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Prediction of biological radiation effects based on ionization clusters (nanodosimetry)
Authors:
Hans Rabus
Abstract:
This article reviews approaches that link the formation of ionization clusters in nanometric volumes to radiobiological effectiveness. The corresponding models are presented using harmonized terminology and notation. They are categorized into three classes according to the most important, often implicit model rationale: (a) models that use a nanodosimetric weighting factor for biological effective…
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This article reviews approaches that link the formation of ionization clusters in nanometric volumes to radiobiological effectiveness. The corresponding models are presented using harmonized terminology and notation. They are categorized into three classes according to the most important, often implicit model rationale: (a) models that use a nanodosimetric weighting factor for biological effectiveness derived from frequency distributions of ionization clusters in a single target; (b) models that account for the synergistic effects of pairs of ionization clusters formed in different targets; (c) models that account for 'macroscopic' situations involving many nanometric targets and derive radiation quantities from the particle fluence. Further conceptual differences between the models and their underlying assumptions are discussed, such as the fact that some models are mechanistic while others only aim to elucidate correlations. Eventually, an attempt is made to identify the key open questions in this field that still need to be addressed.
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Submitted 29 June, 2026;
originally announced June 2026.
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Active learning-based variance reduction for Monte Carlo simulations: A feasibility study for the nanodosimetry around a gold nanoparticle
Authors:
Leo Thomas,
Miriam Schwarze,
Hans Rabus
Abstract:
Objective: This work presents a data-driven importance sampling-based variance reduction (VR) scheme inspired by active learning. The method is applied to the estimation of an optimal impact-parameter distribution in the calculation of ionization clusters around a gold nanoparticle (NP). Here, such an optimal importance distribution can not be inferred from principle. Approach: An iterative optimi…
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Objective: This work presents a data-driven importance sampling-based variance reduction (VR) scheme inspired by active learning. The method is applied to the estimation of an optimal impact-parameter distribution in the calculation of ionization clusters around a gold nanoparticle (NP). Here, such an optimal importance distribution can not be inferred from principle. Approach: An iterative optimization procedure is set up that uses a Gaussian Process Sampler to propose optimal sampling distributions based on a loss function. The loss is constructed based on appropriate heuristics. The optimization code obtains estimates of the number of ionization clusters in shells around the NP by interfacing with a Geant4 simulation via a dedicated Transmission Control Protocol (TCP) interface. Main results: It is shown that the so-derived impact-parameter distribution easily outperforms the actual, uniform irradiation case. The results resemble those obtained with other VR schemes but do still slightly overestimate background contributions. Significance: While the method presented is a proof-of-principle, it provides a novel method of estimating importance distributions in ill-posed scenarios. The presented TCP interface described here is a simple and efficient method to expose compiled Geant4 code to other scripts, written for example, in Python.
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Submitted 1 November, 2025;
originally announced November 2025.
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Cluster Dose Prediction in Carbon Ion Therapy: Using Transfer Learning from a Pretrained Dose Prediction U-Net
Authors:
Miriam Schwarze,
Hui Khee Looe,
Björn Poppe,
Leo Thomas,
Hans Rabus
Abstract:
The cluster dose concept offers an alternative to the radiobiological effectiveness (RBE)-based model for describing radiation-induced biological effects. This study examines the application of a neural network to predict cluster dose distributions, with the goal of replacing the computationally intensive simulations currently required. Cluster dose distributions are predicted using a U-Net that w…
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The cluster dose concept offers an alternative to the radiobiological effectiveness (RBE)-based model for describing radiation-induced biological effects. This study examines the application of a neural network to predict cluster dose distributions, with the goal of replacing the computationally intensive simulations currently required. Cluster dose distributions are predicted using a U-Net that was initially pretrained on conventional dose distributions. Using transfer learning techniques, the decoder path is adapted for cluster dose estimation. Both the training and pretraining datasets include head and neck regions from multiple patients and carbon ion beams of varying energies and positions. Monte Carlo (MC) simulations were used to generate the ground truth cluster dose distributions. The U-Net enables cluster dose estimation for a single pencil beam within milliseconds using a graphics processing unit (GPU). The predicted cluster dose distributions deviate from the ground truth by less than 0.35%. This proof-of-principle study demonstrates the feasibility of accurately estimating cluster doses within clinically acceptable computation times using machine learning (ML). By leveraging a pretrained neural network and applying transfer learning techniques, the approach significantly reduces the need for large-scale, computationally expensive training data.
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Submitted 28 October, 2025;
originally announced October 2025.
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Cross-Section-Based Scaling Method for Material-Specific Cluster Dose Calculations -- A Proof of Concept
Authors:
Miriam Schwarze,
Hui Khee Looe,
Björn Poppe,
Leo Thomas,
Hans Rabus
Abstract:
Cross-section data unavailability for non-water materials in track structure simulation software necessitates nanodosimetric quantity transformation from water to other materials. Cluster dose calculation transformation initially employed mass-density-based scaling - an approach resulting in a physically unrealistic material-independence of the cluster dose equation. This study introduces an alter…
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Cross-section data unavailability for non-water materials in track structure simulation software necessitates nanodosimetric quantity transformation from water to other materials. Cluster dose calculation transformation initially employed mass-density-based scaling - an approach resulting in a physically unrealistic material-independence of the cluster dose equation. This study introduces an alternative scaling method based on material-specific ionization cross-sections. The mean free path ratio of the materials for both the primary particles of the track structure simulation and for the secondary electrons served as the scaling factor. The approach was demonstrated through a cluster dose calculation for a carbon ion beam in a realistic head geometry and compared to the previous scaling method. The proposed cross-section-based scaling method resulted in a physically expected increase in cluster dose values for denser materials, which was not visible in the original scaling approach. The introduced scaling approach can be used to determine cluster dose distributions in heterogeneous geometries, a fundamental requirement for its integration into radiotherapy treatment planning frameworks.
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Submitted 24 October, 2025;
originally announced October 2025.
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Exploring Machine Learning Models for Physical Dose Calculation in Carbon Ion Therapy Using Heterogeneous Imaging Data -- A Proof of Concept Study
Authors:
Miriam Schwarze,
Hui Khee Looe,
Björn Poppe,
Pichaya Tappayuthpijarn,
Leo Thomas,
Hans Rabus
Abstract:
Background: Accurate and fast dose calculation is essential for optimizing carbon ion therapy. Existing machine learning (ML) models have been developed for other radiotherapy modalities. They use patient data with uniform CT imaging properties. Purpose: This study investigates the application of several ML models for physical dose calculation in carbon ion therapy and compares their ability to ge…
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Background: Accurate and fast dose calculation is essential for optimizing carbon ion therapy. Existing machine learning (ML) models have been developed for other radiotherapy modalities. They use patient data with uniform CT imaging properties. Purpose: This study investigates the application of several ML models for physical dose calculation in carbon ion therapy and compares their ability to generalize to CT data with varying resolutions. Among the models examined is a Diffusion Model, which is tested for the first time for the calculation of physical dose distributions. Methods: A dataset was generated using publicly available CT images of the head and neck region. Monoenergetic carbon ion beams were simulated at various initial energies using Geant4 simulation software. A U-Net architecture was developed for dose prediction based on distributions of material density in patients and of absorbed dose in water. It was trained as a Generative Adversarial Network (GAN) generator, a Diffusion Model noise estimator, and as a standalone network. Their performances were compared with two models from literature. Results: All models produced dose distributions deviating by less than 2% from that obtained by a full Monte Carlo simulation, even for a patient not seen during training. Dose calculation time on a GPU was in the range of 3 ms to 15 s. The resource-efficient U-Net appears to perform comparably to the more computationally intensive GAN and Diffusion Model. Conclusion: This study demonstrates that ML models can effectively balance accuracy and speed for physical dose calculation in carbon ion therapy. Using the computationally efficient U-Net can help conserve resources. The generalizability of the models to different CT image resolutions enables the use for different patients without extensive retraining.
