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The in vivo evolution of radiotherapy necessitates innovative platforms for preclinical investigation, bridging the gap between bench research and clinical applications. Understanding the nuances of radiation response, specifically tailored to proton and photon therapies, is critical for optimizing treatment outcomes. Within this context, preclinical in vivo experimental setups incorporating image guidance for both photon and proton therapies are pivotal, enabling the translation of findings from small animal models to clinical settings. The SAPPHIRE project represents a milestone in this pursuit, presenting the installation of the small animal radiation therapy integrated beamline (SmART+ IB, Precision X-Ray Inc., Madison, Connecticut, USA) designed for preclinical image-guided proton and photon therapy experiments at University Proton Therapy Dresden. Through Monte Carlo simulations, low-dose on-site cone beam computed tomography imaging and quality assurance alignment protocols, the project ensures the safe and precise application of radiation, crucial for replicating clinical scenarios in small animal models. The creation of Hounsfield lookup tables and comprehensive proton and photon beam characterizations within this system enable accurate dose calculations, allowing for targeted and controlled comparison experiments. By integrating these capabilities, SAPPHIRE bridges preclinical investigations and potential clinical applications, offering a platform for translational radiobiology research and cancer therapy advancements., (Creative Commons Attribution license.)

Purpose: The low sensitivity and limitation to water phantoms of convection-dependent MRI magnitude signal-based proton beam visualization hinder its in vivo applicability in MR-integrated proton beam therapy. The purpose of the present study was, therefore, to assess possible contrast mechanisms for MRI phase signal-based proton beam visualization that can potentially be exploited to enhance the sensitivity of the method and extend its applicability to tissue materials., Methods: To assess whether proton beam-induced magnetic field perturbations, changes in material susceptibility or convection result in detectable changes in the MRI phase signal, water phantom characteristics, experiment timing, and imaging parameters were varied in combined irradiation and imaging experiments using a time-of-flight angiography pulse sequence on a prototype in-beam MRI scanner. Velocity encoding was used to further probe and quantify beam-induced convection., Results: MRI phase signal-based proton beam visualization proved feasible. The observed phase difference contrast was evoked by beam-induced buoyant convection with flow velocities in the mm/s range. Proton beam-induced magnetic field perturbations or changes in magnetic susceptibility did not influence the MRI phase signal. Velocity encoding was identified as a means to enhance the detection sensitivity., Conclusion: Because the MRI phase difference contrast observed during proton beam irradiation of water phantoms is caused by beam-induced convection, this method will unlikely be transferable to tightly compartmentalized tissue wherein flow effects are restricted. However, strong velocity encoded pulse sequences were identified as promising candidates for the future development of MRI-based methods for water phantom-based geometric quality assurance in MR-integrated proton beam therapy., (© 2023 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

The main advantage proton beams offer over photon beams in radiation therapy of cancer patients is the dose maximum at their finite range, yielding a reduction in the dose deposited in healthy tissues surrounding the tumor. Since no direct method exists to measure the beam's range during dose delivery, safety margins around the tumor are applied, compromising the dose conformality and reducing the targeting accuracy. Here, we demonstrate that online MRI can visualize the proton beam and reveal its range during irradiation of liquid-filled phantoms. A clear dependence on beam energy and current was found. These results stimulate research into novel MRI-detectable beam signatures and already find application in the geometric quality assurance for magnetic resonance-integrated proton therapy systems currently under development.

