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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.

Purpose The purpose of this study was to develop a modular dose-delivery system (DDS) for scanned-ion radiotherapy that mitigates against organ motion artifacts by synchronizing the motion of the beam with that of the moving anatomy. Methods We integrated a new motion synchronization system and an existing DDS into two centers. The modular approach to integration utilized an adaptive layer of software and hardware interfaces. The method of synchronization comprised three major tasks, namely, the creation of 3D treatment plans (each representing one phase of respiratory motion and together comprising a 4D plan), monitoring anatomic motion during treatment, and synchronization of the beam to anatomic motion. The synchronization was accomplished in real time by repeatedly selecting and delivering a 3D plan, i.e., the one that most closely corresponded to the current anatomic state, until all plans were delivered. The performance characteristics of the motion mitigation system were tested by delivering 4D treatment plans to a moving phantom and comparing planned and measured dose distributions. Dosimetric performance was considered acceptable when the gamma-index pass rate was >90%, homogeneity-index value was >95%, and conformity-index value was >60%. Selected safety characteristics were tested by introducing errors during treatment and testing DDS response. Results Acceptable dosimetric performance and safety characteristics were observed for all treatment plans. Conclusions We demonstrated, for the first time, that a modular prototype system, synchronizing scanned ion beams with moving targets can deliver conformal, motion-compensated dose distributions. The prototype system was implemented and characterized at GSI and CNAO.

Objective. The purpose of this study was to perform preliminary pre-clinical tests to compare the dosimetric quality of two approaches to treating moving tumors with ion beams: synchronously delivering the beam with the motion of a moving planning target volume (PTV) using the recently developed multi-phase 4D dose delivery (MP4D) approach, and asynchronously delivering the ion beam to a motion-encompassing internal tumor volume (ITV) combined with rescanning. Approach. We created 4D optimized treatment plans with proton and carbon ion beams for two patients who had previously received treatment for non-small cell lung cancer. For each patient, we created several treatment plans, using approaches with and without motion mitigation: MP4D, ITV with rescanning, static deliveries to a stationary PTV, and deliveries to a moving tumor without motion compensation. Two sets of plans were optimized with margins or robust uncertainty scenarios. Each treatment plan was delivered using a recently-developed motion-synchronized dose delivery system (M-DDS); dose distributions in water were compared to measurements using gamma index analysis to confirm the accuracy of the calculations. Reconstructed dose distributions on the patient CT were analyzed to assess the dosimetric quality of the deliveries (conformity, uniformity, tumor coverage, and extent of hotspots). Main results. Gamma index analysis pass rates confirmed the accuracy of dose calculations. Dose coverage was >95% for all static and MP4D treatments. The best conformity and the lowest lung doses were achieved with MP4D deliveries. Robust optimization led to higher lung doses compared to conventional optimization for ITV deliveries, but not for MP4D deliveries. Significance. We compared dosimetric quality for two approaches to treating moving tumors with ion beams. Our findings suggest that the MP4D approach, using an M-DDS, provides conformal motion mitigation, with full target coverage and lower OAR doses.

Charged Particle Therapy (CPT) is a powerful radiotherapy technique for the treatment of deep-seated tumours characterized by a large dose released in the Bragg peak area (corresponding to the tumour region) and a small dose delivered to the surrounding healthy tissues. The precise measurement of the fragments produced in the nuclear interactions of charged particle beams with patient tissues is a crucial task to improve the clinical treatment plans. The FOOT (FragmentatiOn Of Target) experiment is an international project, funded by the Istituto Nazionale di Fisica Nucleare (INFN), aimed to study the dose released by the tissues and particle beams fragmentation. The target (16O, 12C) fragmentation induced by 150-400 MeV/n proton beams will be studied via the inverse kinematic approach, where 16O and 12C therapeutic beams collide on graphite and hydrocarbon target to provide the cross section on Hydrogen. A table-top detector is being developed and it includes a drift chamber as a beam monitor upstream of the target to measure the beam direction, a magnetic spectrometer based on silicon pixel and strip detectors, a scintillating crystal calorimeter able to stop the heavier produced fragments, and a ΔE detector, with TOF capability, for the particle identification. A setup based on the concept of the “Emulsion Cloud Chamber”, coupled with the interaction region of the electronic FOOT setup, will complement the physics program by measuring lighter charged fragments to extend the angular acceptance up to about 70 degrees. In this work, the experimental design and the requirements of the FOOT experiment will be discussed and preliminary results on the emulsion spectrometer tests will be presented.

Carbon-ion beams are increasingly used in the clinical practice for external radiotherapy treatments of deep-seated tumors. At therapeutic energies, carbon ions yield significant secondary products, including neutrons, which may be of concern for the radiation protection of the patient and personnel. We simulated the neutron yield produced by proton and carbon-ion pencil beams impinging on a clinical phantom at three different angles: 15°, 45° and 90°, with respect to the beam axis. We validated the simulated results using the measured response of organic scintillation detectors. We compared the results obtained with FLUKA 2011.2 and MCNPX 2.7.0 based on three different physics models: Bertini, Isabel, and CEM. Over the different ions, energies, and angles, the FLUKA simulation results agree better with the measured data, compared to the MCNPX results. Simulations of carbon ions at low angles exhibit both the highest deviation from measured data and inter-model discrepancy, which is probably due to the different treatment of the pre-equilibrium stage. The reported neutron yield results could help in the comparison of carbon-ion and proton treatments in terms of secondary neutron production for radiation protection applications.

