Prompt gamma timing (PGT) is a promising technique forin vivorange verification in particle therapy, exploiting the time-of-flight between primary particles and prompt gamma rays emitted by nuclear interactions. PGT distribution is highly sensitive to beam energy and target density, which, under controlled detector positioning, makes it particularly valuable in real-time monitoring of particle range, detection of morphological changes, and implementation of adaptive treatment strategies to further optimize dose delivery.Objective.In this study, we investigate for the first time the application of the PGT approach in carbon ion therapy.Approach.Measurements were performed using a dedicated high-performance detection system composed of a silicon strip sensor for primary ion timing and a secondary radiation detector consisting of a LaBr3(Ce) scintillator read out by a SiPM matrix. Carbon ion beams with kinetic energies of 166.41, 268.86, and 398.84 MeV u-1irradiated a homogeneous 30.0 cm thick polymethyl methacrylate target at the National Centre of Oncological Hadrontherapy (Pavia, Italy). The secondary radiation detector was positioned in four different off-beam positions to assess the robustness of the PGT technique. Monte Carlo simulations based on the Geant4 toolkit were carried out for all experimental scenarios to evaluate agreement with measurements and assess the predictive capability of the simulation framework.Main results.A quantitative bin-by-bin comparison of experimental and simulated PGT intensities demonstrated strong agreement within the 95% confidence interval, with no incompatible bins at 166.41 MeV u-1, at most 1% at 268.86 MeV u-1, and up to 8% at 398.84 MeV u-1, depending on detector position. Prompt gammas were identified as the dominant contribution to the detected signals, particularly for detector positions upstream with respect to the primary particle beam, minimizing signal contamination from neutrons and charged fragments.Significance.The validated experimental-simulation framework confirms the capability of the proposed PGT system to resolve energy-dependent differences and highlights its potential for detecting clinically relevant changes in the particle beam range, supporting further development toward real-time monitoring in carbon ion therapy.

This paper presents the measurements of the angular differential cross sections for the forward production of He, Li, Be, B, C, and N nuclei in the fragmentation process of a 400 MeV/nucleon O-16 beam interacting with a graphite target. Due to the limited data available in this energy regime, these measurements of nuclear fragmentation cross sections are relevant to improve nuclear interaction models for particle therapy and space radioprotection applications. The data analyzed in this paper were collected during a measurement campaign carried out at the GSI Helmholtz Center for Heavy Ion Research facility in Darmstadt (Germany) by the FOOT Collaboration. The results are compared with similar results found in the literature and with a previous FOOT measurement of the same process, using the same setup, from a previous pilot run performed at GSI. The pilot run data, however, had limited statistics and only allowed for the measurement of elemental fragmentation cross sections integrated in the setup acceptance. This data set, with statistics more than 100 times larger compared to the data collected in the previous run, enabled the measurement of angular differential cross sections, fully exploiting the granularity of the FOOT Delta E-TOF (time-of-flight) system. Furthermore, a better comprehension of the FOOT apparatus allowed to improve the analysis techniques, leading to a reduction in the final systematic uncertainties. The cross section results have been compared with some of the prominent Monte Carlo models of FLUKA and Geant4 dedicated to the energy range of interest for light ion fragmentation physics.

The FOOT (FragmentatiOn Of Target) experiment aims to measure double differential fragmentation cross-sections for applications in Particle Therapy and space radiation protection. A critical component of the apparatus is its magnetic spectrometer, composed of two Halbach-configured dipole magnets (M1 and M2) using NdFeB permanent magnets, designed for high field uniformity and stability. A full 3D magnetic model was developed using the OPERA solver, incorporating detailed BH curves and a refined meshing strategy to ensure precision along the beam axis. The resulting field map, essential for Monte Carlo simulations in FLUKA, was validated through high-resolution magnetic measurements along the longitudinal and radial axes using a Hall probe. The comparison revealed agreement within 1.4% over most of the field region. Radial scans confirmed uniformity within 1% up to 10 mm from the axis, with minor misalignments attributed to mechanical tolerances. These results confirm the accuracy of the magnetic model and its suitability for precise momentum reconstruction in the FOOT spectrometer.

