Machine learning-enhanced stochastic uncertainty and sensitivity analysis of the ICRP human respiratory tract model for an inhaled radionuclide.

The International Commission on Radiological Protection (ICRP) has developed the reference Human Respiratory Tract Model (HRTM), detailed in ICRP Publications 66 and 130, to estimate the deposition and clearance of inhaled radionuclides. These models utilize reference anatomical and physiological parameters for particle deposition (PD). Biokinetic models further estimate retention and excretion of internalized particulates, aiding the derivation of inhalation dose coefficients (DC). This study aimed to assess variability in deterministic131I biokinetic and dosimetry models through stochastic analysis using the updated HRTM from ICRP Publication 130. The complexities of the ICRP PD model were reconstructed into a new, independent computational model. Comparison with reference data for total PD fractions for reference worker, solely a nose breather, covering activity median aerodynamic diameters from 0.3µm to 20µm, showed a 1.04% relative and 0.7% absolute difference, demonstrating good agreement with ICRP deposition fractions. The deterministic DC module was reconstructed in Python and expanded for stochastic analysis, systematically expanding deposition components from HRTM and assigning probability distribution functions to uncertain parameters. These were integrated into an in-house stochastic radiological exposure dose calculator, utilizing latin hypercube sampling. A case of an occupational radionuclide intake was explored, in which biodistribution and committed effective DC (CEDC) were computed for131I type F, considering a lognormal particle size distribution with a median of 5µm. Results showed the published ICRP reference CEDC marginally exceeds the 75th percentile of observed samples, with log-gamma distribution as the best-fit probability distribution. A Random Forest regression model with SHapley Additive exPlanations was employed for sensitivity analysis to predict feature importance. The analysis identified the HRTM particle transport rates scaling factor, followed by the aerodynamic deposition efficiency in the alveolar interstitial region as the most impactful parameters. This study offers a unique stochastic approach on inhaled particulate metabolism, enhancing radiation consequence management, medical countermeasures, and dose reconstruction for epidemiological studies.

Basis for the ICRP's updated biokinetic model for carbon inhaled as CO2.

The International Commission on Radiological Protection (ICRP) is updating its biokinetic and dosimetric models for occupational intake of radionuclides (OIR) in a series of reports called the OIR series. This paper describes the basis for the ICRP's updated biokinetic model for inhalation of radiocarbon as carbon dioxide (CO2) gas. The updated model is based on biokinetic data for carbon isotopes inhaled as carbon dioxide or injected or ingested as bicarbonate [Formula: see text] The data from these studies are expected to apply equally to internally deposited (or internally produced) carbon dioxide and bicarbonate based on comparison of excretion rates for the two administered forms and the fact that carbon dioxide and bicarbonate are largely carried in a common form (CO2-H[Formula: see text] in blood. Compared with dose estimates based on current ICRP biokinetic models for inhaled carbon dioxide or ingested carbon, the updated model will result in a somewhat higher dose estimate for 14C inhaled as CO2 and a much lower dose estimate for 14C ingested as bicarbonate.

Dosimetry of inhaled 219Rn progeny.

During prostate cancer treatment with 223Ra. 219Rn (actinon) occurs and may be exhaled by the patient. Nurses and other hospital employees may inhale this radionuclide and its decay products. The alpha-emitting decay products of actinon deposited within a body will irradiate tissues and organs. Therefore. it is necessary to evaluate organ doses of actinon progeny. The purpose of this study is to set up a dosimetric method to assess dose coefficients for actinon progeny. The effective dose coefficients were calculated separately for three modes. The unattached mode which concerned the activity median thermodynamic diameter (AMTD) of 1 nm. and the nucleation and accumulation modes which are represented by activity median aerodynamic diameters (AMAD) of 60 and 500 nm respectively. The recent biokinetic models of actinon progeny developed in the Occupational Intakes of Radionuclides (OIR) publications series of the International Commission of Radiological Protection (ICRP) were implemented on BIOKMOD (Biokinetic Modeling) to calculate the number of nuclear transformations per activity intake of actinon progeny. The organ equivalent and effective dose coefficients were determined using the dosimetric approach of the ICRP. The inhalation dose coefficients of actinon progeny are dominated by the contribution of lung dose. The calculated dose coefficients of 211Pb and 211Bi are 5.78 × 10-8 and 4.84 × 10-9 Sv.Bq-1 for unattached particles (AMTD = 1 nm). and 1.4 × 10-8 and 3.55 × 10-9 Sv.Bq-1 for attached particles (AMAD = 60 nm). and 7.37 × 10-9 and 1.91 × 10-9 Sv.Bq-1 for attached particles (AMAD = 500 nm). These values are much closer to those of the recently published ICRP 137.

