A Simplified Cluster Analysis of Electron Track Structure for Estimating Complex DNA Damage Yields.

Complex DNA damage, defined as at least two vicinal lesions within 10-20 base pairs (bp), induced after exposure to ionizing radiation, is recognized as fatal damage to human tissue. Due to the difficulty of directly measuring the aggregation of DNA damage at the nano-meter scale, many cluster analyses of inelastic interactions based on Monte Carlo simulation for radiation track structure in liquid water have been conducted to evaluate DNA damage. Meanwhile, the experimental technique to detect complex DNA damage has evolved in recent decades, so both approaches with simulation and experiment get used for investigating complex DNA damage. During this study, we propose a simplified cluster analysis of ionization and electronic excitation events within 10 bp based on track structure for estimating complex DNA damage yields for electron and X-ray irradiations. We then compare the computational results with the experimental complex DNA damage coupled with base damage (BD) measured by enzymatic cleavage and atomic force microscopy (AFM). The computational results agree well with experimental fractions of complex damage yields, i.e., single and double strand breaks (SSBs, DSBs) and complex BD, when the yield ratio of BD/SSB is assumed to be 1.3. Considering the comparison of complex DSB yields, i.e., DSB + BD and DSB + 2BD, between simulation and experimental data, we find that the aggregation degree of the events along electron tracks reflects the complexity of induced DNA damage, showing 43.5% of DSB induced after 70 kVp X-ray irradiation can be classified as a complex form coupled with BD. The present simulation enables us to quantify the type of complex damage which cannot be measured through in vitro experiments and helps us to interpret the experimental detection efficiency for complex BD measured by AFM. This simple model for estimating complex DNA damage yields contributes to the precise understanding of the DNA damage complexity induced after X-ray and electron irradiations.

Designing lightweight neutron absorbing composites using a comprehensive absorber areal density metric.

Efforts to lightweight neutron absorbing composites are limited by incomplete understandings of the interaction between absorbing particles and their matrices. In this study, analytical models and a more physically representative simulation evaluated the penalty to neutron absorbing performance due to neutron channeling between large absorbing particles. Models and simulation agreed that B4C particles smaller than 100µm and especially those smaller than 10µm did not cause excessive neutron channeling. A more comprehensive neutron absorbing composite design metric - boron-10 equivalent areal density, which considers the particle size penalty and the matrix contribution to absorptivity - was introduced and used to estimate lightweighting via matrix substitution. Calculations using this new metric showed that a non-absorbing Mg matrix reduced mass by up to 35% over Al, constrained by the difference in mass density, while an absorbing Mg-Li matrix reduced mass by up to 60%, exceeding the difference in mass densities alone. Measurement of apparent absorber areal density through two experimental techniques - foil activation and direct counting - validated estimated absorber areal density as a neutron absorbing composite design metric. This updated understanding of the particle size penalty, newly introduced design metric, and experimental validation demonstrate a path to lightweight neutron absorbing composites.

Development of a generalized method to allow the estimation of doses to the ICRP reference adults from CT, on the basis of normalized organ and CTDI dose data determined by Monte Carlo calculation for a range of contemporary scanners.

Objective. Development of a method to provide organ and effective dose coefficients to reference adults for any CT scanner based on values ofCTDImeasured both in air and in standard CT dosimetry phantoms.Approach. Results from previous Monte Carlo simulations for a range of contemporary CT scanners have been analyzed to provide linear models relating values of organ dose (normalized toCTDIfree-in-air), for each slab of 3 reference phantoms (ICRP Male/Female, and AH hermaphrodite), to similarly normalized values ofCTDIin standard CT dosimetry phantoms. Three methods have been investigated to apply the models to values ofCTDIfor a 'new' scanner not previously simulated: a Generic approach using averaged normalized organ dose profiles for whole body exposure of the phantoms; and two processes for matching the scanner, on the basis of normalized organ doses or effective dose (nE103,phan), to one of the 102 sets of dose coefficients previously calculated for 12 contemporary CT scanner models, from 4 manufacturers, operating under a range of conditions.Main results. The merit of each method has been quantitatively assessed when applied to both the present contemporary scanners with each test data set being excluded in turn during the matching process, and also to 3 previously-simulated older scanners. Whereas all three methods appear viable, with all doses being within 1% and 10% for the contemporary and old scanners respectively, matching tonE103,phanis overall the approach preferred in practice, yielding an uncertainty of around 6% in estimated values ofnE103,phan. The present methodology also provides superior performance when compared against some other common normalization factors forE103,phan.Significance. The CT dose model and the data sets will be incorporated into a new CT dosimetry tool that will be made available from UKHSA in support of facilitating improvements in patient protection.

