arXiv subjects

Emanuele Scifoni

Publications and source records attributed to Emanuele Scifoni.

14 recordsLinked to original sources

arXiv2026

Measurement of 80-200 MeV/n $^{16}$O nuclear cross-section on Carbon and Polyethylene targets with the nuclear emulsion detector of the FOOT experiment

Accurate knowledge of nuclear fragmentation cross-sections is essential for optimizing charged particle therapy. In this study, conducted within the framework of the FOOT (FragmentatiOn Of Target) experiment, we present the first measurements with a large angular acceptance of total charge-changing cross-section and the cross-section for the production of fragments (production cross-section) for $^{16}$O ions interacting with Carbon (C) and Polyethylene (C$_2$H$_4$) targets in the kinetic energy range of 80 to 200 MeV/nucleon. Measurements were performed using the Emulsion Cloud Chamber (ECC) technique, which combines high spatial resolution and angular acceptance, up to 45$^\circ$. The results are compared with Monte Carlo model predictions. Moreover, the total charge-changing and fragment production cross-sections for $^{16}$O on Hydrogen in the same energy range are derived.

nucl-ex↗

arXiv2026

Mechanistic driven TCP and NTCP modeling for particle therapy accounting for a broad range of physical irradiation parameters and tissue environmental conditions

In conventional radiotherapy, the probability of controlling tumor growth is quantified using Tumor Control Probability (TCP) models. Instead, the probability of experiencing a side effect after the irradiation of healthy tissues and organs is typically assessed using the concept of Normal Tissue Complication Probability (NTCP), an additional crucial metric for evaluating and comparing treatment plans. This work is dedicated to the development, implementation, and application of a general mechanistic model to describe the effects of particle therapy (PT) on different tissue organizations beyond Poissonian assumptions, extending the Generalized Stochastic Microdosimetric Model (GSM2), i.e., a stochastic radiobiological model that describes the time evolution of DNA lesions in a cell nucleus according to microdosimetric principles, to the study of macroscopic biological systems. Specifically, we extend the biological stage of radiation damage of the GSM2 model to larger spatial and temporal scales, involving cell populations with a specific geometric and functional architecture. The model's single-cell resolution allows it to account for energy deposition and tissue heterogeneity, considering different organ volume effects, cell type distributions, and oxygen gradients for different radiation qualities of the beam, that is, type, energy, and LET of radiation, and various fractionation schemes. We show the interplay between physical and environmental parameters on the induction of side effects on healthy tissues, for different radiation qualities and fractionation schemes, and we highlight the impact of biochemical heterogeneities in the target environment, for tumor response.

physics.med-ph↗

arXiv2026

A combined dose and microdosimetric modeling framework incorporating volume effects correlates with tissue sparing in proton minibeam radiotherapy

Proton minibeam (pMB) radiotherapy, delivers highly heterogeneous dose distributions alternating high-dose peaks and low-dose valleys. This aims to widen the therapeutic window by improving normal tissue sparing while maintaining the same or even better tumour control. The performance of pMB strongly depends on the collimator design and physical parameters. To better understand the physical and radiobiological drivers of this enhanced therapeutic window, we perform a detailed microdosimetric characterization of proton minibeams and assess their impact. We characterize radiation quality with microdosimetry through Monte Carlo simulations. Then we extend the Generalized Stochastic Microdosimetric Model to predict the normal tissue complication probability (NTCP) at different depths in water, 1cm, 2cm, and 4cm, for 100MeV proton minibeams realized with varying configurations of collimator. Results are compared with conventional homogeneous field (HF) irradiation after dose normalization to the tumor. The developed model is applied by considering tissues as divided into several functional subunits, connected by a seriality parameter. Microdosimetric characterization of proton minibeam irradiation shows differences between peak and valley regions in shaping lineal energy spectra, especially at low depth, while radiation quality uniforms progressively getting closer to the tumor. NTCP calculations results suggest an increased sparing effect for pMB over conventional HF. A strong dependence is found on the peak-to-valley dose ratio (PVDR), and on the seriality parameter. Predictions indicate substantial sparing from pMB, especially for PVDR > 15, including relatively serial organs with seriality around 0.7. This integrated dose-microdosimetric-biological framework elucidates how spatial fractionation, radiation quality, and organ architecture collectively shape tissue sparing in pMB.

physics.med-ph↗

arXiv2025

The Biologically Effective Particle Number Ratio (BPNR): a new framework to quantify the therapeutic window in SFRT and other modalities

