Proton Beam Characteristics Research Articles

Phase-change ultrasound contrast agents for proton range verification: towards an in vivo application

Objective.In proton therapy, range uncertainties prevent optimal benefit from the superior depth-dose characteristics of proton beams over conventional photon-based radiotherapy. To reduce these uncertainties we recently proposed the use of phase-change ultrasound contrast agents as an affordable and effective range verification tool. In particular, superheated nanodroplets can convert into echogenic microbubbles upon proton irradiation, whereby the resulting ultrasound contrast relates to the proton range with high reproducibility. Here, we provide a firstin vivoproof-of-concept of this technology.Approach.First, thein vitrobiocompatibility of radiation-sensitive poly(vinyl alcohol) perfluorobutane nanodroplets was investigated using several colorimetric assays. Then,in vivoultrasound contrast was characterized using acoustic droplet vaporization (ADV) and later using proton beam irradiations at varying energies (49.7 MeV and 62 MeV) in healthy Sprague Dawley rats. A preliminary evaluation of thein vivobiocompatibility was performed using ADV and a combination of physiology monitoring and histology.Main results.Nanodroplets were non-toxic over a wide concentration range (<1 mM). In healthy rats, intravenously injected nanodroplets primarily accumulated in the organs of the reticuloendothelial system, where the lifetime of the generated ultrasound contrast (<30 min) was compatible with a typical radiotherapy fraction (<5 min). Spontaneous droplet vaporization did not result in significant background signals. Online ultrasound imaging of the liver of droplet-injected rats demonstrated an energy-dependent proton response, which can be tuned by varying the nanodroplet concentration. However, caution is warranted when deciding on the exact nanodroplet dose regimen as a mild physiological response (drop in cardiac rate, granuloma formation) was observed after ADV.Significance.These findings underline the potential of phase-change ultrasound contrast agents forin vivoproton range verification and provide the next step towards eventual clinical applications.

1167: Dosimetric characterization of range shifter-modulated proton beam in the presence of magnetic field

1167: Dosimetric characterization of range shifter-modulated proton beam in the presence of magnetic field

Quantitative, real-time scintillation imaging for experimental comparison of different dose and dose rate estimations in UHDR proton pencil beams.

Ultra-high dose rate radiotherapy (UHDR-RT) has demonstrated normal tissue sparing capabilities, termed the FLASH effect; however, available dosimetry tools make it challenging to characterize the UHDR beams with sufficiently high concurrent spatial and temporal resolution. Novel dosimeters are needed for safe clinical implementation and improved understanding of the effect ofUHDR-RT. Ultra-fast scintillation imaging has been shown to provide a unique tool for spatio-temporal dosimetry of conventional cyclotron pencil beam scanning (PBS) deliveries, indicating the potential use for characterization of UHDR PBS proton beams. The goal of this work is to introduce this novel concept and demonstrate its capabilities in recording high-resolution dose rate maps at FLASH-capable proton beam currents, as compared to log-based dose rate calculation, internally developed UHDR beam simulation, and a fast point detector (EDGE diode). The light response of a scintillator sheet located at isocenter and irradiated by PBS proton fields (40-210 nA, 250 MeV) was imaged by an ultra-fast iCMOS camera at 4.5-12 kHz sampling frequency. Camera sensor and image intensifier gain were optimized to maximize the dynamic range; the camera acquisition rate was also varied to evaluate the optimal sampling frequency. Large field delivery enabled flat field acquisition for evaluation of system response homogeneity. Image intensity was calibrated to dose with film and the recorded spatio-temporal data was compared to a PPC05 ion chamber, log-based reconstruction, and EDGE diode. Dose and dose rate linearity studies were performed to evaluate agreement under various beam conditions. Calculation of full-field mean and PBS dose rate maps were calculated to highlight the importance of high resolution, full-field information in UHDRstudies. Camera response was linear with dose (R2 = 0.997) and current (R22 = 0.98) in the range from 2-22 Gy and 40-210 nA, respectively, when compared to ion chamber readings. The deviation of total irradiation time calculated with the imaging system from the log file recordings decreased from 0.07% to 0.03% when imaging at 12 kfps versus 4.5 kfps. Planned and delivered spot positions agreed within 0.2 0.1 mm and total irradiation time agreed within 0.2 0.2 ms when compared with the log files, indicating the high concurrent spatial and temporal resolution. For all deliveries, the PBS dose rate measured at the diode location agreed between the imaging and the diode within 3% 2% and with the simulation within 5% 3% CONCLUSIONS: Full-field mapping of dose and dose rate is imperative for complete understanding of UHDR PBS proton dose delivery. The high linearity and various spatiotemporal metric reporting capabilities confirm the continued use of this camera system for UHDR beam characterization, especially for spatially resolved dose rateinformation.