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Submitted 22 September, 2025;
originally announced September 2025.
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Do cell culturing influence the radiosensitizing effect of gold nanoparticles part 2: scrutinizing the methodology producing recent evidence
Authors:
Hans Rabus,
Oswald Msosa Mkanda
Abstract:
When irradiation is performed with gold nanoparticles (AuNPs), a different shape of cells in suspension or adherent to walls may result in different probability of cell survival. In a recent study, differences of up to a factor of 2 were found between the predicted survival of floating and adherent cells. The present work aims to quantify the biases introduced by the simulation setup and the use o…
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When irradiation is performed with gold nanoparticles (AuNPs), a different shape of cells in suspension or adherent to walls may result in different probability of cell survival. In a recent study, differences of up to a factor of 2 were found between the predicted survival of floating and adherent cells. The present work aims to quantify the biases introduced by the simulation setup and the use of voxelized geometry in conjunction with the local effect model for cell survival. The results show that simulated irradiation of a cell near the surface with an incident beam matched to the cell dimensions results in dose values that are by a factor of about 50 lower than the dose to cells deeper in the medium when irradiated with a Co-60 spectrum and lateral beam dimensions in the centimeter range. Furthermore, the number of ionizing photon interactions in gold nanoparticles in a cell near the surface is lower by a factor of about 2 than for cells at 5 mm and 1 cm depth. Using the average dose in voxels of size in the order of 200 nm for assessing cell survival with the local effect model (LEM) leads to an underestimation of the number of lesions from a single ionized AuNP by roughly two orders of magnitude and thus to an overestimation of cell survival. The effect of cell geometry on the survival rate was examined for approximate cell geometries and 100 kV x-ray irradiation, for which the probability of photon interaction in gold nanoparticles is by more than two orders of magnitude higher than for Co-60 irradiation. The results show that the effects are negligible for 5 nm nanoparticles at the concentration of AuNPs considered in preceding work. For 50 nm nanoparticles and thus a thousand times higher mass fraction of gold, significant reduction in cell survival is found, with a clear additional reduction predicted by the LEM as compared to the prediction based on mean dose to the nucleus.
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Submitted 25 June, 2025;
originally announced June 2025.
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Do cell culturing influence the radiosensitizing effect of gold nanoparticles part 1: scrutinizing recent evidence for data consistency
Authors:
Hans Rabus,
Oswald Msosa Mkanda
Abstract:
In radiobiological experiments, the cells can either float in suspension or adhere to the walls of the sample holder. When irradiation is performed in the presence of dose modifying agents such as gold nanoparticles (AuNPs), the different shapes of the floating or adherent cells may imply a different dose to the nucleus, with biological consequences such as cell survival. Recently, it has been rep…
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In radiobiological experiments, the cells can either float in suspension or adhere to the walls of the sample holder. When irradiation is performed in the presence of dose modifying agents such as gold nanoparticles (AuNPs), the different shapes of the floating or adherent cells may imply a different dose to the nucleus, with biological consequences such as cell survival. Recently, it has been reported that the survival rate varies by up to a factor of 1.5 for the two cell geometries and by up to a factor of 2 for different orientation of the cells with respect to the incident beam. These results are examined in this paper and possible methodological issues are analyzed. This analysis shows that the simulation setup corresponds to the case of cells in the dose build-up region near the surface of a water phantom, where different depths result in different dose and survival probabilities. The validation of the simulations by comparison with experimental data is misleading, as the apparent agreement is due to a neglect of the quadratic term of the linear-quadratic survival model. The analysis further shows that the reported step-like changes between the survival predicted from the mean dose and the LEM could be explained by the fact that in the entire simulation only in one event an ionizing interaction of a photon took place in an AuNP. It is shown that the probability of this is in the permille range and that the total number of electrons leaving an AuNP, estimated from the reported electron spectrum, is three orders of magnitude higher than the value estimated from the expectation of photon interactions in the AuNPs. This contradiction would be resolved if the AuNP diameter in the simulations were a factor of 10 larger than intended. Another possible explanation for the discrepancies is a hidden bias in the simulation geometry, for example, if the distribution of AuNPs was non-uniform.
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Submitted 24 June, 2025;
originally announced June 2025.
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Impact of metal nanoparticles on cell survival predicted by the local effect model for cells in suspension and tissue. Part 1: Theoretical framework
Authors:
Hans Rabus,
Leo Thomas
Abstract:
This work investigates the change in cell survival predicted by the local effect model (LEM) for an irradiated cell containing metal nanoparticles (MNPs) depending on the distribution of neighboring cells and the uptake of MNPs into the cells. In this first part of the paper, the theoretical framework is described, which is based on analytical weighting functions for the energy deposition around a…
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This work investigates the change in cell survival predicted by the local effect model (LEM) for an irradiated cell containing metal nanoparticles (MNPs) depending on the distribution of neighboring cells and the uptake of MNPs into the cells. In this first part of the paper, the theoretical framework is described, which is based on analytical weighting functions for the energy deposition around a single metal nanoparticle and radially symmetric distributions of MNPs. The weighting functions allow calculation of the radial profile of the absorbed dose in the cell nucleus as well as the mean dose and the mean square of the dose in the nucleus. The latter two quantities determine cell survival according to the LEM. The weighting functions are applied to isolated cells in a localized MNP distribution, cells in solution, and densely packed cells in tissue. It is shown that only for the idealistic case of complete uptake of MNPs it is sufficient to consider an isolated cell, as this otherwise leads to a significant underestimation in more realistic situations. In the case of cells in tissue, the MNP concentration within the range of secondary particles around the cell must be taken into account. Different packing densities of the cells may lead to values differing by up to 30% for the mean dose in the cell nucleus, depending on the conceived scenario for the uptake of MNPs. The weighting function offers a versatile method for assessing cell survival under irradiation in the presence of MNPs by the LEM, which is more general than previously reported approaches.
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Submitted 3 May, 2025;
originally announced May 2025.