Spatially Fractionated Radiation Therapy (SFRT) produces highly heterogeneous dose distributions, for which conventional metrics such as peak, valley, or average dose can yield ambiguous or inconsistent estimates of therapeutic window changes. These dose descriptors are not uniquely linked to biological outcome, complicating comparisons between modalities. We introduce the Biologically Effective Particle Number Ratio (BPNR), a model-independent and outcome-based framework that quantifies therapeutic window changes using directly measurable delivery quantities rather than spatial dose metrics. BPNR is defined as the ratio of total particle numbers (proportional to monitor units, MU) required to reach specified levels of tumor control probability (TCP) and normal tissue complication probability (NTCP). The relative BPNR (RBPNR) compares therapeutic windows across modalities and avoids ambiguities of spatial dose averaging by relying solely on biological endpoints. As an illustration, we apply the framework to preclinical proton minibeam radiotherapy (pMBRT) versus conventional proton therapy. The absence of normal tissue complications at the highest tested MU in the pMBRT arm yields an RBPNR > 1.4, indicating a widened therapeutic window. The BPNR/RBPNR methodology provides a concise, experimentally grounded, and modality-agnostic way to quantify therapeutic window changes, with potential applications across SFRT, FLASH, high-LET radiation, and combination therapies.

physics.med-ph↗

arXiv2024

A multiscale radiation biophysical stochastic model describing the cell survival response at ultra-high dose rate

Ultra-high dose-rate (UHDR) radiotherapy, characterized by an extremely high radiation delivery rate, represents one of the most recent and promising frontier in radiotherapy. UHDR radiotherapy, addressed in the field as FLASH radiotherapy, is a disruptive treatment modality with several benefits, including significantly shorter treatment times, unchanged effectiveness in treating tumors, and clear reductions in side effects on normal tissues. While the benefits of UHDR irradiation have been well highlighted experimentally, the biological mechanism underlying the FLASH effect is still unclear and highly debated. Nonetheless, to effectively use UHDR radiotherapy in clinics, understanding the driving biological mechanism is paramount. Since the concurrent involvement of multiple scales of radiation damage has been suggested, we developed the MultiScale Generalized Stochastic Microdosimetric Model (MS-GSM2), a multi-stage extension of the GSM2, which is a probabilistic model describing the time evolution of the DNA damage in an irradiated cell nucleus. The MS-GSM2 can investigate several chemical species combined effects, DNA damage formation, and time evolution. We demonstrate that the MS-GSM2 can predict various in-vitro UHDR experimental results across various oxygenation levels, radiation types, and energies. The MS-GSM2 can accurately describe the empirical trend of dose and dose rate-dependent cell sensitivity over a wide range, consistently describing multiple aspects of the FLASH effect and reproducing the main evidence from the in-vitro experimental data. Our model also proposes a consistent explanation for the differential outcomes observed in normal tissues and tumors, in-vivo and in-vitro.

physics.bio-ph↗

arXiv2023

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.

physics.med-ph↗

arXiv2023

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.

physics.med-ph↗

arXiv2021

May oxygen depletion explain the FLASH effect? A chemical track structure analysis

Background and purpose: Recent observations in animal models show that ultra-high dose rate ("FLASH") radiation treatment significantly reduces normal tissue toxicity maintaining an equivalent tumor control. The dependence of this "FLASH" effect on target oxygenation has led to the assumption that oxygen "depletion" could be its major driving force. Materials and Methods: In a bottom-up approach starting from the chemical track evolution of 1 MeV electrons in oxygenated water simulated with the TRAX-CHEM Monte Carlo code, we determine the oxygen consumption and radiolytic reactive oxygen species production following a short radiation pulse. Based on these values, the effective dose weighted by oxygen enhancement ratio (OER) or the in vitro cell survival under dynamic oxygen pressure is calculated and compared to that of conventional exposures, at constant OER. Results: We find an excellent agreement of our Monte Carlo predictions with the experimental value for radiolytic oxygen removal from oxygenated water. However, the application of the present model to published radiobiological experiment conditions shows that oxygen depletion can only have a negligible impact on radiosensitivity through oxygen enhancement, especially at typical experimental oxygenations where a FLASH effect has been observed. Conclusion: We show that the magnitude and dependence of the "oxygen depletion" hypothesis are not consistent with the observed biological effects of FLASH irradiation. While oxygenation plays an undoubted role in mediating the FLASH effect, we conclude that state-of-the-art radiation chemistry models do not support oxygen depletion and radiation-induced transient hypoxia as the main mechanism.

