Ultra-high dose rate dosimetry for pre-clinical experiments with mm-small proton fields.

PURPOSE: To characterize an experimental setup for ultra-high dose rate (UHDR) proton irradiations, and to address the challenges of dosimetry in millimetre-small pencil proton beams. METHODS: At the PSI Gantry 1, high-energy transmission pencil beams can be delivered to biological samples and detectors up to a maximum local dose rate of âˆ¼9000 Gy/s. In the presented setup, a Faraday cup is used to measure the delivered number of protons up to ultra-high dose rates. The response of transmission ion-chambers, as well as of different field detectors, was characterized over a wide range of dose rates using the Faraday cup as reference. RESULTS: The reproducibility of the delivered proton charge was better than 1 % in the proposed experimental setup. EBT3 films, Al2O3:C optically stimulated luminescence detectors and a PTW microDiamond were used to validate the predicted dose. Transmission ionization chambers showed significant volume ion-recombination (>30 % in the tested conditions) which can be parametrized as a function of the maximum proton current density. Over the considered range, EBT3 films, inorganic scintillator-based screens and the PTW microDiamond were demonstrated to be dose rate independent within ±3 %, ±1.8 % and ±1 %, respectively. CONCLUSIONS: Faraday cups are versatile dosimetry instruments that can be used for dose estimation, field detector characterization and on-line dose verification for pre-clinical experiments in UHDR proton pencil beams. Among the tested detectors, the commercial PTW microDiamond was found to be a suitable option to measure real time the dosimetric properties of narrow pencil proton beams for dose rates up to 2.2 kGy/s.

A static beam delivery device for fast scanning proton arc-therapy.

Arc-therapy is a dose delivery technique regularly applied in photon radiation therapy, and is currently subject of great interest for proton therapy as well. In this technique, proton beams are aimed at a tumor from different continuous ranges of incident directions (so called 'arcs'). This technique can potentially yield a better dose conformity around the tumor and a very low dose in the surrounding healthy tissue. Currently, proton-arc therapy is performed by rotating a proton gantry around the patient, adapting the normally used dose-delivery method to the arc-specific motion of the gantry. Here we present first results from a feasibility study of the conceptual design of a new static fast beam delivery device/system for proton-arc therapy, which could be used instead of a gantry. In this novel concept, the incident angle of proton beams can be set rapidly by only changing field strengths of small magnets. This device eliminates the motion of the heavy gantry and related hardware. Therefore, a reduction of the total treatment time is expected. In the feasibility study presented here, we concentrate on the concept of the beam transport. Based on several simple, but realistic assumptions and approximations, proton tracking calculations were performed in a 3D magnetic field map, to calculate the beam transport in this device and to investigate and address several beam-optics challenges. We propose and simulate corresponding solutions and discuss their outcomes. To enable the implementation of some usually applied techniques in proton therapy, such as pencil beam scanning, energy modulation and beam shaping, we present and discuss our proposals. Here we present the concept of a new idea to perform fast proton arc-scanning and we report on first results of a feasibility study. Based on these results, we propose several options and next steps in the design.

Faraday cup for commissioning and quality assurance for proton pencil beam scanning beams at conventional and ultra-high dose rates.

Recently, proton therapy treatments delivered with ultra-high dose rates have been of high scientific interest, and the Faraday cup (FC) is a promising dosimetry tool for such experiments. Different institutes use different FC designs, and either a high voltage guard ring, or the combination of an electric and a magnetic field is employed to minimize the effect of secondary electrons. The authors first investigate these different approaches for beam energies of 70, 150, 230 and 250 MeV, magnetic fields between 0 and 24 mT and voltages between -1000 and 1000 V. When applying a magnetic field, the measured signal is independent of the guard ring voltage, indicating that this setting minimizes the effect of secondary electrons on the reading of the FC. Without magnetic field, applying the negative voltage however decreases the signal by an energy dependent factor up to 1.3% for the lowest energy tested and 0.4% for the highest energy, showing an energy dependent response. Next, the study demonstrates the application of the FC up to ultra-high dose rates. FC measurements with cyclotron currents up to 800 nA (dose rates of up to approximately 1000 Gy s-1) show that the FC is indeed dose rate independent. Then, the FC is applied to commission the primary gantry monitor for high dose rates. Finally, short-term reproducibility of the monitor calibration is quantified within single days, showing a standard deviation of 0.1% (one sigma). In conclusion, the FC is a promising, dose rate independent tool for dosimetry up to ultra-high dose rates. Caution is however necessary when using a FC without magnetic field, as a guard ring with high voltage alone can introduce an energy dependent signal offset.

Uncertainty quantification analysis and optimization for proton therapy beam lines.

