Universal and dynamic ridge filter for pencil beam scanning particle therapy: a novel concept for ultra-fast treatment delivery.

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)

Ultra-fast pencil beam scanning proton therapy for locally advanced non-small-cell lung cancers: field delivery within a single breath-hold.

PURPOSE The use of motion mitigation techniques such as breath-hold can reduce the dosimetric uncertainty of lung cancer proton therapy. We studied the feasibility of pencil beam scanning (PBS) proton therapy field delivery within a single breath-hold at PSI's Gantry 2. METHODS In PBS proton therapy, the delivery time for a field is determined by the beam-on time and the dead time between proton spots (the time required to change the energy and/or lateral position). We studied ways to reduce beam-on and lateral scanning time, without sacrificing dosimetric plan quality, aiming at a single field delivery time of 15 seconds at maximum. We tested this approach on 10 lung cases with varying target volumes. To reduce the beam-on time, we increased the beam current at the isocenter by developing new beam optics for PSI's PROSCAN beamline and Gantry 2. To reduce the dead time between the spots, we used spot-reduced plan optimization. RESULTS We found that it is possible to achieve conventional fractionated (2 Gy(RBE)/fraction) and hypofractionated (6 Gy(RBE)/fraction) field delivery times within a single breath-hold (<15 sec) for a variety non-small-cell lung cancer cases. CONCLUSION In summary, the combination of spot reduction and improved beam line transmission is a promising approach for the treatment of mobile tumours within clinically achievable breath-hold durations

Optimal Configuration of Proton-Therapy Accelerators for Relative-Stopping-Power Resolution in Proton Computed Tomography

The determination of relative stopping power (RSP) via proton computed tomography (pCT) of a patient is dependent in part on the knowledge of the incoming proton kinetic energies; the uncertainty in these energies is in turn determined by the proton source—typically a cyclotron. Here, we show that reducing the incident proton beam energy spread may significantly improve RSP determination in pCT. We demonstrate that the reduction of beam energy spread from the typical 1.0% (at 70 MeV) down to 0.2% can be achieved at the proton currents needed for imaging at the Paul Scherrer Institut 250-MeV cyclotron. Through a simulated pCT imaging system, we find that this effect results in RSP resolutions as low as 0.2% for materials such as cortical bone, up to 1% for lung tissue. Several materials offer further improvement when the beam (residual) energy is also chosen such that the detection mechanisms used provide the optimal RSP resolution

Catalytic activity imperative for nanoparticle dose enhancement in photon and proton therapy.

Nanoparticle-based radioenhancement is a promising strategy for extending the therapeutic ratio of radiotherapy. While (pre)clinical results are encouraging, sound mechanistic understanding of nanoparticle radioenhancement, especially the effects of nanomaterial selection and irradiation conditions, has yet to be achieved. Here, we investigate the radioenhancement mechanisms of selected metal oxide nanomaterials (including SiO2, TiO2, WO3 and HfO2), TiN and Au nanoparticles for radiotherapy utilizing photons (150 kVp and 6 MV) and 100 MeV protons. While Au nanoparticles show outstanding radioenhancement properties in kV irradiation settings, where the photoelectric effect is dominant, these properties are attenuated to baseline levels for clinically more relevant irradiation with MV photons and protons. In contrast, HfO2 nanoparticles retain some of their radioenhancement properties in MV photon and proton therapies. Interestingly, TiO2 nanoparticles, which have a comparatively low effective atomic number, show significant radioenhancement efficacies in all three irradiation settings, which can be attributed to the strong radiocatalytic activity of TiO2, leading to the formation of hydroxyl radicals, and nuclear interactions with protons. Taken together, our data enable the extraction of general design criteria for nanoparticle radioenhancers for different treatment modalities, paving the way to performance-optimized nanotherapeutics for precision radiotherapy

Comparing radiolytic production of H2O2 and development of Zebrafish embryos after ultra high dose rate exposure with electron and transmission proton beams.

