Equivalence of pure propane and propane TE gases for microdosimetric measurements.

A tissue-equivalent proportional counter (TEPC) simulates micrometric volumes of tissue if the energy deposited in the counter cavity is the same as that in the tissue volume. Nevertheless, a TEPC measures only the ionisations created in the gas, which are later converted into imparted energy. Therefore, the equivalence of the simulated diameter (Dρ) in two gases should be based on the equality of the mean number of ions pairs in the gas rather than on the imparted energy. Propane-based tissue-equivalent gas is the most commonly used gas mixture at present, but it has the drawback that its composition may change with time. From this point of view, the use of pure propane offers practical advantages: higher gas gain and longer stability. In this work, microdosimetric measurements performed with pure propane, at site sizes 0.05 mg cm(-2) ≤ Dρ ≤ 0.3 mg cm(-2), demonstrate that the response of a propane-filled detector in gamma and in neutron fields is almost the same if an appropriate gas density is used.

Nanodosimetric descriptors of the radiation quality of carbon ions.

In view of the emerging interest of carbon ions in radiotherapy and of the strong correlation between the track structure and the radiobiological effectiveness of ionising radiations, the track-structure properties of (12)C-ions were studied at particle energies close to the Bragg peak. To perform the investigations, ionisation-cluster-size distributions for nanometre-sized target volumes were measured with the track-nanodosimeter installed at the TANDEM-ALPI accelerator complex at LNL, and calculated using a dedicated Monte Carlo simulation code. The resulting cluster-size distributions are used to derive particular descriptors of particle track structure. Here, the main emphasis is laid on the mean ionisation-cluster size M1 and the cumulative probability Fk of measuring cluster sizes ν ≥ k. From the radiobiological point of view, Fk is of particular interest because an increasing k corresponds to an increase of damages of higher complexity. In addition, Fk saturates with increasing radiation quality like radiobiological cross sections as a function of linear energy transfer. Results will be presented and discussed for (12)C-ions at 96 and 240 MeV.

Nanodosimetric track structure in homogeneous extended beams.

Physical aspects of particle track structure are important in determining the induction of clustered damage in relevant subcellular structures like the DNA and higher-order genomic structures. The direct measurement of track-structure properties of ionising radiation is feasible today by counting the number of ionisations produced inside a small gas volume. In particular, the so-called track-nanodosimeter, installed at the TANDEM-ALPI accelerator complex of LNL, measures ionisation cluster-size distributions in a simulated subcellular structure of dimensions 20 nm, corresponding approximately to the diameter of the chromatin fibre. The target volume is irradiated by pencil beams of primary particles passing at specified impact parameter. To directly relate these measured track-structure data to radiobiological measurements performed in broad homogeneous particle beams, these data can be integrated over the impact parameter. This procedure was successfully applied to 240 MeV carbon ions and compared with Monte Carlo simulations for extended fields.

Lineal energy calibration of a spherical TEPC.

Tissue-equivalent proportional counters (TEPCs) do not always allow built-in calibration alpha-particle sources, and the lineal energy calibration of these counters must be performed with an external radiation able to penetrate the detector walls. The irradiation field can be used for calibration if a particular marker point of known lineal energy is identified in the measured spectrum. This point is often identified with the proton edge, which corresponds to the maximum energy deposited by protons in the given volume. If the proton edge cannot be identified precisely in the measured spectrum, a gamma source can be used instead, identifying the maximum lineal energy due to electrons (e-edge). The technique was already described and applied for cylindrical TEPCs, allowing a calibration with an overall uncertainty smaller than 5 % (Conte et al. Lineal energy calibration of mini tissue equivalent gas-proportional counters (TEPC). AIP Conf. Proc. 1530, 171-178 (2013)). In the present work, this study was repeated for spherical detectors. First a marker point was identified in the microdosimetric spectrum of a (137)Cs gamma source, then a precise value of lineal energy was assigned to it. Gas pressures were varied to simulate diameters from 0.5 and 3 µm at density 1 g cm(-3). A simple power equation is given for allowing calibration of TEPCs filled with C3H8-TE gas at different pressures, using an external (137)Cs gamma source.

Influence of the physical data to calibrate TEPCs.

