Roberto Catalano

Aims: Radiotherapy (RT) with a single application of ionizing radiation [Stereotactic Arrhythmia Radioablation (STAR)] has been suggested as a non-invasive alternative to radiofrequency in ablating ventricular tachycardia (VT). Emerging data reveal that STAR may suppress VT without substrate destruction by enhancing impulse conduction instead, through increased expression of NaV1.5 channels and connexin 43. The study aims to investigate electrophysiology and intracellular Ca2+ dynamics in cardiomyocytes from mice subjected to in vivo RT. The emerging data led us to evaluate biochemical changes potentially linking electrophysiological response to ionizing irradiation. Methods and results: Cardiomyocytes isolated 2 weeks after RT with low-dose (15 Gy) or high-dose (25 Gy) were compared to those of sham-treated mice (CTRL). We evaluated: (i) the properties of the transient (INaT) and sustained (INasus) components of INa; (ii) action potential (AP) parameters, including the prevalence of early afterdepolarizations (EADs); (iii) intracellular Ca2+ dynamics; (iv) CaMKII phosphorylation, and (v) reactive oxygen species (ROS) content. 25 Gy RT (i) increased INaT and, to a larger extent, INasus (increased INasus/INaT ratio); (ii) increased AP amplitude, +dV/dtMAX and duration (APD) and facilitated EADs; (iii) depressed intracellular Ca2+ dynamics. 15 Gy RT had similar but smaller effects (dose-dependency). 25 Gy RT reduced CaMKII phosphorylation but increased cell ROS content, thus providing a mechanism for the late component of INa (INaL) enhancement. Conclusion: The results support the view that STAR may suppress VT by increasing conduction velocity, with APD prolongation providing an additional mechanism. On the other hand, INasus enhancement and Ca2+ handling depression may impair electrical stability and contractility in the irradiated region.

The HASPIDE project of INFN exploits hydrogenated amorphous silicon (a-Si:H) as a sensitive material for innovative detectors, mainly focused on dosimetry both for standard and FLASH radiotherapy, but also fo other applications. The detector, deposited on a thin and flexible substrate of polyimide, has been developed with different contacts configurations during past years, giving rise to the necessity to compare them in order to determine which configuration is best, for a specific application. In particular, three types of contacts are under exam in this work: the first one is a classical n-i-p junction, where a thick layer of intrinsic a-Si:H material is sandwiched between n- and p-doped layers of hydrogenated amorphous silicon; the second configuration is a charge-selective contacts device (CSC), where the doped regions are replaced with metal oxides which selectively enhance the mobility of one charge-carrier, blocking the other and the last one is the hybrid type, in which the intrinsic region is coupled with a n-doped layer on the bottom and a hole selective metal oxide on the top. This work aims to give a comparison in the performance of three devices differing only in the contact configuration, in terms of dark current analysis and sensitivity to X-ray beams, so that the characteristics of each one can be analyzed and exploited.

The INFN HASPIDE project investigates hydrogenated amorphous silicon (a-Si:H) as an innovative detector technology for dosimetry in FLASH radiotherapy. Conventional dosimeters, such as ionization chambers, show non-linear behavior when exposed to ultra-high dose-per-pulse beams used in FLASH radiotherapy, where several Grays are delivered in microsecond pulses. Thanks to its radiation hardness, mechanical flexibility and compatibility with large-area deposition, a-Si:H is a promising material for in-vivo and surface dosimetry. This work presents the response of a thin a-Si:H detector exposed to a high-dose-per-pulse 10 MeV electron beam, together with an analytical model used to describe the single-pulse dynamics and extract quantitative parameters. Measurements were performed at the University of Torino using a modified clinical LINAC operated in Ultra High Dose Rate regime, where the single-pulses satisfy the FLASH criteria. The a-Si:H detector, read out with a TetrAMM picoammeter (100 kHz sampling frequency), resolves individual radiation pulses with high repeatability. Both pulse charge and peak current scale linearly with the applied electric field up to 6 V (2.4 V/μm), beyond which the readout electronics saturates. The analytical model is validated through direct comparison with raw data, showing excellent agreement in extracted pulse parameters.

Objective. This study aims to perform a comprehensive microdosimetric characterization of a clinical helium ion beam at the Heidelberg ion-beam Therapy center, assessing radiation quality along a spread-out Bragg peak (SOBP) and providing experimental data to support the biological effectiveness of helium ions in clinical applications. Approach. Microdosimetric spectra were measured at several water depths within the SOBP using two solid-state detectors: a silicon and a synthetic single-crystal diamond detector. Microdosimetric quantities, including dose-mean lineal energy ( y D ) and frequency-mean lineal energy ( y F ), were derived. Monte Carlo simulations with the Geant4 toolkit replicated the experimental setup to validate the measured quantities. The modified microdosimetric kinetic model was also applied to estimate the relative biological effectiveness at 10% survival (RBE₁₀). SAOS-2 and U2OS clonogenic assays were performed under identical irradiation conditions at the same facility to benchmark the RBE predictions. Main results. The experimental results demonstrated a progressive increase in y D values along the beam path, peaking at the distal edge of the SOBP, consistent with the simulated dose-averaged linear energy transfer distribution. The RBE₁₀ values estimated by the two solid-state detectors showed good agreement with the experimental data from clonogenic assays, within the associated uncertainties. Significance. These findings underscore the utility of advanced solid-state detectors for helium beam characterization and highlight the importance of microdosimetry in improving radiobiological modeling. The results provide further evidence supporting the clinical potential of helium ion therapy, particularly for tumors requiring high precision and maximal healthy tissue sparing.