Since many years proton therapy is an effective treatment solution against deep-seated tumors. A precise quantification of sources of uncertainty in each proton therapy aspect (e.g. accelerator, beam lines, patient positioning, treatment planning) is of profound importance to increase the accuracy of the dose delivered to the patient. Together with Monte Carlo techniques, a new research field called Uncertainty Quantification (UQ) has been recently introduced to verify the robustness of the treatment planning. In this work we present the first application of UQ as a method to identify typical errors in the transport lines of a cyclotron-based proton therapy facility and analyze their impact on the properties of the therapeutic beams. We also demonstrate the potential of UQ methods in developing optimized beam optics solutions for high-dimensional problems. Sensitivity analysis and surrogate models offer a fast way to exclude unimportant parameters frcomplex optimization problems such as the design of a superconducting gantry performed at Paul Scherrer Institute in Switzerland.

Achalasia and associated esophageal cancer risk: What lessons can we learn from the molecular analysis of Barrett's-associated adenocarcinoma?

Idiopathic achalasia and Barrett's esophagus (BE) are preneoplastic conditions of the esophagus. BE increases the risk of esophageal adenocarcinoma (EAC), while achalasia is associated with both EAC and esophageal squamous cell carcinoma (ESCC). However, while the molecular mechanisms underlying the transformation of esophageal epithelial cells in BE are relatively well characterized, less is known regarding these processes in achalasia. Nevertheless, both conditions are associated with chronic inflammation and BE can occur in achalasia patients, and it is likely that similar processes underlie cancer risk in both diseases. The present review will discuss possible lessons that we can learn from the molecular analysis of BE for the study of achalasia-associated cancer and contrast findings in BE with those in achalasia. First, we will describe cellular fate during development of BE, EAC, and ESCC, and consider the inflammatory status of the epithelial barrier in BE and achalasia in terms of its contribution to carcinogenesis. Next, we will summarize current data on genetic alterations and molecular pathways involved in these processes. Lastly, the plausible role of the microbiota in achalasia-associated carcinogenesis and its contribution to abnormal lower esophageal sphincter (LES) functioning, the maintenance of chronic inflammatory status and influence on the esophageal mucosa through carcinogenic by-products, will be discussed.

Large energy acceptance gantry for proton therapy utilizing superconducting technology.

When using superconducting (SC) magnets in a gantry for proton therapy, the gantry will benefit from some reduction in size and a large reduction in weight. In this contribution we show an important additional advantage of SC magnets in proton therapy treatments. We present the design of a gantry with a SC bending section and achromatic beam optics with a very large beam momentum acceptance of [Formula: see text]15% (corresponding to about [Formula: see text]30% in the energy domain). Due to the related very large energy acceptance, approximately 70% of the treatments can be performed without changing the magnetic field for synchronization with energy modulation. In our design this is combined with a 2D lateral scanning system and a fast degrader mounted in the gantry, so that this gantry will be able to perform pencil beam scanning with very rapid energy variations at the patient, allowing a significant reduction of the irradiation time. We describe the iterative process we have applied to design the magnets and the beam transport, for which we have used different codes. COSY Infinity and OPAL have been used to design the beam transport optics and to track the particles in the magnetic fields, which are produced by the magnets designed in Opera. With beam optics calculations we have derived an optimal achromatic beam transport with the large momentum acceptance of the proton pencil beam and we show the agreement with particle tracking calculations in the 3D magnetic field map. A new cyclotron based facility with this gantry will have a significantly smaller footprint, since one can refrain from the standard degrader and energy selection system behind the cyclotron. In the treatments, this gantry will enable a very fast proton beam delivery sequence, which may be of advantage for treatments in moving tissue.

Study of the radioactivity induced in air by a 15-MeV proton beam.

Radioactivity induced by a 15-MeV proton beam extracted into air was studied at the beam transport line of the 18-MeV cyclotron at the Bern University Hospital (Inselspital). The produced radioactivity was calculated and measured by means of proportional counters located at the main exhaust of the laboratory. These devices were designed for precise assessment of air contamination for radiation protection purposes. The main produced isotopes were (11)C, (13)N and (14)O. Both measurements and calculations correspond to two different irradiation conditions. In the former, protons were allowed to travel for their full range in air. In the latter, they were stopped at the distance of 1.5 m by a beam dump. Radioactivity was measured continuously in the exhausted air starting from 2 min after the end of irradiation. For this reason, the short-lived (14)O isotope gave a negligible contribution to the measured activity. Good agreement was found between the measurements and the calculations within the estimated uncertainties. Currents in the range of 120-370 nA were extracted in air for 10-30 s producing activities of 9-22 MBq of (11)C and (13)N. The total activities for (11)C and (13)N per beam current and irradiation time for the former and the latter irradiation conditions were measured to be (3.60 ± 0.48) × 10(-3) MBq (nA s)(-1) and (2.89 ± 0.37) × 10(-3) MBq (nA s)(-1), respectively.