Tissue-equivalent proportional counters (TEPCs) measure distributions of ionisations, produced in the gas cavity by the radiation field which are afterwards converted into distributions of energy imparted by applying a calibration factor. To calibrate the pulse-height spectra, first, a marker point must be identified in the measured spectrum. Then, an accurate value of lineal energy must be assigned to this marker. A common marker that is often used for calibration is the so-called proton-edge (p-edge). It is a distinctive feature of a proton or neutron spectrum which corresponds to the maximum amount of energy that a proton can deposit in the active volume of the detector. A precise method to identify the marker point was applied to identify the p-edge with an uncertainty below 1 %. To evaluate the final uncertainty of the calibration, the uncertainty of the energy value assigned to the p-edge must also be considered. This value can be evaluated using different energy-range tables. This study investigates how the choice of different input databases for calibration purposes influences the calibration. The effect of three different frequently used sets of input data was analysed for pure propane gas and for propane-TE gas mixture.

Track structure of carbon ions: measurements and simulations.

The likelihood of radiation to produce clustered damages in irradiated biological tissue and the reparability of such damages are closely related to the stochastics of localised ionising interactions within small volumes of nanometre sizes, determined by the particle track structure. Track structure investigations in nanometre-sized volumes have been subject of research for several decades, mainly by means of Monte Carlo simulations. Today, the 'track-nanodosimeter', installed at the TANDEM-ALPI accelerator complex of LNL, is a measuring device able to count the electrons produced in a 20-nm equivalent sensitive site (De Nardo et al. A detector for track-nanodosimetry. Nucl. Instrum. Methods. Phys. Res. A 484: , 312-326 (2002)). It allows studying track structure properties both in the near neighbourhood of a primary particle trajectory and separately in the penumbra region. An extended study for different ionising particles of medical interest has been recently performed with the track-nanodosimeter (Conte et al. Track structure of light ions: experiments and simulations. New J. Phys. 14: , 093010, (2012)). Here, new experimental data and results of Monte Carlo simulations for 240- and 96-MeV (12)C-ions are presented and discussed.

An upgraded track structure model: experimental validation.

The track nanodosemeter developed at the National Laboratories of Legnaro (LNL), Italy allows the direct investigation of the properties of particle tracks, by measuring ionisation-cluster-size distributions caused by ionising particles within a 'nanometre-sized' target volume while passing it at a well-specified impact parameter. To supplement the measurements, a dedicated Monte Carlo code was developed which is able to reproduce the general shape of measured cluster-size distributions with a satisfactory quality. To reduce the still existing quantitative differences between measured and simulated data, the validity of cross sections used in the Monte Carlo model was revisited again, taking into account the large amount of data available now from recent track structure measurements at LNL. Here, special emphasis was laid on a deeper and detailed investigation of the cross sections applied to calculate the energy of secondary electrons after impact ionisation of primary particles: the cross sections due to the HKS model and the so-called Rudd model. Representative results for 240 MeV (12)C-ions are presented.

Microdosimetric assessment of the radiation quality of a therapeutic proton beam: comparison between numerical simulation and experimental measurements.

Using protons for the treatment of ocular melanoma (especially of posterior pole tumours), the radiation quality of the beam must be precisely assessed to preserve the vision and to minimise the damage to healthy tissue. The radiation quality of a therapeutic proton beam at the Centre Antoine Lacassagne in Nice (France) was measured using microdosimetric techniques, i.e. a miniaturised version of a tissue-equivalent proportional counter. Measurements were performed in a 1-µm site at different depths in a Lucite phantom. Experimental data showed a significant increase in the beam quality at the distal edge of the spread-out Bragg peak (SOBP). In this paper, the numerical simulation of the experimental setup is done with the FLUKA Monte Carlo radiation transport code. The calculated microdosimetric spectra are compared with the measured ones at different depths in tissue for a monoenergetic proton beam (E=62 MeV) and for a modulated SOBP. Numerically and experimentally predicted relative biological effectiveness values are in good agreement. The calculated frequency-averaged and dose-averaged lineal energy mean values are consistent with measured data.

Bayesian analysis of nanodosimetric ionisation distributions due to alpha particles and protons.

Track-nanodosimetry has the objective to investigate the stochastic aspect of ionisation events in particle tracks, by evaluating the probability distribution of the number of ionisations produced in a nanometric target volume positioned at distance d from a particle track. Such kind of measurements makes use of electron (or ion) gas detectors with detecting efficiencies non-uniformly distributed inside the target volume. This fact makes the reconstruction of true ionisation distributions, which correspond to an ideal efficiency of 100%, non-trivial. Bayesian unfolding has been applied to ionisation distributions produced by 5.4 MeV alpha particles and 20 MeV protons in cylindrical volumes of propane of 20 nm equivalent size, positioned at different impact parameters with respect to the primary beam. It will be shown that a Bayesian analysis performed by subdividing the target volume in sub-regions of different detection efficiencies is able to provide a good reconstruction of the true nanodosimetric ionisation distributions.