50-Channel Ionoacoustic Sensor for 60 MeV Proton Beam Characterization in Hadron Therapy Applications

This paper presents the design of a piezoelectric multichannel sensor optimized for sensing weak ionoacoustic signals generated at the Bragg peak (BP) of pulsed proton beams, with interesting possible applications in real-time monitoring of oncological hadron therapy treatments. To overcome current single-channel detector limitations and acquire the weak acoustic signals of clinical scenarios (60–200 MeV proton energy and few mGy dose deposition), the hereby presented detector overcomes the state-of-the-art approach (based on time-domain correlation i.e., averaging different beam pulses) by using spatial correlation (i.e., averaging signals from different detector channels) to increase the SNR without increasing the delivered dose. The detector design is tailored around the experimental environment characteristics (signal amplitude, signal frequency, relative BP-detector position) of a clinical proton beam (60 MeV, 2 mGy/pulse dose deposition). The detector design was characterized by a complete cross-domain simulation of the physical (proton beam), acoustic (wave propagation) and electrical (sensor and electronics frequency response and noise) environments. It achieves a clear 10 dB single-pulse SNR (2 mGy total dose) and allows to locate the BP with 125 μm precision (< 3% w.r.t. the particle range). Finally, the detector was experimentally validated by a piezoelectric acoustic testbench and has shown the capability to localize an acoustic source in 2D with sub-millimeter accuracy by using a multilateration-based BP detection algorithm.

A scintillator detector for spatio-spectral characterization of proton beams at high repetition rate

A scintillator detector for spatio-spectral characterization of proton beams at high repetition rate

Proton Bragg curve and energy reconstruction using an online scintillator stack detector.

Real-time measurement and characterization of laser-driven proton beams have become crucial with the advent of high-repetition-rate laser acceleration. Common passive diagnostics such as radiochromic film (RCF) are not suitable for real-time operation due to time-consuming post-processing; therefore, a novel approach is needed. Various scintillator-based detectors have recently gained interest as real-time substitutes to RCF-thanks to their fast response for a wide range of dose deposition rates. This work introduces a compact, scalable, and cost-effective scintillator-based device for proton beam measurements in real-time suitable for the laser-plasma environment. An advanced signal processing technique was implemented based on detailed Monte Carlo simulations, enabling an accurate unfolding of the proton energy and the depth-dose deposition curve. The quenching effect was accounted for based on Birks' law with the help of the Monte Carlo simulations. The detector was tested in a proof-of-principle experiment at a conventional cyclotron accelerating protons up to 35MeV of energy. The signal comparison with a standard RCF stack was also performed during the test of the device, showing an excellent agreement between the two diagnostics. Such devices would be suitable for both conventional and laser-driven proton beam characterization.

PO-1838 Characterization of a ultra-high dose rate proton beam for preclinical experiments.

PO-1838 Characterization of a ultra-high dose rate proton beam for preclinical experiments.

Ultra-fast, high spatial resolution single-pulse scintillation imaging of synchrocyclotron pencil beam scanning proton delivery

Objective. To demonstrates the ability of an ultra-fast imaging system to measure high resolution spatial and temporal beam characteristics of a synchrocyclotron proton pencil beam scanning (PBS) system. Approach. An ultra-fast (1 kHz frame rate), intensified CMOS camera was triggered by a scintillation sheet coupled to a remote trigger unit for beam on detection. The camera was calibrated using the linear (R 2 > 0.9922) dose response of a single spot beam to varying currents. Film taken for the single spot beam was used to produce a scintillation intensity to absolute dose calibration. Main results. Spatial alignment was confirmed with the film, where the x and y-profiles of the single spot cumulative image agreed within 1 mm. A sample brain patient plan was analyzed to demonstrate dose and temporal accuracy for a clinically-relevant plan, through agreement within 1 mm to the planned and delivered spot locations. The cumulative dose agreed with the planned dose with a gamma passing rate of 97.5% (2 mm/3%, 10% dose threshold). Significance. This is the first system able to capture single-pulse spatial and temporal information for the unique pulse structure of a synchrocyclotron PBS systems at conventional dose rates, enabled by the ultra-fast sampling frame rate of this camera. This study indicates that, with continued camera development and testing, target applications in clinical and FLASH proton beam characterization and validation are possible.

