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Objective. Compton camera imaging shows promise as a range verification technique in proton therapy. This work aims to assess the performance of a machine learning model in Compton camera imaging for proton beam range verification improvement. Approach. The presented approach was used to recognize Compton events and estimate more accurately the prompt gamma (PG) energy in the Compton camera to reconstruct the PGs emission profile during proton therapy. This work reports the results obtained from the Geant4 simulation for a proton beam impinging on a polymethyl methacrylate (PMMA) target. To validate the versatility of such an approach, the produced PG emissions interact with a scintillating fiber-based Compton camera. Main results. A trained multilayer perceptron (MLP) neural network shows that it was possible to achieve a notable three-fold increase in the signal-to-total ratio. Furthermore, after event selection by the trained MLP, the loss of full-energy PGs was compensated by means of fitting an MLP energy regression model to the available data from true Compton (signal) events, predicting more precisely the total deposited energy for Compton events with incomplete energy deposition. Significance. A considerable improvement in the Compton camera's performance was demonstrated in determining the distal falloff and identifying a few millimeters of target displacements. This approach has shown great potential for enhancing online proton range monitoring with Compton cameras in future clinical applications., (Creative Commons Attribution license.)

Within the frame of the CLaRyS collaboration, we discuss the assets of using a reduced-intensity in vivo treatment control phase during one or a few beam spots at the beginning of a particle therapy session. By doing so we can improve considerably the conditions for secondary radiation detection and particle radiography. This also makes Time-of-Flight (ToF) resolutions of 100 ps rms feasible for both the transmitted particles and secondary radiations, by means of a single-projectile counting mode using a beam-tagging monitor with time and position registration. This opens up new perspectives for prompt-gamma timing and Compton imaging for range verification. ToF-based proton computed tomography (CT) and ToF-assisted secondary proton vertex imaging in carbon therapy are also discussed, although for the latter, no evidence of any benefit at small observation angles is anticipated. The reduction of the beam intensity during one or a few spots on the various accelerators for particle therapy should not significantly reduce the patient workflow.

• Novel Compton camera design based on heavy inorganic scintillating fibers and SiPMs. • Optimization of geometry and selection of scintillating material for the detector. • Monte Carlo study for determination of expected detector performance. • Determination of event rate in clinical conditions, energy and position resolution. • Study indicates that the proposed detector is feasible for proton therapy monitoring. One of the big challenges for proton therapy is the development of tools for online monitoring of the beam range, which are suited to operate in clinical conditions and can be included in the clinical practice. A Compton camera based on stacks of heavy scintillating fibers used for prompt-gamma imaging is a promising approach for this task. It provides full, three-dimensional information on the deposited dose distribution while showing a high detection efficiency and rate capability due to its high granularity. The investigation of the rate capability and detection efficiency of such a camera under clinical conditions by means of Geant 4 simulations is presented along with the event construction algorithm. The results hint towards a very low pile-up rate in the detector and a relatively high detection efficiency, so that imaging of a single proton beam spot appears to be an achievable goal. [ABSTRACT FROM AUTHOR]

Purpose/objective(s): Online proton range/dose verification based on measurements of proton‐induced positron emitters is a promising strategy for quality assurance in proton therapy. Because of the nonlinear correlation between the dose distribution and the activity distribution of positron emitters in addition to the presence of noise, machine learning approaches were proposed to establish their relationship. Materials/methods: Simulations were carried out with a spot‐scanning proton system using GATE‐8.0 and Geant4‐10.3 toolkit with a computed tomography (CT)‐based patient phantom. The one‐dimensional (1D) distributions of positron emitters and radiation dose were obtained. A feedforward neural network classification model comprising two hidden layers, was developed to estimate whether the range is within a preset threshold. A recurrent neural network (RNN) regression model comprising three layers and ten neurons in each hidden layer was developed to estimate dose distribution. The performance was quantitatively studied in terms of mean squared error (MSE) and mean absolute error (MAE) under different signal‐to‐noise ratio (SNR) values. Results: The feasibility of proton range and dose verification using the proposed neural network framework was demonstrated. The feedforward NN model achieves high classification accuracy close to 100% for individual classes without bias. The RNN model is able to accurately predict the 1D dose distribution for different energies and irradiation positions. When the SNR of the input activity profiles is above 4, the framework is able to predict with an MAE of ~0.60 mm and an MSE of ~0.066. Moreover, the model demonstrates a good capability of generalization. Conclusions: The RNN model is found to be effective in identifying the relationship between the distributions of dose and positron emitters. The machine learning‐based framework and RNN models may be a useful tool to allow for accurate online range and dose verification based on proton‐induced positron emitters. [ABSTRACT FROM AUTHOR]

