An Artificial Intelligence-based model for cell killing prediction: development, validation and explainability analysis of the ANAKIN model

The present work develops ANAKIN: an Artificial iNtelligence bAsed model for (radiation induced) cell KIlliNg prediction. ANAKIN is trained and tested over 513 cell survival experiments with different types of radiation contained in the publicly available PIDE database. We show how ANAKIN accurately predicts several relevant biological endpoints over a wide broad range on ions beams and for a high number of cell--lines. We compare the prediction of ANAKIN to the only two radiobiological model for RBE prediction used in clinics, that is the Microdosimetric Kinetic Model (MKM) and the Local Effect Model (LEM version III), showing how ANAKIN has higher accuracy over the all considered biological endpoints. At last, via modern techniques of Explainable Artificial Intelligence (XAI), we show how ANAKIN predictions can be understood and explained, highlighting how ANAKIN is in fact able to reproduce relevant well-known biological patterns, such as the overkilling effect

Integrating microdosimetric in vitro RBE models for particle therapy into TOPAS MC using the MicrOdosimetry-based modeling for RBE Assessment (MONAS) tool

We present MONAS (MicrOdosimetry-based modelliNg for relative biological effectiveness (RBE) ASsessment) toolkit. MONAS is a TOPAS Monte Carlo extension, that combines simulations of microdosimetric distributions with radiobiological microdosimetry-based models for predicting cell survival curves and dose-dependent RBE. MONAS expands TOPAS microdosimetric extension, by including novel specific energy scorers. These spectra are used as physical input to three different formulations of the Microdosimetric Kinetic Model (MKM), and to the Generalized Stochastic Microdosimetric Model (GSM2), to predict dose-dependent cell survival fraction and RBE. MONAS predictions are then validated against experimental microdosimetric spectra and in vitro survival fraction data. We present two different applications of the code: i) the depth-RBE curve calculation from a passively scattered proton SOBP, and ii) the calculation of the 3D RBE distribution on a real head and neck patient geometry treated with protons. MONAS can estimate dose dependent RBE and cell survival curves from experimentally validated microdosimetric spectra with four clinically relevant radiobiological models. From the radiobiological characterization of a proton SOBP field, we observe the well-known trend of increasing RBE values at the distal edge of the radiation field. The 3D RBE map calculated confirmed the trend observed in the analysis of the SOBP, with the highest RBE values found in the distal edge of the target. MONAS extension offers a comprehensive microdosimetry-based framework for assessing the biological effects of particle radiation in both research and clinical environments, contributing to bridging the gap between a microdosimetric description of the radiation field and its application in proton therapy treatment with variable RBE

Measurement of charged particle yields from therapeutic beams in view of the design of an innovative hadrontherapy dose monitor

Particle Therapy (PT) is an emerging technique, which makes use of charged particles to efficiently cure different kinds of solid tumors. The high precision in the hadrons dose deposition requires an accurate monitoring to prevent the risk of under-dosage of the cancer region or of over-dosage of healthy tissues. Monitoring techniques are currently being developed and are based on the detection of particles produced by the beam interaction into the target, in particular: charged particles, result of target and/or projectile fragmentation, prompt photons coming from nucleus de-excitation and back-to-back γ s, produced in the positron annihilation from β + emitters created in the beam interaction with the target. It has been showed that the hadron beam dose release peak can be spatially correlated with the emission pattern of these secondary particles. Here we report about secondary particles production (charged fragments and prompt γ s) performed at different beam and energies that have a particular relevance for PT applications: 12C beam of 80 MeV/u at LNS, 12C beam 220 MeV/u at GSI, and 12C, 4He, 16O beams with energy in the 50–300 MeV/u range at HIT. Finally, a project for a multimodal dose-monitor device exploiting the prompt photons and charged particles emission will be presented

Use of remdesivir in children with covid-19 infection: A quick narrative review

SARS-CoV-2 infection has a severe course in a small percentage of children. Remdesivir has shown promising results in reducing hospitalisation time in adults, but data on mortality rate are conflicting and few studies are available on its use use in antivirals in children. We performed a quick narrative review of the available literature data regarding the usage of remdesivir in children and neonates. In children, remdesivir showed good safety profile, however bradicardia events have been reported in children. Remdesivir is cur-rently recommended by several guidelines in some subgroups of children with severe COVID-19, and should also be considered in critically ill patients, always in the context of the overall clinical picture and drug avail-ability. (www.actabiomedica.it)

A compact Time-Of-Flight detector for space applications: The LIDAL system

Abstract LIDAL (Light Ion Detector for ALTEA system) is a compact detector designed to upgrade ALTEA (Anomalous Long Term Effects on Astronauts) silicon detector apparatus, in order to study in detail the low-Z part of ions spectrum inside the International Space Station (ISS) and to enhance the Particle Identification (PID) capability of the system. The new detector is designed to trigger ALTEA and to perform Time-Of-Flight measurements. It is based on plastic scintillators for fast timing applications read by Photo-Multiplier-Tubes (PMTs). A custom Front End Electronics (FEE) has been designed to reach time resolutions less than 100 ps ( σ ) for protons. A LIDAL prototype has been developed at the University of Rome Tor Vergata to test the timing performance of the scintillators, the PMTs and of the custom FEE using the proton beam line at the TIFPA (Trento Institute for Fundamentals Physics Applications) center in Trento, Italy. The results of these tests are reported and discussed. They have also been used for a preliminary evaluation of the Particle Identification (PID) capability of the final LIDAL-ALTEA detector system in response to the ions spectra expected on-board the ISS

Proton Interaction Vertex Imaging With Silicon-Pixel CMOS Telescope For Carbon Therapy Quality control

International audienceMonitoring of the dose deposition during carbon ion therapy is a crucial issue for the quality control of such treatments. Recent studies have demonstrated that an ion-range control with millimeter resolution is feasible on a pencil-beam basis in homogeneous targets with prompt gamma detection for proton beams [1] and with Proton Interaction Vertex Imaging (PIVI) for carbon beams [2]. The present communication aims at describing our experimental and Monte Carlo simulation results. [1] J. Smeets et al., Phys. Med. Biol. 57 (2012) 3371-3405 [2] P. Henriquet et al., Phys. Med. Biol. 57 (2012) 4655-466

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

Real-Time Online Monitoring of the Ion Range by Means of Prompt Secondary Radiations

International audiencePrompt secondary radiations such as gamma rays and protons can be used for ion-range monitoring during ion therapy either on an energy-slice basis or on a pencil-beam basis. We present a review of the ongoing activities in terms of detector developments, imaging, experimental and theoretical physics issues concerning the correlation between the physical dose and hadronic processe