Proton therapy's full potential is limited by uncertainties that prevent optimal dose distribution. Monitoring techniques can reduce these uncertainties and enable adaptive treatment planning. Spatiotemporal Emission Reconstruction from Prompt-Gamma Timing (SER-PGT) is a promising method that provides insights into both particle range and stopping power, whose calculation would normally require knowledge about patient tissue properties that cannot be directly measured. We present the first experimental results using a 226.9 MeV synchrotron-proton beam impinging on a homogeneous phantom at a sub-clinical intensity (2 - 4 x 10^7 pps). SER-PGT uses data from a multi-detector setup: a thin and segmented Low Gain Avalanche Diode for proton detection and Lanthanum Bromide-based crystals for photon detection. The estimated stopping power profile showed an 8

The fragmentation cross sections of carbon ion beams with kinetic energies of 115 - 353 MeV/u impinging on thin targets of graphite (C), polyvinyl-toluene (C_9H_10) and PMMA (C_2O_5H_8) have been measured at 90^o and 60^o at the CNAO particle therapy center (Pavia, Italy). The presented measurements are a complete reanalysis by the FOOT collaboration of already published elemental cross section on composite targets, in order to refine the analysis, improve the systematic uncertainties and show the comparison with the FLUKA Monte Carlo code calculations. In this work, the kinetic energy at production of measured fragments has been completely redefined, together with the efficiencies computation. The new analysis strategy has been successfully validated against the Monte Carlo cross sections. Two detection arms were positioned at two different angles to perform the measurement at 90^o and 60^o. The fragment species have been identified in charge (Z_id = H) and mass (M_id = ^1H, ^2H, ^3H) combining the information of the deposited energy in thin plastic scintillators, of the deposited energy in a thick LYSO crystal and of the fragments Time of Flight (ToF) measurement. The ToF was also used to compute the fragments measured kinetic energy. The cross sections are presented as a function of the fragments kinetic energy at production thanks to an unfolding technique applied to the data.

The FOOT experiment of INFN is devoted to the measurement of the nuclear fragmentation double differential cross sections useful for the improvement of calculation models adopted in hadrontherapy and radioprotection. A detailed Monte Carlo simulation of the FOOT magnetic spectrometer has been implemented in order to optimize the design and to guide data analysis. This task has been accomplished by means of the FLUKA Monte Carlo code. The input files of the FLUKA simulations are created from the software framework of the experiment, in order to have a consistent generation and description of geometry and materials in both simulation and data analysis. In addition, this ensures the possibility of processing both simulated and real data with the same data analysis procedures. Databases containing specific parameters describing the setup employed in each different data taking campaign are used. A customized event-by-event output of the Monte Carlo code has been developed. It can be read out by the general software framework of FOOT, enabling access to the generation history of all particles in the same event. This output structure therefore gives the possibility to perform a detailed analysis and study of all relevant processes, allowing the detailed tracking reconstruction of all individual particles. Examples of results are presented.

Goal: In-beam Positron Emission Tomography (PET) is a technique for in-vivo non-invasive treatment monitoring for proton therapy. To detect anatomical changes in patients with PET, various analysis methods exist, but their clinical interpretation is problematic. The goal of this work is to investigate whether the gamma-index analysis, widely used for dose comparisons, is an appropriate tool for comparing in-beam PET distributions. Focusing on a head-and-neck patient, we investigate whether the gamma-index map and the passing rate are sensitive to progressive anatomical changes. Methods/materials: We simulated a treatment course of a proton therapy patient using FLUKA Monte Carlo simulations. Gradual emptying of the sinonasal cavity was modeled through a series of artificially modified CT scans. The in-beam PET activity distributions from three fields were evaluated, simulating a planar dual head geometry. We applied the 3D-gamma evaluation method to compare the PET images with a reference image without changes. Various tolerance criteria and parameters were tested, and results were compared to the CT-scans. Results: Based on 210 MC simulations we identified appropriate parameters for the gamma-index analysis. Tolerance values of 3 mm/3% and 2 mm/2% were suited for comparison of simulated in-beam PET distributions. The gamma passing rate decreased with increasing volume change for all fields. Conclusion: The gamma-index analysis was found to be a useful tool for comparing simulated in-beam PET images, sensitive to sinonasal cavity emptying. Monitoring the gamma passing rate behavior over the treatment course is useful to detect anatomical changes occurring during the treatment course.