Beam monitoring in particle therapy is a critical task that, because of the high flux and the time structure of the beam, can be challenging for the instrumentation. Recent developments in thin silicon detectors with moderate internal gain, optimized for timing applications (Ultra Fast Silicon Detectors, UFSD), offer a favourable technological option to conventional ionization chambers. Thanks to their fast collection time and good signal-to-noise ratio, properly segmented sensors allow discriminating and counting single protons up to the high fluxes of a therapeutic beam, while the excellent time resolution can be exploited for measuring the proton beam energy using time-of-flight techniques. We report here the results of the first tests performed with UFSD detector pads on a therapeutic beam. It is found that the signal of protons can be easily discriminated from the noise, and that the very good time resolution is confirmed. However, a careful design is necessary to limit large pile-up inefficiencies and early performance degradation due to radiation damage.

In a carbon ion treatment the nuclear fragmentationof both target and beam projectiles impacts on the dose releasedon the tumor and on the surrounding healthy tissues. Carbon ionfragmentation occurring inside the patient body has to be stud-ied in order to take into account this contribution. These dataare also important for the development of the range monitoringtechniques with charged particles. The production of chargedfragments generated by carbon ion beams of 115-353 MeV/ukinetic energy impinging on carbon, oxygen, and hydrogen tar-gets has been measured at the CNAO particle therapy center(Pavia, Italy). The use of thin targets of graphite (C), PMMA(C2O5H8) and polyvinyl-toluene [plastic scintillator (PS), CbHa]allowed to measure fragments production cross sections, exploit-ing a time-of-flight (ToF) technique. PS detectors have been usedto perform the ToF measurements, while LYSO crystals havebeen used for the deposited energy measurement and to performparticle identification. Cross sections have been measured at 90◦and 60◦with respect to the beam direction. The measured pro-ton, deuteron, and triton differential production cross sectionson C, O, and H, obtained exploiting the target subtraction strat-egy, are presented here as a function of the fragment kineticenergy.

This article describes the updated GSI radiotherapy research facility (Cave M) located at the GSI Helmholtz Center for Heavy Ion Research in Darmstadt, Germany. This facility was upgraded by modernizing the beamline that supported a pilot project in carbon ion cancer therapy in Europe from 1997 to 2008. Descriptions are provided of the modernized beamline, related hardware components and treatment delivery system. The performance specifications and general characteristics for each major component are described, along with example pre-clinical test results of selected components. These upgrades to Cave M allow for investigating novel therapy methods. The radiotherapy research facility is located on a beamline of the heavy ion synchrotron (Schwer-Ionen-Synchrotron, or SIS-18) accelerator complex, capable of delivering 0.1 to 2 GeV/u charged particle beams, ranging from protons to uranium. This beamline contains components for fast beam gating, aborting, focusing, scanning, monitoring, and shifting the range of the beam. The beam scanning magnets, position detectors, and beam monitors are described, along with tests of functionality and performance. A dose delivery system (DDS) was adapted from a clinical unit at the National Centre for Oncological Hadrontherapy (CNAO), Pavia, Italy, and consists of modular real-time hardware and software. The DDS was modified to enable research on adaptively-managed patient motion through the use of libraries of 4D-optimized radiation treatment plans, an unsolved problem of importance for treating moving tumors. The system is modular and is designed to support future research studies, such as high dose rate (Flash) radiotherapy and radioactive ion beams. A series of validation tests confirmed the functionality and performance of various key components and systems. For example, an end-to-end test revealed that dosimetric spatial homogeneity of over 95% was achieved for square treatment fields. More generally, all performance characteristics that were tested satisfied anticipated clinical requirements.

The University of Torino (UniTO) and the National Institute for Nuclear Physics (INFN-TO) are investigating the use of Ultra Fast Silicon Detectors (UFSD) for beam monitoring in radiobiological experiments with therapeutic proton beams. The single particle identification approach of solid state detectors aims at increasing the sensitivity and reducing the response time of the conventional monitoring devices, based on gas detectors. Two prototype systems are being developed to count the number of beam particles and to measure the beam energy with time-of-flight (ToF) techniques. The clinically driven precision (< 1%) in the number of particles delivered and the uncertainty < 1 mm in the depth of penetration (range) in radiobiological experiments (up to 108 protons/s fluxes) are the goals to be pursued. The future translation into clinics would allow the implementation of faster and more accurate treatment modalities, nowadays prevented by the limits of state-of-the-art beam monitors. The experimental results performed with clinical proton beams at CNAO (Centro Nazionale di Adroterapia Oncologica, Pavia) and CPT (Centro di Protonterapia, Trento) showed a counting inefficiency 2, and a deviation of few hundreds of keV of measured beam energies with respect to nominal ones. The progresses of the project are reported.