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Evaluation of the uncertainty in calculating nanodosimetric quantities due to the use of different interaction cross sections in Monte Carlo track structure codes
Authors:
Carmen Villagrasa,
Giorgio Baiocco,
Zine-El-Abidine Chaoui,
Michael Dingfelder,
Sébastien Incerti,
Pavel Kundrát,
Ioanna Kyriakou,
Yusuke Matsuya,
Takeshi Kai,
Alessio Paris,
Yann Perrot,
Marcin Pietrzak,
Jan Schuemann,
Hans Rabus
Abstract:
This study evaluates the uncertainty in nanodosimetric calculations caused by variations in interaction cross sections within Monte Carlo Track Structure (MCTS) simulation codes. Nanodosimetry relies on accurately simulating particle interactions at the molecular scale. Different MCTS codes employ distinct physical models and datasets for electron interactions in liquid water, a surrogate for biol…
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This study evaluates the uncertainty in nanodosimetric calculations caused by variations in interaction cross sections within Monte Carlo Track Structure (MCTS) simulation codes. Nanodosimetry relies on accurately simulating particle interactions at the molecular scale. Different MCTS codes employ distinct physical models and datasets for electron interactions in liquid water, a surrogate for biological tissues. The paper focuses on the Ionization Cluster Size Distribution (ICSD) generated by electrons of varying energies in nanometric volumes. Seven MCTS codes were tested using their native cross sections and a common dataset derived from averaging data used in the participating codes. The results reveal significant discrepancies among the codes in ICSDs and derived biologically relevant nanodosimetric quantities such as mean ionization numbers (M1) and probabilities of obtaining two or more ionizations (F2). The largest variations were observed for low-energy electrons, where the contribution from interaction cross sections dominates the overall uncertainties. For instance, M1 values for ICSDs of electron of 20 eV can differ by around 45 % (RSD) and 34 % (RSD) was found for F2 values of ICSDs of electrons of 50 eV. Using common cross sections substantially reduced the discrepancies, suggesting that cross section datasets are the primary source of variability. Finally, estimates of deoxyribonucleic acid (DNA) damage using the PARTRAC code highlight tht cross section variations have a non-negligible impact simulated biological outcomes, particularly for double-strand breaks (DSBs) Indeed, despite the fact that many other parameters in the simulation that can greatly differ from one code to another, the different interaction cross-sections studied in this work can lead to differences in the number of DSBs calculated with the PARTRAC code of up to 15%.
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Submitted 17 February, 2025;
originally announced February 2025.
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On a revised concept of an event that allows linking nanodosimetry and microdosimetry in nanometric sites with macroscopic dosimetry
Authors:
Hans Rabus,
Leo Thomas
Abstract:
This work reviews the concepts of an event used in micro- and nanodosimetry and analyzes how single event distributions could theoretically be derived from probability distributions related to interactions of the primary particle which produce secondary electrons. It is shown that the corresponding mathematical expressions of conditional ionization cluster size distributions are alike those for th…
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This work reviews the concepts of an event used in micro- and nanodosimetry and analyzes how single event distributions could theoretically be derived from probability distributions related to interactions of the primary particle which produce secondary electrons. It is shown that the corresponding mathematical expressions of conditional ionization cluster size distributions are alike those for the single event frequency distribution of energy imparted, particularly when all tracks are considered which intersect the volume in which interactions of the primary particle can result in energy deposits in the site. Track structure simulations of proton with energies between 1 MeV and 100 MeV are used to study how the occurrence of events depends on site size, beam radius, and proton energy. The range of impact parameters of particle tracks that contribute to energy imparted in a site appears not to depend on whether any energy deposits or only energy deposits by ionizations are considered. Since there is no longer a one-to-one correspondence between tracks passing a site and the occurrence of an event, it is proposed to use the fluence for which on average one event occurs as a substitute for single events. For protons, the product of this fluence and the site cross section or the average number of tracks necessary for an event shows an interesting dependence on site size and particle energy with asymptotic values close to unity for large sites and proton energies below 10 MeV. For a proton energy of 1 MeV, a minimum of the number of tracks is observed for sites between 5 nm and 10 nm diameter. The relative differences between the numbers of track per event on average obtained with different options of Geant4-DNA are in the order of 10 % and illustrate the need for further investigations into cross-section datasets and their uncertainties.
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Submitted 19 February, 2025; v1 submitted 1 December, 2024;
originally announced December 2024.
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A Comparative Experimental and Theoretical Study on Doubly Differential Electron-Impact Ionization Cross Sections of Pyrimidine
Authors:
M. Dinger,
W. Y. Baek,
H. Rabus
Abstract:
To provide a comprehensive data set for track structure-based simulations of radiation damage in DNA, doubly differential electron-impact ionization cross sections of pyrimidine, a building block of the nucleobases cytosine and thymine, were measured for primary electron energies between 30 eV and 1 keV as a function of emission angle and secondary electron energy. The measurements were performed…
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To provide a comprehensive data set for track structure-based simulations of radiation damage in DNA, doubly differential electron-impact ionization cross sections of pyrimidine, a building block of the nucleobases cytosine and thymine, were measured for primary electron energies between 30 eV and 1 keV as a function of emission angle and secondary electron energy. The measurements were performed for secondary electron energies from 4 eV to about half of the primary electron energy and for emission angles between 25° and 135°. Based on the experimental doubly differential ionization cross sections, singly differential and total ionization cross sections of pyrimidine were determined and compared to calculations using the BEB model. In addition to the measurements, a theoretical approach for calculating triply and doubly differential ionization cross section was developed, which is based on the distorted wave Born approximation, a single center expansion of molecular orbitals and an averaging of the T-matrix over different molecular orientations. The calculated doubly differential ionization cross sections of pyrimidine show a qualitatively good agreement with the experimental results.
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Submitted 17 April, 2024;
originally announced April 2024.
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Intercomparison exercise on Monte Carlo simulations of electron spectra and energy depositions by a single gold nanoparticle under X-ray irradiation
Authors:
Wei Bo Li,
Hans Rabus,
Carmen Villagrasa,
Jan Schuemann
Abstract:
Computational approaches, such as Monte Carlo (MC) radiation transport simulations, are used to estimate the dosimetric effects of GNPs, where results differing by orders of magnitudes have been reported by different investigators. This has motivated an intercomparison exercise, which was conducted as a joint activity of EURADOS Working Groups 6 "Computational Dosimetry" and 7 "Internal Dosimetry"…
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Computational approaches, such as Monte Carlo (MC) radiation transport simulations, are used to estimate the dosimetric effects of GNPs, where results differing by orders of magnitudes have been reported by different investigators. This has motivated an intercomparison exercise, which was conducted as a joint activity of EURADOS Working Groups 6 "Computational Dosimetry" and 7 "Internal Dosimetry". The aim of this exercise was to determine the extent of such discrepancies between the results obtained by different researchers and different codes in a very simple simulation setup.
Several individual EURADOS associate members and two code developer groups from outside Europe participated in this exercise applying seven different MC codes to perform the simulations of a simple defined geometry set-up of one single GNP irradiated in water by kilo-voltage X-rays. Two GNP diameters of 50 nm and 100 nm of were considered and two photon spectra as generated by X-ray tubes operated at 50 kV and 100 kV peak voltages. The geometry set-up and X-ray spectra were provided by the EURADOS task group. The participants were asked to determine for each combination of GNP size and X-ray spectrum the dose enhancement ratio (DER) of 10 nm-thick water shells up to 1000 nm and 1 $μ$m-thick water shells up to 50 $μ$m around the GNP. Furthermore, the electron spectra emitted from the GNP and the energy depositions in water shells around it were also to be reported.
