BACKGROUND:While pencil beam scanning (PBS) with motion mitigation such as re-scanning, breath hold, or gating is well established for treating moving targets in clinical practice, the precision for Spatially Fractionated Radiation Therapy (SFRT) using proton minibeams introduces presents a unique challenge. The sub-millimeter precision required for SFRT cannot be achieved with typical PBS spot sizes (millimeters), necessitating multi-slit beam collimation, which reduces the dose rate and reintroduces motion as a critical issue. In this study, we report on our experience with minibeam irradiations of chorioallantoic membranes (CAM) of chick embryos and discuss potential solutions to the motion problem. METHODS:The first experiment was conducted at a PBS gantry using 130 MeV protons and a 6 cm thick copper multi-slit collimator with 0.3 mm wide slits and 1 mm spacing. To achieve a target peak dose of 30 Gy, CAM samples were irradiated with more than 10 re-scans. Due to a 91% beam loss in the collimator, the total irradiation time extended to two min. RESULTS:Post-irradiation analysis using gafchromic film revealed smearing of the minibeam profiles, while biological tissue analysis uncovered unexpected and disrupted dose effects, likely caused by irregular CAM movement during irradiation. A subsequent experiment, incorporating additional setup optimizations such as reduced air gap and increased dose rate, shortened the irradiation time to below one min. This led to sharper dose profiles with negligible variation in valley dose and peak width, although a reduction in peak dose of 8%-13% was still observed. This variation is considered acceptable for our biological experiments. CONCLUSIONS:For clinical applications, minibeam re-scanning is likely to be feasible only under ultra-high dose rate conditions (e.g., those required to induce the FLASH effect), where sufficiently short irradiation times minimize motion-induced dose degradation.

Sub-millimetre precision is a crucial criterion for beam delivery in Pencil Beam Scanning (PBS) proton therapy. Nowadays, most of the therapy systems use PBS technique where single beams with a regulated number of protons are delivered sequentially to different locations within the target. Beam energy defines the depth of the beam in the target and scanner magnets deflect the beam to the desired lateral position. The PSI Gantry 2 was among the first gantries to use the PBS technique. Available clinical proton beam energies ranging from 70 MeV to 230 MeV are achieved by de-grading a 250 MeV beam, initially provided by a super-conducting cyclotron. Beam scanning is performed just before the last bending magnet producing a nearly parallel beam at iso-centre with a well-focused beam over the full scan area of 20x12 cm(2). We developed a calibration algorithm for the scanner magnets in order to achieve the desirable precision of the beam in the target. Measuring the beam position with a strip ion chamber in the gantry nozzle, we parametrized the propagation of the beam to the target calculating the beam angle at different scan positions as well as all gantry angles. During 10 years of operation we performed regular Quality Assurance (QA) tests to validate parameters obtained during the system commissioning. The QA data proved a stable system operation and no parametrization update was required so far. In this contribution, we describe the calibration pro-cess of scanning magnets with respect to beam position at the iso-centre and show the stability of this implementation over the time.

Objective. The treatment of mobile tumours using Pencil Beam Scanning (PBS) has become more prevalent in the last decade. However, to achieve the same beam delivery quality as for static tumours, treatments have to be combined with motion mitigation techniques, not limited but including, breath hold, gating and re-scanning, which typically prolong treatment time. In this article we present a novel method of bi-directional energy modulation and demonstrate our initial experience in improvement of treatment efficiency. Approach. At Paul Scherrer Institute Gantry 2 mobile tumours are treated by combining PBS with gating and volumetric re-scanning (VR), where the target volume is irradiated multiple times. Initial implementation of VR used only descending beam energies, creating a substantial dead time due to the beam-line initialization (ramping) before each re-scan. In 2019 we commissioned an energy meandering strategy that allows us to avoid beam line ramping in-between energy series while maintaining beam delivery quality. Main results. The measured beam parameters difference for both energy sequence are in the order of the typical daily variations: 0.2 mm in beam position and 0.2 mm in range. Using machine log files, we performed point-to-point dose difference calculations between original and new applications where we observed dose differences of less than 2%. After three years of operation employing bi-directional energy modulation, we have analysed the individual beam delivery time for 181 patients and have compared this to simulations of the timing behaviour assuming uni-directional energy sequence application. Depending on treatment complexity, we obtained plan delivery time reductions of up to 55%, with a median time gain of 17% for all types of treatments. Significance. Bi-directional energy modulation can help improving patient treatment efficiency by reducing delivery times especially for complex and specialised irradiations. It could be implemented in many existing facilities without significant additional hardware upgrades.

