Analysis methods for in-beam PET images in proton therapy treatment verification: a comparison based on Monte Carlo simulations

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.Comment: 9 pages, 5 figure

Full-beam performances of a PET detector with synchrotron therapeutic proton beams

Treatment quality assessment is a crucial feature for both present and nextgeneration ion therapy facilities. Several approaches are being explored, based on prompt radiation emission or on PET signals by β+;-decaying isotopes generated by beam interactions with the body. In-beam PET monitoring at synchrotron-based ion therapy facilities has already been performed, either based on inter-spill data only, to avoid the influence of the prompt radiation, or including both in-spill and inter-spill data. However, the PET images either suffer of poor statistics (inter-spill) or are more influenced by the background induced by prompt radiation (in-spill). Both those problems are expected to worsen for accelerators with improved duty cycle where the inter-spill interval is reduced to shorten the treatment time. With the aim of assessing the detector performance and developing techniques for background reduction, a test of an in-beam PET detector prototype was performed at the CNAO synchrotron-based ion therapy facility in full-beam acquisition modality. Data taken with proton beams impinging on PMMA phantoms showed the system acquisition capability and the resulting activity distribution, separately reconstructed for the in-spill and the inter-spill data. The coincidence time resolution for in-spill and inter-spill data shows a good agreement, with a slight deterioration during the spill. The data selection technique allows the identification and rejection of most of the background originated during the beam delivery. The activity range difference between two different proton beam energies (68 and 72 MeV) was measured and found to be in submillimeter agreement with the expected result. However, a slightly longer (2 mm) absolute profile length is obtained for in-spill data when compared to inter-spill data

Similarities and differences between myocarditis following COVID-19 mRNA vaccine and multiple inflammatory syndrome with cardiac involvement in children

despite the multiple benefits of vaccination, cardiac adverse events following COVID-19 immunization (c-AEFI) have been reported. these events as well as the severe cardiac involvement reported in Multisystem inflammatory syndrome in children (MIS-C) appear more frequent in young adult males. herein, we firstly report on the inflammatory profiles of patients experiencing c-AEFI in comparison with age, pubertal age and gender matched MIS-C with cardiac involvement. Proteins related to systemic inflammation were found higher in MIS-C compared to c-AEFI, whereas a higher level in proteins related to myocardial injury was found in c-AEFI. In addition, higher levels of DHEAS, DHEA, and cortisone were found in c-AEFI which persisted at follow-up. No anti-heart muscle and anti-endothelial cell antibodies have been detected. overall current comparative data showed a distinct inflammatory and androgens profile in c-AEFI patients which results to be well restricted on heart and to persist months after the acute event

Inter-fractional monitoring of 12 C ions treatments: results from a clinical trial at the CNAO facility

The high dose conformity and healthy tissue sparing achievable in Particle Therapy when using C ions calls for safety factors in treatment planning, to prevent the tumor under-dosage related to the possible occurrence of inter-fractional morphological changes during a treatment. This limitation could be overcome by a range monitor, still missing in clinical routine, capable of providing on-line feedback. The Dose Profiler (DP) is a detector developed within the INnovative Solution for In-beam Dosimetry in hadronthErapy (INSIDE) collaboration for the monitoring of carbon ion treatments at the CNAO facility (Centro Nazionale di Adroterapia Oncologica) exploiting the detection of charged secondary fragments that escape from the patient. The DP capability to detect inter-fractional changes is demonstrated by comparing the obtained fragment emission maps in different fractions of the treatments enrolled in the first ever clinical trial of such a monitoring system, performed at CNAO. The case of a CNAO patient that underwent a significant morphological change is presented in detail, focusing on the implications that can be drawn for the achievable inter-fractional monitoring DP sensitivity in real clinical conditions. The results have been cross-checked against a simulation study