This EURADOS report summarizes the motivation and background for the exercise, the tasks to be solved, the codes used, the results reported by the participants, the consistency checks applied in their evaluation and a best estimates and uncertainty bands derived from the final results for the energy spectra of emitted electrons and the energy imparted in the vicinity of the GNP.
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Submitted 12 February, 2024;
originally announced March 2024.
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Radial dependence of ionization clustering around a gold nanoparticle
Authors:
Leo Thomas,
Miriam Schwarze,
Hans Rabus
Abstract:
This work explores the enhancement of ionization clusters around a gold nanoparticle (NP), indicative of the induction of DNA lesions, a potential trigger for cell-death. Monte Carlo track structure simulations were performed to determine (a) the fluence of incident photons and electrons in water around a gold NP under charged particle equilibrium conditions and (b) the density of ionization clust…
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This work explores the enhancement of ionization clusters around a gold nanoparticle (NP), indicative of the induction of DNA lesions, a potential trigger for cell-death. Monte Carlo track structure simulations were performed to determine (a) the fluence of incident photons and electrons in water around a gold NP under charged particle equilibrium conditions and (b) the density of ionization clusters produced on average as well as conditional on the occurrence of at least one interaction in the nanoparticle using Associated Volume Clustering. Absorbed dose was determined for comparison with a recent benchmark intercomparison. Reported quantities are normalized to primary fluence, allowing to establish a connection to macroscopic dosimetric quantities. The modification of the electron fluence spectrum by the gold NP is minor and mainly occurs at low energies. The net fluence of electrons emitted from the NP is dominated by electrons resulting from photon interactions. Smaller NPs cause noticeable peaks in the conditional frequency of clusters at distances around 50 nm to 100 nm from the NP surface. The number of clusters per energy imparted is increased at distances of up to 150 nm, and accordingly the enhancement in clustering notably surpasses that of dose enhancement. This work highlights the necessity of nanodosimetric analysis and suggests increased ionization clustering near the nanoparticles due to the emission of low energy Auger electrons. Whereas the electron component of the radiation field plays an important role in determining the background contribution to ionization clustering and energy imparted, the dosimetric effects of nanoparticles are governed by the interplay of secondary electron production by photon interaction (including low energy Auger electrons) and their ability to leave the nanoparticle.
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Submitted 7 March, 2024;
originally announced March 2024.
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Nanodosimetric investigation of the track structure of therapeutic carbon ion radiation. Part 2: Detailed radiation transport and track structure simulation
Authors:
Miriam Schwarze,
Gerhard Hilgers,
Hans Rabus
Abstract:
Previously reported nanodosimetric measurements of therapeutic-energy carbon ions penetrating simulated tissue have produced results that are incompatible with the predicted mean energy of the carbon ions in the nanodosimeter and previous experiments with lower energy monoenergetic beams. The purpose of this study is to explore the origin of these discrepancies. Detailed simulations using the Gean…
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Previously reported nanodosimetric measurements of therapeutic-energy carbon ions penetrating simulated tissue have produced results that are incompatible with the predicted mean energy of the carbon ions in the nanodosimeter and previous experiments with lower energy monoenergetic beams. The purpose of this study is to explore the origin of these discrepancies. Detailed simulations using the Geant4 toolkit were performed to investigate the radiation field in the nanodosimeter and provide input data for track structure simulations, which were performed with a developed version of the PTra code. The Geant4 simulations show that with the narrow-beam geometry employed in the experiment, only a small fraction of the carbon ions traverse the nanodosimeter and their mean energy is between 12 % and 30 % lower than the targeted values. Only about one-third or less of these carbon ions hit the trigger detector. The track structure simulations indicate that the observed enhanced ionization cluster sizes are mainly due to coincidences with events in which carbon ions miss the trigger detector. In addition, the discrepancies observed for high absorber thicknesses of carbon ions traversing the target volume could be explained by assuming an increase in thickness or interaction cross-sections in the order of 1 %. The results show that even with strong collimation of the radiation field, future nanodosimetric measurements of clinical carbon ion beams will require large trigger detectors to register all events with carbon ions traversing the nanodosimeter. Energy loss calculations of the primary beam in the absorbers are insufficient and should be replaced by detailed simulations when planning such experiments. Uncertainties of the interaction cross-sections in simulation codes may shift the Bragg peak position.
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Submitted 14 August, 2024; v1 submitted 29 February, 2024;
originally announced February 2024.
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Nanodosimetric investigation of the track structure of therapeutic carbon ion radiation. Part 1: Measurement of ionization cluster size distributions
Authors:
Gerhard Hilgers,
Miriam Schwarze,
Hans Rabus
Abstract:
At the Heidelberg Ion-Beam Therapy Center, the track structure of carbon ions of therapeutic energy after penetrating layers of simulated tissue was investigated for the first time. Measurements were conducted with carbon ion beams of different energies and polymethyl methacrylate (PMMA) absorbers of different thicknesses to realize different depths in the phantom along the pristine Bragg peak. Io…
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At the Heidelberg Ion-Beam Therapy Center, the track structure of carbon ions of therapeutic energy after penetrating layers of simulated tissue was investigated for the first time. Measurements were conducted with carbon ion beams of different energies and polymethyl methacrylate (PMMA) absorbers of different thicknesses to realize different depths in the phantom along the pristine Bragg peak. Ionization cluster size (ICS) distributions resulting from the mixed radiation field behind the PMMA absorbers were measured using an ion-counting nanodosimeter. Two different measurements were carried out: (i) variation of the PMMA absorber thickness with constant carbon ion beam energy and (ii) combined variation of PMMA absorber thickness and carbon ion beam energy such that the kinetic energy of the carbon ions in the target volume is constant. The data analysis revealed unexpectedly high mean ICS values compared to stopping power calculations and the data measured at lower energies in earlier work. This suggests that in the measurements the carbon ion kinetic energies behind the PMMA absorber may have deviated considerably from the expected values obtained by the calculations. In addition, the results indicate the presence of a marked contribution of nuclear fragments to the measured ICS distributions, especially if the carbon ion does not cross the target volume.
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Submitted 14 August, 2024; v1 submitted 12 February, 2024;
originally announced February 2024.
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Comment on "Investigation of the anisotropic distribution of microdosimetric quantities in the vicinity of X-ray-irradiated gold nanoparticles" by Derrien et al. [Radiation Physics and Chemistry 213, 111232 (2023)]
Authors:
Hans Rabus
Abstract:
In their recent article, Derrien et al. (Derrien et al., 2023) study the anisotropy of microdosimetric quantities for spherical sites of several sizes placed around spherical gold nanoparticles of several diameters irradiated by monoenergetic photons. This comment points out that (1) the reported single event distributions of specific energy may be biased due to overcounting. (2) by considering on…
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In their recent article, Derrien et al. (Derrien et al., 2023) study the anisotropy of microdosimetric quantities for spherical sites of several sizes placed around spherical gold nanoparticles of several diameters irradiated by monoenergetic photons. This comment points out that (1) the reported single event distributions of specific energy may be biased due to overcounting. (2) by considering only energy imparted by electrons produced in photon interactions in the nanoparticle, the magnitude of the anisotropy is overestimated by up to orders of magnitude with respect to an irradiation under conditions of secondary particle equilibrium.
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Submitted 11 December, 2023;
originally announced December 2023.
