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Amaldi, U., Bonomi, R., Braccini, S., Crescenti, M., Degiovanni, A., Garlasche, M., et al. (2010). Accelerators for hadrontherapy: From Lawrence cyclotrons to linacs. Nucl. Instrum. Methods Phys. Res. A, 620(2-3), 563–577.
Abstract: Hadrontherapy with protons and carbon ions is a fast developing methodology in radiation oncology. The accelerators used and planned for this purpose are reviewed starting from the cyclotrons used in the thirties. As discussed in the first part of this paper, normal and superconducting cyclotrons are still employed, together with synchrotrons, for proton therapy while for carbon ion therapy synchrotrons have been till now the only option. The latest developments concern a superconducting cyclotron for carbon ion therapy, fast-cycling high frequency linacs and 'single room' proton therapy facilities. These issues are discussed in the second part of the paper by underlining the present challenges, in particular the treatment of moving organs.
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Borja-Lloret, M., Barrientos, L., Bernabeu, J., Lacasta, C., Muñoz, E., Ros, A., et al. (2023). Influence of the background in Compton camera images for proton therapy treatment monitoring. Phys. Med. Biol., 68(14), 144001–16pp.
Abstract: Objective. Background events are one of the most relevant contributions to image degradation in Compton camera imaging for hadron therapy treatment monitoring. A study of the background and its contribution to image degradation is important to define future strategies to reduce the background in the system. Approach. In this simulation study, the percentage of different kinds of events and their contribution to the reconstructed image in a two-layer Compton camera have been evaluated. To this end, GATE v8.2 simulations of a proton beam impinging on a PMMA phantom have been carried out, for different proton beam energies and at different beam intensities. Main results. For a simulated Compton camera made of Lanthanum (III) Bromide monolithic crystals, coincidences caused by neutrons arriving from the phantom are the most common type of background produced by secondary radiations in the Compton camera, causing between 13% and 33% of the detected coincidences, depending on the beam energy. Results also show that random coincidences are a significant cause of image degradation at high beam intensities, and their influence in the reconstructed images is studied for values of the time coincidence windows from 500 ps to 100 ns. Significance. Results indicate the timing capabilities required to retrieve the fall-off position with good precision. Still, the noise observed in the image when no randoms are considered make us consider further background rejection methods.
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Borys, D. et al, & Brzezinski, K. (2022). ProTheRaMon-a GATE simulation framework for proton therapy range monitoring using PET imaging. Phys. Med. Biol., 67(22), 224002–15pp.
Abstract: Objective. This paper reports on the implementation and shows examples of the use of the ProTheRaMon framework for simulating the delivery of proton therapy treatment plans and range monitoring using positron emission tomography (PET). ProTheRaMon offers complete processing of proton therapy treatment plans, patient CT geometries, and intra-treatment PET imaging, taking into account therapy and imaging coordinate systems and activity decay during the PET imaging protocol specific to a given proton therapy facility. We present the ProTheRaMon framework and illustrate its potential use case and data processing steps for a patient treated at the Cyclotron Centre Bronowice (CCB) proton therapy center in Krakow, Poland. Approach. The ProTheRaMon framework is based on GATE Monte Carlo software, the CASToR reconstruction package and in-house developed Python and bash scripts. The framework consists of five separated simulation and data processing steps, that can be further optimized according to the user's needs and specific settings of a given proton therapy facility and PET scanner design. Main results. ProTheRaMon is presented using example data from a patient treated at CCB and the J-PET scanner to demonstrate the application of the framework for proton therapy range monitoring. The output of each simulation and data processing stage is described and visualized. Significance. We demonstrate that the ProTheRaMon simulation platform is a high-performance tool, capable of running on a computational cluster and suitable for multi-parameter studies, with databases consisting of large number of patients, as well as different PET scanner geometries and settings for range monitoring in a clinical environment. Due to its modular structure, the ProTheRaMon framework can be adjusted for different proton therapy centers and/or different PET detector geometries. It is available to the community via github (Borys et al 2022).
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Briz, J. A., Nerio, A. N., Ballesteros, C., Borge, M. J. G., Martinez, P., Perea, A., et al. (2022). Proton Radiographs Using Position-Sensitive Silicon Detectors and High-Resolution Scintillators. IEEE Trans. Nucl. Sci., 69(4), 696–702.