The Prompt Gamma Timing (PGT) method provides the assessment of particle range by measuring the time of flight between the primary particle and PG detection. This non-invasive and real-time approach is a tool to monitor the therapy’s effectiveness and reduce uncertainties in treatment planning. We report the first PGT results obtained with carbon ion beams at the sub-clinical rate at the CNAO (Pavia, IT). The experimental setup relies on a silicon strip sensor to measure the transit time of the primaries and a detector based on a monolithic LaBr3-crystal coupled to a Silicon PhotoMultiplier matrix. Homogeneous and in-homogeneous phantoms have been irradiated with carbon ion beams of energy equal to $398 \mathrm{MeV} / \mathrm{u}$. The obtained results are promising, and further tests are foreseen to address clinical rates and prove the applicability of this approach to clinics.

Objective.Particle therapy treatments are currently limited by uncertainties of the delivered dose. Verification techniques like Prompt-Gamma-Timing-based Stopping Power Estimation (PGT-SPE) may allow for reduction of safety margins in treatment planning.Approach.From Prompt-Gamma-Timing measurements, we reconstruct the spatiotemporal distribution of prompt gamma emissions, which is linked to the average motion of the primary particles. The stopping power is determined by fitting a model of the average particle motion. Here, we compare a previously published implementation of the particle motion model with an alternative formulation and present two formulations to automatically select the hyperparameters of our procedure. The performance was assessed using Monte-Carlo simulations of proton beams (60 MeV-219 MeV) impinging on a homogeneous PMMA phantom.Main results.The range was successfully determined within a standard deviation of 3 mm for proton beam energies from 70 MeV to 219 MeV. Stopping power estimates showed errors below 5% for beam energies above 160 MeV. At lower energies, the estimation performance degraded to unsatisfactory levels due to the short range of the protons. The new motion model improved the estimation performance by up to 5% for beam energies from 100 MeV to 150 MeV with mean errors ranging from 6% to 18%. The automated hyperparameter optimization matched the average error of previously reported manual selections, while significantly reducing the outliers.Significance.The data-driven hyperparameter optimization allowed for a reproducible and fast evaluation of our method. The updated motion model and evaluation at new beam energies bring us closer to applying PGT-SPE in more complex scenarios. Direct comparison of stopping power estimates between treatment planning and measurements during irradiation would offer a more direct verification than other secondary-particle-based techniques.

In-beam PET (Positron Emission Tomography) is one of the most precise techniques for in-vivo range monitoring in hadron therapy. Our objective was to demonstrate the feasibility of a short irradiation run for range verification before a carbon-ion treatment. To do so a PMMA target was irradiated with a 220 MeV/u carbon-ion beam and annihilation coincidences from short-lived positron emitters were acquired after irradiations lasting 0.6 s. The experiments were performed at the synchrotron-based facility CNAO (Italian National Center of Oncological Hadrontherapy) by using the INSIDE in-beam PET detector. The results show that, with 3·107 carbon ions, the reconstructed positron emitting nuclei distribution is in good agreement with the predictions of a detailed FLUKA Monte Carlo study. Moreover, the radio-nuclei production is sufficiently abundant to determine the average ion beam range with a σ of 1 mm with a 6 s measurement of the activity distribution. Since the data were acquired when the beam was off, the proposed rapid calibration method can be applied to hadron beams extracted from accelerators with very different time structures.

Purpose: Carbon ion therapy treatments can be monitored non-invasively with in-beam Positron Emission Tomography (PET). At CNAO the INSIDE in-beam PET scanner has been used in a clinical trial (NCT03662373) to monitor cancer treatments with proton and carbon therapy. In this work we present the analysis results of carbon therapy data, acquired during the first phase of the clinical trial, analyzing data of nine patients treated at CNAO for various malignant tumors in the head-and-neck region. Materials and methods: The patient group contained two patients requiring replanning, and seven patients without replanning, based on established protocols. For each patient the PET images acquired along the course of treatment were compared with a reference, applying two analysis methods: the beam-eye-view (BEV) method and the γ-index analysis. Time trends in several parameters were investigated, as well as the agreement with control CTs, if available. Results: Regarding the BEV-method, the average sigma value σ was 3.7 mm of range difference distributions for patients without changes (sensitivity of the INSIDE detector). The 3D-information obtained from the BEV analysis was partly in agreement with what was observed in the control CT. The data quality and quantity was insufficient for a definite interpretation of the time trends. Conclusion: We analyzed carbon therapy data acquired with the INSIDE in-beam PET detector using two analysis methods. The data allowed to evaluate sensitivity of the INSIDE detector for carbon therapy and to make several recommendations for the future.

