected slow clearance zone. In conclusion, although particle deposition is inhomogeneous, clearance can significantly decrease the degree of spatial non-uniformity of the particles. Therefore, for a correct assessment of doses at local levels, it is important to consider both deposition and clearance. Although future research may overwrite some of the model assumptions on the nature of mucus, the authors think that most of the current predictions will hold.

3D-modelling of radon-induced cellular radiobiological effects in bronchial airway bifurcations: direct versus bystander effects.

PURPOSE: The primary objective of this paper was to investigate the distribution of radiation doses and the related biological responses in cells of a central airway bifurcation of the human lung of a hypothetical worker of the New Mexico uranium mines during approximately 12 hours of exposure to short-lived radon progenies. MATERIALS AND METHODS: State-of-the-art computational modelling techniques were applied to simulate the relevant biophysical and biological processes in a central human airway bifurcation. RESULTS: The non-uniform deposition pattern of inhaled radon daughters caused a non-uniform distribution of energy deposition among cells, and of related cell inactivation and cell transformation probabilities. When damage propagation via bystander signalling was assessed, it produced more cell killing and cell transformation events than did direct effects. If bystander signalling was considered, variations of the average probabilities of cell killing and cell transformation were supra-linear over time. CONCLUSIONS: Our results are very sensitive to the radiobiological parameters, derived from in vitro experiments (e.g., range of bystander signalling), applied in this work and suggest that these parameters may not be directly applicable to realistic three-dimensional (3D) epithelium models.

Effect of site-specific bronchial radon progeny deposition on the spatial and temporal distributions of cellular responses.

Inhaled short-lived radon progenies may deposit in bronchial airways and interact with the epithelium by the emission of alpha particles. Simulation of the related radiobiological effects requires the knowledge of space and time distributions of alpha particle hits and biological endpoints. Present modelling efforts include simulation of radioaerosol deposition patterns in a central bronchial airway bifurcation, modelling of human bronchial epithelium, generation of alpha particle tracks, and computation of spatio-temporal distributions of cell nucleus hits, cell killing and cell transformation events. Simulation results indicate that the preferential radionuclide deposition at carinal ridges plays an important role in the space and time evolution of the biological events. While multiple hits are generally rare for low cumulative exposures, their probability may be quite high at the carinal ridges of the airway bifurcations. Likewise, cell killing and transformation events also occur with higher probability in this area. In the case of uniform surface activities, successive hits as well as cell killing and transformation events within a restricted area (say 0.5 mm(2)) are well separated in time. However, in the case of realistic inhomogeneous deposition, they occur more frequently within the mean cycle time of cells located at the carinal ridge even at low cumulative doses. The site-specificity of radionuclide deposition impacts not only on direct, but also on non-targeted radiobiological effects due to intercellular communication. Incorporation of present results into mechanistic models of carcinogenesis may provide useful information concerning the dose-effect relationship in the low-dose range.

Generalized tularemia in a vervet monkey (Chlorocebus aethiops) and a patas monkey (Erythrocebus patas) in a zoo.

Generalized tularemia was diagnosed in a vervet monkey (Chlorocebus aethiops) and a patas monkey (Erythrocebus patas), both of which died suddenly in the Szeged Zoo, Szeged, Hungary. Macroscopic lesions in each animal included disseminated, grayish-white foci in the lungs, lymph nodes, spleen, liver, and kidney. All focal lesions were characterized microscopically as purulent to pyogranulomatous to granulomatous inflammation with necrosis. Francisella tularensis subsp. holarctica strains were isolated from tissue samples on modified Francis agar after mouse passage and identified by a commercial carbon-source utilization test and polymerase chain reaction-based amplification and sequencing of a portion of the 16S ribosomal RNA gene.

Stochastic aspects of primary cellular consequences of radon inhalation.

In this study, a composite, biophysical mechanism-based microdosimetric model was developed for the assessment of the primary cellular consequences of radon inhalation. Based on the concentration of radio-aerosols in the inhaled air and the duration of exposure, this mathematical approach allows the computation of the distribution of cellular burdens and the resulting distribution of cellular inactivation and oncogenic transformation probabilities within the epithelium of the human central airways. The composite model is composed of three major parts. The first part is a lung-particle interaction model applying computational fluid and particle dynamics (CFPD) methods. The second part is a lung dosimetry model that quantifies the cellular distribution of radiation exposure within the bronchial epithelium. The third part of the composite model is the unit-track-length model, which allows the prediction of the biological outcome of the exposure at the cellular level. Computations were made for different exposure durations for a miner working in a New Mexico uranium mine. The spatial pattern of the exposed cell nuclei along the epithelium, the distributions of single and multiple alpha-particle hits, the distributions of cell nucleus doses, and cell inactivation and cell transformation probabilities as a function of the number of inhalations (length of exposure) were investigated and compared for up to 500 inhalations.