Abstract: Proton therapy is a cancer treatment technique currently in growth since it offers advantages with respect to conventional X-ray and gamma-ray radiotherapy. In particular, better control of the dose deposition allowing to reach higher conformity in the treatments causing less secondary effects. However, in order to take full advantage of its potential, improvements in treatment planning and dose verification are required. A new prototype of proton computed tomography scanner is proposed to design more accurate and precise treatment plans for proton therapy. Our prototype is formed by double-sided silicon strip detectors and scintillators of LaBr3(Ce) with high energy resolution and fast response. Here, the results obtained from an experiment performed using a 100-MeV proton beam are presented. Proton radiographs of polymethyl methacrylate (PMMA) samples of 50-mm thickness with spatial patterns in aluminum were taken. Their properties were studied, including reproduction of the dimensions, spatial resolution, and sensitivity to different materials. Structures of up to 2 mm are well resolved and the sensitivity of the system was enough to distinguish the thicknesses of 10 mm of aluminum or PMMA. The spatial resolution of the images was 0.3 line pairs per mm (MTF-10%). This constitutes the first step to validate the device as a proton radiography scanner.
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Brzezinski, K. et al. (2023). Detection of range shifts in proton beam therapy using the J-PET scanner: a patient simulation study. Phys. Med. Biol., 68(14), 145016–17pp.
Abstract: Objective. The Jagiellonian positron emission tomography (J-PET) technology, based on plastic scintillators, has been proposed as a cost effective tool for detecting range deviations during proton therapy. This study investigates the feasibility of using J-PET for range monitoring by means of a detailed Monte Carlo simulation study of 95 patients who underwent proton therapy at the Cyclotron Centre Bronowice (CCB) in Krakow, Poland. Approach. Discrepancies between prescribed and delivered treatments were artificially introduced in the simulations by means of shifts in patient positioning and in the Hounsfield unit to the relative proton stopping power calibration curve. A dual-layer, cylindrical J-PET geometry was simulated in an in-room monitoring scenario and a triple-layer, dual-head geometry in an in-beam protocol. The distribution of range shifts in reconstructed PET activity was visualized in the beam's eye view. Linear prediction models were constructed from all patients in the cohort, using the mean shift in reconstructed PET activity as a predictor of the mean proton range deviation. Main results. Maps of deviations in the range of reconstructed PET distributions showed agreement with those of deviations in dose range in most patients. The linear prediction model showed a good fit, with coefficient of determination r (2) = 0.84 (in-room) and 0.75 (in-beam). Residual standard error was below 1 mm: 0.33 mm (in-room) and 0.23 mm (in-beam). Significance. The precision of the proposed prediction models shows the sensitivity of the proposed J-PET scanners to shifts in proton range for a wide range of clinical treatment plans. Furthermore, it motivates the use of such models as a tool for predicting proton range deviations and opens up new prospects for investigations into the use of intra-treatment PET images for predicting clinical metrics that aid in the assessment of the quality of delivered treatment.
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Hueso-Gonzalez, F., Berthold, J., Wohlfahrt, P., Bortfeld, T., Khamfongkhruea, C., Tattenberg, S., et al. (2024). Inter-center comparison of proton range verification prototypes with an anthropomorphic head phantom. Phys. Med. Biol., 69(22), 225010–14pp.
Abstract: Objective. To compare in reproducible and equalized conditions the performance of two independent proton range verification systems based on prompt gamma-ray detectors from two different proton therapy centers. Approach. An anthropomorphic head phantom with calibrated stopping power, serving as ground truth, was irradiated with comparable treatment plans, spot positions and energies in both facilities. Clinical beam current, tumor contour and dose were used. The absolute range measurement was compared to the expected value according to the ground truth. The statistical precision was assessed by repeating each measurement ten times. Sensitivity to relative range shifts was evaluated by introducing 2 mm and 5 mm plastic slabs on half of the field. Main results. The resulting absolute range accuracy was within 2.4 mm in all cases. Relative range shifts were detected with deviations lower than 14%. Significance. The performance of both systems was deemed worthy of clinical application for the detection of range deviations. This study represents the first comparison of independent prompt gamma-ray-based proton range verification systems under equalized conditions with realistic treatment fields and beam currents.
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Martin-Luna, P., Esperante, D., Casaña, J. V., Fernandez Prieto, A., Fuster-Martinez, N., Rivas, I. G., et al. (2025). Effects of the passive voltage divider in a photomultiplier tube: Analytical model, simulations and experimental validation. Sens. Actuator A-Phys., 381, 116057–11pp.