Track nanodosimetry of 20-MeV protons at 20 nm.

Track nanodosimetry is the theoretical and experimental research which studies the stochastic aspects of ionisation yield produced by ionising particles in nanometric target volumes, positioned at different distances from the primary particle track. The STARTRACK experimental set-up, mounted on the +50° beam line at the Tandem-Alpi particle accelerator of Legnaro National Laboratories, has been conceived to give an experimental basis to nanodosimetric calculations. STARTRACK is a detection system able to measure the ionisation cluster-size distributions in a 20 nm propane site, by counting the electrons set in motion by different ion tracks, with the resolution of one electron. The 'sensitive volume' SV can be moved at different distances from the primary particle track (different impact parameter). Distributions of 20-MeV protons have been measured and compared with Monte Carlo calculations.

A nanodosimetric model of radiation-induced clustered DNA damage yields.

We present a nanodosimetric model for predicting the yield of double strand breaks (DSBs) and non-DSB clustered damages induced in irradiated DNA. The model uses experimental ionization cluster size distributions measured in a gas model by an ion counting nanodosimeter or, alternatively, distributions simulated by a Monte Carlo track structure code developed to simulate the nanodosimeter. The model is based on a straightforward combinatorial approach translating ionizations, as measured or simulated in a sensitive gas volume, to lesions in a DNA segment of one-two helical turns considered equivalent to the sensitive volume of the nanodosimeter. The two model parameters, corresponding to the probability that a single ion detected by the nanodosimeter corresponds to a single strand break or a single lesion (strand break or base damage) in the equivalent DNA segment, were tuned by fitting the model-predicted yields to previously measured double-strand break and double-strand lesion yields in plasmid DNA irradiated with protons and helium nuclei. Model predictions were also compared to both yield data simulated by the PARTRAC code for protons of a wide range of different energies and experimental DSB and non-DSB clustered DNA damage yield data from the literature. The applicability and limitations of this model in predicting the LET dependence of clustered DNA damage yields are discussed.

Analysis of the CONRAD computational problems expressing only stochastic uncertainties: neutrons and protons.

Within the scope of CONRAD (A Coordinated Action for Radiation Dosimetry) Work Package 4 on Computational Dosimetry jointly collaborated with the other research actions on internal dosimetry, complex mixed radiation fields at workplaces and medical staff dosimetry. Besides these collaborative actions, WP4 promoted an international comparison on eight problems with their associated experimental data. A first set of three problems, the results of which are herewith summarised, dealt only with the expression of the stochastic uncertainties of the results: the analysis of the response function of a proton recoil telescope detector, the study of a Bonner sphere neutron spectrometer and the analysis of the neutron spectrum and dosimetric quantity H(p)(10) in a thermal neutron facility operated by IRSN Cadarache (the SIGMA facility). A second paper will summarise the results of the other five problems which dealt with the full uncertainty budget estimate. A third paper will present the results of a comparison on in vivo measurements of the (241)Am bone-seeker nuclide distributed in the knee. All the detailed papers will be presented in the WP4 Final Workshop Proceedings.

Proton-induced frequency distributions of ionization cluster size in propane.

The frequency distribution of clustered ionizations produced by a proton beam was measured in a nanodosimetric volume of the size of a DNA segment by means of an ion-counting nanodosimeter in the energy range from 0.4 to 3.5 MeV. In order to meet the needs of the ion-counting nanodosimeter, the accelerator's primary beam was reduced in intensity by means of Rutherford scattering. The comparison between experimental results and Monte Carlo simulations show a good agreement in the energy dependence of the mean cluster size, while the experimental cluster size distributions show a higher amount of large ionization clusters compared with those obtained with the simulations.

W values of protons in liquid water.

The W values of protons in liquid water were calculated for energies from 0.1 keV to 10 MeV using the continuous slowing down approximation as well as three models for the calculation of the differential ionisation cross-sections of water for protons published in recent years. The W values determined by means of the three models differ only marginally from each other and lie between 25 and 26 eV at proton energies >5 MeV. This high-energy W value is approximately 3 eV lower than that in water vapour.

New descriptors of radiation quality based on nanodosimetry, a first approach.

After a short overview on the latest developments in nanodosimetry, measured frequency distributions of ionisation cluster size caused by 4.6 MeV alpha-particles or low-energy electrons in 'nanometric' volumes of nitrogen are compared with cluster-size distributions for liquid water cylinders that are equal in size to segments of DNA of 10 base-pairs length. Such frequency distributions are, to a greater part, governed by the same basic physical interaction data as those to be expected, if charged particles interact with DNA segments. Quantities derived from ionisation cluster-size distributions should, therefore, behave as a function of radiation quality similarly to the yields of single or double strand breaks in the DNA. To test this assumption, extensive Monte Carlo simulations were performed for electrons in the energy range between 12.5 eV and 100 keV for protons at energies between 0.7 MeV and 250 MeV and for alpha-particles in the energy range between 2 MeV and 100 MeV. The results are then compared with the yields of single- or double-strand breaks in the DNA, taken from the literature.