Hadrontherapy is a method for treating cancer with very targeted dose distributions and enhanced radiobiological effects. To fully exploit these advantages, in vivo range monitoring systems are required. These devices measure, preferably during the treatment, the secondary radiation generated by the beam-tissue interactions. However, since correlation of the secondary radiation distribution with the dose is not straightforward, Monte Carlo (MC) simulations are very important for treatment quality assessment. The INSIDE project constructed an in-beam PET scanner to detect signals generated by the positron-emitting isotopes resulting from projectile-target fragmentation. In addition, a FLUKA-based simulation tool was developed to predict the corresponding reference PET images using a detailed scanner model. The INSIDE in-beam PET was used to monitor two consecutive proton treatment sessions on a patient at the Italian Center for Oncological Hadrontherapy (CNAO). The reconstructed PET images were updated every 10 s providing a near real-time quality assessment. By half-way through the treatment, the statistics of the measured PET images were already significant enough to be compared with the simulations with average differences in the activity range less than 2.5 mm along the beam direction. Without taking into account any preferential direction, differences within 1 mm were found. In this paper, the INSIDE MC simulation tool is described and the results of the first in vivo agreement evaluation are reported. These results have justified a clinical trial, in which the MC simulation tool will be used on a daily basis to study the compliance tolerances between the measured and simulated PET images.

Purpose: To describe the dosimetric commissioning and quality assurance (QA) of the actively scanned proton and carbon ion beams at the Italian National Center for Oncological Hadrontherapy. Methods: The laterally integrated depth-dose-distributions (IDDs) were acquired with the PTW Peakfinder, a variable depth water column, equipped with two Bragg peak ionization chambers. fluka Monte Carlo code was used to generate the energy libraries, the IDDs in water, and the fragment spectra for carbon beams. EBT3 films were used for spot size measurements, beam position over the scan field, and homogeneity in 2D-fields. Beam monitor calibration was performed in terms of number of particles per monitor unit using both a Farmer-type and an Advanced Markus ionization chamber. The beam position at the isocenter, beam monitor calibration curve, dose constancy in the center of the spread-out-Bragg-peak, dose homogeneity in 2D-fields, beam energy, spot size, and spot position over the scan field are all checked on a daily basis for both protons and carbon ions and on all beam lines. Results: The simulated IDDs showed an excellent agreement with the measured experimental curves. The measured full width at half maximum (FWHM) of the pencil beam in air at the isocenter was energy-dependent for both particle species: in particular, for protons, the spot size ranged from 0.7 to 2.2 cm. For carbon ions, two sets of spot size are available: FWHM ranged from 0.4 to 0.8 cm (for the smaller spot size) and from 0.8 to 1.1 cm (for the larger one). The spot position was accurate to within ±1 mm over the whole 20 × 20 cm2 scan field; homogeneity in a uniform squared field was within ±5% for both particle types at any energy. QA results exceeding tolerance levels were rarely found. In the reporting period, the machine downtime was around 6%, of which 4.5% was due to planned maintenance shutdowns. Conclusions: After successful dosimetric beam commissioning, quality assurance measurements performed during a 24-month period show very stable beam characteristics, which are therefore suitable for performing safe and accurate patient treatments.

Purpose: This paper describes the system for the dose delivery currently used at the Centro Nazionale di Adroterapia Oncologica (CNAO) for ion beam modulated scanning radiotherapy. Methods: CNAO Foundation, Istituto Nazionale di Fisica Nucleare and University of Torino have designed, built, and commissioned a dose delivery system (DDS) to monitor and guide ion beams accelerated by a dedicated synchrotron and to distribute the dose with a full 3D scanning technique. Protons and carbon ions are provided for a wide range of energies in order to cover a sizable span of treatment depths. The target volume, segmented in several layers orthogonally to the beam direction, is irradiated by thousands of pencil beams which must be steered and held to the prescribed positions until the prescribed number of particles has been delivered. For the CNAO beam lines, these operations are performed by the DDS. The main components of this system are two independent beam monitoring detectors, called BOX1 and BOX2, interfaced with two control systems performing the tasks of real-time fast and slow control, and connected to the scanning magnets and the beam chopper. As a reaction to any condition leading to a potential hazard, a DDS interlock signal is sent tomore » the patient interlock system which immediately stops the irradiation. The essential tasks and operations performed by the DDS are described following the data flow from the treatment planning system through the end of the treatment delivery. Results: The ability of the DDS to guarantee a safe and accurate treatment was validated during the commissioning phase by means of checks of the charge collection efficiency, gain uniformity of the chambers, and 2D dose distribution homogeneity and stability. A high level of reliability and robustness has been proven by three years of system activity needing rarely more than regular maintenance and working with 100% uptime. Four identical and independent DDS devices have been tested showing comparable performances and are presently in use on the CNAO beam lines for clinical activity. Conclusions: The dose delivery system described in this paper is one among the few worldwide existing systems to operate ion beam for modulated scanning radiotherapy. At the time of writing, it has been used to treat more than 350 patients and it has proven to guide and control the therapeutic pencil beams reaching performances well above clinical requirements. In particular, in terms of dose accuracy and stability, daily quality assurance measurements have shown dose deviations always lower than the acceptance threshold of 5% and 2.5%, respectively.« less