Unchanged cardiovascular and respiratory outcomes in healthy C57Bl/6 mice after in utero exposure to ionizing radiation.

BACKGROUND: Advancements in medical technologies that utilize ionizing radiation have led to improved diagnosis and patient outcomes, however, the effect of ionizing radiation on the patient is still debated. In the case of pregnancy, the potential effects are not only to the mother but also to the fetus. The aim of this study was to determine if exposure from ionizing radiation during pregnancy alters the development of the cardiovascular and respiratory system of the offspring. MATERIALS AND METHODS: Pregnant C57Bl/6 mice were whole-body irradiated at gestational day 15 with a 137Cs gamma radiation emitting source at 0 mGy (sham), 50 mGy, 300 mGy, or 1000 mGy. Post weaning weight and blood pressure measurements were taken weekly for both male and female pups until euthanasia at 16-17 weeks postnatal age. Immediately following, the trachea was cannulated, and the lungs and heart excised. The lung was then examined to assess respiratory physiological outcomes. RESULTS AND CONCLUSIONS: In utero exposures to 1000 mGy caused significant growth reduction compared to sham irradiated, which remained persistent for both male and female pups. Growth restriction was not observed for lower exposures. There was no significant change in any cardiovascular or respiratory outcomes measured. Overall, intrauterine exposures to ionizing radiation does not appear to significantly alter the development of the cardiovascular and respiratory system in C57Bl/6 pups up to 17 weeks postnatal age.

A theoretical model of the application of RF energy to the airway wall and its experimental validation.

BACKGROUND: Bronchial thermoplasty is a novel technique designed to reduce an airway's ability to contract by reducing the amount of airway smooth muscle through controlled heating of the airway wall. This method has been examined in animal models and as a treatment for asthma in human subjects. At the present time, there has been little research published about how radiofrequency (RF) energy and heat is transferred to the airways of the lung during bronchial thermoplasty procedures. In this manuscript we describe a computational, theoretical model of the delivery of RF energy to the airway wall. METHODS: An electro-thermal finite-element-analysis model was designed to simulate the delivery of temperature controlled RF energy to airway walls of the in vivo lung. The model includes predictions of heat generation due to RF joule heating and transfer of heat within an airway wall due to thermal conduction. To implement the model, we use known physical characteristics and dimensions of the airway and lung tissues. The model predictions were tested with measurements of temperature, impedance, energy, and power in an experimental canine model. RESULTS: Model predictions of electrode temperature, voltage, and current, along with tissue impedance and delivered energy were compared to experiment measurements and were within ± 5% of experimental averages taken over 157 sample activations.The experimental results show remarkable agreement with the model predictions, and thus validate the use of this model to predict the heat generation and transfer within the airway wall following bronchial thermoplasty. CONCLUSIONS: The model also demonstrated the importance of evaporation as a loss term that affected both electrical measurements and heat distribution. The model predictions showed excellent agreement with the empirical results, and thus support using the model to develop the next generation of devices for bronchial thermoplasty. Our results suggest that comparing model results to RF generator electrical measurements may be a useful tool in the early evaluation of a model.

Absorption of plutonium compounds in the respiratory tract.