Nanodosimetry, the metrological tool for connecting radiation physics with radiation biology.

It is generally accepted that the early damage to genes or cells by ionising radiation starts with the early damage to segments of the DNA, at least, to the greater part. This damage is the result of the spatial distribution of inelastic interactions of single ionising particles within the DNA or in its neighbourhood and is, in consequence, determined by the stochastics of particle interactions in volumes a few nanometre in size. Due to the latter fact radiation damage strongly depends on radiation quality and cannot be described satisfactorily in detail by macroscopic quantities like absorbed dose or linear energy transfer (LET). It can, however, be described approximately by the probability distribution of ionisation cluster-size formation in nanometric target volumes of liquid water (nanodosimetry). One aim of nanodosimetry is, therefore, to measure the radiation induced frequency distribution of ionisation cluster-size formation in liquid water, as a substitute for sub-cellular material, in volumes which are comparable in size with those of the most probable radio-sensitive volumes of biological systems. After a short description of the main aspects of cluster-size formation by ionising particles, an overview is given about the measuring principles applied in present-day nanodosimetric measurements. Afterwards, physical principles are discussed which can be used to convert ionisation cluster-size distributions measured in gases into those caused by ionising radiation in liquid water. In a final section, the probability distribution of ionisation cluster-size formation in liquid water is discussed from the point of view of damage formation to segments of the DNA.

First attempts at prediction of DNA strand-break yields using nanodosimetric data.

We present the first results of our attempts to correlate yields of ionisation clusters in a gas model of DNA and corresponding double-strand break (DSB) yields in irradiated plasmids, using a simple statistical model of DNA lesion formation. Based on the same statistical model, we also provide a comparison of simulated nanodosimetric data for electrons and published DSB yields obtained with the PARTRAC code.

Simulation of the measured ionisation-cluster distributions of alpha-particles in nanometric volumes of propane.

In the last years, the probability of the formation of ionisation clusters by primary alpha particles at 5.4 MeV in nanometric volumes of propane (20.6 and 24.0 nm in a material of density 1.0 g cm(-3)) was studied experimentally and by Monte Carlo simulation. Calculations were performed taking into account the single electron detection efficiency of the track-nanodosimetric counter, which was estimated on the base of Monte Carlo calculations of electron transport inside the detector. Now a new evaluation of the efficiency has been performed, pointing out a value lower than previously estimated. Besides, the efficiency of the counter in resolving temporally the collected electrons has been calculated, together with its effect on the measured distribution. On the base of these evaluations, a new comparison has been performed between measurements and calculations, pointing out a better agreement than previously reported.

Ionization ranges of protons in water vapour in the energy range 1-100 keV.

Projected ranges of protons in water vapour were experimentally determined for proton energies from 1 to 100 keV by counting the total number of ionizations produced by protons during their slow down. Using these experimental ranges and semiemprical detour factors, the stopping powers of water vapour for protons were derived and compared with semiempirical data.

Ionisation cluster-size formation by electrons: from macroscopic to nanometric target sizes.

An indispensable prerequisite for a deeper understanding of specified physical, chemical or biological changes initiated in matter when being exposed to ionising radiation is a detailed knowledge of particle track structure. Here, the structure of electron tracks is of particular interest since electrons are set in motion in large numbers as secondary particles during the slow down of any kind of ionising radiation in matter. From the point of view of radiation induced early damage to genes and cells, which starts with the early damage to segments of the DNA molecule, the most effective secondary electrons are those at energies of a few hundred eV since the yield of double-strand breaks induced by such electrons in the DNA shows a maximum. This can be explained by the fact that in water cylinders, 2 nm in diameter and height (as a substitute to small segments of the DNA), the probability of the electron-induced formation of ionisation cluster sizes greater than or equal to two is highest also at initial electron energies of a few hundred eV. In view of this promising feature of ionisation cluster-size distributions formed by low-energy electrons in nanometric targets of liquid water for explaining particular radio-biological endpoints, it is the aim of the present work to investigate the properties of cluster-size formation by electrons as a function of target size. Here, main emphasis is laid on the behaviour of cluster-size distributions if the target size is reduced from macroscopic to nanometric volumes.