Ionization Clusters Research Articles

Nanodosimetric investigation of the track structure of therapeutic carbon ion radiation part2: detailed simulation

Objectivea previous study reported nanodosimetric measurements of therapeutic-energy carbon ions penetrating simulated tissue. The results 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.Approachdetailed 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.Main resultsthe 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 values estimated using the SRIM software. 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%.Significancethe 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.

Nanodosimetric investigation of the track structure of therapeutic carbon ion radiation part 1: measurement of ionization cluster size distributions

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.

Radial dependence of ionization clustering around a gold nanoparticle irradiated by X-rays under charged particle equilibrium

Objective.This work explores the enhancement of ionization clustering and its radial dependence around a gold nanoparticle (NP), indicative of the induction of DNA lesions, a potential trigger for cell-death.Approach.Monte Carlo track structure simulations were performed to determine (a) the spectral 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 NP 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.Main results.The modification of the electron spectral fluence 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. Similar to the known dose enhancement, increased ionization clustering is limited to a distance from the NP surface of up to200nm. The number of clusters per energy imparted is increased at distances of up to150nm, and accordingly the enhancement in clustering notably surpasses that of dose enhancement. Smaller NPs cause noticeable peaks in the conditional frequency of clusters between50nm-100nmfrom the NP surface.Significance.This work shows that low energy electrons emitted by NPs lead to an increase of ionization clustering in their vicinity exceeding that of energy imparted. While 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 NPs are governed by the interplay of secondary electron production by photon interaction and their ability to leave the NP.

Lithium inelastic cross-sections and their impact on micro and nano dosimetry of boron neutron capture

Objective. To present a new set of lithium-ion cross-sections for (i) ionization and excitation processes down to 700 eV, and (ii) charge-exchange processes down to 1 keV u−1. To evaluate the impact of the use of these cross-sections on micro a nano dosimetric quantities in the context of boron neutron capture (BNC) applications/techniques. Approach. The Classical Trajectory Monte Carlo method was used to calculate Li ion charge-exchange cross sections in the energy range of 1 keV u−1 to 10 MeV u−1. Partial Li ion charge states ionization and excitation cross-sections were calculated using a detailed charge screening factor. The cross-sections were implemented in Geant4-DNA v10.07 and simulations and verified using TOPAS-nBio by calculating stopping power and continuous slowing down approximation (CSDA) range against data from ICRU and SRIM. Further microdosimetric and nanodosimetric calculations were performed to quantify differences against other simulation approaches for low energy Li ions. These calculations were: lineal energy spectra (yf(y) and yd(y)), frequency mean lineal energy yF― , dose mean lineal energy yD― and ionization cluster size distribution analysis. Microdosimetric calculations were compared against a previous MC study that neglected charge-exchange and excitation processes. Nanodosimetric results were compared against pure ionization scaled cross-sections calculations. Main results. Calculated stopping power differences between ICRU and Geant4-DNA decreased from 33.78% to 6.9%. The CSDA range difference decreased from 621% to 34% when compared against SRIM calculations. Geant4-DNA/TOPAS calculated dose mean lineal energy differed by 128% from the previous Monte Carlo. Ionization cluster size frequency distributions for Li ions differed by 76%–344.11% for 21 keV and 2 MeV respectively. With a decrease in the N 1 within 9% at 10 keV and agreeing after the 100 keV. With the new set of cross-sections being able to better simulate low energy behaviors of Li ions. Significance. This work shows an increase in detail gained from the use of a more complete set of low energy cross-sections which include charge exchange processes. Significant differences to previous simulation results were found at the microdosimetric and nanodosimetric scales that suggest that Li ions cause less ionizations per path length traveled but with more energy deposits. Microdosimetry results suggest that the BNC’s contribution to cellular death may be mainly due to alpha particle production when boron-based drugs are distributed in the cellular membrane and beyond and by Li when it is at the cell cytoplasm regions.

Ionization Detail Parameters for DNA Damage Evaluation in Charged Particle Radiotherapy: Simulation Study Based on Cell Survival Database.

