Interobserver delineation variability of computed tomography-based radiomic features of the parotid gland.

PURPOSE: To assess the interobserver delineation variability of radiomic features of the parotid gland from computed tomography (CT) images and evaluate the correlation of these features for head and neck cancer (HNC) radiotherapy patients. MATERIALS AND METHODS: Contrast-enhanced CT images of 20 HNC patients were utilized. The parotid glands were delineated by treating radiation oncologists (ROs), a selected RO and AccuContour auto-segmentation software. Dice similarity coefficients (DSCs) between each pair of observers were calculated. A total of 107 radiomic features were extracted, whose robustness to interobserver delineation was assessed using the intraclass correlation coefficient (ICC). Pearson correlation coefficients (r) were calculated to determine the relationship between the features. The influence of excluding unrobust features from normal tissue complication probability (NTCP) modeling was investigated for severe oral mucositis (grade ≥3). RESULTS: The average DSC was 0.84 (95% confidence interval, 0.83-0.86). Most of the shape features demonstrated robustness (ICC ≥0.75), while the first-order and texture features were influenced by delineation variability. Among the three observers investigated, 42 features were sufficiently robust, out of which 36 features exhibited weak correlation (|r|<0.8). No significant difference in the robustness level was found when comparing manual segmentation by a single RO or automated segmentation with the actual clinical contour data made by treating ROs. Excluding unrobust features from the NTCP model for severe oral mucositis did not deteriorate the model performance. CONCLUSION: Interobserver delineation variability had substantial impact on radiomic features of the parotid gland. Both manual and automated segmentation methods contributed similarly to this variation.

CBCT-to-CT Translation Using Registration-Based Generative Adversarial Networks in Patients with Head and Neck Cancer.

Recently, deep learning with generative adversarial networks (GANs) has been applied in multi-domain image-to-image translation. This study aims to improve the image quality of cone-beam computed tomography (CBCT) by generating synthetic CT (sCT) that maintains the patient's anatomy as in CBCT, while having the image quality of CT. As CBCT and CT are acquired at different time points, it is challenging to obtain paired images with aligned anatomy for supervised training. To address this limitation, the study incorporated a registration network (RegNet) into GAN during training. RegNet can dynamically estimate the correct labels, allowing supervised learning with noisy labels. The study developed and evaluated the approach using imaging data from 146 patients with head and neck cancer. The results showed that GAN trained with RegNet performed better than those trained without RegNet. Specifically, in the UNIT model trained with RegNet, the mean absolute error (MAE) was reduced from 40.46 to 37.21, the root mean-square error (RMSE) was reduced from 119.45 to 108.86, the peak signal-to-noise ratio (PSNR) was increased from 28.67 to 29.55, and the structural similarity index (SSIM) was increased from 0.8630 to 0.8791. The sCT generated from the model had fewer artifacts and retained the anatomical information as in CBCT.

Correction: Suwanbut et al. Assessment of Fetal Dose and Health Effect to the Fetus from Breast Cancer Radiotherapy during Pregnancy. Life 2022, 12, 84.

In the original publication [...].

Assessment of Fetal Dose and Health Effect to the Fetus from Breast Cancer Radiotherapy during Pregnancy.

Decision for radiotherapy during the first trimester of pregnancy may occur, as patients may not realize their pregnancy at the very early stage. Since radiation dose can affect fetal development, the aim of this study was to evaluate fetal dose and associated deterministic effects and risks to the fetus from breast cancer radiotherapy of an 8-week pregnant patient. PHITS (Particle and Heavy Ion Transport code System) Monte Carlo simulation and the J-45 computational pregnancy phantom were used to simulate breast cancer radiotherapy from a 6 MV TrueBeam linear accelerator using the three dimensional-conformal radiotherapy (3D-CRT) technique with a prescribed dose to the planning target volume (PTV) of 50 Gy. Once the fetal dose was evaluated, the occurrence of the deterministic effects and risks for developing stochastic effects in the fetus were assessed using the recommendations of NCRP Report No. 174, AAPM Report No. 50, and ICRP Publication 84. The fetal dose was evaluated to be 3.37 ± 2.66 mGy, suggesting that the fetus was expected to have no additional deterministic effects, while the risks for developing cancer and malfunctions were similar to that expected from exposure to background radiation. The comparison with the other studies showed that accurate consideration of fetal position and size was important for dose determination in the fetus, especially at the early pregnancy stage when the fetus is very small.

