The biological action of ionizing charged particles is initiated at the DNA level, and the effectiveness with which the initial physical effect changes into measurable biological damage is likely ruled by the stochastics of ionizations produced by the incident ions in subcellular nanometric volumes. Based on this hypothesis, experimental nanodosimetry aims at establishing a new concept of radiation quality that builds on measurable characteristics of the particle track structure at the nanometer scale. Three different nanodosimetric detection systems have been developed to date that allow measurements of the number of ionizations produced by the passage of a primary particle in a nanometer-size gas volume (in unit density scale). Within the Italian project MITRA (MIcrodosimetry and TRAck structure), funded by the Italian Istituto Nazionale di Fisica Nucleare (INFN) and the EMRP Joint Research Project ‘BioQuaRT’ (Biologically Weighted Quantities in Radiotherapy), experiments have been carried out, in which the frequency distribution of ionizations produced by proton and carbon ion beams of given energy was measured with the three nanodosimetric detectors. Descriptors of the track structure can be derived from these distributions. In particular, the first moment M₁, representing the mean number of ionizations produced in the target volume, and the cumulative probability F_k of measuring a number ν ≥ k of ionizations. The correlation between measured nanodosimetric quantities and experimental radiobiological data available in the literature is here presented and discussed.

Nanodosimetry is a branch of dosimetry for investigation and modeling of the interaction pattern of ionizing radiation in nanometre site-sizes (at unit density), which dates back to the 1970’s (Pszona S. A track ion counter. Proceedings of Fifth Symposium on Microdosimetry EUR 5452 d-e-f, Published by the Commission of the European Communities, Luxemburg, pp. 1107–1122 (1976)). To date, the different experimental approaches have lead to developing of three fully functional nanodosimeters: the Jet Counter operated at NCBJ, the Ion Counter operated at PTB and Startrack Counter operated at INFN-LNL. Descriptions of each nanodosimeter as well as of the techniques used to investigate the track structure of ionizing particles are presented.

The Italian National Centre for Oncological Hadrontherapy (CNAO) has been treating patients since 2011 with carbon-ion beams using the active-scanning modality. In such irradiation modality, the beam spot, which scans the treatment area, is characterised by very high particle-fluence rates (more than 10⁵ s⁻¹ mm⁻²). Moreover, the Bragg-peak is only ~1 mm-FWHM. Commercial tissue-equivalent proportional counters (TEPC), like the Far West Technologies LET-½, are large, hence they have limited capability to measure at high counting fluence rates. In this study we have used two home-made detectors, a mini-TEPC 0.81 mm² in sensitive area and a silicon telescope 0.125 mm² in sensitive area, to perform microdosimetric measurements in the therapeutic carbon-ion beam of CNAO. A monoenergetic carbon-ion beam of 189.5 ± 0.3 MeV/u scanning a 3 × 3 cm² area has been used. Spectral differences are visible in the low y-value region, but the mean microdosimetric values, measured with the two detectors, result to be pretty consistent, as well as the microdosimetric spectra in the high y-value region.

It is generally recognized that the biological response to irradiation by light ions is initiated by complex damages at the DNA level. In turn, the occurrence of complex DNA damages is related to spatial and temporal distribution of ionization and excitation events, i.e., the particle track structure. It is the aim of the present study to investigate the correlation between the distribution of ionizations at the nanometric scale and the probability to induce biological damage. By means of Monte Carlo track structure simulations, the mean ionization yield $M_1$ and the cumulative probabilities $F_1$, $F_2$, and $F_3$ of at least one, two and three ionizations, respectively, were calculated in spherical volumes of water-equivalent diameters equal to 1, 2, 5 and 10 nm. When plotted as a function of $M_1$, the quantities $F_1$, $F_2$ and $F_3$ are distributed along almost unique curves, largely independent of particle type and velocity. However, the shape of the curves depends on the size of the sensitive volume. When the site size is 1 nm, biological cross sections are strongly correlated to combined probabilities of $F_2$ and $F_3$ calculated in the spherical volume, and the proportionality factor is the saturation value of biological cross sections.

This paper explores the role of microdosimetry in boron neutron capture therapy (BNCT), a cancer treatment involving the selective accumulation of boron-containing compounds in cancer cells, followed by neutron irradiation. Neutron interactions with ¹⁰B induces a nuclear reaction, releasing densely ionizing particles, specifically alpha particles and recoiling lithium-7 nuclei. These particles deposit their energy within a small tissue volume, potentially targeting cancer cells while sparing healthy tissue. The microscopic energy distribution, subject to significant fluctuations due to the short particle range, influences treatment efficacy. Microdosimetry, by studying this distribution, plays a crucial role in optimizing BNCT treatment planning. The methodology employs paired tissue equivalent proportional counters (TEPCs), one with cathode walls enriched with boron and the other without. Precise assessment of boron concentration is essential, as well as the ability to extrapolate results to the actual ¹⁰B concentration within the treatment region. The effective ¹⁰B concentrations within four boronated TEPCs, containing 10, 25, 70, and 100 ppm of ¹⁰B, have been determined. Results show variations of less than 3% from nominal values. Additionally, dose enhancement due to BNC interactions was measured and found to be proportional to the ¹⁰B concentration, with a proportionality factor of 7.7 × 10⁻³ per ppm of boron. Based on these findings, a robust procedure is presented for assessing the impact of BNCT in the treatment region, considering potential variations in boron content relative to the TEPC used.

A Monte Carlo simulation tool has been developed, based on the physical models of the Geant4-DNA extension of Geant4, to study the ionisation pattern of charged particles in a multi-target environment. The tool allows to code easily the geometry to build a simulation with multiple targets, since several parameters can be changed interactively and independently via macro commands. In this work a set of nanometric target spheres is embedded in a cylindrical water phantom 20 nm in height and 40 nm in diameter. The targets are randomly distributed in such a way that they do not overlap and are contained within a smaller cylindrical volume 20 nm in diameter and height. The water phantom is irradiated by ions which are shot parallel to the central axis and randomly distributed over the cross section of the inner cylinder. Two different types of simulations are performed. In one, the penumbra of secondary electrons is fully simulated, in the other the transport of secondary electrons is carried out only if they are produced inside one of the targets, and the electron track is terminated when it leaves the sphere of production. First results are presented and discussed.