In order to optimise the monitoring of potentially exposed workers, it is desirable to determine specific values of absorption for the compounds handled. This study derives specific values of absorption rates for different chemical forms of plutonium from in vitro and animal (monkeys, dogs, mice, rats) experiments, and from human contamination cases. Different published experimental data have been reinterpreted here to derive values for the absorption parameters, f(r), s(r) and s(s), used in the human respiratory tract model currently adopted by the International Commission on Radiological Protection (ICRP). The consequences of the use of these values were investigated by calculating related committed effective doses per unit intake. Average and median estimates were calculated for f(r), s(r), and s(s) for each plutonium compound, that can be used as default values for specific chemical forms instead of the current reference types. Nevertheless, it was shown that the use of the current ICRP reference absorption types provides reasonable approximations. Moreover, this work provides estimates of the variability in pulmonary absorption and, therefore, facilitates analyses of the uncertainties associated with assessments, either from bioassay measurements or from prospective calculations, of intake and dose.

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.

The Influence of Aerosol Density and Shape Factor on the Assessment of Internal Exposure to 239Pu.

Internal exposure due to inhalation of aerosols depends on the ratio of aerodynamic shape factor (χ) to aerosol mass density (ρ). Inhaled aerosol parameters may differ from the default ρ and χ values provided by the International Commission on Radiological Protection, which are adopted for the assessment of internal exposures. This paper focuses on the influences of χ/ρ on the assessment of internal exposure to Pu for reference workers. Regional deposition fractions are found to decrease with increasing χ/ρ, and larger decreases are observed with smaller activity median aerodynamic diameter aerosols, while the slow clearance fractions (fs) in the tracheobronchial region are more sensitive for larger activity median aerodynamic diameter aerosols. Results from biokinetics calculations reveal that both the time-dependent content (excretion) and cumulative activities are determined mainly for particles initially deposited in the alveolar-interstitial region, while fs affects the local cumulative activities in the tracheobronchial region. χ/ρ is proven to have different influences for aerosols with different activity median aerodynamic diameters. The default χ/ρ values can be used when activity median aerodynamic diameters are greater than 1 µm, while one should pay attention to the value of χ/ρ when activity median aerodynamic diameters are less than 1 µm, where significant influence may be anticipated.

A Monte Carlo method for calculating Bayesian uncertainties in internal dosimetry.

This paper presents a novel Monte Carlo method (WeLMoS, Weighted Likelihood Monte-Carlo sampling method) that has been developed to perform Bayesian analyses of monitoring data. The WeLMoS method randomly samples parameters from continuous prior probability distributions and then weights each vector by its likelihood (i.e. its goodness of fit to the measurement data). Furthermore, in order to quality assure the method, and assess its strengths and weaknesses, a second method (MCMC, Markov chain Monte Carlo) has also been developed. The MCMC method uses the Metropolis algorithm to sample directly from the posterior distribution of parameters. The methods are evaluated and compared using an artificially generated case involving an exposure to a plutonium nitrate aerosol. In addition to calculating the uncertainty on internal dose, the methods can also calculate the probability distribution of model parameter values given the observed data. In other words, the techniques provide a powerful tool to obtain the estimates of parameter values that best fit the data and the associated uncertainty on these estimates. Current applications of the methodology, including the determination of lung solubility parameters, from volunteer and cohort data, are also discussed.

AIDE: internal dosimetry software.

AIDE (Activity and Internal Dose Estimates) is a software for calculating activities in compartments and committed doses due to occupational exposures, and for performing intake and dose estimates using bioassay data. It has been continuously developed and tested for more than 20 years. Its calculation core has been applied in several situations, like performing all dose estimates due to (137)Cs intakes, which occurred during the Goiania accident in 1987; performing quality assurance of the ICRP Task Group on Dose Calculations regarding calculations of activities in compartments and generation of dose coefficients for adults due to intakes by inhalation, ingestion and injection of several radionuclides; and producing the tables of activities in compartments and dose coefficients using the NCRP Wound Model for the NCRP report. It provides several capabilities like performing calculations using modified Human Respiratory Tract Model parameters for the mechanical transport, blood absorption and partitions of deposit in the AI region. The existing systemic models can also be modified or new ones can be entered. All estimate procedures are in accordance with the methods presented in the ICRP-78 Publication, in the IAEA Safety Reports Series no. 37 and in the IDEAS Project Guidelines 2006.