Proton beam range verification by means of ionoacoustic measurements at clinically relevant doses using a correlation-based evaluation.

The Bragg peak located at the end of the ion beam range is one of the main advantages of ion beam therapy compared to X-Ray radiotherapy. However, verifying the exact position of the Bragg peak within the patient online is a major challenge. The goal of this work was to achieve submillimeter proton beam range verification for pulsed proton beams of an energy of up to 220 MeV using ionoacoustics for a clinically relevant dose deposition of typically 2 Gy per fraction by i) using optimal proton beam characteristics for ionoacoustic signal generation and ii) improved signal detection by correlating the signal with simulated filter templates. A water tank was irradiated with a preclinical 20 MeV proton beam using different pulse durations ranging from 50 ns up to 1 μs in order to maximise the signal-to-noise ratio (SNR) of ionoacoustic signals. The ionoacoustic signals were measured using a piezo-electric ultrasound transducer in the MHz frequency range. The signals were filtered using a cross correlation-based signal processing algorithm utilizing simulated templates, which enhances the SNR of the recorded signals. The range of the protons is evaluated by extracting the time of flight (ToF) of the ionoacoustic signals and compared to simulations from a Monte Carlo dose engine (FLUKA). Optimised SNR of 28.0 ± 10.6 is obtained at a beam current of 4.5 μA and a pulse duration of 130 ns at a total peak dose deposition of 0.5 Gy. Evaluated ranges coincide with Monte Carlo simulations better than 0.1 mm at an absolute range of 4.21 mm. Higher beam energies require longer proton pulse durations for optimised signal generation. Using the correlation-based post-processing filter a SNR of 17.8 ± 5.5 is obtained for 220 MeV protons at a total peak dose deposition of 1.3 Gy. For this clinically relevant dose deposition and proton beam energy, submillimeter range verification was achieved at an absolute range of 303 mm in water. Optimal proton pulse durations ensure an ideal trade-off between maximising the ionoacoustic amplitude and minimising dose deposition. In combination with a correlation-based post-processing evaluation algorithm, a reasonable SNR can be achieved at low dose levels putting clinical applications for online proton or ion beam range verification into reach.

MOQUI: an open-source GPU-based Monte Carlo code for proton dose calculation with efficient data structure

Objective. Monte Carlo (MC) codes are increasingly used for accurate radiotherapy dose calculation. In proton therapy, the accuracy of the dose calculation algorithm is expected to have a more significant impact than in photon therapy due to the depth-dose characteristics of proton beams. However, MC simulations come at a considerable computational cost to achieve statistically sufficient accuracy. There have been efforts to improve computational efficiency while maintaining sufficient accuracy. Among those, parallelizing particle transportation using graphic processing units (GPU) achieved significant improvements. Contrary to the central processing unit, a GPU has limited memory capacity and is not expandable. It is therefore challenging to score quantities with large dimensions requiring extensive memory. The objective of this study is to develop an open-source GPU-based MC package capable of scoring those quantities. Approach. We employed a hash-table, one of the key-value pair data structures, to efficiently utilize the limited memory of the GPU and score the quantities requiring a large amount of memory. With the hash table, only voxels interacting with particles will occupy memory, and we can search the data efficiently to determine their address. The hash-table was integrated with a novel GPU-based MC code, moqui. Main results. The developed code was validated against an MC code widely used in proton therapy, TOPAS, with homogeneous and heterogeneous phantoms. We also compared the dose calculation results of clinical treatment plans. The developed code agreed with TOPAS within 2%, except for the fall-off and regions, and the gamma pass rates of the results were >99% for all cases with a 2 mm/2% criteria. Significance. We can score dose-influence matrix and dose-rate on a GPU for a 3-field H&N case with 10 GB of memory using moqui, which would require more than 100 GB of memory with the conventionally used array data structure.