The ultimate goal of radiotherapy using external beams is to maximize the dose delivered to the tumor while minimizing the radiation given to surrounding healthy critical organs. Prompt Gamma Spectroscopy (PGS) has been proposed for range control of particle beams along with the determination of the elemental composition of irradiated tissues. We aim at developing a PGS system for the German Cancer Research Center – DKFZ that takes advantage of the superior selectivity of Helium and Carbon beams accelerated at the Heidelberg Ion-Beam Therapy Center. Preliminary tests with protons accelerated with an IBA C230 cyclotron located at the Universitäts Protonen Therapie Dresden were performed at OncoRay – National Center for Radiation Re-search in Oncology. We present results obtained with a PGS system composed of CeBr3 detectors (Ø 2’’ × 2’’) and (Ø 1.5’’ × 3’’) coupled to a Hamamatsu R13089 photomulti-plier tube and plugged to a Target U100 Spectrometer. Such system provides accurate time-of-flight measurements to increase the signal-to-noise ratio relative to neutron-induced background. First measurements resulted from the irradiation of PMMA and water phantoms, and graphite and aluminum bricks. Several PG energy lines ranging from 0.511 MeV up to 8 MeV were identified and compared with reference re-sults. Two further experiments consisted in irradiating PMMA phantoms in a slit- and semi-collimated configuration with mono-energetic proton beams of 165 MeV and 224 MeV, respectively. Results acquired by means of trans-versal PGS at different phantom depths, ranging from 6 cm before the Bragg peak (BP) to 3.5 cm beyond the BP in 5 mm steps with a 1 cm slit collimation (tungsten) showed a slight decrease of PG yields after the BP. Similar measurements with a semi-opened collimation configuration demonstrated a steeper decrease of PG yields after the BP.

Objective. Prompt-gamma imaging encompasses several approaches to the online monitoring of the beam range or deposited dose distribution in proton therapy. We test one of the imaging techniques - a coded mask approach - both experimentally and via simulations. Approach. Two imaging setups have been investigated experimentally. Each of them comprised a structured tungsten collimator in the form of a modified uniformly redundant array mask and a LYSO:Ce scintillation detector of fine granularity. The setups differed in detector dimensions and operation mode (1D or 2D imaging). A series of measurements with radioactive sources have been conducted, testing the performance of the setups for near-field gamma imaging. Additionally, Monte Carlo simulations of a larger setup of the same type were conducted, investigating its performance with a realistic gamma source distribution occurring during proton therapy. Main results. The images of point-like sources reconstructed from two small-scale prototypes' data using the maximum-likelihood expectation maximisation algorithm constitute the experimental proof of principle for the near-field coded-mask imaging modality, both in the 1D and the 2D mode. Their precision allowed us to calibrate out certain systematic offsets appearing due to the limited alignment accuracy of setup elements. The simulation of the full-scale setup yielded a mean distal falloff retrieval precision of 0.72 mm in the studies for beam energy range 89.5-107.9 MeV and with 1 × 10 8 protons (a typical number for distal spots). The implemented algorithm of image reconstruction is relatively fast-a typical procedure needs several seconds. Significance. Coded-mask imaging appears a valid option for proton therapy monitoring. The results of simulations let us conclude that the proposed full-scale setup is competitive with the knife-edge-shaped and the multi-parallel slit cameras investigated by other groups., (Creative Commons Attribution license.)