Objective.In pencil beam scanning particle therapy, a short treatment delivery time is paramount for the efficient treatment of moving targets with motion mitigation techniques (such as breath-hold, rescanning, and gating). Energy and spot position change time are limiting factors in reducing treatment time. In this study, we designed a universal and dynamic energy modulator (ridge filter, RF) to broaden the Bragg peak, to reduce the number of energies and spots required to cover the target volume, thus lowering the treatment time.Approach. Our RF unit comprises two identical RFs placed just before the isocenter. Both RFs move relative to each other, changing the Bragg peak's characteristics dynamically. We simulated different Bragg peak shapes with the RF in Monte Carlo simulation code (TOPAS) and validated them experimentally. We then delivered single-field plans with 1 Gy/fraction to different geometrical targets in water, to measure the dose delivery time using the RF and compare it with the clinical settings.Main results.Aligning the RFs in different positions produces different broadening in the Bragg peak; we achieved a maximum broadening of 2.5 cm. With RF we reduced the number of energies in a field by more than 60%, and the dose delivery time by 50%, for all geometrical targets investigated, without compromising the dose distribution transverse and distal fall-off.Significance. Our novel universal and dynamic RF allows for the adaptation of the Bragg peak broadening for a spot and/or energy layer based on the requirement of dose shaping in the target volume. It significantly reduces the number of energy layers and spots to cover the target volume, and thus the treatment time. This RF design is ideal for ultra-fast treatment delivery within a single breath-hold (5-10 s), efficient delivery of motion mitigation techniques, and small animal irradiation with ultra-high dose rates (FLASH).

Spot-scanning is a highly dynamic treatment method in proton therapy, tailored to each tumor shape individually. By superimposing many single spots in all three spatial axes, a prescribed dose is applied to the tumor volume. To minimize dose inhomogeneity across this volume, tight constraints on the beam position accuracy apply: for a dose inhomogeneity below 1%, a longitudinal beam position accuracy of the order of 1 mm is necessary, whereas in the lateral plane, the accuracy needs to be roughly one order of magnitude better. Longitudinal position control is achieved through selecting the beam energy; laterally, this is achieved by two sweeper magnets, allowing position changes within milliseconds. Such dynamics and accuracy constraints require an online measurement of the beam position to enable and maintain high treatment quality assurance. Gantry 2 at the Center for Proton Therapy at PSI operates a plane parallel strip ionization chamber for this purpose as the final beamline element before the patient. The foil-based detector design is optimized for an in-situ placement in the beam axis and keeps beam disturbance at a minimum. A strip pitch of 2 mm allows to reconstruct the Gaussian shape beam profile with the desired accuracy. These beam profiles are analyzed (and verified) during a treatment on a spot-by-spot basis, before the next spot is applied, introducing a dead time after every spot. Applying 50, 000 spots in a treatment introduces the challenge to data acquisition and - processing in terms of keeping treatment times reasonable. Data pileup and long dead times are mitigated by optimized front-end electronics and early-stage data processing, without compromising data quality and the accuracy of the measured beam position.