Organ dose conversion coefficients in CT scans for Korean adult males and females.

Dose monitoring in CT patients requires accurate dose estimation but most of the CT dose calculation tools are based on Caucasian computational phantoms. We established a library of organ dose conversion coefficients for Korean adults by using four Korean adult male and two female voxel phantoms combined with Monte Carlo simulation techniques. We calculated organ dose conversion coefficients for head, chest, abdomen and pelvis, and chest-abdomen-pelvis scans, and compared the results with the existing data calculated from Caucasian phantoms. We derived representative organ doses for Korean adults using Korean CT dose surveys combined with the dose conversion coefficients. The organ dose conversion coefficients from the Korean adult phantoms were slightly greater than those of the ICRP reference phantoms: up to 13% for the brain doses in head scans and up to 10% for the dose to the small intestine wall in abdominal scans. We derived Korean representative doses to major organs in head, chest, and AP scans using mean CTDIvol values extracted from the Korean nationwide surveys conducted in 2008 and 2017. The Korean-specific organ dose conversion coefficients should be useful to readily estimate organ absorbed doses for Korean adult male and female patients undergoing CT scans.

Organ dose calculator for diagnostic nuclear medicine patients based on the ICRP reference voxel phantoms and biokinetic models.

The exponential growth in the use of nuclear medicine procedures represents a general radiation safety concern and stresses the need to monitor exposure levels and radiation-related long term health effects in NM patients. In the current study, following our previous work on NCINM version 1 based on the UF/NCI hybrid phantom series, we calculated a comprehensive library of S values using the ICRP reference pediatric and adult voxel phantoms and established a library of biokinetic data from multiple ICRP Publications, which were then implemented into NCINM version 2. We calculated S values in two steps: calculation of specific absorbed fraction (SAF) using a Monte Carlo radiation transport code combined with the twelve ICRP pediatric and adult voxel phantoms for a number of combinations of source and target region pairs; derivation of S values from the SAFs using the ICRP nuclear decay data. We also adjusted the biokinetic data of 105 radiopharmaceuticals from multiple ICRP publications to match the anatomical description of the ICRP voxel phantoms. Finally, we integrated the ICRP phantom-based S values and adjusted biokinetic data into NCINM version 2. The ratios of cross-fire SAFs from NCINM 2 to NCINM 1 for the adult phantoms varied widely from 0.26 to 5.94 (mean = 1.24, IQR = 0.77-1.55) whereas the ratios for the pediatric phantoms ranged from 0.64 to 1.47 (mean = 1.01, IQR = 0.98-1.03). The ratios of absorbed dose coefficients from NCINM 2 over those from ICRP publications widely varied from 0.43 (colon for99mTc-ECD) to 2.57 (active marrow for99mTc-MAG3). NCINM 2.0 should be useful for dosimetrists and medical physicists to more accurately estimate organ doses for various nuclear medicine procedures.

CT scanner-specific organ dose coefficients generated by Monte Carlo calculation for the ICRP adult male and female reference computational phantoms.