physics.bio-ph↗

arXiv2020

The FragmentatiOn Of Target Experiment (FOOT) and its DAQ system

The FragmentatiOn Of Target (FOOT) experiment aims to provide precise nuclear cross-section measurements for two different fields: hadrontherapy and radio-protection in space. The main reason is the important role the nuclear fragmentation process plays in both fields, where the health risks caused by radiation are very similar and mainly attributable to the fragmentation process. The FOOT experiment has been developed in such a way that the experimental setup is easily movable and fits the space limitations of the experimental and treatment rooms available in hadrontherapy treatment centers, where most of the data takings are carried out. The Trigger and Data Acquisition system needs to follow the same criteria and it should work in different laboratories and in different conditions. It has been designed to acquire the largest sample size with high accuracy in a controlled and online-monitored environment. The data collected are processed in real-time for quality assessment and are available to the DAQ crew and detector experts during data taking.

physics.ins-det↗

arXiv2019

Investigations on physical and biological range uncertainties in Krakow proton beam therapy centre

Physical and biological range uncertainties limit the clinical potential of Proton Beam Therapy (PBT). In this proceedings, we report on two research projects, which we are conducting in parallel and which both tackle the problem of range uncertainties. One aims at developing software tools and the other at developing detector instrumentation. Regarding the first, we report on our development and pre-clinical application of a GPU-accelerated Monte Carlo (MC) simulation toolkit Fred. Concerning the letter, we report on our investigations of plastic scintillator based PET detectors for particle therapy delivery monitoring. We study the feasibility of Jagiellonian-PET detector technology for proton beam therapy range monitoring by means of MC simulations of the $β^+$ activity induced in a phantom by proton beams and present preliminary results of PET image reconstruction. Using a GPU-accelerated Monte Carlo simulation toolkit Fred and plastic scintillator based PET detectors we aim to improve patient treatment quality with protons.

physics.med-ph↗

arXiv2009

Spectra of secondary electrons generated in water by energetic ions

The energy distributions of secondary electrons produced by energetic carbon ions (in the energy range used, e.g., in hadron therapy), incident on liquid water, are discussed. For low-energy ions, a new parameterization of the singly-differential ionization cross sections is introduced, based on tuning the position of the Bragg peak. The resulting parameterization allows a fast calculation of the energy spectra of secondary electrons at different depths along the ion's trajectory, especially near the Bragg peak. At the same time, this parameterization provides penetration depths for a broad range of initial-ion energies within the therapeutically-accepted error. For high-energy ions, the energy distribution is obtained with a use of the dielectric response function approach. Different models are compared and discussed.

physics.bio-ph↗

arXiv2009

On the robustness of the ammonia thermometer

Ammonia inversion lines are often used as probes of the physical conditions in the dense ISM. The excitation temperature between the first two para metastable (rotational) levels is an excellent probe of the gas kinetic temperature. However, the calibration of this ammonia thermometer depends on the accuracy of the collisional rates with H2. Here we present new collisional rates for ortho-NH3 and para-NH3 colliding with para-H2 (J=0) and we investigate the effects of these new rates on the excitation of ammonia. Scattering calculations employ a new, high accuracy, potential energy surface computed at the coupled-cluster CCSD(T) level with a basis set extrapolation procedure. Rates are obtained for all transitions involving ammonia levels with J <= 3 and for kinetic temperatures in the range 5-100 K. We find that the calibration curve of the ammonia thermometer -- which relates the observed excitation temperature between the first two para metastable levels to the gas kinetic temperature -- does not change significantly when these new rates are used. Thus, the calibration of ammonia thermometer appears to be robust. Effects of the new rates on the excitation temperature of inversion and rotation-inversion transitions are also found to be small.

astro-ph.GA↗

arXiv2008

Physics of ion beam cancer therapy: a multi-scale approach

We propose a multi-scale approach to understand the physics related to ion-beam cancer therapy. It allows the calculation of the probability of DNA damage as a result of irradiation of tissues with energetic ions, up to 430 MeV/u. This approach covers different scales, starting from the large scale, defined by the ion stopping, followed by a smaller scale, defined by secondary electrons and radicals, and ending with the shortest scale, defined by interactions of secondaries with the DNA. We present calculations of the probabilities of single and double strand breaks of DNA, suggest a way to further expand such calculations, and also make some estimates for glial cells exposed to radiation.

physics.bio-ph↗

arXiv2008

Ion-beam therapy: from electron production in tissue like media to DNA damage estimations

Radiation damage induced by ion beams is traditionally treated at different levels of theoretical approaches, for the different scales and mechanisms involved.We present here details of a combined approach that, from a method at a nanoscopic scale, attempts to merge with higher scales existing results, by tuning the analytical method employed when extended to larger scale and so yielding a consistent picture of the entire process. Results will show the possibility to get a good agreement with macroscale methods and, on the other hand, to produce a reliable electron energy spectra to be used for DNA damage estimations.

physics.bio-ph↗