Details of excitation and ionization acts hide a description of the biological effects of charged particle traversal through living tissue. Nanodosimetry enables the introduction of novel quantities that characterize and quantify the particle track structure while also serving as a foundation for assessing biological effects based on this quantification. This presents an opportunity to enhance the planning of charged particle radiotherapy by taking into account the ionization detail. This work uses Monte Carlo simulations with Geant4-DNA code for a wide variety of charged particles and their radiation qualities to analyze the distribution of ionization cluster sizes within nanometer-scale volumes, similar to DNA diameter. By correlating these results with biological parameters extracted from the PIDE database for the V79 cell line, a novel parameter R2 based on ionization details is proposed for the evaluation of radiation quality in terms of biological consequences, i.e., radiobiological cross section for inactivation. By incorporating the probability p of sub-lethal damage caused by a single ionization, we address limitations associated with the usually proposed nanodosimetric parameter Fk for characterizing the biological effects of radiation. We show that the new parameter R2 correlates well with radiobiological data and can be used to predict biological outcomes.

Capture enhanced neutron irradiation for the treatment of the Alzheimer Disease: Micro-nanodosimetric characterization of beta amyloid peptide samples

Alzheimer Disease (AD) is the most common cause of dementia. 46.8 million people live with AD worldwide, with numbers projected to almost double every 20 years. The etiological mechanisms underlying the neuropathological changes in AD remain unclear. The beta amyloid peptide Aβ is considered to be the main culprit of the pathological processes. NECTAR (NEutron Capture-enhanced Treatment of neurotoxic Amyloid aggRegates) project proposes an alternative and revolutionary strategy to address AD, investigating the safety, feasibility and effectiveness of a Capture-Enhanced Neutron Irradiation to structurally damage Aβ aggregates, by exploiting capture agent vectors containing B-10 and Gd-157.Among many others, one of the goals of the project is to perform calculations and measurements of microdosimetric and nanodosimetric quantities to characterize the effect of reaction products at local level and to link it to the fibrils depolymerization process. In this framework, a new low-pressure tissue-equivalent proportional counter (TEPC) was designed and developed. The system is a wall-free TEPC able to measure micro-nanometric dose deposition for different biological samples. It is characterized by two main features: i) a wall-less structure allows the charged particles produced by the sample to access the sensitive volume, where their effects are studied; ii) a trigger system enables the assessment of the number of ionizations induced in the sensitive volume related to a single primary particle for obtaining nandosimetric information.The prototype system was tested in the PGNAA (Prompt Gamma Neutron Activation Analysis) facility of the LENA reactor (Pavia) to directly study secondary particles from Aβ fibrils, loaded with Boron. Results of the micro-nanodosimetric characterization of high LET secondaries from Aβ-fibrils were compared to a reference Boron sample. For a 500 nm simulated site size, the presence of Boron in the Aβ sample greatly populates microdosimetric spectra at high lineal energy values. Instead, lower LET particles (photons, protons) from reactions on the other Aβ aggregate solution molecules populate the low lineal energy portion of the distribution.The nanodosimetric distributions highlights the presence of different field components on the nanodosimetric spectra: low LET particles (protons/electrons) produce small ionization clusters, while alpha and Lithium ions induce larger clusters, thus have a higher biological effect. The nanodosimetric measurements have been compared with Monte Carlo simulations performed with a track-structure code, showing a good agreement.This multi-level approach provides a deeper physical understanding of the mixed secondaries field coming from B-enriched target, as well as a reference for the biological effect on Aβ fibrils at nanometer level. These preliminary measurements represent the first microdosimetric and nanodosimetric characterization of the secondary mixed field directly emitted by a biological sample irradiated with neutrons.

Primary study of the relative and compound biological effectiveness model for boron neutron capture therapy based on nanodosimetry.

