Characterisation of the secondary-neutron production in particle therapy treatments with the MONDO tracking detector

Particle Therapy (PT) is a non-invasive technique that exploits charged light ions for the irradiation of tumours that cannot be effectively treated with surgery or conventional radiotherapy. While the largest dose fraction is released to the tumour volume by the primary beam, a non-negligible amount of additional dose is due to the beam fragmentation that occurs along the path towards the target volume. In particular, the produced neutrons are particularly dangerous as they can release their energy far away from the treated area, increasing the risk of developing a radiogenic secondary malignant neoplasm after undergoing a treatment. A precise measurement of the neutron flux, energy spectrum and angular distributions is eagerly needed in order to improve the treatment planning system software, so as to predict the normal tissue toxicity in the target region and the risk of late complications in the whole body. The MONDO (MOnitor for Neutron Dose in hadrOntherapy) project is dedicated to the characterisation of the secondary ultra-fast neutrons ([20-400] MeV energy range) produced in PT. The neutron tracking system exploits the reconstruction of the recoil protons produced in two consecutive (n, p) elastic scattering interactions to measure simultaneously the neutron incoming direction and energy. The tracker active media is a matrix of thin squared scintillating fibers arranged in orthogonally oriented layers that are read out by a sensor (SBAM) based on SPAD (Single-Photon Avalanche Diode) detectors developed in collaboration with the Fondazione Bruno Kessler (FBK)

Development of an adverse outcome pathway for cranio-facial malformations: A contribution from in silico simulations and in vitro data

Mixtures of substances sharing the same molecular initiating event (MIE) are supposed to induce additive effects. The proposed MIE for azole fungicides is CYP26 inhibition with retinoic acid (RA) local increase, triggering key events leading to craniofacial defects. Valproic acid (VPA) is supposed to imbalance RA-regulated gene expression trough histone deacetylases (HDACs) inhibition. The aim was to evaluate effects of molecules sharing the same MIE (azoles) and of such having (hypothetically) different MIEs but which are eventually involved in the same adverse outcome pathway (AOP). An in silico approach (molecular docking) investigated the suggested MIEs. Teratogenicity was evaluated in vitro (WEC). Abnormalities were modelled by PROAST software. The common target was the branchial apparatus. In silico results confirmed azole-related CYP26 inhibition and a weak general VPA inhibition on the tested HDACs. Unexpectedly, VPA showed also a weak, but not marginal, capability to enter the CYP 26A1 and CYP 26C1 catalytic sites, suggesting a possible role of VPA in decreasing RA catabolism, acting as an additional MIE. Our findings suggest a new more complex picture. Consequently two different AOPs, leading to the same AO, can be described. VPA MIEs (HDAC and CYP26 inhibition) impinge on the two converging AOPs

In-room test results at CNAO of an innovative PT treatments online monitor (Dose Profiler)

The use of C, He and O ions as projectiles in Particle Therapy (PT) treatments is getting more and more widespread as a consequence of their enhanced relative biological effectiveness and oxygen enhancement ratio, when compared to the protons one. The advantages related to the incoming radiation improved efficacy are requiring an accurate online monitor of the dose release spatial distribution. Such monitor is necessary to prevent unwanted damage to the tissues surrounding the tumour that can arise, for example, due to morphological changes occurred in the patient during the treatment with respect to the initial CT scan. PT treatments with ions can be monitored by detecting the secondary radiation produced by the primary beam interactions with the patient body along the path towards the target volume. Charged fragments produced in the nuclear process of projectile fragmentation can be emitted at large angles with respect to the incoming beam direction and can be detected with high efficiency in a nearly background-free environment. The Dose Profiler (DP) detector, developed within the INSIDE project, is a scintillating fibre tracker that allows an online reconstruction and backtracking of such secondary charged fragments. The construction and preliminary in-room tests performed on the DP, carried out using the 12C ions beam of the CNAO treatment centre using an anthropomorphic phantom as a target, will be reviewed in this contribution. The impact of the secondary fragments interactions with the patient body will be discussed in view of a clinical application. Furthermore, the results implications for a pre-clinical trial on CNAO patients, foreseen in 2019, will be discussed