Abstract: The effects of the passive resistive voltage divider network in a photomultiplier tube (PMT) have been investigated by developing an in-house Monte Carlo simulation code and compared with experimental measurements and an analytical model. The simulation code follows an iterative procedure that takes into account the transport and amplification of the electrons within the device depending on the electrostatic fields produced by the electrode voltages. The PMT gain, dynode voltages, rise time and transit time have been studied as a function of the photocathode current and supply voltage. A good agreement between the analytical model, the simulations and numerous experimental measurements using a Hamamatsu R13408-100 PMT has been obtained. The simulation results endorse the use of logistic functions within the analytical model to account for the collection efficiency in the last dynode stages. This works deepens the understanding of passive voltage dividers and develops an advanced behavioral circuit model of photomultiplier tubes. Although validated fora single PMT, the proposed methodology is applicable to any PMT model. This aids in optimizing the design of fully active voltage dividers, to be applied in extremely pulsed applications with high count rates such as prompt gamma-ray imaging during proton therapy.
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Martin-Luna, P., Esperante, D., Prieto, A. F., Fuster-Martinez, N., Rivas, I. G., Gimeno, B., et al. (2024). Simulation of electron transport and secondary emission in a photomultiplier tube and validation. Sens. Actuator A-Phys., 365, 114859–10pp.
Abstract: The electron amplification and transport within a photomultiplier tube (PMT) has been investigated by developing an in-house Monte Carlo simulation code. The secondary electron emission in the dynodes is implemented via an effective electron model and the Modified Vaughan's model, whereas the transport is computed with the Boris leapfrog algorithm. The PMT gain, rise time and transit time have been studied as a function of supply voltage and external magnetostatic field. A good agreement with experimental measurements using a Hamamatsu R13408-100 PMT was obtained. The simulations have been conducted following different treatments of the underlying geometry: three-dimensional, two-dimensional and intermediate (2.5D). The validity of these approaches is compared. The developed framework will help in understanding the behavior of PMTs under highly intense and irregular illumination or varying external magnetic fields, as in the case of prompt gamma-ray measurements during pencil-beam proton therapy; and aid in optimizing the design of voltage dividers with behavioral circuit models.
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Ortega, P. G., Torres-Espallardo, I., Cerutti, F., Ferrari, A., Gillam, J. E., Lacasta, C., et al. (2015). Noise evaluation of Compton camera imaging for proton therapy. Phys. Med. Biol., 60(5), 1845–1863.
Abstract: Compton Cameras emerged as an alternative for real-time dose monitoring techniques for Particle Therapy (PT), based on the detection of prompt-gammas. As a consequence of the Compton scattering process, the gamma origin point can be restricted onto the surface of a cone (Compton cone). Through image reconstruction techniques, the distribution of the gamma emitters can be estimated, using cone-surfaces backprojections of the Compton cones through the image space, along with more sophisticated statistical methods to improve the image quality. To calculate the Compton cone required for image reconstruction, either two interactions, the last being photoelectric absorption, or three scatter interactions are needed. Because of the high energy of the photons in PT the first option might not be adequate, as the photon is not absorbed in general. However, the second option is less efficient. That is the reason to resort to spectral reconstructions, where the incoming. energy is considered as a variable in the reconstruction inverse problem. Jointly with prompt gamma, secondary neutrons and scattered photons, not strongly correlated with the dose map, can also reach the imaging detector and produce false events. These events deteriorate the image quality. Also, high intensity beams can produce particle accumulation in the camera, which lead to an increase of random coincidences, meaning events which gather measurements from different incoming particles. The noise scenario is expected to be different if double or triple events are used, and consequently, the reconstructed images can be affected differently by spurious data. The aim of the present work is to study the effect of false events in the reconstructed image, evaluating their impact in the determination of the beam particle ranges. A simulation study that includes misidentified events (neutrons and random coincidences) in the final image of a Compton Telescope for PT monitoring is presented. The complete chain of detection, from the beam particle entering a phantom to the event classification, is simulated using FLUKA. The range determination is later estimated from the reconstructed image obtained from a two and three-event algorithm based on Maximum Likelihood Expectation Maximization. The neutron background and random coincidences due to a therapeutic-like time structure are analyzed for mono-energetic proton beams. The time structure of the beam is included in the simulations, which will affect the rate of particles entering the detector.
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Roman, F. L., Abler, D., Kanellopoulos, V., Amoros, G., Davies, J., Dosanjh, M., et al. (2013). Hadron therapy information sharing prototype. J. Radiat. Res., 54, 56–60.
Abstract: The European PARTNER project developed a prototypical system for sharing hadron therapy data. This system allows doctors and patients to record and report treatment-related events during and after hadron therapy. It presents doctors and statisticians with an integrated view of adverse events across institutions, using open-source components for data federation, semantics, and analysis. There is a particular emphasis upon semantic consistency, achieved through intelligent, annotated form designs. The system as presented is ready for use in a clinical setting, and amenable to further customization. The essential contribution of the work reported here lies in the novel data integration and reporting methods, as well as the approach to software sustainability achieved through the use of community-supported open-source components.
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