The current radiobiological model employed for boron neutron capture therapy (BNCT) treatment planning, which relies on microdosimetry, fails to provide an accurate representation the biological effects of BNCT. The precision in calculating the relative biological effectiveness (RBE) and compound biological effectiveness (CBE) plays a pivotal role in determining the therapeutic efficacy of BNCT. Therefore, this study focuses on how to improve the accuracy of the biological effects of BNCT. The purpose of this study is to propose new radiation biology models based on nanodosimetry to accurately assess RBE and CBE for BNCT. Nanodosimetry, rooted in ionization cluster size distributions (ICSD), introduces a novel approach to characterize radiation quality by effectively delineating RBE through the ion track structure at the nanoscale. In the context of prior research, this study presents a computational model for the nanoscale assessment of RBE and CBE. We establish a simplified model of DNA chromatin fiber using the Monte Carlo code TOPAS-nBio to evaluate the applicability of ICSD to BNCT and compute nanodosimetric parameters. Our investigation reveals that both homogeneous and heterogeneous nanodosimetric parameters, as well as the corresponding biological model coefficients α and β, along with RBE values, exhibit variations in response to varying intracellular 10B concentrations. Notably, the nanodosimetric parameter effectively captures the fluctuations in model coefficients α and RBE. Our model facilitates a nanoscale analysis of BNCT, enabling predictions of nanodosimetric quantities for secondary ions as well as RBE, CBE, and other essential biological metrics related to the distribution of boron. This contribution significantly enhances the precision of RBE calculations and holds substantial promise for future applications in treatment planning.

Creating uniform cluster dose spread-out Bragg peaks for proton and carbon beams.

Preliminary data have shown a close association of the generalized ionization cluster size dose (in short, cluster dose) with cell survival, independent of particle type, and energy, when cluster dose is derived from an ionization detail parameter preferred for its association with cell survival. Such results suggest cluster dose has the potential to replace RBE-weighted dose in proton and ion beam radiotherapy treatment plan optimization, should a uniform cluster dose lead to comparable biological effects. However, further preclinical investigations are warranted to confirm this premise. To present an analytical approach to create uniform cluster dose spread-out Bragg peaks (SOBP) for evaluation of the potential of cluster dose to result in uniform biological effect. We modified the coefficients of the Bortfeld and Schlegel weight formula, an analytical method typically used for the creation of radiation dose SOBP in particle therapy, to produce uniform cluster dose SOBP of different widths (1-5cm) at relevant clinical proton and carbon beam energies. Optimum parameters were found by minimization of the ratio between the maximum and minimum cluster dose in the SOBP region using the Nelder-Mead method. The coefficients of the Bortfeld and Schlegel weight formula leading to uniform cluster dose SOBPs were determined for each combination of beam energy and SOBP width studied. The uniformity of the resulting cluster dose SOBPs, calculated as the relative difference between the maximum and minimum cluster dose within the SOBP, was within 0.3%-3.5% for the evaluated proton beams and 1.3%-3.4% for the evaluated carbon beams. The modifications to the analytical approach to create radiation dose SOBPs resulted in uniform cluster dose proton and carbon SOBPs over a wide range of beam energies and SOBP widths. Such SOBPs should prove valuable in preclinical investigations for the selection of nanodosimetric quantities to be used in proton and ion therapy treatment planning.

Ionization detail parameters and cluster dose: a mathematical model for selection of nanodosimetric quantities for use in treatment planning in charged particle radiotherapy

Objective. To propose a mathematical model for applying ionization detail (ID), the detailed spatial distribution of ionization along a particle track, to proton and ion beam radiotherapy treatment planning (RTP). Approach. Our model provides for selection of preferred ID parameters (I p ) for RTP, that associate closest to biological effects. Cluster dose is proposed to bridge the large gap between nanoscopic I p and macroscopic RTP. Selection of I p is demonstrated using published cell survival measurements for protons through argon, comparing results for nineteen I p : N k , k = 2, 3, …, 10, the number of ionizations in clusters of k or more per particle, and F k , k = 1, 2, …, 10, the number of clusters of k or more per particle. We then describe application of the model to ID-based RTP and propose a path to clinical translation. Main results. The preferred I p were N 4 and F 5 for aerobic cells, N 5 and F 7 for hypoxic cells. Significant differences were found in cell survival for beams having the same LET or the preferred N k . Conversely, there was no significant difference for F 5 for aerobic cells and F 7 for hypoxic cells, regardless of ion beam atomic number or energy. Further, cells irradiated with the same cluster dose for these I p had the same cell survival. Based on these preliminary results and other compelling results in nanodosimetry, it is reasonable to assert that I p exist that are more closely associated with biological effects than current LET-based approaches and microdosimetric RBE-based models used in particle RTP. However, more biological variables such as cell line and cycle phase, as well as ion beam pulse structure and rate still need investigation. Significance. Our model provides a practical means to select preferred I p from radiobiological data, and to convert I p to the macroscopic cluster dose for particle RTP.