Stray radiation produced by ultra-high dose-rates (UHDR) proton pencil beams is characterized using ASIC-chip semiconductor pixel detectors. A proton pencil beam with an energy of 220 MeV was utilized to deliver dose rates (DR) ranging from conventional radiotherapy DRs up to 270 Gy/s. A MiniPIX Timepix3 detector equipped with a silicon sensor and integrated readout electronics was used. The chip-sensor assembly and chipboard on water-equivalent backing were detached and immersed in the water-phantom. The deposited energy, particle flux, DR, and the linear energy transfer (LET(Si)) spectra were measured in the silicon sensor at different positions both laterally, at different depths, and behind the Bragg peak. At low-intensity beams, the detector is operated in the event-by-event data-driven mode for high-resolution spectral tracking of individual particles. This technique provides precise energy loss response and LET(Si) spectra with radiation field composition resolving power. At higher beam intensities a rescaling of LET(Si) can be performed as the distribution of the LET(Si) spectra exhibits the same characteristics regardless of the delivered DR. The integrated deposited energy and the absorbed dose can be thus measured in a wide range. A linear response of measured absorbed dose was obtained by gradually increasing the delivered DR to reach UHDR beams. Particle tracking of scattered radiation in data-driven mode could be performed at DRs up to 0.27 Gy/s. In integrated mode, the saturation limits were not reached at the measured out-of-field locations up to the delivered DR of over 270 Gy/s. A good agreement was found between measured and simulated absorbed doses., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Associazione Italiana di Fisica Medica e Sanitaria. Published by Elsevier Ltd. All rights reserved.)

Purpose: To report on experimental results of a high spatial resolution silicon-based detector exposed to therapeutic quality proton beams in a 0.95 T transverse magnetic field. These experimental results are important for the development of accurate and novel dosimetry methods in future potential real-time MRI-guided proton therapy systems., Methods: A permanent magnet device was utilized to generate a 0.95 T magnetic field over a 4 × 20 × 15 cm 3 volume. Within this volume, a high-resolution silicon diode array detector was positioned inside a PMMA phantom of 4 × 15 × 12 cm 3 . This detector contains two orthogonal strips containing 505 sensitive volumes spaced at 0.2 mm apart. Proton beams collimated to a circle of 10 mm diameter with nominal energies of 90 MeV, 110 MeV, and 125 MeV were incident on the detector from an edge-on orientation. This allows for a measurement of the Bragg peak at 0.2 mm spatial resolution in both the depth and lateral profile directions. The impact of the magnetic field on the proton beams, that is, a small deflection was also investigated. A Geant4 Monte Carlo simulation was performed of the experimental setup to aid in interpretation of the results., Results: The nominal Bragg peak for each proton energy was successfully observed with a 0.2 mm spatial resolution in the 0.95 T transverse magnetic field in both a depth and lateral profiles. The proton beam deflection (at 0.95 T) was a consistent 2 ±0.5 mm at the center of the magnetic volume for each beam energy. However, a pristine Bragg peak was not observed for each energy. This was caused by the detector packaging having small air gaps between layers of the phantom material surrounding the diode array. These air gaps act to degrade the shape of the Bragg peak, and further to this, the nonwater equivalent silicon chip acts to separate the Bragg peak into multiple peaks depending on the proton path taken. Overall, a promising performance of the silicon detector array was observed, however, with a qualitative assessment rather than a robust quantitative dosimetric evaluation at this stage of development., Conclusions: For the first time, a high-resolution silicon-based radiation detector has been used to measure proton beam Bragg peak deflections in a phantom due to a strong magnetic field. Future efforts are required to optimize the detector packaging to strengthen the robustness of the dosimetric quantities obtained from the detector. Such high-resolution silicon diode arrays may be useful in future efforts in MRI-guided proton therapy research., (© 2019 American Association of Physicists in Medicine.)