The Dynamics of Poor Systems of Galaxies

We assemble and observe a sample of poor galaxy systems that is suitable for testing N-body simulations of hierarchical clustering (Navarro, Frenk, & White 1997; NFW) and other dynamical halo models (e.g., Hernquist 1990). We (1) determine the parameters of the density profile rho(r) and the velocity dispersion profile sigma(R), (2) separate emission-line galaxies from absorption-line galaxies, examining the model parameters and as a function of spectroscopic type, and (3) for the best-behaved subsample, constrain the velocity anisotropy parameter, beta, which determines the shapes of the galaxy orbits. The NFW universal profile and the Hernquist (1990) model both provide good descriptions of the spatial data. In most cases an isothermal sphere is ruled out. Systems with declining sigma(R) are well-matched by theoretical profiles in which the star-forming galaxies have predominantly radial orbits (beta > 0); many of these galaxies are probably falling in for the first time. There is significant evidence for spatial segregation of the spectroscopic classes regardless of sigma(R).Comment: 36 pages, 20 figures, and 5 tables. To appear in the Astrophysical Journa

Scintillating fiber devices for particle therapy applications

Particle Therapy (PT) is a radiation therapy technique in which solid tumors are treated with charged ions and exploits the achievable highly localized dose delivery, allowing to spare healthy tissues and organs at risk. The development of a range monitoring technique to be used on-line, during the treatment, capable to reach millimetric precision is considered one of the important steps towards an optimization of the PT efficacy and of the treatment quality. To this aim, charged secondary particles produced in the nuclear interactions between the beam particles and the patient tissues can be exploited. Besides charged secondaries, also neutrons are produced in nuclear interactions. The secondary neutron component might cause an undesired and not negligible dose deposition far away from the tumor region, enhancing the risk of secondary malignant neoplasms that can develop even years after the treatment. An accurate neutron characterization (flux, energy and emission profile) is hence needed for a better evaluation of long-term complications. In this contribution two tracker detectors, both based on scintillating fibers, are presented. The first one, named Dose Profiler (DP), is planned to be used as a beam range monitor in PT treatments with heavy ion beams, exploiting the charged secondary fragments production. The DP is currently under development within the INSIDE (Innovative Solutions for In-beam DosimEtry in hadrontherapy) project. The second one is dedicated to the measurement of the fast and ultrafast neutron component produced in PT treatments, in the framework of the MONDO (MOnitor for Neutron Dose in hadrOntherapy) project. Results of the first calibration tests performed at the Trento Protontherapy center and at CNAO (Italy) are reported, as well as simulation studies

Measurement of secondary particle production induced by particle therapy ion beams impinging on a PMMA target

Particle therapy is a technique that uses accelerated charged ions for cancer treatment and combines a high irradiation precision with a high biological effectiveness in killing tumor cells [1]. Informations about the secondary particles emitted in the interaction of an ion beam with the patient during a treatment can be of great interest in order to monitor the dose deposition. For this purpose an experiment at the HIT (Heidelberg Ion-Beam Therapy Center) beam facility has been performed in order to measure fluxes and emission profiles of secondary particles produced in the interaction of therapeutic beams with a PMMA target. In this contribution some preliminary results about the emission profiles and the energy spectra of the detected secondaries will be presente

Dual functions of Macpiwi1 in transposon silencing and stem cell maintenance in the flatworm Macrostomum lignano