Purpose: The first Italian hospital‐based facility for hadrontherapy is the Centro Nazionale di Adroterapia Oncologica (CNAO) which started the clinical activity on September 2011 with protonsbeams. The control of the treatment is performed online by the Dose Delivery (DD) system which guides the whole treatment by measuring beam characteristics as number of delivered particles and beam position. The author will present the comparison between the required and delivered quantities. Methods: The CNAO facility is based on a synchrotron designed to accelerate and deliver proton and carbonion beams in the clinical ranges. Unlike most of the proton‐therapy centres, the delivery technique adopted at CNAO is the “quasi‐discrete” active scanning where dedicated magnets are used to drive a pencil beam through the target and the beam is normally not switched off during the transition between adjacent spots. These operations are performed by the DD system which, based on the treatment planning and the online analysis of dedicated beam monitor chambers, drives the scanning magnets. Spot by spot the DD records data which allow the comparison between the measured number of particles and position and the prescription. Results: The data collected by the dose delivery during the treatments were analyzed in detail, each treatment consisting in more than 30 identical fractions. This allows checking the stability and the accuracy of the CNAO delivery over identical spot sequences. The comparison between the measured number of particles, the measured position of each spot, and the corresponding prescribed quantities will be presented in detail. Critical points will be discussed together with the proposed improvement of the system. Conclusions: The results confirm the good performance of the CNAO beam delivery obtained during the commissioning phase.

To fully exploit the physics potentials of particle therapy in delivering dose with high accuracy and selectivity, charged particle therapy needs further improvement. To this scope, a multidisciplinary project (MoVeIT) of the Italian National Institute for Nuclear Physics (INFN) aims at translating research in charged particle therapy into clinical outcome. New models in the treatment planning system are being developed and validated, using dedicated devices for beam characterization and monitoring in radiobiological and clinical irradiations. Innovative silicon detectors with internal gain layer (LGAD) represent a promising option, overcoming the limits of currently used ionization chambers. Two devices are being developed: one to directly count individual protons at high rates, exploiting the large signal-to-noise ratio and fast collection time in small thicknesses (1 ns in 50 μm) of LGADs, the second to measure the beam energy with time-of-flight techniques, using LGADs optimized for excellent time resolutions (Ultra Fast Silicon Detectors, UFSDs). The preliminary results of first beam tests with therapeutic beam will be presented and discussed.

Charged particle therapy delivered using scanned pencil beams shows the potential to produce better dose conformity than conventional radiotherapy, although the dose distributions are more sensitive to anatomical changes and patient motion. Therefore, the introduction of engines to monitor the dose as it is being delivered is highly desirable, in order to enhance the development of adaptive treatment techniques in hadrontherapy. A tool for fast dose distributions analysis is presented, which integrates on GPU a Fast Forward Planning, a Fast Image Deformation algorithm, a fast computation of Gamma-Index and Dose-Volume Histogram. The tool is being interfaced with the Dose Delivery System and the Optical Tracking System of a synchrotron-based facility to investigate the feasibility to quantify, spill by spill, the effects of organ movements on dose distributions during treatment deliveries with protons and carbon-ions. The dose calculation and comparison times for a patient treated with protons on a 61.3 cm3 planning target volume, a CT matrix of 512x512x125 voxels, and a computation matrix of 170x170x125 voxels are within 1 s per spill. In terms of accuracy, the absolute dose differences compared with benchmarked Treatment Planning System results are negligible (

The integration of Monte Carlo (MC) transport codes into a particle therapy facility could be more easily achieved thanks to dedicated software tools. MC approach has been applied to several purposes at CNAO (Centro Nazionale di Adroterapia Oncologica), such as database generation for the treatment planning system, quality assurance calculations and biologically related simulations. In this paper we describe another application of the MC code and its tools by analyzing the impact of the dose delivery and range uncertainties on patient dose distributions.

Introduction Pencil beam scanning technique used at CNAO requires beam characteristics to be carefully assessed and periodically checked to guarantee patient safety. This study aimed at characterizing the Lynx® detector (IBA Dosimetry) for commissioning and periodic quality assurance (QA) for proton and carbon ion beams, as compared to EBT3 films, currently used for QA checks. Methods and materials The Lynx® is a 2-D high-resolution dosimetry system consisting of a scintillating screen coupled with a CCD camera, in a compact light-tight box. The scintillator was preliminarily characterized in terms of short-term stability, linearity with number of particles, image quality and response dependence on iris setting and beam current; Lynx® was then systematically tested against EBT3 films. The detector response dependence on radiation LET was also assessed. Results Preliminary results have shown that Lynx is suitable to be used for commissioning and QA checks for proton and carbon ion scanning beams; the cross-check with EBT3 films showed a good agreement between the two detectors, for both single spot and scanned field measurements. The strong LET dependence of the scintillator due to quenching effect makes Lynx® suitable only for relative 2-D dosimetry measurements. Conclusion Lynx® appears as a promising tool for commissioning and periodic QA checks for both protons and carbon ion beams. This detector can be used as an alternative of EBT3 films, allowing real-time measurements and analysis, with a significant time sparing.