Pediatric Phantom Dosimetry of Kodak 9000 Cone-beam Computed Tomography.

PURPOSE: The purpose of the study was to evaluate the radiation dose of the Kodak 9000 cone-beam computed tomography (CBCT) device for different anatomical areas using a pediatric phantom. METHODS: Absorbed doses resulting from maxillary and mandibular region three by five cm CBCT volumes of an anthropomorphic 10-year-old child phantom were acquired using optical stimulated dosimetry. Equivalent doses were calculated for radiosensitive tissues in the head and neck area, and effective dose for maxillary and mandibular examinations were calculated following the 2007 recommendations of the International Commission on Radiological Protection (ICRP). RESULTS: Of the mandibular scans, the salivary glands had the highest equivalent dose (1,598 microsieverts [µSv]), followed by oral mucosa (1,263 µSv), extrathoracic airway (pharynx, larynx, and trachea; 859 µSv), and thyroid gland (578 µSv). For the maxilla, the salivary glands had the highest equivalent dose (1,847 µSv), followed closely by oral mucosa (1,673 µSv), followed by the extrathoracic airway (pharynx, larynx, and trachea; 1,011 µSv) and lens of the eye (202 µSv). CONCLUSION: Compared to previous research of the Kodak 9000, completed with the adult phantom, a child receives one to three times more radiation for mandibular scans and two to 10 times more radiation for maxillary scans.

Inclusion of thin target and source regions in alimentary and respiratory tract systems of mesh-type ICRP adult reference phantoms.

It is not feasible to define very small or complex organs and tissues in the current voxel-type adult reference computational phantoms of the International Commission on Radiological Protection (ICRP), which limit dose coefficients for weakly penetrating radiations. To address the problem, the ICRP is converting the voxel-type reference phantoms into mesh-type phantoms. In the present study, as a part of the conversion project, the micrometer-thick target and source regions in the alimentary and respiratory tract systems as described in ICRP Publications 100 and 66 were included in the mesh-type ICRP reference adult male and female phantoms. In addition, realistic lung airway models were simulated to represent the bronchial (BB) and bronchiolar (bb) regions. The electron specific absorbed fraction (SAF) values for the alimentary and respiratory tract systems were then calculated and compared with the values calculated with the stylized models of ICRP Publications 100 and 66. The comparisons show generally good agreement for the oral cavity, oesophagus, and BB, whereas for the stomach, small intestine, large intestine, extrathoracic region, and bb, there are some differences (e.g. up to ~9 times in the large intestine). The difference is mainly due to anatomical difference in these organs between the realistic mesh-type phantoms and the simplified stylized models. The new alimentary and respiratory tract models in the mesh-type ICRP reference phantoms preserve the topology and dimensions of the voxel-type ICRP phantoms and provide more reliable SAF values than the simplified models adopted in previous ICRP Publications.

Targeted cytoplasmic irradiation and autophagy.

The effect of ionizing irradiation on cytoplasmic organelles is often underestimated because the general dogma considers direct DNA damage in the nuclei to be the primary cause of radiation induced toxicity. Using a precision microbeam irradiator, we examined the changes in mitochondrial dynamics and functions triggered by targeted cytoplasmic irradiation with α-particles. Mitochondrial dysfunction induced by targeted cytoplasmic irradiation led to activation of autophagy, which degraded dysfunctional mitochondria in order to maintain cellular energy homeostasis. The activation of autophagy was cytoplasmic irradiation-specific and was not detected in nuclear irradiated cells. This autophagic process was oxyradical-dependent and required the activity of the mitochondrial fission protein dynamin related protein 1 (DRP1). The resultant mitochondrial fission induced phosphorylation of AMP activated protein kinase (AMPK) which leads to further activation of the extracellular signal-related kinase (ERK) 1/2 with concomitant inhibition of the mammalian target of rapamycin (mTOR) to initiate autophagy. Inhibition of autophagy resulted in delayed DNA damage repair and decreased cell viability, which supports the cytoprotective function of autophagy. Our results reveal a novel mechanism in which dysfunctional mitochondria are degraded by autophagy in an attempt to protect cells from toxic effects of targeted cytoplasmic radiation.