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Comment on "Reproducibility study of Monte Carlo simulations for nanoparticle dose enhancement and biological modeling of cell survival curves" by Velten et al. [Biomed Phys Eng Express 2023;9:045004]
Authors:
Hans Rabus
Abstract:
This comment highlights two methodological issues with the recent article by Velten et al. [Biomed Phys Eng Express 2023;9:045004]
This comment highlights two methodological issues with the recent article by Velten et al. [Biomed Phys Eng Express 2023;9:045004]
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Submitted 10 September, 2023; v1 submitted 12 August, 2023;
originally announced August 2023.
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Article Commentary on "Microdosimetric and radiobiological effects of gold nanoparticles at therapeutic radiation energies" [T.M. Gray et al., IJRB 2023, 99(2), 308-317]
Authors:
Hans Rabus,
Miriam Schwarze,
Leo Thomas
Abstract:
In the recently published article by T.M. Gray et al. "Microdosimetric and radiobiological effects of gold nanoparticles at therapeutic radiation energies" (IJRB 2023, 99(2), 308-317) results of Monte Carlo simulations and radiobiological assays on the dosimetric effects of gold nanoparticles were presented. This commentary points out that the results of the two parts of the study are in contradic…
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In the recently published article by T.M. Gray et al. "Microdosimetric and radiobiological effects of gold nanoparticles at therapeutic radiation energies" (IJRB 2023, 99(2), 308-317) results of Monte Carlo simulations and radiobiological assays on the dosimetric effects of gold nanoparticles were presented. This commentary points out that the results of the two parts of the study are in contradiction and that the predicted magnitude of dose enhancement and its dependence on the shape of the nanoparticle appear implausible. Possible reasons for these observations are discussed.
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Submitted 22 April, 2023;
originally announced April 2023.
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Comment on "Biological modeling of gold nanoparticle enhanced radiotherapy for proton therapy" by Lin et al. [Phys. Med. Biol. 60 (2015) 4149-4168]
Authors:
Hans Rabus
Abstract:
In their article published in Phys. Med. Biol. 60 (2015) 4149-4168, Lin et al studied the radiosensitizing effect of gold nanoparticles (GNPs) using radiation transport simulations and a biological model for the survival of irradiated cells. This comment points out several caveats to the methodlogy used by Lin et al. that may not be evident to readers and may contribute to confusion in the literat…
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In their article published in Phys. Med. Biol. 60 (2015) 4149-4168, Lin et al studied the radiosensitizing effect of gold nanoparticles (GNPs) using radiation transport simulations and a biological model for the survival of irradiated cells. This comment points out several caveats to the methodlogy used by Lin et al. that may not be evident to readers and may contribute to confusion in the literature about the radiation effects of gold nanoparticles. The two main caveats are the high mass fraction of gold considered and a potential problem with the modified local effect model used to predict cell survival.
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Submitted 10 February, 2023; v1 submitted 5 January, 2023;
originally announced January 2023.
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Comment on "Comparing gold nano-particle enhanced radiotherapy with protons, megavoltage photons and kilovoltage photons: A Monte Carlo simulation" by Lin et al [Phys. Med. Biol. 59 (2014) 7675-7689]
Authors:
Hans Rabus
Abstract:
In their article published in Phys. Med. Biol. 59 (2014) 7675-7689, Lin et al studied the dose enhancement of of gold nanoparticles (GNPs) for proton therapy, which they compared with the case of photon irradiation. This comment points out two caveats to the methodlogy used by Lin et al that may not be evident to readers and may contribute to confusion in the literature about the dose enhancement…
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In their article published in Phys. Med. Biol. 59 (2014) 7675-7689, Lin et al studied the dose enhancement of of gold nanoparticles (GNPs) for proton therapy, which they compared with the case of photon irradiation. This comment points out two caveats to the methodlogy used by Lin et al that may not be evident to readers and may contribute to confusion in the literature about the dose enhancement by gold nanoparticles.
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Submitted 10 February, 2023; v1 submitted 5 January, 2023;
originally announced January 2023.
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Experimental benchmark data for Monte Carlo simulated radiation effects of gold nanoparticles. Part II: Comparison of measured and simulated electron spectra from gold nanofoils
Authors:
Jorge Borbinha,
Liset de la Fuente Rosales,
Philine Hepperle,
Heidi Nettelbeck,
Woon Yong Baek,
Salvatore Di Maria,
Hans Rabus
Abstract:
Electron emission spectra of a thin gold foil after photon interaction were measured over the energy range between 50 eV and 9500 eV to provide reference data for Monte Carlo radiation-transport simulations. Experiments were performed with the HAXPES spectrometer at the PETRA III high-brilliance beamline P22 at DESY (Hamburg, Germany) for photon energies just below and above each of the gold L-edg…
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Electron emission spectra of a thin gold foil after photon interaction were measured over the energy range between 50 eV and 9500 eV to provide reference data for Monte Carlo radiation-transport simulations. Experiments were performed with the HAXPES spectrometer at the PETRA III high-brilliance beamline P22 at DESY (Hamburg, Germany) for photon energies just below and above each of the gold L-edges, i.e., at 11.9 keV, 12.0 keV, 13.7 keV, 13.8 keV, 14.3 keV, and 14.4 keV. The data were analyzed to obtain the absolute values of the particle radiance of the emitted electrons per incident photon flux. Simulations of the experiment were performed using the Monte Carlo radiation-transport codes Penelope and Geant4. Comparison of the measured and simulated results shows good qualitative agreement. When simulation results are convolved with curves that take into account the effect of lifetime broadening, line shapes of photoelectron and Auger peaks similar to those observed experimentally are obtained. On an absolute scale, the experiments tend to give higher electron radiance values at the lower photon energies studied as well as at the higher photon energies for electron energies below the energy of the Au L3 photoelectron. This is attributed to the linear polarization of the photon beam in the experiments which is not considered in the simulation codes.
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Submitted 9 April, 2023; v1 submitted 14 December, 2022;
originally announced December 2022.
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Experimental benchmark data for Monte Carlo simulated radiation effects of gold nanoparticles. Part I: Experiment and raw data analysis
Authors:
Hans Rabus,
Philine Hepperle,
Christoph Schlueter,
Andrei Hloskovsky,
Woon Yong Baek
Abstract:
Electron emission spectra of gold nanoparticles (AuNPs) after photon interaction were measured over the energy range between 50 eV and 9500 eV to provide reference data for Monte Carlo radiation-transport simulations. Experiments were performed with the HAXPES spectrometer at the PETRA III high-brilliance beamline P22 at DESY (Hamburg, Germany) for photon energies below and above each of the gold…
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Electron emission spectra of gold nanoparticles (AuNPs) after photon interaction were measured over the energy range between 50 eV and 9500 eV to provide reference data for Monte Carlo radiation-transport simulations. Experiments were performed with the HAXPES spectrometer at the PETRA III high-brilliance beamline P22 at DESY (Hamburg, Germany) for photon energies below and above each of the gold L-edges, i.e., at 11.9 keV, 12.0 keV, 13.7 keV, 13.8 keV, 14.3 keV, and 14.4 keV. The study focused on a sample with gold nanoparticles with an average diameter of 11.0 nm on a thin carbon foil. Additional measurements were performed on a sample with 5.3 nm gold nanoparticles and on reference samples of gold and carbon foils. Further measurements were made to calibrate the photon flux monitor, to characterize the transmission function of the electron spectrometer and to determine the size of the photon beam. This allowed the determination of the absolute values of the spectral particle radiance of secondary electrons per incident photon flux. The paper presents the experimental and raw data analysis procedures, reviews the data obtained for the nanoparticle samples and discusses their limitations.
