Localization of anatomical changes in patients during proton therapy with in-beam PET monitoring: a voxel-based morphometry approach exploiting Monte Carlo simulations

Purpose: In-beam positron emission tomography (PET) is one of the modalities that can be used for in vivo noninvasive treatment monitoring in proton therapy. Although PET monitoring has been frequently applied for this purpose, there is still no straightforward method to translate the information obtained from the PET images into easy-to-interpret information for clinical personnel. The purpose of this work is to propose a statistical method for analyzing in-beam PET monitoring images that can be used to locate, quantify, and visualize regions with possible morphological changes occurring over the course of treatment. Methods: We selected a patient treated for squamous cell carcinoma (SCC) with proton therapy, to perform multiple Monte Carlo (MC) simulations of the expected PET signal at the start of treatment, and to study how the PET signal may change along the treatment course due to morphological changes. We performed voxel-wise two-tailed statistical tests of the simulated PET images, resembling the voxel-based morphometry (VBM) method commonly used in neuroimaging data analysis, to locate regions with significant morphological changes and to quantify the change. Results: The VBM resembling method has been successfully applied to the simulated in-beam PET images, despite the fact that such images suffer from image artifacts and limited statistics. Three dimensional probability maps were obtained, that allowed to identify interfractional morphological changes and to visualize them superimposed on the computed tomography (CT) scan. In particular, the characteristic color patterns resulting from the two-tailed statistical tests lend themselves to trigger alarms in case of morphological changes along the course of treatment. Conclusions: The statistical method presented in this work is a promising method to apply to PET monitoring data to reveal interfractional morphological changes in patients, occurring over the course of treatment. Based on simulated in-beam PET treatment monitoring images, we showed that with our method it was possible to correctly identify the regions that changed. Moreover we could quantify the changes, and visualize them superimposed on the CT scan. The proposed method can possibly help clinical personnel in the replanning procedure in adaptive proton therapy treatments

In-vivo range verification analysis with in-beam PET data for patients treated with proton therapy at CNAO

Morphological changes that may arise through a treatment course are probably one of the most significant sources of range uncertainty in proton therapy. Non-invasive in-vivo treatment monitoring is useful to increase treatment quality. The INSIDE in-beam Positron Emission Tomography (PET) scanner performs in-vivo range monitoring in proton and carbon therapy treatments at the National Center of Oncological Hadrontherapy (CNAO). It is currently in a clinical trial (ID: NCT03662373) and has acquired in-beam PET data during the treatment of various patients. In this work we analyze the in-beam PET (IB-PET) data of eight patients treated with proton therapy at CNAO. The goal of the analysis is twofold. First, we assess the level of experimental fluctuations in inter-fractional range differences (sensitivity) of the INSIDE PET system by studying patients without morphological changes. Second, we use the obtained results to see whether we can observe anomalously large range variations in patients where morphological changes have occurred. The sensitivity of the INSIDE IB-PET scanner was quantified as the standard deviation of the range difference distributions observed for six patients that did not show morphological changes. Inter-fractional range variations with respect to a reference distribution were estimated using the Most-Likely-Shift (MLS) method. To establish the efficacy of this method, we made a comparison with the Beam's Eye View (BEV) method. For patients showing no morphological changes in the control CT the average range variation standard deviation was found to be 2.5 mm with the MLS method and 2.3 mm with the BEV method. On the other hand, for patients where some small anatomical changes occurred, we found larger standard deviation values. In these patients we evaluated where anomalous range differences were found and compared them with the CT. We found that the identified regions were mostly in agreement with the morphological changes seen in the CT scan

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

Synthetic CT imaging for PET monitoring in proton therapy: a simulation study

: 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

The foot (Fragmentation Of Target) experiment

Particle therapy uses proton or12C 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. In12C 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 these16O,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 Î\u94E 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

The Foot (Fragmentation Of Target) Experiment

Particle therapy uses proton or12C 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. In12C 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 these16O,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 Î\u94E 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

The FOOT (Fragmentation Of Target) Experiment

International audienceParticle therapy uses protons or 12C beams for the treatment of deep-seated solid tumors. Due to the features of the energy deposition of charged particles in matter, a limited 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. This has to be carefully taken into account since different ions have different effectiveness in producing a biological damage. In 12C treatments the main concern are long range forward emitted secondary ions produced in projectile fragmentation that release dose in the healthy tissue after the tumor. Instead, in a 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 MeV proton beam will be studied by means of the inverse kinematic approach. 16O,12C therapeutic beams, at the quoted kinetic energy per nucleon, collide on graphite and hydrocarbons target. The cross section on Hydrogen can be then extracted by subtraction. This configuration explores also the projectile fragmentation of these 16O,12C beams, or other ions of therapeutic interest, such as 4He for instance. The detector includes a magnetic spectrometer based on silicon pixel and strip detectors, a scintillating crystal calorimeter able to stop the heavier produced fragments, and a ∆E detector, with TOF capability, to achieve the needed energy resolution and particle identification. In addition to the electronic apparatus, an alternative setup based on the concept of the “Emulsion Cloud Chamber”, coupled with the interaction region of the electronic FOOT setup, will provide the measurement of lighter charged fragments: protons, deuterons, tritons and Helium nuclei. The FOOT data taking is foreseen in the available experimental rooms existing in the presently operational charged particle therapy facilities in Europe, and possibly at GSI. An initial phase with the emulsion setup will start in early 2018, while the complete electronic detector will take data starting in 2019. In this work a general description of the FOOT experiment and of its expected performances is presented

The FOOT FragmentatiOn Of Target Experiment

International audienceIn proton-therapy clinical practice a constant RBE equal to 1.1 is adopted, regardless of the demonstrated RBE variations, which depends on physical and biological parameters. Among other mechanisms, nuclear interactions might influence the proton-RBE due to secondary heavier particles produced by target fragmentation that can significantly contribute to the total dose: an un-wanted and undetermined increase of normal tissues complications probability may occur. The FOOT experiment is designed to study these processes. Target ($^{16}$O,$^{12}$C) fragmentation induced by 150 − 250 M eV proton beam will be studied via inverse kinematic approach, where $^{16}$O and $^{12}$C therapeutic beams, with the same kinetic energy per nucleon of the proton, collide on graphite and hydrocarbons target to provide the cross section on Hydrogen (to explore also the projectile fragmentation). The detector design, the performances and expected resolution results obtained form Monte Carlo study, based on the FLUKA code will be presented