Purpose The aim of this work was the commissioning of delivery procedures for the treatment of moving targets in scanning pencil beam hadrontherapy. Methods EBT3 films fixed to the Anzai Respiratory Phantom were exposed to carbon ion scanned homogeneous fields (E = 332 MeV/u). To evaluate the interplay effect, field size and flatness for 3 different scenarios were compared to static condition: gated irradiation or repainting alone and combination of both. Respiratory signal was provided by Anzai pressure sensor or optical tracking system (OTS). End-exhale phase and 1 s gating window were chosen (2.5 mm residual motion). Dose measurements were performed using a PinPoint ionization chamber inserted into the Brainlab ET Gating Phantom. A sub-set of tests was also performed using proton beams. Results The combination of gating technique and repainting (N = 5) showed excellent results (6.1% vs 4.3% flatness, identical field size and dose deviation within 1.3%). Treatment delivery time was acceptable. Dose homogeneity for gated irradiation alone was poor. Both Anzai sensor and OTS appeared suitable for providing respiratory signal. Comparisons between protons and carbon ions showed that larger beam spot sizes represent more favorable condition for minimizing motion effect. Conclusion Results of measurements performed on different phantoms showed that the combination of gating and layered repainting is suitable to treat moving targets using scanning ion beams. Abdominal compression using thermoplastic masks, together with multi-field planning approach and multi-fractionation, have also been assessed as additional strategies to mitigate the effect of patient respiration in the clinical practice.

Purpose The quality assurance (QA) procedures in particle therapy centers with active beam scanning make extensive use of films, which do not provide immediate results. The purpose of this work is to verify whether the 2D MatriXX detector by IBA Dosimetry has enough sensitivity to replace films in some of the measurements. Methods MatriXX is a commercial detector composed of 32 × 32 parallel plate ionization chambers designed for pre-treatment dose verification in conventional radiation therapy. The detector and GAFCHROMIC® films were exposed simultaneously to a 131.44 MeV proton and a 221.45 MeV/u carbon-ion therapeutic beam at the CNAO therapy center of Pavia – Italy, and the results were analyzed and compared. Results The sensitivity MatriXX on the beam position, beam width and field flatness was investigated. For the first two quantities, a method for correcting systematic uncertainties, dependent on the beam size, was developed allowing to achieve a position resolution equal to 230 μm for carbon ions and less than 100 μm for protons. The beam size and the field flatness measured using MatriXX were compared with the same quantities measured with the irradiated film, showing a good agreement. Conclusions The results indicate that a 2D detector such as MatriXX can be used to measure several parameters of a scanned ion beam quickly and precisely and suggest that the QA would benefit from a new protocol where the MatriXX detector is added to the existing systems.

Purpose We describe the interface developed at the National Center for Oncological Hadrontherapy in Pavia to provide the dose delivery systems with real time respiratory motion information captured with an optical tracking system. An experimental study is presented to assess the technical feasibility of the implemented organ motion compensation framework, by analyzing the film response when irradiated with proton beams. Methods The motion monitoring solution is based on a commercial hardware for motion capture running in-house developed software for respiratory signal processing. As part of the integration, the latency of data transmission to the dose delivery system was experimentally quantified and accounted for by signal time prediction. A respiratory breathing phantom is presented and used to test tumor tracking based either on the optical measurement of the target position or internal-external correlation models and beam gating, as driven by external surrogates. Beam tracking was tested considering the full target motion excursion (25×18 mm), whereas it is limited to 6×2 mm in the gating window. The different motion mitigation strategies were evaluated by comparing the experimental film responses with respect to static irradiation conditions. Dose inhomogeneity (IC) and conformity (CI) are provided as main indexes for dose quality assessment considering the irradiation in static condition as reference. Results We measured 20.6 ms overall latency for motion signal processing. Dose measurements showed that beam tracking largely preserved dose homogeneity and conformity, showing maximal IC and CI variations limited to +0.10 and −0.01 with respect to the static reference. Gating resulted in slightly larger discrepancies (ΔIC=+0.20, ΔCI=−0.13) due to uncompensated residual motion in the gating window. Conclusions The preliminary beam tracking and gating results verified the functionality of the prototypal solution for organ motion compensation based on optical monitoring.