Synchronized high-speed scintillation imaging of proton beams, generated by a gantry-mounted synchrocyclotron, on a pulse-by-pulse basis.

With the emergence of more complex and novel proton delivery techniques, there is a need for quality assurance tools with high spatiotemporal resolution to conveniently measure the spatial and temporal properties of the beam. In this context, scintillation-based dosimeters, if synchronized with the radiation beam and corrected for ionization quenching, are appealing. To develop a synchronized high-speed scintillation imaging system for characterization and verification of the proton therapy beams on a pulse-by-pulse basis. A 30cm×30cm×5cm block of BC-408 plastic scintillator placed in a light-tight housing was irradiated by proton beams generated by a Mevion S250 proton therapy synchrocyclotron. A high-speed camera system, placed perpendicular to the beam direction and facing the scintillator, was synchronized to the accelerator's pulses to capture images. Opening and closing of the camera's shutter was controlled by setting a proper time delay and exposure time, respectively. The scintillation signal was recorded as a set of two-dimensional (2D) images. Empirical correction factors were applied to the images to correct for the nonuniformity of the pixel sensitivity and quenching of the scintillator. Proton range and modulation were obtained from the corrected images. The camera system was able to capture all data on a pulse-by-pulse basis at a rate of ∼504 frames per second. The applied empirical correction method for ionization quenching was effective and the corrected composite image provided a 2D map of dose distribution. The measured range (depth of distal 90%) through scintillation imaging agreed within 1.2mm with that obtained from ionization chamber measurement. A high-speed camera system capable of capturing scintillation signals from individual proton pulses was developed. The scintillation imaging system is promising for rapid proton beam characterization and verification.

Transmission and homogenization of laser-driven proton beams with broadband spectra

<p indent="0mm">Over the past few decades, laser accelerators made continuous progress. Thanks to the ultra-high electric field gradient (100 GV/m) generated by the interaction of laser and plasma, protons can be accelerated to MeV energy at a micron scale, being expected to be a new generation of widely used compact accelerators. The laser-driven proton beam has the characteristics of μm-level size (point source), ampere-level peak current, broadband energy spectrum, and large divergence angle. Irradiation applications need a uniform dose distribution, requiring the transformation from a point source to a large area of uniformly distributed particles. Increase of utilization efficiency requires that beams with energy spread as large as possible can be transmitted, while the chromatic aberrations pose a challenge to the homogenization of the beams, including the homogenization of the beams with the same energy and different initial divergence angles, and the homogenization of the beams with different energies. The weak focusing of the constant gradient magnetic field can focus in the horizontal and vertical directions at the same time, and analyze the energy in the horizontal direction. The integration of focusing and energy analysis can achieve achromatic transmission, or significantly reduce the influence of chromatic aberrations. This paper studies the transmission characteristics of proton beams in weak-focusing magnetic fields. The homogenized transformation for protons with the same energy in the horizontal direction from a point to a large area by point-to-parallel imaging is demonstrated. Point-to-parallel imaging is not a necessary condition for homogenization; transformation without point-to-parallel imaging in the vertical direction also obtains good homogeneity. The conditions for positional achromaticity in the horizontal direction are explored, and the transmission and homogenization of proton beams with 20% energy spread can be achieved with appropriate design. In positional achromatic transmission, the chromatic aberrations still have influence, causing the proton beam with large energy spread to deviate from the center of the beamline in the horizontal direction. In order to reduce the influence of chromatic aberrations, a special steering magnet is designed after the weak-focusing magnet to correct the divergence angle in the horizontal direction. The relationship between the correction amount of divergence angle and the position in the horizontal direction is obtained through parameter scanning, which can be well fitted by a 4 order polynomial. After correcting the divergence angle, the proton beam with large energy spread returns to the center of the beamline at the beamline exit. With a slit and energy spectrum shaping, proton beams with 80% energy spread can be obtained for irradiation with better uniformity. When the deflection radius is designed to be <sc>0.65 m,</sc> the weak-focusing beamline can transmit proton beams with <sc>1–20 MeV</sc> energy, 80% energy spread, and an initial divergence angle of ±50 mrad. After changing the magnetic field direction, electron beams with <sc>1–200 MeV</sc> energy, 40% energy spread can be transmitted. The transmission and homogenization of the proton beam with 80% energy spread greatly improves the utilization efficiency. Higher energy particle beams can be delivered using superconducting or pulsed magnet technology. The study found that the influence of chromatic aberrations is much larger in the beam transmission with a quadrupole triplet lens (strong focusing), and as energy cannot be accurately analyzed, it is difficult to improve. In comparison, the weak-focusing magnetic fields have significant advantages for beam homogenization.