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Submitted 9 April, 2023; v1 submitted 9 December, 2022;
originally announced December 2022.
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EURADOS Working Group 6, Computational Dosimetry, a history of promoting good practice via intercomparisons and training
Authors:
Rick Tanner,
Stefano Agosteo,
Hans Rabus
Abstract:
This paper is the editorial of a special issue of Radiation Measurements on EURADOS intercomparisons in computational dosimetry. The articles in this special issue cover complex problems in terms of geometry, particle types, energy ranges, coupled calculations and also scale, with the possibility of performing Monte Carlo calculations on micro and nano dosimetric scales now feasible. A summary of…
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This paper is the editorial of a special issue of Radiation Measurements on EURADOS intercomparisons in computational dosimetry. The articles in this special issue cover complex problems in terms of geometry, particle types, energy ranges, coupled calculations and also scale, with the possibility of performing Monte Carlo calculations on micro and nano dosimetric scales now feasible. A summary of the exercises is provided in the first article of the Special Issue, which presents the findings and common conclusions from the ten articles reporting the results of the different exercises. One of these issues was the correct assessment of bone marrow dose, which prompted the inclusion of an article in this special issue explaining the ICRP-recommended method for bone marrow dosimetry.
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Submitted 4 August, 2022;
originally announced August 2022.
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Repair kinetics of DSB-foci induced by proton and helium ion microbeams of different energies
Authors:
Ana Belchior,
João F. Canhoto,
Ulrich Giesen,
Frank Langner,
Hans Rabus,
Reinhard Schulte
Abstract:
In this work, the induction and repair of radiation-induced 53BP1 foci were studied in human umbilical vein endothelial cells irradiated at the PTB microbeam with protons and α-particles of different energies. The data were analyzed in terms of the mean number of 53BP1 foci induced by the different ion beams. The number of 53BP1 foci found at different times post-irradiation suggests that the disa…
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In this work, the induction and repair of radiation-induced 53BP1 foci were studied in human umbilical vein endothelial cells irradiated at the PTB microbeam with protons and α-particles of different energies. The data were analyzed in terms of the mean number of 53BP1 foci induced by the different ion beams. The number of 53BP1 foci found at different times post-irradiation suggests that the disappearance of foci follows first order kinetics. The mean number of initially produced foci shows the expected increase with LET. The most interesting finding of this work is that the absolute number of persistent foci increases with LET but not their fraction. Furthermore, protons seem to produce more persistent foci as compared to α-particles of even higher LET. This may be seen as experimental evidence that protons may be more effective in producing severe DNA lesions, as was already shown in other work, and that LET may not be the best suited parameter to characterize radiation quality
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Submitted 15 July, 2023; v1 submitted 17 June, 2022;
originally announced June 2022.
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Correlated ionisations in two spatially separated nanometric volumes in the track structure of 241Am alpha particles: comparison with Monte Carlo simulations
Authors:
Gerhard Hilgers,
Thomas Braunroth,
Hans Rabus
Abstract:
The production of two double strand breaks in spatially separated locations on the DNA molecule can cause the loss of a whole DNA loop, which can be of substantial length depending on the geometrical position of the two damaged sites and depends on the degree of correlation between ionisation clusters formed in sites of several nanometres in size. In the first part of this paper, nanodosimetric me…
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The production of two double strand breaks in spatially separated locations on the DNA molecule can cause the loss of a whole DNA loop, which can be of substantial length depending on the geometrical position of the two damaged sites and depends on the degree of correlation between ionisation clusters formed in sites of several nanometres in size. In the first part of this paper, nanodosimetric measurements of alpha particle tracks in 1.2 mbar H2O, 1.2 mbar C3H8 and 1.2 mbar C4H8O with the PTB ion counter nanodosimeter were reported. In this second part, the focus is on the geometrical characterisation of the two sites simulated with the nanodosimeter in the three target gases and on the comparison of the measurement results with Monte Carlo simulations. The measurements in 1.2 mbar C3H8 were simulated with a version of the track structure code PTra dedicated to modelling the PTB ion counter nanodosimeter. Further simulations were performed with Geant4-DNA for 241Am alpha particle tracks in liquid water. Simulations of the measurements and the actual measurement results are found to be in good agreement for the investigated irradiation geometries.
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Submitted 20 May, 2022;
originally announced May 2022.
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Lessons learnt from the recent EURADOS intercomparisons in computational dosimetry
Authors:
Hans Rabus,
Maria Zankl,
Jose Maria Gomez-Ros,
Carmen Villagrasa,
Jonathan Eakins,
Christelle Huet,
Hrvoje Brkic,
Rick Tanner
Abstract:
Organized by Working Group 6 "Computational Dosimetry" of the European Radiation Dosimetry Group (EURADOS), a group of intercomparison exercises was conducted in which participants were asked to solve predefined problems in computational dosimetry. The results of these comparisons were published in a series of articles in this virtual special issue of Radiation Measurements. This paper reviews the…
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Organized by Working Group 6 "Computational Dosimetry" of the European Radiation Dosimetry Group (EURADOS), a group of intercomparison exercises was conducted in which participants were asked to solve predefined problems in computational dosimetry. The results of these comparisons were published in a series of articles in this virtual special issue of Radiation Measurements. This paper reviews the experience gained from the various exercises and highlights the resulting conclusions for future exercises, as well as regarding the state of the art and the need for development in terms of quality assurance for computational dosimetry techniques.
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Submitted 15 May, 2022;
originally announced May 2022.
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A new Standard DNA damage (SDD) data format
Authors:
J. Schuemann,
A. McNamara,
J. W. Warmenhoven,
N. T. Henthorn,
K. Kirkby,
M. J. Merchant,
S. Ingram,
H. Paganetti,
KD. Held,
J. Ramos-Mendez,
B. Faddegon,
J. Perl,
D. Goodhead,
I. Plante,
H. Rabus,
H. Nettelbeck,
W. Friedland,
P. Kundrat,
A. Ottolenghi,
G. Baiocco,
S. Barbieri,
M. Dingfelder,
S. Incerti,
C. Villagrasa,
M. Bueno
, et al. (26 additional authors not shown)
Abstract:
Our understanding of radiation induced cellular damage has greatly improved over the past decades. Despite this progress, there are still many obstacles to fully understanding how radiation interacts with biologically relevant cellular components to form observable endpoints. One hurdle is the difficulty faced by members of different research groups in directly comparing results. Multiple Monte Ca…
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Our understanding of radiation induced cellular damage has greatly improved over the past decades. Despite this progress, there are still many obstacles to fully understanding how radiation interacts with biologically relevant cellular components to form observable endpoints. One hurdle is the difficulty faced by members of different research groups in directly comparing results. Multiple Monte Carlo codes have been developed to simulate damage induction at the DNA scale, while at the same time various groups have developed models that describe DNA repair processes with varying levels of detail. These repair models are intrinsically linked to the damage model employed in their development, making it difficult to disentangle systematic effects in either part of the modelling chain. The modelling chain typically consists of track structure Monte Carlo simulations of the physics interactions creating direct damages to the DNA; followed by simulations of the production and initial reactions of chemical species causing indirect damages. After the DNA damage induction, DNA repair models combine the simulated damage patterns with biological models to determine the biological consequences of the damage. We propose a new Standard data format for DNA Damage to unify the interface between the simulation of damage induction and the biological modelling of cell repair processes. Such a standard greatly facilitates inter model comparisons, providing an ideal environment to tease out model assumptions and identify persistent, underlying mechanisms. Through inter model comparisons, this unified standard has the potential to greatly advance our understanding of the underlying mechanisms of radiation induced DNA damage and the resulting observable biological effects.