Avocado is a subtropical fruit with ever increasing demand in the UK market. All year round consumption is supported by a wide range of suppliers across the world. Inevitably, disparities in preharvest conditions and differences in transit time result in undesired fruit quality variability throughout the year. In order to understand these differences, a scoping study was undertaken on fruit imported into the UK where not only demand but also costumer complaints are high. Fruit were harvested in Peru and South Africa (SA) in April-March (early season), June (middle) and August (late). Avocado fruits were transported at 5°C for 33-39 days when imported from Peru and for 25-36 days from SA. Each origin and season was individually investigated. During shelf life (18°C) mesocarp firmness was assessed as an indicator of fruit ripeness. Fatty acid profiles and sugar content was measured to evaluate whether fatty acids and sugar concentrations could be used to discriminate between fruits from different origin or harvest. Generally, higher firmness charac-terised fruit from SA and a faster softening process was noticed in late season fruit. The main biochemical markers also changed according to origin and harvest time. For instance, results showed a higher ratio between monounsaturated vs. saturated fatty acids in fruit from SA (between 2.7 and 3.0) compared to fruit from Peru (2.0-2.2). Moreover, the mannoheptulose content was higher in fruit from Peru when harvested early in the season (106 μg mg-1). However, regardless of origin and harvest season mannoheptulose content declined with fruit ripening, adding evidence to the previously hypothesised role of C7 carbohydrates in the regulation of avocado fruit ripening.

Quasidiscrete scanning is a delivery strategy for proton and ion beam therapy in which the beam is turned off when a slice is finished and a new energy must be set but not during the scanning between consecutive spots. Different scanning paths lead to different dose distributions due to the contribution of the unintended transit dose between spots. In this work an algorithm to optimize the scanning path for quasidiscrete scanned beams is presented. The classical simulated annealing algorithm is used. It is a heuristic algorithm frequently used in combinatorial optimization problems, which allows us to obtain nearly optimal solutions in acceptable running times. A study focused on the best choice of operational parameters on which the algorithm performance depends is presented. The convergence properties of the algorithm have been further improved by using the next-neighbor algorithm to generate the starting paths. Scanning paths for two clinical treatments have been optimized. The optimized paths are found to be shorter than the back-and-forth, top-to-bottom (zigzag) paths generally provided by the treatment planning systems. The gamma method has been applied to quantify the improvement achieved on the dose distribution. Results show a reduction of the transit dose when the optimized paths are used. The benefit is clear especially when the fluence per spot is low, as in the case of repainting. The minimization of the transit dose can potentially allow the use of higher beam intensities, thus decreasing the treatment time. The algorithm implemented for this work can optimize efficiently the scanning path of quasidiscrete scanned particle beams. Optimized scanning paths decrease the transit dose and lead to better dose distributions.

A 64-channel circuit Application Specific Integrated Circuit (ASIC) for charge measurement has been designed in CMOS 0.35mm technology and characterized with electrical tests. The ASIC has been conceived to be used as a front-end for dosimetry and beam monitoring detector read-out. For that application, the circuitry is housed at a few centimeters from the irradiated area of the detectors and therefore radiation damages can affect the chip performances. The ASIC has been tested on an X-ray beam. In this paper, the results of the test and an estimate of the expected lifetime of the ASIC in a standard radio-therapeutical treatment environment are presented. An increase of the background current of 2 fA/Gy has been observed at low doses, whilst the gain changes by less than 3% when irradiated up to 15 kGy. Furthermore it has been assessed that, when used as an on-line beam monitor and the annealing effect has been taken into account, the background current increase is � 440 fA/year.

A 64-channel charge measurement (Application-Specific Integrated Circuit) ASIC has been designed and tested: it is intended to serve as a front-end electronic read-out for detectors to monitor and measure radiotherapeutical beams. The ASIC has been designed in a CMOS 0.35 μm technology with particular attention to the linearity over a wide input range and can accept currents of both polarities. The linearity is better than 1.5% for a dynamic range of the input current between 500 pA and 3 μA. For a charge resolution of 350 fC, the spread (r.m.s.) of the gain is less than 1%.

To describe the dosimetric commissioning and quality assurance (QA) of the actively scanned proton and carbon ion beams at the Italian National Center for Oncological Hadrontherapy.The laterally integrated depth-dose-distributions (IDDs) were acquired with the PTW Peakfinder, a variable depth water column, equipped with two Bragg peak ionization chambers. fluka Monte Carlo code was used to generate the energy libraries, the IDDs in water, and the fragment spectra for carbon beams. EBT3 films were used for spot size measurements, beam position over the scan field, and homogeneity in 2D-fields. Beam monitor calibration was performed in terms of number of particles per monitor unit using both a Farmer-type and an Advanced Markus ionization chamber. The beam position at the isocenter, beam monitor calibration curve, dose constancy in the center of the spread-out-Bragg-peak, dose homogeneity in 2D-fields, beam energy, spot size, and spot position over the scan field are all checked on a daily basis for both protons and carbon ions and on all beam lines.The simulated IDDs showed an excellent agreement with the measured experimental curves. The measured full width at half maximum (FWHM) of the pencil beam in air at the isocenter was energy-dependent for both particle species: in particular, for protons, the spot size ranged from 0.7 to 2.2 cm. For carbon ions, two sets of spot size are available: FWHM ranged from 0.4 to 0.8 cm (for the smaller spot size) and from 0.8 to 1.1 cm (for the larger one). The spot position was accurate to within ± 1 mm over the whole 20 × 20 cm(2) scan field; homogeneity in a uniform squared field was within ± 5% for both particle types at any energy. QA results exceeding tolerance levels were rarely found. In the reporting period, the machine downtime was around 6%, of which 4.5% was due to planned maintenance shutdowns.After successful dosimetric beam commissioning, quality assurance measurements performed during a 24-month period show very stable beam characteristics, which are therefore suitable for performing safe and accurate patient treatments.