Track-structure modes in particle and heavy ion transport code system (PHITS): application to radiobiological research.

PURPOSE: In radiation physics, Monte Carlo radiation transport simulations are powerful tools to evaluate the cellular responses after irradiation. When investigating such radiation-induced biological effects, it is essential to perform track structure simulations by explicitly considering each atomic interaction in liquid water at the sub-cellular and DNA scales. The Particle and Heavy-Ion Transport code System (PHITS) is a Monte Carlo code which enables to calculate track structure at DNA scale by employing the track-structure modes for electrons, protons and carbon ions. In this paper, we review the recent development status and future prospects of the track-structure modes in the PHITS code. CONCLUSIONS: To date, the physical features of these modes have been verified using the available experimental data and Monte Carlo simulation results reported in literature. These track-structure modes can be used for calculating microdosimetric distributions to estimate cell survival and for estimating initial DNA damage yields. The use of PHITS track-structure mode is expected not only to clarify the underlying mechanisms of radiation effects but also to predict curative effects in radiation therapy. The results of PHITS simulations coupled with biophysical models will contribute to the radiobiological studies by precisely predicting radiation-induced biological effects based on the Monte Carlo approach.

Verification of KURBUC-based ion track structure mode for proton and carbon ions in the PHITS code.

The particle and heavy ion transport code system (PHITS) is a general-purpose Monte Carlo radiation transport simulation code. It has the ability to handle diverse particle types over a wide range of energy. The latest PHITS development enables the generation of track structure for proton and carbon ions (1H+, 12C6+) based on the algorithms in the KURBUC code, which is considered as one of the most verified track-structure codes worldwide. This ion track-structure mode is referred to as the PHITS-KURBUC mode. In this study, the range, radial dose distributions, and microdosimetric distributions were calculated using the PHITS-KURBUC mode. Subsequently, they were compared with the corresponding data obtained from the original KURBUC and from other studies. These comparative studies confirm the successful inclusion of the KURBUC code in the PHITS code. As results of the synergistic effect between the macroscopic and microscopic radiation transport codes, this implementation enabled the detailed calculation of the microdosimetric and nanodosimetric quantities under complex radiation fields, such as proton beam therapy with the spread-out Bragg peak.

Microdosimetry of proton and carbon ions.

PURPOSE: To investigate microdosimetry properties of 160 MeV/u protons and 290 MeV/u(12)C ion beams in small volumes of diameters 10-100 nm. METHODS: Energy distributions of primary particles and nuclear fragments in the beams were calculated from simulations with the general purpose code SHIELD-HIT, while energy depositions by monoenergetic ions in nanometer volumes were obtained from the event-by-event Monte Carlo track structure ion code PITS99 coupled with the electron track structure code KURBUC. RESULTS: The results are presented for frequencies of energy depositions in cylindrical targets of diameters 10-100 nm, dose distributions yd(y) in lineal energy y, and dose-mean lineal energies yD. For monoenergetic ions, the yD was found to increase with an increasing target size for high-linear energy transfer (LET) ions, but decrease with an increasing target size for low-LET ions. Compared to the depth dose profile of the ion beams, the maximum of the yD depth profile for the 160 MeV proton beam was located at ∼ 0.5 cm behind the Bragg peak maximum, while the yD peak of the 290 MeV/u (12)C beam coincided well with the peak of the absorbed dose profile. Differences between the yD and dose-averaged linear energy transfer (LETD) were large in the proton beam for both target volumes studied, and in the (12)C beam for the 10 nm diameter cylindrical volumes. The yD determined for 100 nm diameter cylindrical volumes in the (12)C beam was approximately equal to the LETD. The contributions from secondary particles to the yD of the beams are presented, including the contributions from secondary protons in the proton beam and from fragments with atomic number Z = 1-6 in the (12)C beam. CONCLUSIONS: The present investigation provides an insight into differences in energy depositions in subcellular-size volumes when irradiated by proton and carbon ion beams. The results are useful for characterizing ion beams of practical importance for biophysical modeling of radiation-induced DNA damage response and repair in the depth profiles of protons and carbon ions used in radiotherapy.