Improvement of the hybrid approach between Monte Carlo simulation and analytical function for calculating microdosimetric probability densities in macroscopic matter

Objective. Estimation of the probability density of the microdosimetric quantities in macroscopic matter is indispensable for applying the concept of microdosimetry to medical physics and radiological protection. The Particle and Heavy Ion Transport code System (PHITS) enables estimating the microdosimetric probability densities due to its unique hybrid modality between the Monte Carlo and analytical approaches called the microdosimetric function. It can convert the deposition energies calculated by the macroscopic Monte Carlo radiation transport simulation to microdosimetric probability densities in water using an analytical function based on the track-structure simulations. Approach. In this study, we improved this function using the latest track-structure simulation codes implemented in PHITS. The improved function is capable of calculating the probability densities of not only the conventional microdosimetric quantities such as lineal energy but also the number of ionization events occurring in a target site, the so-called ionization cluster size distribution, for arbitrary site diameters from 3 nm to 1 μm. Main results. The accuracy of the improved function was well verified by comparing the microdosimetric probability densities measured by tissue-equivalent proportional counters with the corresponding data calculated in this study. Test calculations for clonogenic cell survival using the improved function coupled with the modified microdosimetric kinetic model suggested a slight increase of its relative biological effectiveness compared with our previous estimations. As a new application of the improved function, we calculated the relative biological effectiveness of the single-strand break and double-strand break yields for proton irradiations using the updated PHITS coupled with the simplified DNA damage estimation model, and confirmed its equivalence in accuracy and its superiority in computational time compared to our previously proposed method based on the track-structure simulation. Significance. From these features, we concluded that the improved function could expand the application fields of PHITS by bridging the gap between microdosimetry and macrodosimetry.

Particle identification with the cluster counting technique for the IDEA drift chamber

IDEA (Innovative Detector for an Electron–positron Accelerator) is a general-purpose detector concept, designed to study electron–positron collisions in a wide energy range in a very large circular leptonic collider. Its drift chamber is designed to provide an efficient tracking, a high precision momentum measurement and an excellent particle identification by exploiting the application of the cluster counting technique. To investigate the potential of the cluster counting techniques on physics events, a simulation of the ionization cluster generation is needed, therefore we developed an algorithm which can use the energy deposit information provided by the Geant4 toolkit to reproduce, in a fast and convenient way, the cluster number and cluster size distributions. The results obtained confirm that the cluster counting technique allows to reach a resolution two times better than the traditional dE/dx method. A beam test has been performed during November 2021 at CERN on the H8 beam line to validate the simulations results, to define the limiting effects for a fully efficient cluster counting and to count the number of electron clusters released by an ionizing track at a fixed βγ as a function of the track angle. The simulation and the beam test results will be described briefly in this issue.

A variable gain front-end electronics for drift chambers

The cluster counting/timing technique in a drift chamber allows to have a bias free impact parameter estimate. The application of this technique requires to measuring and counting the arrival times of each individual ionization cluster to a sense wire. In a Helium based gas mixture the rise time of the signal from a cluster is approximately 1 ns, therefore a readout electronic front-end with high linearity, low distortion and sufficiently high bandwidth is required. Furthermore, it would be useful for the readout electronics to be able to easily adapt its gain to the detector’s operating point. The use of a variable gain amplifier (VGA) allows to meet the needs arising from the changed operating conditions of the detector. The market offers components capable of satisfying all these needs with dimensions compatible with high-density drift chambers. A high linear, low distortion, remotely controllable, about 1GHz bandwidth and compact VGA is presented together with the measurements performed.