The foot (Fragmentation Of Target) experiment

Particle therapy uses proton or 12C beams for the treatment of deep-seated solid tumors. Due to the features of energy deposition of charged particles a small amount of dose is released to the healthy tissue in the beam entrance region, while the maximum of the dose is released to the tumor at the end of the beam range, in the Bragg peak region. However nuclear interactions between beam and patient tissues induce fragmentation both of projectile and target and must be carefully taken into account. In 12C treatments the main concern are long range fragments due to projectile fragmentation that release dose in the healthy tissue after the tumor, while in proton treatment the target fragmentation produces low energy, short range fragments along all the beam range. The FOOT experiment (FragmentatiOn Of Target) is designed to study these processes. Target nuclei (16O,12C) fragmentation induced by 150-250 AMeV proton beam will be studied via inverse kinematic approach. 16O,12C therapeutic beams, with the quoted kinetic energy, collide on graphite and hydrocarbons target to provide the cross section on Hydrogen. This configuration explores also the projectile fragmentation of these 16O,12C beams. The detector includes a magnetic spectrometer based on silicon pixel detectors and drift chamber, a scintillating crystal calorimeter with TOF capabilities, able to stop the heavier fragments produced, and a \u394E detector to achieve the needed energy resolution and particle identification. An alternative setup of the experiment will exploit the emulsion chamber capabilities. A specific emulsion chambers will be coupled with the interaction region of the FOOT setup to measure the production in target fragmentation of light charged fragments as protons, deuterons, tritons and Helium nuclei. The FOOT data taking is foreseen at the CNAO experimental room and will start during early 2018 with the emulsion setup, while the complete electronic detector will take data since 2019

FOOT: a new experiment to measure nuclear fragmentation at intermediate energies

Summary: Charged particle therapy exploits proton or 12C beams to treat deep-seated solid tumors. Due to the advantageous characteristics of charged particles energy deposition in matter, the maximum of the dose is released to the tumor at the end of the beam range, in the Bragg peak region. However, the beam nuclear interactions with the patient tissues induces fragmentation both of projectile and target nuclei and needs to be carefully taken into account. In proton treatments, target fragmentation produces low energy, short range fragments along all the beam range, which deposit a non negligible dose in the entry channel. In 12C treatments the main concern is represented by long range fragments due to beam fragmentation that release their dose in the healthy tissues beyond the tumor. The FOOT experiment (FragmentatiOn Of Target) of INFN is designed to study these processes, in order to improve the nuclear fragmentation description in next generation Treatment Planning Systems and the treatment plans quality. Target (16O and 12C nuclei) fragmentation induced by –proton beams at therapeutic energies will be studied via an inverse kinematic approach, where 16O and 12C therapeutic beams impinge on graphite and hydrocarbon targets to provide the nuclear fragmentation cross section on hydrogen. Projectile fragmentation of 16O and 12C beams will be explored as well. The FOOT detector includes a magnetic spectrometer for the fragments momentum measurement, a plastic scintillator for ΔE and time of flight measurements and a crystal calorimeter to measure the fragments kinetic energy. These measurements will be combined in order to make an accurate fragment charge and isotopic identification. Keywords: Hadrontherapy, Nuclear fragmentation cross sections, Tracking detectors, Scintillating detector

Performance of the ToF detectors in the foot experiment

The FOOT (FragmentatiOn Of Target) experiment aims to deter- mine the fragmentation cross-sections of nuclei of interest for particle therapy and radioprotection in space. The apparatus is composed of several detectors that allow fragment identification in terms of charge, mass, energy and direction. The frag- ment time of flight (ToF) along a lever arm of ∼2 m is used for particle ID, requiring a resolution below 100ps to achieve a sufficient resolution in the fragment atomic mass identification. The timing performance of the ToF system evaluated with 12C and 16O beams is reviewed in this contribution

Charge identification of fragments with the emulsion spectrometer of the FOOT experiment

The FOOT (FragmentatiOn Of Target) experiment is an international project designed to carry out the fragmentation cross-sectional measurements relevant for charged particle therapy (CPT), a technique based on the use of charged particle beams for the treatment of deep-seated tumors. The FOOT detector consists of an electronic setup for the identification of Z ≥ 3 fragments and an emulsion spectrometer for Z ≤ 3 fragments. The first data taking was performed in 2019 at the GSI facility (Darmstadt, Germany). In this study, the charge identification of fragments induced by exposing an emulsion detector, embedding a C2 H4 target, to an oxygen ion beam of 200 MeV/n is discussed. The charge identification is based on the controlled fading of nuclear emulsions in order to extend their dynamic range in the ionization response