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Submitted 11 January, 2022;
originally announced January 2022.
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Intercomparison of micro- and nanodosimetry Monte Carlo simulations: an approach to assess the influence of different cross-sections for low-energy electrons on the dispersion of results
Authors:
Carmen Villagrasa,
Hans Rabus,
Giorgio Baiocco,
Yann Perrot,
Alessio Parisi,
Lara Struelens,
Rui Qiu,
Michael Beuve,
Floriane Poignant,
Marcin Pietrzak,
Heidi Nettelbeck
Abstract:
An intercomparison of microdosimetric and nanodosimetric quantities simulated Monte Carlo codes is in progress with the goal of assessing the uncertainty contribution to simulated results due to the uncertainties of the electron interaction cross-sections used in the codes. In the first stage of the intercomparison, significant discrepancies were found for nanodosimetric quantities as well as for…
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An intercomparison of microdosimetric and nanodosimetric quantities simulated Monte Carlo codes is in progress with the goal of assessing the uncertainty contribution to simulated results due to the uncertainties of the electron interaction cross-sections used in the codes. In the first stage of the intercomparison, significant discrepancies were found for nanodosimetric quantities as well as for microdosimetric simulations of a radiation source placed at the surface of a spherical water scoring volume. This paper reports insight gained from further analysis, including additional results for the microdosimetry case where the observed discrepancies in the simulated distributions could be traced back to the difference between track-structure and condensed-history approaches. Furthermore, detailed investigations into the sensitivity of nanodosimetric distributions to alterations in inelastic electron scattering cross-sections are presented which were conducted in the lead up to the definition of an approach to be used in the second stage of the intercomparison to come. The suitability of simulation results for assessing the sought uncertainty contributions from cross-sections is discussed and a proposed framework is described.
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Submitted 25 October, 2021; v1 submitted 18 August, 2021;
originally announced August 2021.
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Characterisation of the PTB ion counter nanodosimeter's target volume and its equivalent size in terms of liquid H2O
Authors:
Gerhard Hilgers,
Thomas Braunroth,
Hans Rabus
Abstract:
For the first time a dedicated investigation of the target size of a nanodosimeter device has been carried out in order to investigate to what extent measured ionisation cluster size distributions can serve as benchmark data for modelling approaches, with particular focus on the target size in terms of liquid H2O. To this end, measurements with alpha particles from a 241Am source were carried out…
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For the first time a dedicated investigation of the target size of a nanodosimeter device has been carried out in order to investigate to what extent measured ionisation cluster size distributions can serve as benchmark data for modelling approaches, with particular focus on the target size in terms of liquid H2O. To this end, measurements with alpha particles from a 241Am source were carried out using three different target gases, H2O, C3H8 and C4H8O. For each of the three target gases, three different drift-time windows were applied to realise three different target sizes. A method has been developed to determine the dimensions of the simulated nanometric target volume in liquid H2O for cylindrical and spherical shape, as often used in approaches to model radiation effects to DNA. Simulations with nanometric targets of dimensions determined with this method agree very well with the corresponding measurements. Scaling of the spatial distribution of the extraction efficiency for different target gases and drift-time windows, which corresponds to the nanodosimeter's target volume, in terms of liquid H2O using ($ρλ_{ion}$)-ratios has also been investigated and proved to yield an estimate of the target volume in liquid H2O. Thus, it can be concluded that ionisation cluster size distributions measured with a nanodosimeter device are suited as benchmark data for approaches that model radiation induced damage to DNA in nanometric volumes of liquid H2O in simple geometries such as cylinders or spheres, provided that the nanodosimeter's target volume is characterised accordingly. By proper selection of drift-time window length as well as target gas and density a wide range of target volume dimensions in terms of liquid H2O can be realised with the PTB Ion Counter nanodosimeter according to specific requirements of modelling approaches.
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Submitted 21 May, 2021;
originally announced May 2021.
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Consistency checks of results from a Monte Carlo code intercomparison for emitted electron spectra and energy deposition around a single gold nanoparticle irradiated by X-rays
Authors:
H. Rabus,
W. B. Li,
H. Nettelbeck,
J. Schuemann,
C. Villagrasa,
M. Beuve,
S. Di Maria,
B. Heide,
A. P. Klapproth,
F. Poignant,
R. Qiu,
B. Rudek
Abstract:
Organized by the European Radiation Dosimetry Group (EURADOS), a Monte Carlo code intercomparison exercise was conducted where participants simulated the emitted electron spectra and energy deposition around a single gold nanoparticle (GNP) irradiated by X-rays. In the exercise, the participants scored energy imparted in concentric spherical shells around a spherical volume filled with gold or wat…
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Organized by the European Radiation Dosimetry Group (EURADOS), a Monte Carlo code intercomparison exercise was conducted where participants simulated the emitted electron spectra and energy deposition around a single gold nanoparticle (GNP) irradiated by X-rays. In the exercise, the participants scored energy imparted in concentric spherical shells around a spherical volume filled with gold or water as well as the spectral distribution of electrons leaving the GNP. Initially, only the ratio of energy deposition with and without GNP was to be reported. During the evaluation of the exercise, however, the data for energy deposition in the presence and absence of the GNP were also requested. A GNP size of 50 nm and 100 nm diameter was considered as well as two different X-ray spectra (50 kVp and 100kVp). This introduced a redundancy that can be used to cross-validate the internal consistency of the simulation results. In this work, evaluation of the reported results is presented in terms of integral quantities that can be benchmarked against values obtained from physical properties of the radiation spectra and materials involved. The impact of different interaction cross-section datasets and their implementation in the different Monte Carlo codes is also discussed.
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Submitted 23 November, 2021; v1 submitted 15 May, 2021;
originally announced May 2021.