Intercomparison of nanodosimetric distributions in nitrogen simulated with Geant4 and PTra track structure codes

To facilitate the use of Geant4-DNA for radiation transport simulations in micro- and nanodosimeters, which are physically operated with tissue-equivalent gases such as nitrogen (and propane), this work aims to extend the cross section data available in Geant4-DNA to include those of nitrogen for electron energies ranging from 1 MeV down to the ionisation threshold. To achieve this, interaction cross section data for nitrogen that have been used with the in-house PTB PTra track structure code have been implemented in the current state-of-the-art Geant4-DNA simulation toolkit. An intercomparison has been performed between the two codes to validate this implementation. To quantify the agreement between the cross section models for nitrogen adopted in PTra and those implemented in Geant4-DNA, the simulation results of both codes were analysed using three physical parameters describing the ionisation cluster size distribution (ICSD): mean ionisation cluster size, variance of the cluster size and the probability to obtain a single ionisation within the target. Statistical analysis of the results indicates that the interaction cross section models for nitrogen used in PTra (elastic scattering, impact ionisations and electronic excitations) have been successfully implemented in Geant4-DNA. In addition, simulated ICSDs were compared to those measured with the Jet Counter nanodosimeter for energies between 100 and 2000 eV. For greater energies, the ICRP data for LET and particle range were used as a reference. The modified Geant4-DNA code and data successfully passed all these benchmarks fulfilling the requirement for their public release in the next version of the Geant4 toolkit.

Correlated ionisations in two spatially separated nanometric volumes within the track structure of 241Am alpha particles: comparison with Monte Carlo simulations

The production of two double strand breaks in spatially separated locations on the DNA molecule can cause the loss of a whole DNA loop. This loss, which can be of substantial length depending on the geometrical position of the two damaged sites, depends on the degree of correlation between ionisation clusters formed in sites of several nanometres in size. The first part of this paper reported on 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. 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 PTra, a track structure code 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 experiment were found to be in good agreement with the measurements for the investigated irradiation geometries.

A double-strand-break model for the relative biological effectiveness of electrons based on ionization clustering.

The effectiveness of ionizing radiation regarding DNA damage induction depends on its spatial energy deposition pattern. For electrons an increased effectiveness is observed at low kinetic energies due to the enhanced density of energy deposition events at electron track ends. A model is presented, which enables the calculation of the double-strand-break (DSB) yield and the relative biological effectiveness (RBE) for DSB induction of electrons. The model applies the mean free path between two ionizations and the assumption that two ionizations within a certain threshold distance are necessary to potentially lead to a DSB. Next to an expression for the electron RBE according to its common definition, a local RBE is determined, which describes the electrons' local effectiveness at a defined point on their track. This local RBE allows a better understanding of microscopic processes resulting from radiation and can be used, for instance, to describe the mean effectiveness of the mixed electron radiation field as a function of the radial distance to the center of an ion track. The presented model reflects the experimentally observed increased effectiveness of low-energetic electrons. It will be used in a future work to improve RBE predictions for ions performed with the local effect model.

Electrostatic field simulations and dynamic Monte Carlo simulations of a nanodosimetric detector

Nanodosimetry uses physical quantities based on ionization cluster size distributions to model the biological effectiveness of different radiation qualities. A nanodosimetric detector in operation is the FIRE (Frequency of Ion Registration) detector, but further design optimization of the detector is required. The simulations presented in this work will help guide future developments of the detector.Within the FIRE detector, the produced ions drift towards a dielectric plate hole, within which they are strongly accelerated towards the cathode and produce an electron avalanche through impact ionization. The electron avalanche is measured at the signal readout. COMSOL Multiphysics was used to calculate the electrostatic fields and Garfield＋＋ was used to simulate ion drift trajectories and electron avalanche formation employing Monte Carlo methods.The dependency of electron avalanche formation on experimental parameters, such as pressure or electric field configuration, was studied and compared to experimental results. Based on the funneling effect ions experience within the drift region, a calculation method for obtaining an optimized hole pitch for future multi-hole detector designs was presented. The results presented in this work offer valuable insights into the inner workings of the FIRE detector, as well as make clarify how different experimental parameters influence signal creation.