Purpose: In vivo range verification in proton therapy is a critical step to help minimize range and dose uncertainty. We propose to employ a time reversal (TR)‐based approach using proton‐induced acoustics (protoacoustics) to reconstruct pressure/dose distribution in heterogeneous tissues. Methods: The dose distribution of mono‐energetic proton pencil beam in a CT‐based patient phantom was calculated by Monte Carlo simulation. K‐wave toolbox was used to investigate protoacoustic pressurization, propagation and reconstruction in 2D. To address the tissue heterogeneity effect, a number of physical parameters, including mass density (ρ), speed of sound (c), volumetric thermal expansion coefficient (αV), isobaric specific heat capacity (Cp) and attenuation power law prefactor (α0), were empirically converted from CT number. The performance was evaluated using two figures of merit: mean square error (MSE) of pressure profiles and Bragg peak localization error (ΔBP). The impact of six parameters of the TR inversion was examined, including number of sensors, sampling duration, sampling timestep, spill time, noise level and number of iterations. Results: The quantitative accuracy of TR reconstruction and its dependency on the selected parameters is presented. Under optimum conditions, the positioning accuracy of the Bragg peak can be controlled below 1 mm. For instance, MSE is 0.0123 and ΔBP is 0.59 mm under the following conditions (32 sensors, sampling duration: 600 µs, sampling timestep: 40 ns, spill time: 1 µs, no noise). Conclusions: The feasibility of TR‐based protoacoustic reconstruction in 2D for proton range verification was first demonstrated. The approach is not only applicable to pencil beam, but also has potential to be extended to passive scattering systems. [ABSTRACT FROM AUTHOR]

• Characteristics of prompt gamma (PG) emission from helium ions are highlighted in comparison to proton and carbon beams. • The relationship of PG angular distribution and time-of-flight spectra can be utilized for optimizing primary PG detection. • Hybrid PG detections to utilize their energy, time and spatial characteristics are desirable. In this paper we investigate the emission and detection characteristics of prompt gamma (PG) rays for in vivo range verification during hadron therapy, using Geant4 simulations. Proton, 4He and 12C beams of varying energy are incident on water phantoms. The PG production yield, energy spectral characteristics and spatial correlation with the Bragg Peak (BP) have been quantified. Further, the angular distributions for PG detection with respect to a point-of-reference on the phantom surface have been explored. The temporal properties of PG emission and time-of-flight (TOF) of PG detection have also been investigated in correlation with the changing particle beam range. Our results show that the primary PG rays from nuclear interactions of the primary beam exhibit the closest correlation to the beam range but its signal is significantly masked by the concurrent secondary PG rays, particularly for heavier ions such as carbon ion beams. The PG TOF spectroscopy encodes the essential information of the beam range but requires high time resolution measurements to retrieve it. A hybrid PG detection system to utilize the energy, timing and spatial characteristics of PG rays is desirable for BP tracking in real-time. [ABSTRACT FROM AUTHOR]

Purpose: Daily verification of the proton beam range in proton radiation therapy is a vital part of the quality assurance (QA) program. The objective of this work is to study the use of a multilayer Faraday cup (MLFC) to perform a quick and precise daily range verification of proton beams produced by a synchrotron. Methods: Proton beam depth dose measurements were performed at room iso‐center in water using PTW water tank and Bragg Peak ion chamber. The IBA Giraffe, calibrated against the water tank data, was used to measure the water equivalent thickness (WET) of the sample copper plates. The WET measurements provided the range calibration factors for the MLFC. To establish a baseline for in room measurements, range measurements for energies from 70 to 250 MeV in steps of 10 MeV were performed using the Pyramid MLFC at room iso‐center. For the daily range verification measurements, the MLFC is permanently placed at the end of the beam line, inside the accelerator vault. The daily range constancy is performed for five representative beam energies; namely 70, 100, 150, 200, and 250 MeV. Data collected over a period of more than 100 days are analyzed and presented. Results: The measured WET values of the copper plates increased with increasing energy. The centroid channel number in the MLFC where the protons stop, was converted to depth in water and compared to the depth of the distal 80% (d80) obtained from the water tank measurements. The depths agreed to within 2 mm, with the maximum deviation of 1.97 mm observed for 250 MeV beam. The daily variation in the ranges measured by the MLFC was within ±0.5 mm. The total time to verify five proton beam ranges varies between 4 and 5 min. Conclusion: Based on the result of our measurements, the MLFC can be used for a daily range constancy check with submillimeter accuracy. It is a quick and simple method to perform range constancy verification on a daily basis. [ABSTRACT FROM AUTHOR]