We present a quick and easy method for the calibration of a matrix of sensors. The algorithm is based on a three-step irradiation procedure which relies only on the constancy of the delivered fluence at each step. With this method the gain of each sensor is derived relative to a reference detector. The algorithm has been applied to a matrix of (32 x 32) ionization chambers. After the calibration coefficients have been applied, by comparing the response of the matrix of chambers to a reference detector over a large field, we determined that the fluence measurement of individual chambers is better than 0.7%. The algorithm solves the cumbersome problem of the relative gain calibration of a matrix of a large number of sensors.

Preliminary results are presented from a test of a parallel plate ionization chamber with the anode segmented in strips (MOPI) to be used as a beam monitor for therapeutical treatments on the 62 MeV proton beam line of the INFN-LNS Superconducting Cyclotron. Ocular pathologies have been treated at the Catana facility since March 2002. The detector, placed downstream of the patient collimator, will allow the measurement of the relevant beam diagnostic parameters during treatment such as integrated beam fluence, for dose determination; the beam baricentre, width and asymmetry will be obtained from the fluence profile sampled with a resolution of about 100 Urn at a rate up to 1 kHz with no dead time. In this test, carried out at LNS, the detector has been exposed to different beam shapes and the integrated fluence derived by the measured beam profiles has been compared with that obtained with other dosimeters normally used for treatment. The skewness of the beam profile has been measured and shown to be suitable to on-line check variations of the beam shape.

A pixel-segmented ionization chamber has been designed and built by Torino University and INFN. The detector features a 24 x 24 cm2 active area divided in 1024 independent cylindrical ionization chambers and can be read out in 500 micros without introducing dead time; the digital charge quantum can be adjusted between 100 fC and 800 fC. The sensitive volume of each single ionization chamber is 0.07 cm3. The purpose of the detector is to ease the two-dimensional (2D) verifications of fields with complex shapes and large gradients. The detector was characterized in a PMMA phantom using 60Co and 6 MV x-ray photon beams. It has shown good signal linearity with respect to dose and dose rate to water. The average sensitivity of a single ionization chamber was 2.1 nC/Gy, constant within 0.5% over one month of daily measurements. Charge collection efficiency was 0.985 at the operating polarization voltage of 400 V and 3.5 Gy/min dose rate. Tissue maximum ratio and output factor have been compared with a Farmer ionization chamber and were found in good agreement. The dose profiles have been compared with the ones obtained with an ionization chamber in water phantom for the field sizes supplied by a 3D-Line dynamic multileaf collimator. These results show that this detector can be used for 2D dosimetry of x-ray photon beams, supplying a good spatial resolution and sensibly reducing the time spent in dosimetric verification of complex radiation fields.

Tumor therapy takes advantage of the energy deposition of radiation to concentrate high doses in the target while sparing healthy tissue. Elective pathologies for highly conformal radiotherapies such as photon Intensity Modulated Radiotherapy (IMRT) and radiotherapy with hadrons are head and neck, eye, prostate and in general all tumors that are either deep or located close to critical organs. In the world there are several centers that are using such techniques and a common problem that is being experienced is the verification of treatment plans and monitoring of the beam. We have designed and built two detectors that allow 2D and 3D measurements of dose and fluence of such beams. The detectors allow measurements on big surfaces, up to 25∗25 cm2. The active media are parallel plate, strip and pixel segmented ionization chambers with front-end Very Large Scale Integration (VLSI) readout and PC based data acquistion. The description of dosimeter, chamber and electronics will be given with results from beam tests and therapy plan verification.

A VLSI chip based on a recycling integrator has been designed and built to be used as front-end readout of detectors for dosimetry and beam monitoring. The chip is suitable for measurements with both conventional radiotherapy accelerators (photon or electron beams) and with hadron accelerators (proton or light ion beams). As the chips might be located at few centimeters from the irradiation area and they are meant to be used in routine hospital practice, it is mandatory to assert their damage to both electromagnetic and neutron irradiation. We have tested a few chips on a X-ray beam and on thermal and fast neutron beams. Results of the tests are reported and an estimate of the expected lifetime of the chip for routine use is given.