Geant4-DNA modeling of nanodosimetric quantities in the Jet Counter for alpha particles

The purpose of this work was to validate the calculation accuracy of nanodosimetric quantities in Geant4-DNA track structure simulation code. We implemented the Jet Counter (JC) nanodosimeter geometry in the simulation platform and quantified the impact of the Geant4-DNA physics models and JC detector performance on the ionization cluster size distributions (ICSD). ICSD parameters characterize the quality of radiation field and are supposed to be correlated to the complexity of the initial DNA damage in nanoscale and eventually the response of biological systems to radiation. We compared Monte Carlo simulations of ICSD in JC geometry performed using Geant4-DNA and PTra codes with experimental data collected for alpha particles at 3.8 MeV. We investigated the impact of simulation and experimental settings, i.e., three Geant4-DNA physics models, three sizes of a nanometer sensitive volume, gas to water density scaling procedure, JC ion extraction efficiency and the presence of passive components of the detector on the ICSD and their parameters. We found that ICSD in JC geometry obtained from Geant4-DNA simulations in water correspond well to ICSD measurements in nitrogen gas for all investigated settings, while the best agreement is for Geant4-DNA physics option 4. This work also discusses the accuracy and robustness of ICSD parameters in the context of the application of track structure simulation methods for treatment planning in particle therapy.

Characterisation of the PTB ion counter nanodosimeter's target volume and its equivalent size in terms of liquid H2O

The pattern of inelastic interactions in subcellular targets, especially in DNA, is largely responsible for radiation-induced damage to tissue. The track structure of ionising particles is therefore of particular importance in view of the biological effectiveness of ionising radiation.In approaches to model radiation effects to DNA, track structure details on the nanometre scale and the specifics of the target geometry play an important role. Hence, reliable experimental benchmark data for these models require detailed knowledge on the size and shape of the target volume of the devices used to measure quantities related to track structure in simulated nanometric target volumes.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, for the first time with particular focus on the equivalent target size in terms of liquid H2O. To this end, measurements with alpha particles from a241Am 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 (ρλion)-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.

Experimental nanodosimetry: Track structure of 80 MeV boron ions

The radiobiological effects of ionising radiations are strongly correlated to the local density of lesions produced in micrometre- and nanometre-sized subcellular structures, and thus to the track structure properties of interacting particles. These properties have been studied mainly by means of Monte Carlo simulations, however experimental methodologies and instruments have also been developed that allow to measure the stochastics of ionisations produced in a nanometric sensitive volume (SV) by charged particles crossing it or passing nearby at specified distances. The number ν of ionisations produced in SV by the passage of a single primary ionising particle is measured, and the measurement is repeated many times to produce a probability distribution P(ν), called ionisation cluster size distribution. Measurable quantities can be derived that correlate with the biological effectiveness of the specific radiation quality (ion type and velocity). In view of the emerging interest of carbon ions in radiotherapy, it is important to characterize not only the track structure of carbon ions but also that of other light ions that are produced in nuclear interactions. This work presents first experimental results for boron ions at 80 MeV. Ionisation cluster size distributions were measured with the Startrack-Counter installed at the TANDEM-ALPI accelerator complex at the Legnaro National Laboratories (LNL) of the Italian Istituto Nazionale di Fisica Nucleare (INFN) and simulated by means of a dedicated Monte Carlo code. Measurements and simulations were performed for particles that traverse directly the sensitive volume or pass nearby at specified impact parameters.

First measurements of ionization cluster-size distributions with a compact nanodosimeter.

A nanodosimeter is a type of detector which measures single ionizations in a small gaseous volume in order to obtain ionization cluster size probability distributions for characterization of radiation types. Working nanodosimeter detectors are usually bulky machines which require a lot of space. In this work, the authors present a compact ceramic nanodosimeter detector and report on first measurements of cluster size distributions of 5MeV alpha particles. Single ionization measurements are achieved by applying a weak electric field to collect positive ions in a hole in a ceramic plate. Inside the ceramic plate, due to a strong electric field, the ions are accelerated and produce impact-ionizations. The resulting electron avalanche is detected in a read-out electrode. A Bayesian unfolding algorithm is then applied to the experimentally obtained cluster size distributions to reconstruct the true cluster size distributions. Experimentally obtained cluster size distributions by the compact nanodosimeter detector are presented. The reconstructed cluster size distributions agreed well with Monte Carlo simulated cluster size distributions for small volumes (diameter=2.5nm). For larger volumes, discrepancies between the reconstructed cluster size distributions and cluster size distributions from Monte Carlo simulations were observed. For the first time, ionization cluster size probability distributions could be obtained by a small and compact nanodosimeter detector. This signifies the achievement of a critical step toward the wide application of nanodosimetric characterization of radiation types including in clinical environments.