Purpose: To demonstrate robustness of thermooacoustic range verification to acoustic heterogeneity and discrepancies between assumed and true propagation speed, i.e., soundspeed errors. Methods: A beam sweeper was used to deliver 250 ns pulses that deposited 0.26 Gy of 16 MeV protons and 2.3 Gy of 60 MeV helium ions into water and oil targets, respectively. Thermoacoustic signals were detected by a 96‐channel ultrasound array with a 1–4 MHz sensitivity band (−6 dB), bandpass filtered and backprojected to create thermoacoustic images in the plane of the ultrasound array. The same soundspeed and transducer array were used to estimate range and generate the ultrasound images onto which Bragg peak locations were overlaid. An air‐gap phantom that displaced the Bragg peak by 6.5 mm demonstrated accuracy. Robustness to soundspeed errors was demonstrated in a waterbath as the assumed propagation speed scanner setting was altered by ±5%. Tissue‐mimicking gelatin and a bone sample were introduced to demonstrate robustness to acoustic heterogeneity relative to ultrasound images of the underlying morphology. Results: Single ion pulse measurements sufficed during the helium run, but signal averaging was required for protons. Range and entry point into the target were estimated from data collected by transducers placed at least 6 cm distal to the Bragg peak. When ultrasound images depicted the air–target interface where the beam enters, estimates of the entry point agreed with ultrasound images and range estimates agreed with Monte Carlo simulations to within 300 μm, even when thermoacoustic emissions traveled through a strongly scattering bone sample. Estimated Bragg peak locations were translated 6.5 mm by the air‐gap phantom and correctly identified scenarios when the beam stopped inside the bone. Conclusions: Soundspeed errors dilate and acoustic heterogeneities deform ultrasound images. When thermoacoustic receivers are co‐located with the ultrasound imaging array, the same transformations shift thermoacoustic range estimates. Therefore, thermoacoustic range verification is robust relative to ultrasound images of underlying anatomy. When the treatment target is visible in ultrasound, e.g., prostate, online thermoacoustic range estimates could verify that the treatment spot is inside the target. [ABSTRACT FROM AUTHOR]

Objective. We designed a geometrical solution for a small animal in-beam positron emission tomography (PET) scanner to be used in the project SIRMIO (Small animal proton irradiator for research in molecular image-guided radiation-oncology). The system is based on 56 scintillator blocks of pixelated LYSO crystals. The crystals are arranged providing a pyramidal-step shape to optimize the geometrical coverage in a spherical configuration. Approach. Different arrangements have been simulated and compared in terms of spatial resolution and sensitivity. The chosen setup enables us to reach a good trade-off between a solid angle coverage and sufficient available space for the integration of additional components of the first design prototype of the SIRMIO platform. The possibility of moving the mouse holder inside the PET scanner furthermore allows for achieving the optimum placement of the irradiation area for all the possible tumor positions in the body of the mouse. The work also includes a study of the scintillator material where LYSO and GAGG are compared with a focus on the random coincidence noise due to the natural radioactivity of Lutetium in LYSO, justifying the choice of LYSO for the development of the final system. Main results. The best imaging performance can be achieved with a sub-millimeter spatial resolution and sensitivity of 10% in the center of the scanner, as verified in thorough simulations of point sources. The simulation of realistic irradiation scenarios of proton beams in PMMA targets with/without air gaps indicates the ability of the proposed PET system to detect range shifts down to 0.2 mm. Significance. The presented results support the choice of the identified optimal design for a novel spherical in-beam PET scanner which is currently under commissioning for application to small animal proton and light ion irradiation, and which might find also application, e.g. for biological image-guidance in x-ray irradiation., (Creative Commons Attribution license.)