We explore the use of gas-filled plasma-discharge capillaries for laser wakefield acceleration (LWFA) by employing a hybrid system that integrates an external high-voltage source to driven an electrical discharge, generate plasma within the capillary channel before to the main laser pulse. The process enhances plasma formation, boosts operational efficiency, and maintains laser intensity over multiple Rayleigh lengths, enabling high-energy electron acceleration. The electrical discharge creates a stable, uniform plasma environment, improving beam charge, energy stability, and reducing energy spread. This uniform plasma ensures better laser coupling and mitigates instabilities, leading to improved beam quality. This method supports efficient acceleration and the production of very-high-energy electron (VHEE) pencil beams (250 MeV) in a compact, cost-effective system designed for radiobiological studies at the future I-LUCE (INFN-Laser indUCEd Radiation Production) facility at the Istituto Nazionale di Fisica Nucleare-Laboratori Nazionali del Sud (INFN-LNS) in Catania, Italy. The system aims to generate high-energy electron beams tailored for VHEE and FLASH radiotherapy (FLASH-RT) applications. In this paper, we present simulations of capillaries performed using COMSOL Multiphysics software, where plasma density is obtained as a function of the applied voltage. We analyze plasma behavior under varying voltage and compare the results with experimental data, demonstrating the model's accuracy in predicting plasma characteristics and its potential to optimize discharge conditions.

This paper presents a comprehensive study of hydrogenated amorphous silicon (a-Si)-based detectors, utilizing electrical characterization, Raman spectroscopy, photoemission, and inverse photoemission techniques. The unique properties of a-Si have sparked interest in its application for radiation detection in both physics and medicine. Although amorphous silicon (a-Si) is inherently a highly defective material, hydrogenation significantly reduces defect density, enabling its use in radiation detector devices. Spectroscopic measurements provide insights into the intricate relationship between the structure and electronic properties of a-Si, enhancing our understanding of how specific configurations, such as the choice of substrate, can markedly influence detector performance. In this study, we compare the performance of a-Si detectors deposited on two different substrates: crystalline silicon (c-Si) and flexible Kapton. Our findings suggest that detectors deposited on Kapton exhibit reduced sensitivity, despite having comparable noise and leakage current levels to those on crystalline silicon. We hypothesize that this discrepancy may be attributed to the substrate material, differences in film morphology, and/or the alignment of energy levels. Further measurements are planned to substantiate these hypotheses.

Based on considerable interest to enlarge the experimental database of radioresistant cells after their irradiation with helium ions, HTB140, MCF-7 and HTB177 human malignant cells are exposed to helium ion beams having different linear energy transfer (LET). The cells are irradiated along the widened 62 MeV/u helium ion Bragg peak, providing LET of 4.9, 9.8, 23.4 and 36.8 keV/µm. Numerical simulations with the Geant4 toolkit are used for the experimental design. Cell survival is evaluated and compared with reference γ-rays. DNA double strand breaks are assessed via γ-H2AX foci. With the increase of LET, surviving fractions at 2 Gy decrease, while RBE (2 Gy, γ) gradually increase. For HTB140 cells, above the dose of 4 Gy, a slight saturation of survival is observed while the increase of RBE (2 Gy, γ) remains unaffected. With the increase of LET the increase of γ-H2AX foci is revealed at 0.5 h after irradiation. There is no significant difference in the number of foci between the cell lines for the same LET. From 0.5 to 24 h, the number of foci drops reaching its residual level. For each time point, there are small differences in DNA DSB among the three cell lines. Analyses of data acquired for the three cell lines irradiated by helium ions, having different LET, reveal high elimination capacity and creation of a large number of DNA DSB with respect to γ-rays, and are between those reported for protons and carbon ions.

Proton beam therapy is considered a step forward with respect to electromagnetic radiation, thanks to the reduction in the dose delivered. Among unwanted effects to healthy tissue, cardiovascular complications are a known long-term radiotherapy complication. The transcriptional response of cardiac tissue from xenografted BALB/c nude mice obtained at 3 and 10 days after proton irradiation covering both the tumor region and the underlying healthy tissue was analyzed as a function of dose and time. Three doses were used: 2 Gy, 6 Gy, and 9 Gy. The intermediate dose had caused the greatest impact at 3 days after irradiation: at 2 Gy, 219 genes were differently expressed, many of them represented by zinc finger proteins; at 6 Gy, there were 1109, with a predominance of genes involved in energy metabolism and responses to stimuli; and at 9 Gy, there were 105, mainly represented by zinc finger proteins and molecules involved in the regulation of cardiac function. After 10 days, no significant effects were detected, suggesting that cellular repair mechanisms had defused the potential alterations in gene expression. The nonlinear dose–response curve indicates a need to update the models built on photons to improve accuracy in health risk prediction. Our data also suggest a possible role for zinc finger protein genes as markers of proton therapy efficacy.