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Investigation into the foundations of the track-event theory of cell survival and the radiation action model based on nanodosimetry
Authors:
Sonwabile Arthur Ngcezu,
Hans Rabus
Abstract:
This work aims at carving out more clearly the basic assumptions behind the "track-event theory" (TET) and its derivate radiation action model based on nanodosimetry (RAMN) by clearly distinguishing between effects of tracks at the cellular level and the induction of lesions in subcellular targets. It is demonstrated that the model assumptions of Poisson distribution and statistical independence o…
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This work aims at carving out more clearly the basic assumptions behind the "track-event theory" (TET) and its derivate radiation action model based on nanodosimetry (RAMN) by clearly distinguishing between effects of tracks at the cellular level and the induction of lesions in subcellular targets. It is demonstrated that the model assumptions of Poisson distribution and statistical independence of the frequency of single and clustered DNA lesions are dispensable for multi-event distributions, because they follow from the Poisson distribution of the number of tracks affecting the considered target volume. It is also shown that making these assumptions for the single-event distributions of the number of lethal and sublethal lesions within a cell would lead to an essentially exponential dose dependence of survival for practically relevant values of the absorbed dose. Furthermore, it is elucidated that the model equation used in the literature for consideration of repair within the TET is based on the assumption that DNA lesions induced by different tracks are repaired independently and that the model equation is presumably inconsistent with the model assumptions and requires an additional model parameter. Furthermore, the methodology for deriving model parameters from nanodosimetric properties of particle track structure is critically assessed. Based on data from proton track simulations it is shown that the assumption of statistically independent targets leads to a prediction of negligible frequency of clustered DNA damage. An approach is outlined how track structure could be considered in determining the model parameters, and the implications for TET and RAMN are discussed.
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Submitted 24 August, 2021; v1 submitted 15 May, 2021;
originally announced May 2021.
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Is the track-event theory of cell survival internally consistent?
Authors:
Sonwabile Arthur Ngcezu,
Hans Rabus
Abstract:
The "track event theory" (TET) has been developed in recent years as an alternative to the phenomenological linear-quadratic model for cell survival under exposure to ionizing radiation, particularly for heavy charged particles. The TET is based on a few simple model assumptions including the possibility to derive some of the model parameters from nanodosimetry. This work intends to carve out more…
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The "track event theory" (TET) has been developed in recent years as an alternative to the phenomenological linear-quadratic model for cell survival under exposure to ionizing radiation, particularly for heavy charged particles. The TET is based on a few simple model assumptions including the possibility to derive some of the model parameters from nanodosimetry. This work intends to carve out more clearly the basic assumptions behind the TET and to critically review the resulting mathematical model equations. It is demonstrated that the model assumptions of Poisson distribution and statistical independence of the frequency distributions of so-called one-track and two-track events follow from the Poisson distribution of the number of tracks affecting the considered target volume. It is also shown that the modified TET model equation used in the literature for consideration of repair is inconsistent with the model assumptions and requires an additional model parameter. Furthermore, the derivation of the model parameters from nanodosimetric properties of particle track structure is revealed to lead to a pure exponential dose dependence when the potentially large number of relevant nanometric target volumes inside a cell nucleus is accounted for.
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Submitted 31 January, 2021;
originally announced February 2021.
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Intercomparison of Monte Carlo calculated dose enhancement ratios for gold nanoparticles irradiated by X-rays: assessing the uncertainty and correct methodology for extended beams
Authors:
H. Rabus,
W. B. Li,
C. Villagrasa,
J. Schuemann,
P. A. Hepperle,
L. de la Fuente Rosales,
M. Beuve,
S. Di Maria,
A. P. Klapproth,
C. Y. Li,
F. Poignant,
B. Rudek,
H. Nettelbeck
Abstract:
Results of a Monte Carlo code intercomparison exercise for simulations of the dose enhancement from a gold nanoparticle (GNP) irradiated by X-rays have been recently reported. To highlight potential differences between codes, the dose enhancement ratios (DERs) were shown for the narrow-beam geometry used in the simulations, which leads to values significantly higher than unity over distances in th…
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Results of a Monte Carlo code intercomparison exercise for simulations of the dose enhancement from a gold nanoparticle (GNP) irradiated by X-rays have been recently reported. To highlight potential differences between codes, the dose enhancement ratios (DERs) were shown for the narrow-beam geometry used in the simulations, which leads to values significantly higher than unity over distances in the order of several tens of micrometers from the GNP surface. As it has come to our attention that the figures in our paper have given rise to misinterpretation as showing 'the' DERs of GNPs under diagnostic X-ray irradiation, this article presents estimates of the DERs that would have been obtained with realistic radiation field extensions and presence of secondary particle equilibrium (SPE). These DER values are much smaller than those for a narrow-beam irradiation shown in our paper, and significant dose enhancement is only found within a few hundred nanometers around the GNP. The approach used to obtain these estimates required the development of a methodology to identify and, where possible, correct results from simulations whose implementation deviated from the initial exercise definition. Based on this methodology, literature on Monte Carlo simulated DERs has been critically assessed.
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Submitted 19 July, 2021; v1 submitted 11 December, 2020;
originally announced December 2020.
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Nanodosimetry - on the tracks of biological radiation effectiveness
Authors:
Hans Rabus
Abstract:
Biological effectiveness of a certain absorbed dose of ionizing radiation depends on the radiation quality, i. e. the spectrum of ionizing particles and their energy distribution. As has been shown in several studies, the biological effectiveness is related to the pattern of energy deposits on the microscopic scale, the so-called track structure. Clusters of lesions in the DNA molecule within site…
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Biological effectiveness of a certain absorbed dose of ionizing radiation depends on the radiation quality, i. e. the spectrum of ionizing particles and their energy distribution. As has been shown in several studies, the biological effectiveness is related to the pattern of energy deposits on the microscopic scale, the so-called track structure. Clusters of lesions in the DNA molecule within site sizes of few nanometers play a particular role in this context. This work presents a brief overview of nanodosimetric approaches to relate biological effects with track structure derived quantities and experimental techniques to derive such quantities.
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Submitted 15 March, 2019;
originally announced March 2019.
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Measurement of track structure parameters of low and medium energy helium and carbon ions in nanometric volumes
Authors:
G. Hilgers,
M. U. Bug,
H. Rabus
Abstract:
Ionisation cluster size distributions produced in the sensitive volume of an ion-counting wall-less nanodosimeter by monoenergetic carbon ions with energies between 45 MeV and 150 MeV were measured at the TANDEM-ALPI ion accelerator facility complex of the LNL INFN in Legnaro. Those produced by monoenergetic helium ions with energies between 2 MeV and 20 MeV were measured at the accelerator facili…
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Ionisation cluster size distributions produced in the sensitive volume of an ion-counting wall-less nanodosimeter by monoenergetic carbon ions with energies between 45 MeV and 150 MeV were measured at the TANDEM-ALPI ion accelerator facility complex of the LNL INFN in Legnaro. Those produced by monoenergetic helium ions with energies between 2 MeV and 20 MeV were measured at the accelerator facilities of PTB and with a 241Am alpha particle source. C3H8 was used as the target gas. The ionisation cluster size distributions were measured in narrow beam geometry with the primary beam passing the target volume at specified distances from its centre, and in broad beam geometry with a fan-like primary beam. By applying a suitable drift time window, the effective size of the target volume was adjusted to match the size of a DNA segment. The measured data were compared with the results of simulations obtained with the PTB Monte Carlo code PTra. Before the comparison, the simulated cluster size distributions were corrected with respect to the background of additional ionisations produced in the transport system of the ionised target gas molecules. Measured and simulated characteristics of the particle track structure are in good agreement for both types of primary particles and for both types of the irradiation geometry.
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Submitted 10 February, 2017;
originally announced February 2017.