Objective. A new method to estimate the range of an ion beam in a patient during heavy-ion therapy was investigated, which was previously verified for application in proton therapy. Approach. The method consists of placing a hadron tumour marker (HTM) close to the tumour. As the treatment beam impinges on the HTM, the marker undergoes nuclear reactions. When the HTM material is carefully chosen, the activation results in the emission of several delayed, characteristic γ rays, whose intensities are correlated with the remaining range inside the patient. When not just one but two reaction channels are investigated, the ratio between these two γ ray emissions can be measured, and the ratio is independent of any beam delivery uncertainties. Main results. A proof-of-principle experiment with an 16 O ion beam and Ag foils as HTM was successfully executed. The 107 Ag( 16 O, x ) 112 Sb and the 107 Ag( 16 O, x ) 114 Sb reaction channels were identified as suitable for the HTM technique. When only one γ -ray emission is measured, the resulting range-uncertainty estimation is at the 0.5 mm scale. When both channels are considered, a theoretical limit on the range uncertainty of a clinical fiducal marker was found to be ±290 μ m. Significance. Range uncertainty of a heavy-ion beam limits the prescribed treatment plan for cancer patients, especially the direction of the ion beam in relation to any organ at risk. An easy to implement range-verification technique which can be utilized during clinical treatment would allow treatment plans to take full advantage of the sharp fall-off of the Bragg peak without the risk of depositing excessive dose into healthy tissue., (Creative Commons Attribution license.)

Purpose: Range errors constrain treatment planning by limiting choice of ion beam angles and requiring large margins. Ionoacoustic range verification requires recovering the location of an acoustic source from low frequency signals. A priori information is applied to stably overcome resolution limits of inverse acoustic source imaging in this simulation study. In particular, the accuracy and robustness of ionoacoustic range verification for lateral and oblique delivery of high‐energy protons to the prostate is examined. Methods: Dose maps were computed using GEANT4 Monte Carlo simulations via the TOPAS user interface. Thermoacoustic pulses were propagated using k‐Wave software, with initial pressures corresponding to instantaneous dose deposition and piecewise constant maps of tissue properties derived from the planning CT. A database of dose maps with corresponding thermoacoustic emissions and Bragg peak locations, referred to as “control points,” were precomputed. Corresponding thermoacoustic emissions were also precomputed. Pulses were recorded at four coplanar locations corresponding to the outer surface of a virtual transrectal array. To model experimental beam delivery, k‐Wave results were convolved in time with a Gaussian envelope to account for noninstantaneous proton delivery by a synchrocyclotron. Thermoacoustic pulses were bandlimited below 150 kHz, and amplitudes were directly proportional to charge delivered. To test robustness of our method, white noise was added. Range was estimated in a two‐step process. The first step obtained a preliminary range estimate by one‐way beamforming. The second step was taken using data corresponding to the “control point” nearest to the preliminary range estimate. For each receiver, the time of flight difference, ∆t, between the measured and control thermoacoustic signals were accurately estimated by applying the Fourier shift theorem. Receiver‐Bragg peak distance was then estimated by adding vs∆t to the known distance of the control point, where vs is soundspeed. A linear system of equations based upon all receiver locations and distances was solved to recover the Bragg peak location. All simulations were performed relative to the planning CT. Because ultrasound (US) images were not available, results were overlaid onto the planning CT. Results: Beamformed estimates from noise‐free data tracked all beam locations within 1 cm. Final estimates for oblique and lateral beams were accurate to within 1.0 and 1.6 mm respectively. Average errors of final range estimates for oblique beams from data with SNR = 0 dB were no greater than 2.0 mm. Conclusions: Ionoacoustic range verification may improve current practice. Ionoacoustic range estimates can be inherently co‐registered to ultrasound images of underlying anatomy. To ensure estimates are robust in clinical practice, dose maps based upon the planning CT should be overlaid onto ultrasound volumes acquired at time of treatment and acoustic simulations re‐computed to provide a database of control points and corresponding thermoacoustic emissions. Computation times for beamformed estimates are already fast enough for online range verification, but are not accurate enough for a measurement aperture limited to the surface of a transrectal ultrasound probe. Accelerated acoustic simulations will be required to enable online two‐stage correction, but offline calculation is already suitable for adaptive planning. [ABSTRACT FROM AUTHOR]