Proton therapy (PT) is expected to benefit from integration with magnetic resonance (MR) imaging. However, the magnetic field distorts the dose distribution and enhances the dose at tissue-air interfaces by the electron return effect (ERE). The objectives were (a) to provide experimental evidence for the ERE in proton beams and (b) to systematically characterise the dependence of the dose enhancement ratio (DER) on magnetic field strength, orientation, proton energy and voxel size by computer simulations. EBT3 films were irradiated with 200 MeV protons with and without a 0.92 T transverse field of a permanent magnet to determine the DER at effective measurement depths of 0.156 and 0.467 mm from an air interface. High-resolution Monte Carlo simulations were performed to reproduce the irradiation experiments and to calculate the DER for proton energies between 50-200 MeV and magnetic field strengths between 0.35-3 T as function of distance from the air interface. Voxel sizes of 0.05, 0.5 and 1 mm were analysed. DERs of (2.2  ±  0.4)% and (0.5  ±  0.6)% were measured at 0.156 and 0.467 mm from the air interface, respectively. Measurements and simulations agreed within 0.15%. For a 200 MeV proton beam, the maximum DER in 0.05 mm voxels increased with magnetic field strength from 2.6% to 8.2% between 0.35 and 1.5 T, respectively. For a 1.0 T magnetic field, maximum DER increased from 3.2% to 7.6% between 50 and 200 MeV, respectively. Voxel sizes of 0.5 and 1 mm resulted in maximum DER values of 2.6% and 1.4%, respectively. The ERE for proton beams in transverse magnetic fields is measurable. The local dose enhancement is significant, well predictable, decreases rapidly with distance from the air interface, and is negligible beyond 1 mm depth. Its impact on air-filled ionisation chambers and porous tissues (e.g. lung) needs to be considered.

On-line image guidance using magnetic resonance (MR) imaging is expected to improve the targeting accuracy of proton therapy. However, to date no combined system exists. In this study, for the first time a low-field open MR scanner was integrated with a static proton research beam line to test the feasibility of simultaneous irradiation and imaging. The field-of-view of the MR scanner was aligned with the beam by taking into account the Lorentz force induced beam deflection. Various imaging sequences for extremities were performed on a healthy volunteer and on a patient with a soft-tissue sarcoma of the upper arm, both with the proton beam line switched off. T 1 -weighted spin echo images of a tissue-mimicking phantom were acquired without beam, with energised beam line magnets and during proton irradiation. Beam profiles were acquired for the MR scanner's static magnetic field alone and in combination with the dynamic gradient fields during the acquisition of different imaging sequences. It was shown that MR imaging is feasible in the electromagnetically contaminated environment of a proton therapy facility. The observed quality of the anatomical MR images was rated to be sufficient for target volume definition and positioning. The tissue-mimicking phantom showed no visible beam-induced image degradation. The beam profiles depicted no influence due to the dynamic gradient fields of the imaging sequences. This study proves that simultaneous irradiation and in-beam MR imaging is technically feasible with a low-field MR scanner integrated with a static proton research beam line.

Purpose: Given its sensitivity to anatomical variations, proton therapy is expected to benefit greatly from integration with magnetic resonance imaging for online anatomy monitoring during irradiation. Such an integration raises several challenges, as both systems mutually interact. The proton beam will experience quasi-continuous energy loss and energy-dependent electromagnetic deflection at the same time, giving rise to a deflected beam trajectory and an altered dose distribution with a displaced Bragg peak. So far, these effects have only been predicted using Monte Carlo and analytical models, but no clear consensus has been reached and experimental benchmark data are lacking. We measured proton beam trajectories and Bragg peak displacement in a homogeneous phantom placed inside a magnetic field and compared them to simulations., Methods: Planar dose distributions of proton pencil beams (80-180 MeV) traversing the field of a 0.95 T NdFeB permanent magnet while depositing energy in a PMMA slab phantom were measured using EBT3 radiochromic films and simulated using the Geant4 toolkit. Deflected beam trajectories and the Bragg peak displacement were extracted from the measured planar dose distributions and compared against the simulations., Results: The lateral beam deflection was clearly visible on the EBT3 films and ranged from 1 to 10 mm for 80 to 180 MeV, respectively. Simulated and measured beam trajectories and Bragg peak displacement agreed within 0.8 mm for all studied proton energies., Conclusions: These results prove that the magnetic field-induced Bragg peak displacement is both measurable and accurately predictable in a homogeneous phantom at 0.95 T, and allows Monte Carlo simulations to be used as gold standard for proton beam trajectory prediction in similar frameworks for MR-integrated proton therapy., (© 2018 American Association of Physicists in Medicine.)