Assessment of environmental radon hazard using human respiratory tract models.

Radon is a natural radioactive gas derived from geological materials. It has been estimated that about half of the total effective dose received by human beings from all sources of ionizing radiation is attributed to 222Rn and its short-lived progeny. In this paper, the use of human respiratory tract models to assess the health hazard from environmental radon is reviewed. A short history of dosimetric models for the human respiratory tract from the International Commission on Radiological Protection (ICRP) is first presented. The most important features of the newest model published by ICRP in 1994 (as ICRP Publication 66) are then described, including the morphometric model, physiological parameters, radiation biology, deposition of aerosols, clearance model and dose weighting. Comparison between different morphometric models and comparison between different deposition models are then given. Finally, the significance of various parameters in the lung model is discussed, including aerosol parameters, subject related parameters, target and cell related parameters, and parameters that define the absorption of radon from the lungs to blood. Dosimetric calculations gave a dose conversion coefficient of 15 mSv/WLM, which is higher than the value 5 mSv/WLM derived from epidemiological studies. ICRP stated that dosimetric models should only be used for comparison of doses in the human lungs resulted from different exposure conditions.

Human alimentary tract model for radiological protection. ICRP Publication 100. A report of The International Commission on Radiological Protection.

In this report, the ICRP provides a new biokinetic and dosimetric model of the human alimentary tract to replace the Publication 30 (ICRP, 1979) model. The new human alimentary tract model (HATM) will be used together with the human respiratory tract model (HRTM; ICRP, 1994a,b) in future ICRP publications on doses from ingested and inhaled radionuclides. The HATM is applicable to all situations of radionuclide intake by children and adults. It provides age-dependent parameter values for the dimensions of the alimentary tract regions, and associated transit times for the movement of materials through these regions. For adults, gender-dependent parameter values are given for dimensions and transit times. The default assumption is that radionuclide absorption takes place in the small intestine, but the model allows for absorption in other regions and for retention in or on tissues within the alimentary tract when information is available. Doses are calculated to target cells for cancer induction in the oral cavity, oesophagus, stomach, small intestine, and colon. This report provides reviews of information on the transit of materials through the alimentary tract and on radionuclide retention and absorption. It considers data on health effects, principally in order to specify the target cells for cancer induction within the mucosal lining of the tract and to justify approaches taken to dose averaging within regions. Comparisons are made between doses calculated using the HATM and the Publication 30 model for examples of radionuclide ingestion for which absorption is assumed to occur in the small intestine alone. Examples are also given of the effects on doses of considering absorption from other regions and the effect of possible retention in the alimentary tract. This report also considers uncertainties in model assumptions and their effect on doses, including alimentary tract dimensions, transit times, radionuclide absorption values, and the location of targets for cancer induction.

Charged particle equilibrium effects on the electron absorbed fraction in the extrathoracic airways.

Estimates of the dose to the extrathoracic airway (nasal vestibule) from inhaled beta-emitting radionuclides, obtained using the respiratory tract model presented in Publication 66 of the International Commission on Radiological Protection, frequently predict that the basal cells in this region are the most highly irradiated tissues of the body. The dose to the basal cells is averaged over a layer of tissue 10 microm thick located at a depth of 40 microm into the airway assuming that charged particle equilibrium exists. Since the target (basal cell layer) is very small and thin (10 cm(2) area and 10 microm thickness), charged particle equilibrium does not exist. In this work the effect on the absorbed fraction of the lack of charged particle equilibrium is investigated.

Assessment and prevention of radioactive risk due to 222Radon on University Premises in Genoa, Italy.