Objective.Provide analyses of new organ dose coefficients (hereafter also referred to as normalized doses) for CT that have been developed to update the widely-utilized collection of data published 30 years ago in NRPB-SR250.Approach.In order to reflect changes in technology, and also ICRP recommendations concerning use of the computational phantoms adult male (AM) and adult female (AF), 102 series of new Monte Carlo simulations have been performed covering the range of operating conditions for 12 contemporary models of CT scanner from 4 manufacturers. Normalized doses (relative to free air on axis) have been determined for 39 organs, and for every 8 mm or 4.84 mm slab of AM and AF, respectively.Main results.Analyses of results confirm the significant influence (by up to a few tens of percent), on values of normalized organ (or contributions to effective dose (E103,phan)), for whole body exposure arising from selection of tube voltage and beam shaping filter. Use of partial (when available) rather than a Full fan beam reduced both organ and effective dose by up to 7%. Normalized doses to AF were larger than corresponding figures for AM by up to 30% for organs and by 10% forE103,phan. Additional simulations for whole body exposure have also demonstrated that: practical simplifications in the main modelling (point source, single slice thickness, neglect of patient couch and immobility of phantom arms) have sufficiently small (<5%) effect onE103,phan; mis-centring of the phantom away from the axis of rotation by 5 mm (in any direction) leads to changes in normalized organ dose andE103,phanby up to 20% and 6%, respectively; and angular tube current modulation can result in reductions by up to 35% and <15% in normalized organ dose andE103,phan, respectively, for 100% cosine variation.Significance.These analyses help advance understanding of the influence of operational scanner settings on organ dose coefficients for contemporary CT, in support of improved patient protection. The results will allow the future development of a new dose estimation tool.

Organ dose conversion coefficients calculated for Korean pediatric and adult voxel phantoms exposed to external photon fields.

Background: Dose conversion coefficients (DCCs) have been commonly used to estimate radiation dose absorbed in human organs from physical measurements of fluence or kerma. The International Commission on Radiological Protection (ICRP) reported a library of DCCs but few studies were conducted on their applicability to non-Caucasian populations. In the present study, we collected a total of eight Korean pediatric and adult voxel phantoms to calculate organ DCCs for idealized external photon irradiation geometries. Materials and methods: We adopted one pediatric female phantom (ETRI Child), two adult female phantoms (KORWOMAN and HDRK Female), and five adult male phantoms (KORMAN, ETRI Man, KTMAN1, KTMAN2, and HDRK Man). A general-purpose Monte Carlo radiation transport code, MCNPX2.7, was employed to calculate dose conversion coefficients for 13 major radiosensitive organs in six irradiation geometries (antero-posterior, postero-anterior, right lateral, left lateral, rotational, and isotropic) and 33 photon energy bins (0.01 - 20 MeV). Results and discussion: The DCCs for major radiosensitive organs (e.g., lungs and colon) in AP geometry reasonably agreed across the eight Korean phantoms whereas those for deep-seated organs (e.g., gonads) significantly varied. DCCs of the child phantom were overall greater than those of the adult phantoms. Comparison with the ICRP Publication 116 data showed reasonable agreements with Korean phantom-based data. The variations in organ DCCs were well explained using the distribution of organ depths from the phantom surface. Conclusion: A library of dose conversion coefficients for major radiosensitive organs in a series of pediatric and adult Korean voxel phantoms was established and compared with the reference data from ICRP. Comparison with the data from the ICRP reference adult voxel phantoms showed that our Korean phantom-based data is overall in a reasonable agreement with the ICRP reference data.

Predicted ionisation in mitochondria and observed acute changes in the mitochondrial transcriptome after gamma irradiation: a Monte Carlo simulation and quantitative PCR study.

It is a widely accepted that the cell nucleus is the primary site of radiation damage while extra-nuclear radiation effects are not yet systematically included into models of radiation damage. We performed Monte Carlo simulations assuming a spherical cell (diameter 11.5 µm) modelled after JURKAT cells with the inclusion of realistic elemental composition data based on published literature. The cell model consists of cytoplasm (density 1g/cm(3)), nucleus (diameter 8.5 µm; 40% of cell volume) as well as cylindrical mitochondria (diameter 1 µm; volume 0.5 µm(3)) of three different densities (1, 2 and 10 g/cm(3)) and total mitochondrial volume relative to the cell volume (10, 20, 30%). Our simulation predicts that if mitochondria take up more than 20% of a cell's volume, ionisation events will be the preferentially located in mitochondria rather than in the cell nucleus. Using quantitative polymerase chain reaction, we substantiate in JURKAT cells that human mitochondria respond to gamma radiation with early (within 30 min) differential changes in the expression levels of 18 mitochondrially encoded genes, whereby the number of regulated genes varies in a dose-dependent but non-linear pattern (10 Gy: 1 gene; 50 Gy: 5 genes; 100 Gy: 12 genes). The simulation data as well as the experimental observations suggest that current models of acute radiation effects, which largely focus on nuclear effects, might benefit from more systematic considerations of the early mitochondrial responses and how these may subsequently determine cell response to ionising radiation.