At the Paul Scherrer Institute (PSI) in Switzerland, cancer patients are treated with protons. The PSI Gantries work with Pencil Beam Scanning (PBS) technology. For beam profile characterization, a new 2-D planar pixel detector based on Printed Circuit Board technology was developed. The main challenge of the design was the limited amount of 256 readout channels while several thousands of detector signals had to be processed. With PBS, only a few pixels will be hit by the proton beam and give a significant signal, while most of them will not capture any signal. On the detector design, the active area was divided into pixel arrays with equal size, while one array is such big to cover the whole size of the proton beam. By a so-called channel recycling technique, the same pixel number of all pixel arrays were connected together to one readout channel. The proof of concept was verified with a small detector. In the next step, the design was changed such, getting a full-scale detector for Gantry 2. The readout electronics board itself is also a development performed at PSI. A core component of the design is the ADAS1128 chip from ANALOG Devices featuring 128 input channels. The pixel detector is fully integrated into the therapy control system (TCS) through readout electronics with a field-programmable gate array (FPGA) technology. The FPGA technology allows to readout the detector synchronized to the beam delivery. This paper summarizes the features of the pixel detector design, the readout electronics, and shows the first experimental results.

Gantry 2 at PSI is a Pencil Beam Scanning (PBS) cyclotron-based proton therapy system. The main principle of PBS is a sequential dose-spot delivery to all positions (spots) within the tumour. This technique proved to be an effective treatment method for static tumours, however for mobile targets (e.g. lung or liver) organ motion interferes with beam delivery lowering the treatment quality. A common method to mitigate motion effects is to re-scan the treatment volume multiple times. One distinguishes between iso-layered re-scanning (LR) where all re-scans are performed in a single energy layer before moving to the next energy, and volumetric re-scanning (VR) where the whole tumour volume is re-scanned multiple times. Several studies demonstrate the higher effectiveness of VR [1,2,3]. The downside of this re-scanning type is the increase of treatment time due to high number of energy switches and magnet initializations (ramping) between scans. We developed a novel re-scanning concept which increases the dynamics of energy modulation and cuts treatment delivery times in half. Re-evaluating an existing patient treatment plan with this new VR method we demonstrated that our approach with highly dynamic energy modulation allows for a beam delivery precision similar to the standard PBS irradiation.

PURPOSE:Fast energy switching is of fundamental importance to implement motion mitigation techniques in pencil beam scanning proton therapy, allowing efficient irradiation and high patient throughput. However, depending on magnet design, when switching between different energy layers, eddy currents arise in the bending magnets' yoke, damping the speed of the magnetic field change and lengthening the settling time of the magnetic field. In a proton therapy gantry, this can cause a temporary displacement of the beam trajectory and consequently an incorrect beam position in the bending direction, resulting in an unacceptable loss of position precision at isocenter. The precision can be recovered by either increasing the beam off time after an energy change (waiting until the magnetic field is fully settled) or by actively correcting for the misplacement. We studied the transient magnetic field effects at PSI Gantry 2 in order to develop a correction strategy for this beam position misplacement.METHODS:We used position and proton range sensitive detectors (segmented strip chamber and multilayer ionization chambers respectively) to measure the difference between expected and actual proton beam position and range as a function of time. The detectors are automatically triggered, read out, and analyzed by the treatment control system. We studied the effects due to the magnets on the gantry and those upstream of the gantry separately, in order to identify which elements contribute the most to the beam position instability. We then designed a spot position algorithm to be applied with the gantry scanning magnets, to correct for the displacement observed as a function of time and achieve the PSI Gantry 2 clinical target of 1 mm precision at isocenter at all times, even after an energy change.RESULTS:When switching energy layers in a field, we observed an exponentially decaying spot position displacement at isocenter. The effect increases with increasing energy difference between energy layers (ΔE). The initial residuals between expected and measured position are higher than 1 mm for most of the clinical cases at Gantry 2 and fall below 1 mm within about 1 s or more (depending on ΔE). We found no time dependence for the proton range, thus confirming that the displacement is purely due to a beam trajectory displacement resulting from the longer settling time of the magnetic field. A double exponential model, with two time constants and amplitudes depending on ΔE, fits the data and provides an easy model for the correction function. We implemented this correction as a spot position correction, applied by the scanning magnets during field application. After correction, the residuals were below 0.5 mm right after the energy change.CONCLUSIONS:We developed a spot position correction for PSI Gantry 2 which reduces the beam off time needed in current state-of-the-art gantries to settle the magnetic fields in the bending magnets. Thanks to this correction, the spot position is stable within 100 ms of an energy change at Gantry 2. This is low enough to make possible efficient use of motion mitigation techniques.