The physico-chemical and biological response to conventional and UHDR electron and proton beams was investigated, along with conventional photons. The temporal structure and nature of the beam affected both, with electron beam at ≥1400 Gy/s and proton beam at 0.1 and 1260 Gy/s found to be isoefficient at sparing zebrafish embryos

Measurement of jets production in association with a Z boson and in the search for the SM Higgs boson via H →ττ→ℓℓ+4ν \to \tau \tau \to \ell \ell + 4 \nu with ATLAS

Three measurements focussing on the understanding of jet final states in ATLAS, in di-jet, Z and Higgs boson candidate events, using data corresponding to an integrated luminosity of 35 pb−1 in 2010 and 4.7 fb−1 in 2011, are presented. In the first part, a calibration method, based on the transverse momentum balance in di-jet events, is described. The method is used to estimate the uncertainty of the jet energy scale in the forward region. The results show that the parton shower models are limited in reproducing the results in data, mostly for jets of low transverse momentum. In the second part, the differential cross section measurement of the Z -> ll + jets process is reported. Phase space regions not been previously studied at other experiments are investigated. The models used for the theory predictions provide a good description of the data, within the relative uncertainties. In the last part, two contribution to the Higgs searches in the H -> tau tau channel are shown: the modelling of the Z -> tau tau background, and the modelling of jet final states. The Z -> tau tau background is derived from data and validated in the H -> tau tau -> ll + 4nu channel. The modelling of jet final states in simulations is in good agreement with the data, when low-energy pile-up effects are subtracted

FLASH Irradiation with Proton Beams: Beam Characteristics and Their Implications for Beam Diagnostics

FLASH irradiations use dose-rates orders of magnitude higher than commonly used in patient treatments. Such irradiations have shown interesting normal tissue sparing in cell and animal experiments, and, as such, their potential application to clinical practice is being investigated. Clinical accelerators used in proton therapy facilities can potentially provide FLASH beams; therefore, the topic is of high interest in this field. However, a clear FLASH effect has so far been observed in presence of high dose rates (>40 Gy/s), high delivered dose (tens of Gy), and very short irradiation times (<300 ms). Fulfilling these requirements poses a serious challenge to the beam diagnostics system of clinical facilities. We will review the status and proposed solutions, from the point of view of the beam definitions for FLASH and their implications for beam diagnostics. We will devote particular attention to the topics of beam monitoring and control, as well as absolute dose measurements, since finding viable solutions in these two aspects will be of utmost importance to guarantee that the technique can be adopted quickly and safely in clinical practice

A new emittance selection system to maximize beam transmission for low-energy beams in cyclotron-based proton therapy facilities with gantry.

PURPOSE In proton therapy, the potential of using high dose rates in cancer treatment is being explored. High dose rates could improve efficiency and throughput in standard clinical practice, allow efficient utilization of motion mitigation techniques for moving targets, and potentially enhance normal tissue sparing due to the so-called FLASH effect. However, high dose rates are difficult to reach when lower energy beams are applied in cyclotron-based proton therapy facilities, because they result in large beam sizes and divergences downstream of the degrader, incurring large losses from the cyclotron to the patient position (isocenter). In current facilities the emittance after the degrader is reduced using circular collimators; this however does not provide an optimal matching to the acceptance of the following beamline, causing a low transmission for these energies. We, therefore, propose to use a collimation system, asymmetric in both beam size and divergence, resulting in symmetric emittance in both beam transverse planes as required for a gantry system. This new emittance selection, together with a new optics design for the following beamline and gantry, allows a better matching to the beamline acceptance and an improvement of the transmission. METHODS We implemented a custom method to design the collimator sizes and shape required to select high emittance, to be transported by the following beamline using new beam optics (designed with TRANSPORT) to maximize acceptance matching. For predicting the transmission in the new configuration (new collimators + optics) we used Monte Carlo simulations implemented in BDSIM, implementing a model of PSI Gantry 2 which we benchmarked against measurements taken in the current clinical scenario (circular collimators + clinical optics). RESULTS From the BDSIM simulations, we found that the new collimator system and matching beam optics we propose results in an overall transmission from the cyclotron to the isocenter for a 70 MeV beam of 0.72%. This is an improvement of almost a factor of 6 over the current clinical performance (0.13% transmission). The new optics satisfies clinical beam requirements at the isocenter. CONCLUSIONS We developed a new emittance collimation system for PSI's PROSCAN beamline which, by carefully selecting beam size and divergence asymmetrically, increases the beam transmission for low energy beams in current state-of-the-art cyclotron-based proton therapy gantries. With these improvements, we could predict almost 1% transmission for low-energy beams at PSI's Gantry 2. Such a system could be easily be implemented in facilities interested in increasing dose rates for efficient motion mitigation and FLASH experiments alike. This article is protected by copyright. All rights reserved