Energy-Loss Straggling and Delta-Ray Escape in Solid-State Microdosimeters Used in Ion-Beam Therapy

Microdosimetry is increasingly adopted in the characterization of proton and carbon ion beams used in cancer therapy. Spectra and mean values of lineal energy calculated in frequency and dose are seen by many as the tools which, by complementing dosimetric measurements, allow for the most complete characterization of the therapeutic radiation fields. The urgency is now to consolidate the experience and converge to commonly accepted methodologies. In this context, the purpose of this work is to study the effects of the energy-loss straggling and the delta-ray escape, considering slab-sensitive volumes; these are, in fact, the typical shapes of solid-state microdosimeters, which are widely used in investigating light ion therapy beams. The method considers the energy distribution of delta rays resulting from the collision of the impinging ion and, taking into account the escape, convolutes it with itself as many times as the expected number of collisions in the sensitive volume thickness. The resulting distribution is compared to the experimental microdosimetric spectrum showing a substantially good agreement. The extension of the methodology to a wider range of ion energy and detector characteristics is instrumental for a detector-independent microdosimetric assessment of the radiation fields.

The proton irradiation facility for Single-Event effect testing in CIAE*

The proton radiation facility is built at an irradiation terminal of a 100-MeV cyclotron accelerator in the China Institute of Atomic Energy (CIAE). It is mainly used for testing the single-event effect of electronic devices. The part and function of the proton beamline for radiation effects research are introduced. Many detectors and techniques are used to accomplish accurate and reliable dosimetry and characterization of the proton beam. The results of beam characterization such as transmission, energy, lateral profile, and flux are reported. A typical monitoring and measuring system consist of a secondary electron emission monitor (SEM) working in a transmission mode and Faraday cup (FC). A cross-checking method of proton flux accuracy by FC and scintillation detector (SC) is established. The application of the reference single-event upset (SEU) monitor for the characterization of proton beams at different facilities is described. The SEU cross-section of the Reference SEU Monitor has confirmed the flux detection accuracy at CIAE.

Analysis of dose distribution in proton therapy for lung cancer with MCNP code

Proton beam characteristics for proton therapy have been obtained by simulation method using MCNP6 software. The proton beam is modelled as a monodirectional disk with a diameter of 3 cm is 23 cm from the left lung cancer, a sphere with a diameter of 3 cm. The variation of proton beam energy that produces the best isodose in cancer cells is 94 MeV, 104 MeV, and 112 MeV fired alternately at the target from the left. The result is a total equivalent dose in cancer cells of (0.858 ± 0.003) Sv. The scattered amount received by healthy cells in the left lung was (1.39 ± 0.01) mSv, rib (0.12 ± 0.01) mSv, and skin (0.11 ± 0.01) mSv. According to the organ at risk (OAR) provisions, the scattered dose is declared safe. The simulation results prove that proton therapy is a cell targeting therapy. The dose used to kill lung cancer cells is 60 Gy, so with a proton beam of 1 µA, the total exposure time for therapy is (2.31 ± 0.01) minutes.

Mutagenic Effect of Proton Beams Characterized by Phenotypic Analysis and Whole Genome Sequencing in Arabidopsis.

Protons may have contributed to the evolution of plants as a major component of cosmic-rays and also have been used for mutagenesis in plants. Although the mutagenic effect of protons has been well-characterized in animals, no comprehensive phenotypic and genomic analyses has been reported in plants. Here, we investigated the phenotypes and whole genome sequences of Arabidopsis M2 lines derived by irradiation with proton beams and gamma-rays, to determine unique characteristics of proton beams in mutagenesis. We found that mutation frequency was dependent on the irradiation doses of both proton beams and gamma-rays. On the basis of the relationship between survival and mutation rates, we hypothesized that there may be a mutation rate threshold for survived individuals after irradiation. There were no significant differences between the total mutation rates in groups derived using proton beam or gamma-ray irradiation at doses that had similar impacts on survival rate. However, proton beam irradiation resulted in a broader mutant phenotype spectrum than gamma-ray irradiation, and proton beams generated more DNA structural variations (SVs) than gamma-rays. The most frequent SV was inversion. Most of the inversion junctions contained sequences with microhomology and were associated with the deletion of only a few nucleotides, which implies that preferential use of microhomology in non-homologous end joining was likely to be responsible for the SVs. These results show that protons, as particles with low linear energy transfer (LET), have unique characteristics in mutagenesis that partially overlap with those of low-LET gamma-rays and high-LET heavy ions in different respects.