From October 2004 to September 2005, Radon222 activity in high-risk indoor spaces used by employees and students at the University of Genoa was measured with CR-39 nuclear track detectors. The mean concentration in winter (78.9 Bq/m3 +/- 74.92 S.D.) was low in relation to the microenvironment considered. When data were broken down by type and location of the spaces, no significant differences were found, despite the fact that the Genoa conurbation lies on soil of variable geological composition. The dose absorbed by employees was 0.42 mSv/year, with a relative risk of 4.2/1000 cases of Radon-related lung cancer. The dose absorbed by students was 0.28 mSv/year, with a relative risk of 2.5/1000 cases of Radon-related lung cancer. The level of radon activity detected never exceeded the limit of 500 Bq/m3 established by Italian law. Nevertheless, the value of the compound uncertainty index suggested that the real level of Radon contamination could have exceeded 400 Bq/m3 in selected spaces, a value requiring annual concentration tests.

Adaptation of the ICRP publication 66 respiratory tract model to data on plutonium biokinetics for Mayak workers.

The biokinetics of inhaled plutonium were analyzed using compartment models representing their behavior within the respiratory tract, the gastrointestinal tract, and in systemic tissues. The processes of aerosol deposition, particle transport, absorption, and formation of a fixed deposit in the respiratory tract were formulated in the framework of the Human Respiratory Tract Model described in ICRP Publication 66. The values of parameters governing absorption and formation of the fixed deposit were established by fitting the model to the observations in 530 autopsy cases. The influence of smoking on mechanical clearance of deposited plutonium activity was considered. The dependence of absorption on the aerosol transportability, as estimated by in vitro methods (dialysis), was demonstrated. The results of this study were compared to those obtained from an earlier model of plutonium behavior in the respiratory tract, which was based on the same set of autopsy data. That model did not address the early phases of respiratory clearance and hence underestimated the committed lung dose by about 25% for plutonium oxides. Little difference in lung dose was found for nitrate forms.

Influence of radioactive aerosol and biological parameters of inhaled radon progeny on human lung dose.

The present work focuses on assessing the influence of biological and aerosol parameters on human lung dose. The dose conversion factor (DCF), which gives the relationship between the effective dose and the potential alpha energy concentration of inhaled short-lived radon progeny (218Po, 214Pb, 214Bi/214Po) is estimated using a dosimetric approach related to the International Commission on Radiological Protection(ICRP). The calculations are based on the measurements of the distribution of activity size of indoor radon progeny, their unattached fraction (f(b)) and potential alpha energy concentration (E). These experimental data are measured using a low-pressure cascade impactor and a wire-screen diffusion battery. Because of the short half-lives of the investigated nuclides, modifications that simplify the dose calculation are possible. The radioactive aerosol and biological parameters are varied in order to assess the DCF arising from the uncertainty of these parameters. The main emphasis is on the variation of the ventilation rate, breathing mode, critical cells for the induction of lung cancer and the parameters of the attached and unattached activity size distribution of the radon progeny. The investigation shows that the DCF is more than a factor of two higher than the values recommended by the ICRP, namely 3.9 mSv WLM(-1) for the public and 5.1 mSv WLM(-1) for working places. The dose results for indoor aerosol conditions are in the range 2.3-2.6 mSv WLM(-1) depending on the breathing mode.

Radon and Thoron Measured in Petrol and Gas-oil Exhaust Fumes by Using CR-39 and LR-115 II Nuclear Track Detectors: Radiation Doses to the Respiratory Tract of Mechanic Workers.

Mechanic workers are exposed to exhaust fumes when controlling vehicle engines in motion inside repair shops. To assess radiation doses due to radon short-lived progeny from the inhalation of exhaust fumes by mechanic workers, concentrations of these radionuclides were measured in petrol (gasoline) and gas-oil exhaust fumes by evaluating mean critical angles of etching of the CR-39 and LR-115 type II SSNTDs for alpha particles emitted by the radon and thoron decay series. Committed effective doses due to ²¹8Po and ²¹4Po short-lived radon decay products from the inhalation of petrol and gas-oil exhaust fumes by workers were evaluated. A maximum value of 1.35 mSv y⁻¹ due to radon short-lived decay products from the inhalation of gas-oil exhaust fumes by mechanic workers was found, which is lower than the (3-10 mSv y⁻¹) dose limit interval for workers.