PIWI proteins and piRNA pathways are essential for transposon silencing and some aspects of gene regulation during animal germline development. In contrast to most animal species, some flatworms also express PIWIs and piRNAs in somatic stem cells, where they are required for tissue renewal and regeneration. Here, we have identified and characterized piRNAs and PIWI proteins in the emerging model flatworm Macrostomum lignano. We found that M. lignano encodes at least three PIWI proteins. One of these, Macpiwi1, acts as a key component of the canonical piRNA pathway in the germline and in somatic stem cells. Knockdown of Macpiwi1 dramatically reduces piRNA levels, derepresses transposons, and severely impacts stem cell maintenance. Knockdown of the piRNA biogenesis factor Macvasa caused an even greater reduction in piRNA levels with a corresponding increase in transposons. Yet, in Macvasa knockdown animals, we detected no major impact on stem cell self-renewal. These results may suggest stem cell maintenance functions of PIWI proteins in flatworms that are distinguishable from their impact on transposons and that might function independently of what are considered canonical piRNA populations

Charged particle's flux measurement from PMMA irradiated by 80 MeV/u carbon ion beam

Hadrontherapy is an emerging technique in cancer therapy that uses beams of charged particles. To meet the improved capability of hadrontherapy in matching the dose release with the cancer position, new dose monitoring techniques need to be developed and introduced into clinical use. The measurement of the fluxes of the secondary particles produced by the hadron beam is of fundamental importance in the design of any dose monitoring device and is eagerly needed to tune Monte Carlo simulations. We report the measurements done with charged secondary particles produced from the interaction of a 80 MeV/u fully stripped carbon ion beam at the INFN Laboratori Nazionali del Sud, Catania, with a Poly-methyl methacrylate target. Charged secondary particles, produced at 90$\degree$ with respect to the beam axis, have been tracked with a drift chamber, while their energy and time of flight has been measured by means of a LYSO scintillator. Secondary protons have been identified exploiting the energy and time of flight information, and their emission region has been reconstructed backtracking from the drift chamber to the target. Moreover a position scan of the target indicates that the reconstructed emission region follows the movement of the expected Bragg peak position. Exploting the reconstruction of the emission region, an accuracy on the Bragg peak determination in the submillimeter range has been obtained. The measured differential production rate for protons produced with $E^{\rm Prod}_{\rm kin} >$ 83 MeV and emitted at 90$\degree$ with respect to the beam line is: $dN_{\rm P}/(dN_{\rm C}d\Omega)(E^{\rm Prod}_{\rm kin} > 83 {\rm ~MeV}, \theta=90\degree)= (2.69\pm 0.08_{\rm stat} \pm 0.12_{\rm sys})\times 10^{-4} sr^{-1}$.Comment: 13 pages, 9 figure

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

A New Generation of Hydrogen-Fueled Hybrid Propulsion Systems for the Urban Mobility of the Future

The H2-ICE project aims at developing, through numerical simulation, a new generation of hybrid powertrains featuring a hydrogen-fueled Internal Combustion Engine (ICE) suitable for 12 m urban buses in order to provide a reliable and cost-effective solution for the abatement of both CO2 and criteria pollutant emissions. The full exploitation of the potential of such a traction system requires a substantial enhancement of the state of the art since several issues have to be addressed. In particular, the choice of a more suitable fuel injection system and the control of the combustion process are extremely challenging. Firstly, a high-fidelity 3D-CFD model will be exploited to analyze the in-cylinder H2 fuel injection through supersonic flows. Then, after the optimization of the injection and combustion process, a 1D model of the whole engine system will be built and calibrated, allowing the identification of a “sweet spot” in the ultra-lean combustion region, characterized by extremely low NOx emissions and, at the same time, high combustion efficiencies. Moreover, to further enhance the engine efficiency well above 40%, different Waste Heat Recovery (WHR) systems will be carefully scrutinized, including both Organic Rankine Cycle (ORC)-based recovery units as well as electric turbo-compounding. A Selective Catalytic Reduction (SCR) aftertreatment system will be developed to further reduce NOx emissions to near-zero levels. Finally, a dedicated torque-based control strategy for the ICE coupled with the Energy Management Systems (EMSs) of the hybrid powertrain, both optimized by exploiting Vehicle-To-Everything (V2X) connection, allows targeting H2 consumption of 0.1 kg/km. Technologies developed in the H2-ICE project will enhance the know-how necessary to design and build engines and aftertreatment systems for the efficient exploitation of H2 as a fuel, as well as for their integration into hybrid powertrains