In 2016 and 2017, the 8th and 9th 4D treatment planning workshop took place in Groningen (the Netherlands) and Vienna (Austria), respectively. This annual workshop brings together international experts to discuss research, advances in clinical implementation as well as problems and challenges in 4D treatment planning, mainly in spot scanned proton therapy. In the last two years several aspects like treatment planning, beam delivery, Monte Carlo simulations, motion modeling and monitoring, QA phantoms as well as 4D imaging were thoroughly discussed.This report provides an overview of discussed topics, recent findings and literature review from the last two years. Its main focus is to highlight translation of 4D research into clinical practice and to discuss remaining challenges and pitfalls that still need to be addressed and to be overcome.

The Center for Proton Therapy of the Paul Scherrer Institute has a long history of technical innovation and development in the field of proton therapy and related quality assurance (QA). The second proton pencil beam scanning gantry built at the CPT, Gantry 2, is a state-of-the-art system. The unique integration of QA equipment and detectors within the control system of the gantry allows for fast and detailed measurements. Here we present our latest developments in detection systems, their performance for QA and research capabilities in comparison with their commercial equivalent. The QA equipment developed for proton range measurement at Gantry 2 consists of a multi-layer ionization chamber (MLIC). The extensive integration of our detectors with the control system allows fast spot-based measurement. Including the energy change, we can achieve a proton range evaluation within 125 ms. Consequently, our device can measure the proton range alteration caused by material samples for hundreds of energies within less than a minute. This allows us to measure the stopping power of compound material within minutes. We compare the stopping power evaluation using the MLIC against three other techniques. The results show the strong points of the equipment developed in-house, such as the consistency, the reliability and the innovation possibilities.

There are several general recommendations for quality assurance (QA) measures, which have to be performed at proton therapy centres. However, almost each centre uses a different therapy system. In particular, there is no standard procedure for centres employing pencil beam scanning and each centre applies a specific QA program. Gantry 2 is an operating therapy system which was developed at PSI and relies on the most advanced technological innovations. We developed a comprehensive daily QA program in order to verify the main beam characteristics to assure the functionality of the therapy delivery system and the patient safety system. The daily QA program entails new hardware and software solutions for a highly efficient clinical operation. In this paper, we describe a dosimetric phantom used for verifying the most critical beam parameters and the software architecture developed for a fully automated QA procedure. The connection between our QA software and the database allows us to store the data collected on a daily basis and use it for trend analysis over longer periods of time. All the data presented here have been collected during a time span of over two years, since the beginning of the Gantry 2 clinical operation in 2013. Our procedure operates in a stable way and delivers the expected beam quality. The daily QA program takes only 20 min. At the same time, the comprehensive approach allows us to avoid most of the weekly and monthly QA checks and increases the clinical beam availability.

S5363rd ESTRO Forum 2015 the low penetration of kV x-rays limits their useful depth range.An interesting solution is to bring the x-ray tube close to GNP-loaded tumors.But this can result in non-uniform tumor dose distributions.Although a sharp dose falloff is useful in brachytherapy, it may not be desirable for thick tumors.Here, DE was investigated with the additional aim of creating tumor dose uniformity, the idea being that using different concentrations of GNP within the tumor can be potentially useful as a means of compensating dose falloff.Materials and Methods: A miniature intraoperative/ brachytherapy x-ray tube with 40-50 kVp photon spectra was simulated using MCNP.The tube was simulated in a water phantom to obtain its AAPM TG-43 parameters and the model was validated against the results of other investigators.The tube was first simulated underneath a virtually segmented tissue with and without the gold GNP.Then, a 1 cm thick tumor was further subdivided into layers to calculate the dose distribution.Next, layers of different thicknesses at various distances from the tube and also different concentrations of GNP were simulated.Then, DE curves were plotted for different densities of GNP, namely, 7, 15, and 30 mg/ml.To allow the use of MCNP for these simulations, the GNPs were assumed to be uniformly distributed and also sufficiently small to make electron absorption in them negligible.Finally, to obtain better DE and dose homogeneity concomitantly, the distribution of GNP concentrations (in the range 7-30 mg/ml) of the layers were increased progressively with depth in tumor by adopting different models, namely, in linear (model 1), quadratic (model 2), and exponential (model 3) fashions, and their effects were investigated separately.Results: Although increasing the concentration of GNP uniformly within the tumor produced DE at low depths, it caused further inhomogeneity due to the additional attenuation because of the higher atomic number of the GNP.However, increasing the GNP concentration progressively with depth in the tumor produced a better homogeneity index as well as mean DE.Mean DEs, relative to the case of no GNP, for the progressive models 3, 2 and 1 and the uniform GNP (7 mg/ml) distribution model were found to be 50%, 51%, 48%, and 26%, respectively.Also, model 3 offered the best homogeneity index.Conclusions: Under these conditions, progressive addition of GNP with depth in tumor can potentially improve both mean DE and dose homogeneity, while the amount of the improvement is somewhat dependent on the model of concentration increase.Having shown this potential improvement, further studies are required to test the practical feasibility and implementation of this idea.