Use of momentum cooling to achieve flash dose-rates even for low-energy beams in cyclotron-based proton therapy facilities

Background and Aims: In proton therapy, the potential high dose-rates (FLASH) for cancer treatment is currently being explored. If performed with cyclotrons however, energy degradation is required. If performed upstream (using a degrader plus and energy/momentum selection system (ESS)), large beam losses result, whilst if performed downstream, just before the patient, the beam width is substantially compromised. In both cases, the net effect is a loss of dose rate, either by transmission loss or by beam scattering, making the delivery of FLASH dose rates challenging for lower energies. In this work, we have developed a new ESS for upstream energy degradation that replaces slits with a wedge to reduce the momentum spread (‘momentum cooling’) without introducing a significant beam loss. Methods: New ESS was designed using the principle of momentum cooling. A bending magnet is used to bend the proton beam and to achieve a spatial distribution of the beam’s momentum, after which the beam is focused at the location of the wedge using two quadrupole magnets. The thickness of the wedge is chosen such that protons with different momentums will see different thicknesses of material and therefore lose more or less energy in the wedge, resulting in the same momentum p-Δp afterwards. Results: With Monte Carlo (BDSIM) simulations, this ESS concept, along with matched beam optics, results in a 10% beam transmission, from cyclotron to isocenter, for a 70MeV beam, corresponding to a current of e.g. 80nA for 800nA cyclotron current. At the Bragg peak (in water), this provides peak dose-rates of 952Gy/s and 2105Gy/s for 70MeV and 230MeV respectively. Conclusions: The described ESS provides momentum cooling whilst minimizing beam losses, allowing for FLASH dose-rates at low energies from cyclotron-based facilities, and thus paving the way to FLASH irradiations beyond transmission mode

A novel energy selection system to achieve FLASH dose-rates even for low-energy beams in cyclotron-based proton therapy facilities

In proton therapy, the potential of ultra-high (FLASH) dose-rate for cancer treatment is being explored due to its potential for enhancing biological effect, faster hypo-fractionated treatments and for efficient motion mitigation. However, energy degradation for FLASH irradiations using cyclotrons is far from optimal; if performed upstream (as common clinically, using a degrader plus an energy/momentum selection system, or ESS), very large losses result, while if performed downstream, just before the patient, the beam width is substantially compromised. In both cases, the net effect is a loss of dose rate, either by transmission loss or by beam scattering, making the delivery of FLASH dose rates challenging for lower energies. To avoid downstream energy degradation and its effects on the beam shape, we propose using an ESS without momentum selection slits, which compensates the momentum spread in the beam without introducing significant beam loss. In Monte Carlo (BDSIM) simulations, we found that this new ESS concept, along with matched beam optics, results in a significantly increased overall transmission compared to current installations, even achieving 10% beam transmission, from cyclotron to isocenter, for a 70 MeV beam. This corresponds to a current of 80 nA at the isocenter assuming 800nA extracted from the cyclotron. At Bragg peak (in water), we achieved dose-rate of 952 Gy/s and 2105 Gy/s for 70 MeV and 230 MeV beams respectively. Such a system could easily be implemented in future cyclotron based particle facilities to increase dose rates for efficient motion mitigation, hypofractionation and FLASH experiments alike