An innovative beam monitor for particle therapy applications was developed to count protons and carbon ions in clinical beams and was integrated with a Time-to-Digital Converter (TDC) to add the measurement of particles’ crossing time. The detector exploits strip-segmented planar silicon sensors with an active thickness of a few tens of μm and the front-end electronics is based on a 24-channel ASIC (named ABACUS) for the discrimination of the particles’ signals. The proton counting efficiency shows a dependence on the beam energy because of transversal dimension and pile-up effects, whereas an efficiency between 94 and 98 % with lower energy dependence is found for carbon ions. The time measurements with the TDC allow for the study of the time interval between consecutive particles in one strip, which appears to be compatible with the radio-frequency period of the synchrotron. These results indicate that thin silicon sensors and custom front-end readout with high counting rate capability allow for a full 4D tracking of clinical ion beams, opening the way to future technologies for online monitoring systems.

Introduction: Charged Particle Therapy plays a key role in the treatment of deep-seated tumours, because of the advantageous energy deposition culminating in the Bragg peak. However, knowledge of the dose delivered in the entrance channel is limited by the lack of data on the beam and fragmentation of the target.Methods: The FOOT experiment has been designed to measure the cross sections of the nuclear fragmentation of projectile and target with two different detectors: an electronic setup for the identification of Z ≥ 3 fragments and a nuclear emulsion spectrometer for Z ≤ 3 fragments. In this paper, we analyze the data taken by exposing four nuclear emulsion spectrometers, with C and C2H4 targets, to 200 MeV/n and 400 MeV/n oxygen beams at GSI Helmholtzzentrum für Schwerionenforschung (Darmstadt, Germany), and we report the charge identification of produced fragments based on the controlled fading induced on nuclear emulsion films.Results: The goal of identifying fragments as heavy as lithium has been achieved.Discussion: The results will contribute to a better understanding of the nuclear fragmentation process in charged particle therapy and have implications for refining treatment planning in the presence of deep-seated tumors.

Objective. This study addresses a fundamental limitation of in-beam positron emission tomography (IB-PET) in proton therapy: the lack of direct anatomical representation in the images it produces. We aim to overcome this shortcoming by pioneering the application of deep learning techniques to create synthetic control CT images (sCT) from combining IB-PET and planning CT scan data. Approach. We conducted simulations involving six patients who underwent irradiation with proton beams. Leveraging the architecture of a visual transformer (ViT) neural network, we developed a model to generate sCT images of these patients using the planning CT scans and the inter-fractional simulated PET activity maps during irradiation. To evaluate the model’s performance, a comparison was conducted between the sCT images produced by the ViT model and the authentic control CT images—serving as the benchmark. Main results. The structural similarity index was computed at a mean value across all patients of 0.91, while the mean absolute error measured 22 Hounsfield Units (HU). Root mean squared error and peak signal-to-noise ratio values were 56 HU and 30 dB, respectively. The Dice similarity coefficient exhibited a value of 0.98. These values are comparable to or exceed those found in the literature. More than 70% of the synthetic morphological changes were found to be geometrically compatible with the ones reported in the real control CT scan. Significance. Our study presents an innovative approach to surface the hidden anatomical information of IB-PET in proton therapy. Our ViT-based model successfully generates sCT images from inter-fractional PET data and planning CT scans. Our model’s performance stands on par with existing models relying on input from cone beam CT or magnetic resonance imaging, which contain more anatomical information than activity maps.

Background and purpose: In-beam Positron Emission Tomography (PET) is one of the modalities that can be used for in-vivo non-invasive treatment monitoring in proton therapy. PET distributions obtained during various treatment sessions can be compared in order to identify regions that have anatomical changes. The purpose of this work is to test and compare different analysis methods in the context of inter-fractional PET image comparison for proton treatment verification. Methods: For our study we used the FLUKA Monte Carlo code and artificially generated CT scans to simulate in-beam PET distributions at different stages during proton therapy treatment. We compared the Beam-Eye-View method, the Most-Likely-Shift method, the Voxel-Based-Morphology method and the gamma evaluation method to compare PET images at the start of treatment, and after a few weeks of treatment. The results were compared to the CT scan. Results and conclusions: Three-dimensional methods like VBM and gamma are preferred above two-dimensional methods like MLS and BEV if much statistics is available, since the these methods allow to identify the regions with anomalous activity. The VBM approach has as disadvantage that a larger number of MC simulations is needed. The gamma analysis has the disadvantage that no clinical indication exist on tolerance criteria. In terms of calculation time, the BEV and MLS method are preferred. We recommend to use the four methods together, in order to best identify the location and cause of the activity changes.