La Fondazione CNAO ha tra i suoi scopi anche lo svolgimento di attività di ricerca. Il centro CNAO è stato concepito sin dall'inizio con tre sale di trattamento, espandibili fino a cinque, ed una 'sala sperimentale' nella quale le attività di ricerca possano venire svolte senza intralciare e senza essere intralciate dalla attività clinica.Tale sala sperimentale deve essere progettata per essere 'multi-uso', cioè tale da poter venire utilizzata per attività di ricerca nei campi più disparati e non specializzata in un tipo di attività particolare. Possibili argomenti di ricerca sono radiobiologia, sviluppo di monitor di fascio, sviluppo di dosimetri, studi di radiation hardness e molti altri ancora.Lo studio di tale facility ed in particolare lo studio degli aspetti tecnici legati all'ampliamento del complesso dell'acceleratore è stato portato avanti congiuntamente da CNAO e INFN, nell'ambito dell'accordo quadro approvato nel 2009 e del nuovo accordo quadro stipulato nel 2013. Per meglio identificare le necessità dei possibili utenti è stato svolto un sondaggio i cui risultati sono stati considerati nella definizione delle specifiche funzionali della linea e della sala sperimentale. Tale sondaggio è illustrato più avanti in questo documento. In questo documento viene descritto il progetto della sala sperimentale e delle linee di alta e di bassa energie coinvolte. Nella prima parte del documento viene data una descrizione generale del progetto, mentre i dettagli sono generalmente riportati nelle appendici e nei documenti allegati.

We report on the design and test of a 32-channel VLSI chip based on the analog pipeline memory concept. The charge from a strip of a ionization chamber, is stored as a function of time in a switched capacitor array. The cell reading can be done in parallel with the writing.

In this paper we report on the design and test of a 14-channel VLSI chip to perform the current to frequency conversion for parallel plate strip ionization chambers. The chambers measure the intensity and the geometrical characteristics of a therapeutical beam.

A new hadron-therapy facility implementing an active beam scanning technique has been developed at the Italian National Center of Oncological Hadron-therapy (CNAO). This paper presents the design and the characterization of the beam monitor detectors developed for the on-line monitoring and control of the dose delivered during a treatment at CNAO. The detectors are based on five parallel-plate transmission ionization chambers with either a single large electrode or electrodes segmented in 128 strips (strip chambers) and 32×32 pixels (pixel chamber). The detectors are arranged in two independent boxes with an active area larger than 200×200 mm 2 and a total water equivalent thickness along the beam path of about 0.9 mm. A custom front-end chip with 64 channels converts the integrated ionization channels without dead-time. The detectors were tested at the clinical proton beam facility of the Paul Scherrer Institut (PSI) which implements a spot scanning technique, each spot being characterized by a predefined number of protons delivered with a pencil beam in a specified point of the irradiation field. The short-term instability was measured by delivering several identical spots in a time interval of few tenths of seconds and is found to be lower than 0.3%. The non-uniformity, measured by delivering sequences of spots in different points of the detector surface, results to be lower than 1% in the single electrode chambers and lower than 1.5% in the strip and pixel chambers, reducing to less than 0.5% and 1% in the restricted 100×100 mm 2 central area of the detector.

A detector (MOPI) has been developed for the online monitoring of the beam at the Centro di AdroTerapia e Applicazioni Nucleari Avanzate (CATANA), where shallow tumours of the ocular region are treated with 62 MeV protons. At CATANA the beam is passively spread to match the tumour shape. The uniformity of the delivered dose depends on beam geometrical quantities which are checked before each treatment. However, beam instabilities might develop during the irradiation affecting the dose distribution. This paper reports on the use of the MOPI detector to measure the stability of the beam profile during the irradiation in the clinical practice. The results obtained in the treatment of 54 patients are also presented.

Quasidiscrete scanning is a delivery strategy for proton and ion beam therapy in which the beam is turned off when a slice is finished and a new energy must be set but not during the scanning between consecutive spots. Different scanning paths lead to different dose distributions due to the contribution of the unintended transit dose between spots. In this work an algorithm to optimize the scanning path for quasidiscrete scanned beams is presented. The classical simulated annealing algorithm is used. It is a heuristic algorithm frequently used in combinatorial optimization problems, which allows us to obtain nearly optimal solutions in acceptable running times. A study focused on the best choice of operational parameters on which the algorithm performance depends is presented. The convergence properties of the algorithm have been further improved by using the next-neighbor algorithm to generate the starting paths. Scanning paths for two clinical treatments have been optimized. The optimized paths are found to be shorter than the back-and-forth, top-to-bottom (zigzag) paths generally provided by the treatment planning systems. The gamma method has been applied to quantify the improvement achieved on the dose distribution. Results show a reduction of the transit dose when the optimized paths are used. The benefit is clear especially when the fluence per spot is low, as in the case of repainting. The minimization of the transit dose can potentially allow the use of higher beam intensities, thus decreasing the treatment time. The algorithm implemented for this work can optimize efficiently the scanning path of quasidiscrete scanned particle beams. Optimized scanning paths decrease the transit dose and lead to better dose distributions.

Hadrotherapy might be the last chance option for patients with cancers growing deep in the body or surrounded by very sensitive organs. The Italian National Center of Oncological Hadrotherapy (CNAO) in Pavia is a synchrotron based center for the treatment of tumors with protons and carbon ion beams. The result of this sophisticated technique is strongly affected by the beam delivery performances. A powerful on-line system to monitor and deliver particles inside the target will be available at CNAO.

A family of Application Specific Integrated Circuits ( ASICs ) called TERA have been developed for the readout of pixel and strip gas detectors used in radiotherapy applications. The TERA ASICs are based on the charge balancing integration technique in order to obtain a good linearity over a dynamic range of five order of magnitude.