An on-line beam position monitoring and regular beam stability tests are of utmost importance for the Quality Assurance (QA) of the patient treatment at any particle therapy facility. The Gantry 2 at the Paul Scherrer Institute uses a strip ionization chamber for the on-line beam position verification. The design of the strip chamber placed in the beam in front of the patient allows for a small beam penumbra in order to achieve a high-quality lateral beam delivery. The position error of 1 mm in a lateral plane (plane perpendicular to the beam direction) can result in a dose inhomogeneity of more than 5%. Therefore the goal of Gantry 2 commissioning was to reach a sub-millimeter level of the reconstruction accuracy in order to bring a dose uncertainty to a level of 1%. In fact, we observed that for beams offered by Gantry 2 signal profiles in a lateral plane can be reconstructed with a precision of 0.1 mm. This is a necessary criterion to perform a reliable patient treatment. The front end electronics and the whole data processing sequence have been optimized for minimizing the dead time in between two consecutive spots to about 2 ms: the charge collection is performed in about 1 ms, read-out takes place in about 100μs while data verification and logging are completed in less than 1 ms.

We report on the search for electromagnetic and hadronic showers (“cascades”) produced by a diffuse flux of extraterrestrial neutrinos in the AMANDA neutrino telescope. Data for this analysis were recorded during 1001 days of detector livetime in the years 2000–2004. The observed event rates are consistent with the background expectation from atmospheric neutrinos and muons. An upper limit is derived for the diffuse flux of neutrinos of all flavors assuming a flavor ratio of νe:νμ:ντ = 1:1:1 at the detection site. The all-flavor flux of neutrinos with an energy spectrum Φ ∝ E−2 is less than 5.0 × 10−7 GeV s−1 sr−1 cm−2 at a 90% C.L. Here, 90% of the simulated signal would fall within the energy range 40 TeV to 9 PeV. We discuss flux limits in the context of several specific models of extraterrestrial and prompt atmospheric neutrino production.

VISPA is a development environment for high energy physics analyses which enables physicists to combine graphical and textual work. A physics analysis cycle consists of prototyping, performing, and verifying the analysis. The main feature of VISPA is a multipurpose window for visual steering of analysis steps, creation of analysis templates, and browsing physics event data at different steps of an analysis. VISPA follows an experiment-independent approach and incorporates various tools for steering and controlling required in a typical analysis. Connection to different frameworks of high energy physics experiments is achieved by using different types of interfaces. We present the look-and-feel for an example physics analysis at the LHC and explain the underlying software concepts of VISPA.

A measurement of the underlying activity in scattering processes with transverse momentum scale in the GeV region is performed in proton-proton collisions at sqrt(s) = 0.9 TeV, using data collected by the CMS experiment at the LHC. Charged hadron production is studied with reference to the direction of a leading object, either a charged particle or a set of charged particles forming a jet. Predictions of several QCD-inspired models as implemented in PYTHIA are compared, after full detector simulation, to the data. The models generally predict too little production of charged hadrons with pseudorapidity eta < 2, p_T > 0.5 GeV/c, and azimuthal direction transverse to that of the leading object.