Background and purpose A prompt-gamma imaging (PGI) slit-camera was recently applied successfully in clinical proton treatments using pencil beam scanning (PBS) and double scattering (DS). However, its full capability under clinical conditions has still to be systematically evaluated. Here, the performance of the slit-camera is systematically assessed in well-defined error scenarios using realistic treatment deliveries to an anthropomorphic head phantom. Materials and methods The sensitivity and accuracy to detect introduced global and local range shifts with the slit-camera was investigated in PBS and DS irradiations. For PBS, measured PGI information of shifted geometries were compared spot-wise with un-shifted PGI information derived from either a reference measurement or a treatment-plan-based simulation. Furthermore, for DS and PBS the integral PGI signal of the whole field was evaluated. Results Deviations from the treatment plan were detected with an accuracy better than 2 mm in PBS. The PGI simulation accuracy was well below 1 mm. Interfractional comparisons are more affected by measurement noise. The field-integral PGI sum signal allows the detection of global shifts in DS. Conclusions Detection of global and local range shifts under close-to-clinical conditions is possible with the PGI slit-camera. Especially for PBS, high sensitivity and high accuracy in shift detection were found. [ABSTRACT FROM AUTHOR]

The ultimate goal of radiotherapy using external beams is to maximize the dose delivered to the tumor while minimizing the radiation given to surrounding healthy critical organs. Prompt Gamma Spectroscopy (PGS) has been proposed for range control of particle beams along with the determination of the elemental composition of irradiated tissues. We aim at developing a PGS system for the German Cancer Research Center – DKFZ that takes advantage of the superior selectivity of Helium and Carbon beams accelerated at the Heidelberg Ion-Beam Therapy Center. Preliminary tests with protons accelerated with an IBA C230 cyclotron located at the Universitäts Protonen Therapie Dresden were performed at OncoRay – National Center for Radiation Re-search in Oncology. We present results obtained with a PGS system composed of CeBr3 detectors (Ø 2" × 2") and (Ø 1.5" × 3") coupled to a Hamamatsu R13089 photomulti-plier tube and plugged to a Target U100 Spectrometer. Such system provides accurate time-of-flight measurements to increase the signal-to-noise ratio relative to neutron-induced background. First measurements resulted from the irradiation of PMMA and water phantoms, and graphite and aluminum bricks. Several PG energy lines ranging from 0.511 MeV up to 8 MeV were identified and compared with reference re-sults. Two further experiments consisted in irradiating PMMA phantoms in a slit- and semi-collimated configuration with mono-energetic proton beams of 165 MeV and 224 MeV, respectively. Results acquired by means of trans-versal PGS at different phantom depths, ranging from 6 cm before the Bragg peak (BP) to 3.5 cm beyond the BP in 5 mm steps with a 1 cm slit collimation (tungsten) showed a slight decrease of PG yields after the BP. Similar measurements with a semi-opened collimation configuration demonstrated a steeper decrease of PG yields after the BP. [ABSTRACT FROM AUTHOR]

In vivo range verification plays an important role in proton therapy to fully utilize the benefits of the Bragg peak (BP) for delivering high radiation dose to tumor, while sparing the normal tissue. For accurately locating the position of BP, camera equipped with collimators (multi-slit and knife-edge collimator) to image prompt gamma (PG) emitted along the proton tracks in the patient have been proposed for range verification. The aim of the work is to compare the performance of multi-slit collimator and knife-edge collimator for non-invasive proton beam range verification. PG imaging was simulated by a validated GATE/GEANT4 Monte Carlo code to model the spot-scanning proton therapy and cylindrical PMMA phantom in detail. For each spot, 10 8 protons were simulated. To investigate the correlation between the acquired PG profile and the proton range, the falloff regions of PG profiles were fitted with a 3-line-segment curve function as the range estimate. Factors including the energy window setting, proton energy, phantom size, and phantom shift that may influence the accuracy of detecting range were studied. Results indicated that both collimator systems achieve reasonable accuracy and good response to the phantom shift. The accuracy of range predicted by multi-slit collimator system is less affected by the proton energy, while knife-edge collimator system can achieve higher detection efficiency that lead to a smaller deviation in predicting range. We conclude that both collimator systems have potentials for accurately range monitoring in proton therapy. It is noted that neutron contamination has a marked impact on range prediction of the two systems, especially in multi-slit system. Therefore, a neutron reduction technique for improving the accuracy of range verification of proton therapy is needed. [ABSTRACT FROM AUTHOR]