Modelling of cell deaths and cell transformations of inhaled radon in homes and mines based on a biophysical and microdosimetric model.

PURPOSE: In this study a biophysical mechanism-based microdosimetric model was applied to predict the biological effects of inhaled radon progenies in homes and in uranium mines. MATERIALS AND METHODS: The radon daughter concentrations of more than 2000 homes were averaged in case of home exposure and the New Mexico uranium mine data were used in case of exposure in mines. The complex microdosimetric model applied in this work was developed by combining a computational fluid and particle dynamics (CFPD) lung model with a lung dosimetry model that quantify the local distribution of radiation burden and the Unit-Track-Length Model, which characterizes the biological outcome of the exposure. RESULTS: Our results show that the inhomogeneity of radon daughter deposition is stronger in the case of mines. Consequently, the numbers of cells which receive multiple hits and the maxima of radiation burdens are significantly higher in mines. In contrast to this, the distributions and maximum values of cell transformation probabilities are very similar in the two cases. CONCLUSIONS: If the same amounts of inhaled progenies are considered then primary cellular consequences are very similar in case of homes and mines, however, the local maxima of radiation burden are higher in mines.

Effect of inhomogeneous activity distributions and airway geometry on cellular doses in radon lung dosimetry.

The human tracheobronchial system has a very complex structure including cylindrical airway ducts connected by airway bifurcation units. The deposition of the inhaled aerosols within the airways exhibits a very inhomogeneous pattern. The formation of deposition hot spots near the carinal ridge has been confirmed by experimental and computational fluid and particle dynamics (CFPD) methods. In spite of these observations, current radon lung dosimetry models apply infinitely long cylinders as models of the airway system and assume uniform deposition of the inhaled radon progenies along the airway walls. The aim of this study is to investigate the effect of airway geometry and non-uniform activity distributions within bronchial bifurcations on cellular dose distributions. In order to answer these questions, the nuclear doses of the bronchial epithelium were calculated in three different irradiation situations. (1) First, CFPD methods were applied to calculate the distribution of the deposited alpha-emitting nuclides in a numerically constructed idealised airway bifurcation. (2) Second, the deposited radionuclides were randomly distributed along the surface of the above-mentioned geometry. (3) Finally, calculations were made in cylindrical geometries corresponding to the parent and daughter branches of the bifurcation geometry assuming random nuclide activity distribution. In all three models, the same 218Po and 214Po surface activities per tissue volumes were assumed. Two conclusions can be drawn from this analysis: (i) average nuclear doses are very similar in all three cases (minor differences can be attributed to differences in the linear energy transfer (LET) spectra) and (ii) dose distributions are significantly different in all three cases, with the highest doses at the carinal ridge in case 3.

Alpha-hit, cellular dose, cell transformation and inactivation probability distributions of radon progenies in the bronchial epithelium.

A fluid dynamics based model has been used to determine the deposition patterns of inhaled radon daughters in a realistic approach of the bronchial airway geometry. The interaction of the emitted alpha particles with epithelial cells has been analyzed by applying a complex hit probability model (Bronchial Alpha Hit Model). The biological response of the hit cells has been calculated by the Probability-Per-Unit-Track-Length Model, which relates the probability of a specific biological effect to the track length of alpha particles as a function of the particles' LET. The models mentioned above form a complex lung-radon interaction description. The calculations indicate that compared to the average values the transformation and cell killing probabilities are higher at bronchial carinal ridges. In addition, a considerable number of cells possessing a not negligible transformation and cell killing probabilities can also be found in the outer sides of the central zone.

CFD as a tool in risk assessment of inhaled radon progenies.

During the last decade, computational fluid dynamics techniques proved to be a powerful tool in the modelling of biological processes and the design of biomedical devices. In this work, a computational fluid dynamics method was applied to model the transport of inhaled air and radioactive particles within the human respiratory tract. A finite volume numerical approach was used to compute the flow field characteristics and particle trajectories in the lumen of the first five airway generations of the human tracheobronchial tree, leading to the right upper lobe. The computations were performed for breathing and exposure conditions characteristic of uranium mines and homes. Primary radon daughter deposition patterns and energy distributions were computed, exhibiting highly inhomogeneous particle and energy deposition patterns. The results of the present modelling effort can serve as input data in lung cancer risk analysis.