Cross sections for bare and dressed carbon ions in water and neon.

The paper presents calculated cross sections for bare and dressed carbon projectiles of charge states q (0 to 6) with energies 1-10(4) keV u(-1) impacting on molecular water and atomic neon targets. The cross sections of water are of interest for radiobiological studies, but there are very few experimental data for water in any phase, while those for liquid water are non-existent. The more extensive experimental database for the neon target made it possible to test the reliability of the model calculations for the many-electron collision system. The current calculations cover major single and double electronic interactions of low and intermediate energy carbon projectiles. The three-body classical trajectory Monte Carlo (CTMC) method was used for the calculation of one-electron transition probabilities for target ionization, electron capture and projectile electron loss. The many-electron problem was taken into account using statistical methods: a modified independent event model was used for pure (direct) and simultaneous target and projectile ionizations, and the independent particle model for pure electron capture and electron capture accompanied by target ionization. Results are presented for double differential cross sections (DDCS) for total electron emission by carbon projectile impact on neon. For the water target, we present the following: single differential cross sections (SDCS) and DDCS for single target ionization; total cross sections (TCS) for electron emission; TCS for the pure single electronic interactions; equilibrium charge state fractions; and stopping cross sections. The results were found to be in satisfactory agreement with the experimental data in many cases, including DDCS and SDCS for the single target ionization, TCS for the total electron emission and TCS for the pure single electron capture. The stopping cross sections of this work are consistent with the other model calculations for projectile energies ≥800 keV u(-1), but smaller than the other calculations at lower energies. The discrepancy arises from the inclusion of all carbon charge states and coupling between electron capture and target ionization channels, while other models use an average projectile charge. The CTMC model presented here provides a tool for cross section calculations for low and intermediate energy carbon projectiles. The calculated cross sections are required for Monte Carlo track structure simulations of full-slowing-down tracks of carbon ions. The work paves the way for biophysical studies and dosimetry at the cellular and subcellular levels in the Bragg peak area of a therapeutic carbon ion beam.

Microdosimetry of low-energy electrons.

PURPOSE: To investigate differences in energy depositions and microdosimetric parameters of low-energy electrons in liquid and gaseous water using Monte Carlo track structure simulations. MATERIALS AND METHODS: KURBUC-liq (Kyushu University and Radiobiology Unit Code for liquid water) was used for simulating electron tracks in liquid water. The inelastic scattering cross sections of liquid water were obtained from the dielectric response model of Emfietzoglou et al. (Radiation Research 2005;164:202-211). Frequencies of energy deposited in nanometre-size cylindrical targets per unit absorbed dose and associated lineal energies were calculated for 100-5000 eV monoenergetic electrons and the electron spectrum of carbon K edge X-rays. The results for liquid water were compared with those for water vapour. RESULTS: Regardless of electron energy, there is a limit how much energy electron tracks can deposit in a target. Phase effects on the frequencies of energy depositions are largely visible for the targets with diameters and heights smaller than 30 nm. For the target of 2.3 nm by 2.3 nm (similar to dimension of DNA segments), the calculated frequency- and dose-mean lineal energies for liquid water are up to 40% smaller than those for water vapour. The corresponding difference is less than 12% for the targets with diameters ≥ 30 nm. CONCLUSIONS: Condensed-phase effects are non-negligible for microdosimetry of low-energy electrons for targets with sizes smaller than a few tens of nanometres, similar to dimensions of DNA molecular structures and nucleosomes.

An energy-loss model for low- and intermediate-energy carbon projectiles in water.