Parametric Study of Proton Acceleration from Laser-Thin Foil Interaction

We experimentally investigated the accelerated proton beam characteristics such as maximum energy and number by varying the incident laser parameters. For this purpose, we varied the laser energy, focal spot size, polarization, and pulse duration. The proton spectra were recorded using a single-shot Thomson parabola spectrometer equipped with a microchannel plate and a high-resolution charge-coupled device with a wide detection range from a few tens of keV to several MeV. The outcome of the experimental findings is discussed in detail and compared to other theoretical works.

PH-0045: Characterization of proton, carbon and silicon ion beams using scCVD diamond-based microdosimeters

PH-0045: Characterization of proton, carbon and silicon ion beams using scCVD diamond-based microdosimeters

Dose-dependent Changes After Proton and Photon Irradiation in a Zebrafish Model.

The importance of hadron therapy in the cancer management is growing. We aimed to refine the biological effect detection using a vertebrate model. Embryos at 24 and 72 h postfertilization were irradiated at the entrance plateau and the mid spread-out Bragg peak of a 150 MeV proton beam and with reference photons. Radiation-induced DNA double-strand breaks (DSB) and histopathological changes of the eye, muscles and brain were evaluated; deterioration of specific organs (eye, yolk sac, body) was measured. More and longer-lasting DSBs occurred in eye and muscle cells due to proton versus photon beams, albeit in different numbers. Edema, necrosis and tissue disorganization, (especially in the eye) were observed. Dose-dependent morphological deteriorations were detected at ≥10 Gy dose levels, with relative biological effectiveness between 0.99±0.07 (length) and 1.12±0.19 (eye). Quantitative assessment of radiation induced changes in zebrafish embryos proved to be beneficial for the radiobiological characterization of proton beams.

Microdosimetric measurements of a monoenergetic and modulated Bragg Peaks of 62MeV therapeutic proton beam with a synthetic single crystal diamond microdosimeter.

The purpose of this study was to investigate for the first time the performance of a synthetic single crystal diamond detector for the microdosimetric characterization of clinical 62MeV ocular therapy proton beams. A novel diamond microdosimeter with a well-defined sensitive volume was fabricated and tested with a monoenergetic and spread-out Bragg peak (SOBP) of the CATANA therapeutic proton beam in Catania, Italy. The whole sensitive volume of the detector has an active planar-sectional area of 100µm×100µm and a thickness of approximately 6.3 um. Microdosimetric measurements were performed at several water equivalent depths, corresponding to positions of clinical relevance. From the measured spectra, microdosimetric quantities such as the frequency mean lineal energy ( ), dose mean lineal energy ( ) as well as microdosimetric relative biological effectiveness (RBEµ ) values were derived for each depth along both a pristine Bragg curve and SOBP. Finally, Geant4 Monte Carlo simulations were performed modeling the detector geometry and CATANA beamline in order to calculate the average linear energy transfer (LET) values in the diamond active layer and water. The microdosimetric spectra acquired by the diamond microdosimeter show different shapes as a function of the water equivalent depths. No spectral distortion, due to pile-up events and polarization effects, was observed. The experimental spectra have a very low detection threshold due to the electronic noise during the irradiation of about 1keV/μm. The and values were in agreement with expected trends, showing a sharp increase in mean lineal energy at the distal edge of the Bragg peak. In addition, a good agreement between the mean lineal energy values and the calculated average LET ones was also observed. Finally, the RBE values evaluated with the diamond microdosimeter were in excellent agreement with those obtained with a mini tissue equivalent proportional counter as well as with radiobiological measurements in the same proton beam field. The microdosimetric performance of the tested synthetic single crystal diamond microdosimeter clearly indicates its suitability for quality assurance in clinical proton therapy beam.