PURPOSE: To model interaction cross sections and energy loss for carbon projectiles C(0)-C(6+) of 1-10(4) keV/u (u: atomic mass unit) in water. MATERIALS AND METHODS: The classical trajectory Monte Carlo method was used to calculate the ionisation and charge-transfer cross sections. The excitation cross sections were scaled from proton data using equilibrium charges determined from the charge-transfer cross sections. Energy loss was obtained from the singly differential cross sections, and ionisation potentials of the target and projectile. RESULTS: The calculated total ionisation cross sections are consistent with measured data, while the calculated electron-capture cross sections are larger than experimental data by a factor of 3. By scaling the latter to the measured data, the cross sections were made consistent with these data for 1-10 keV/u energies. The present stopping cross sections agree well with experimental data below 10 keV/u, and with other model calculations above 2 MeV/u. Deviation from the latter is found where electron capture is competitive with ionisation, and also arises from different energy-transfer calculations. CONCLUSIONS: In this paper we report our efforts in the developments of full slowing-down Monte Carlo track structure calculations for carbon ions. Further development and refinement of the model are currently underway.

Elastic scattering cross section models used for Monte Carlo simulation of electron tracks in media of biological and medical interest.

PURPOSE: Elastic scattering is important for the spatial distribution of electrons penetrating matter, and thus for the distribution of deposited energy and DNA damage. Scattering media of interest are in particular liquid and gaseous water and gaseous nitrogen. The former are used as surrogates for tissue and cell environments (since more than 70% of the cell consists of water), while cross section data for nitrogen have been scaled and used as input in Monte Carlo (MC) codes simulating scattering in biologically relevant media. A short review is given of electron elastic scattering cross section models used in a biological and medical context and their experimental and theoretical background. CONCLUSIONS: Adequate theories and models exist for calculating elastic electron scattering in gaseous nitrogen and gaseous water (i.e., by free molecules) down to electron energies well below 100 eV. However, elastic electron scattering in liquid water at such low energies is apparently uncertain and not well understood. Further studies in the case of liquid water are thus motivated due to its biological importance.

Physical and biophysical properties of proton tracks of energies 1 keV to 300 MeV in water.

PURPOSE: To investigate physical and biophysical properties of proton tracks 1 keV-300 MeV using Monte Carlo track structure methods. MATERIALS AND METHODS: We present model calculations for cross sections and methods for simulations of full-slowing-down proton tracks. Protons and electrons were followed interaction-by-interaction to cut-off energies, considering elastic scattering, ionisation, excitation, and charge-transfer. RESULTS: Model calculations are presented for singly differential and total cross sections, and path lengths and stopping powers as a measure of the code evaluation. Depth-dose distributions for 160 MeV protons are compared with experimental data. Frequencies of energy loss by electron interactions increase from ∼ 3% for 10 keV to ∼ 77% for 300 MeV protons, and electrons deposit  >70% of the dose in 160 MeV tracks. From microdosimetry calculations, 1 MeV protons were found to be more effective than 5-300 MeV in energy depositions greater than 25, 50, and 500 eV in cylinders of diameters and lengths 2, 10, and 100 nm, respectively. For lower-energy depositions, higher-energy protons are more effective. Decreasing the target size leads to the reduction of frequency- and dose-mean lineal energies for protons <1 MeV, and conversely for higher-energy protons. CONCLUSIONS: Descriptions of proton tracks at molecular levels facilitate investigations of track properties, energy loss, and microdosimetric parameters for radiation biophysics, radiation therapy, and space radiation research.

A model of carbon ion interactions in water using the classical trajectory Monte Carlo method.

In this paper, model calculations for interactions of C(6+) of energies from 1 keV u(-1) to 1 MeV u(-1) in water are presented. The calculations were carried out using the classical trajectory Monte Carlo method, taking into account the dynamic screening of the target core. The total cross sections (TCS) for electron capture and ionisation, and the singly and doubly differential cross sections (SDCS and DDCS) for ionisation were calculated for the five potential energy levels of the water molecule. The peaks in the DDCS for the electron capture to continuum and for the binary-encounter collision were obtained for 500-keV u(-1) carbon ions. The calculated SDCS agree reasonably well with the z(2) scaled proton data for 500 keV u(-1) and 1 MeV u(-1) projectiles, but a large deviation of up to 8-folds was observed for 100-keV u(-1) projectiles. The TCS for ionisation are in agreement with the values calculated from the first born approximation (FBA) at the highest energy region investigated, but become smaller than the values from the FBA at the lower-energy region.