We present the results of an investigation of the prompt-gamma emission from an interaction of a proton beam with phantom materials. Measurements were conducted with a novel setup allowing the precise selection of the investigated depth in the phantom, featuring three different materials composed of carbon, oxygen and hydrogen. We studied two beam energies of 70.54 and 130.87 MeV and two detection angles: 90° and 120°. The results are presented in form of profiles of the prompt-gamma yield as a function of depth. In the analysis we focused on the transitions with the largest cross sections: 12 C 4.44 → g.s. and 16 O 6.13 → g.s. . We compare the profiles obtained under various irradiation conditions, with emphasis on the shape of the distal fall-off. The results are also compared to calculations including different cross-section models. They are in agreement with the model exploiting published cross-section data, but the comparison with the Talys model shows discrepancies. [ABSTRACT FROM AUTHOR]

In this study, the prompt gamma-rays (PGs) produced during the interactions of proton beams of various energies have been investigated using the MCNPX2.6 Monte Carlo code. Having considered a detection setup consisting of a thick lead collimator and a commercial plastic scintillator, the event-by-event data, generated by the PTRAC card of the MCNPX code, when the scintillator is exposed to PGs have been extracted before they are used in a dedicated light transport code, PHOTRACK. The plastic scintillator response when it is moved along the phantom axis determines the flux variation of proton-induced PGs which can be further related to the longitudinal deposition energy profile of protons, i.e. , the Bragg curve. The present study shows that the Bragg peak location is ∼ 3.7 cm after the PG peak for different proton energies of interest. The uncertainty in the Bragg peak location data is about 0.02 cm which can be improved by taking into account the precise electron-transport simulation details. [ABSTRACT FROM AUTHOR]

Proton beams are promising means for treating tumours. Such charged particles stop at a defined depth, where the ionization density is maximum. As the dose deposit beyond this distal edge is very low, proton therapy minimises the damage to normal tissue compared to photon therapy. Nevertheless, inherent range uncertainties cast doubts on the irradiation of tumours close to organs at risk and lead to the application of conservative safety margins. This constrains significantly the potential benefits of protons over photons. In this context, several research groups are developing experimental tools for range verification based on the detection of prompt gammas, a nuclear by-product of the proton irradiation. At OncoRay and Helmholtz-Zentrum Dresden-Rossendorf, detector components have been characterised in realistic radiation environments as a step towards a clinical Compton camera. Corresponding experimental methods and results obtained during the ENTERVISION training network are reviewed. On the other hand, a novel method based on timing spectroscopy has been proposed as an alternative to collimated imaging systems. The first tests of the timing method at a clinical proton accelerator are summarised, its applicability in a clinical environment for challenging the current safety margins is assessed, and the factors limiting its precision are discussed.

Prompt gamma (PG) based range verification can potentially reduce the safety margins in proton therapy. A knife-edge slit camera has been developed in this context using analytical PG simulations as reference for absolute range verification during patient treatment. Geometrical deviations between measurement and simulation could be observed and have to be corrected for in order to improve the range retrieval of the system. A geometrical correction model is derived from Monte Carlo simulations in water. The influence of different parameters is tested and the model is validated in a dedicated benchmark experiment. We found that the geometrical correction improves the agreement between measured and simulated PG profiles resulting in an improved range retrieval and higher accuracy for absolute range verification. An intrinsic offset of 1.4 mm between measurement and simulation is observed in the experimental data and corrected in the PG simulation. In summary, the absolute range verification capabilities of a PG camera have been improved by applying a geometrical correction model.

The potential of proton therapy is currently limited due to large safety margins. We estimated the potential reduction of clinical margins when using prompt gamma imaging (PGI) for online treatment verification of prostate cancer. For two adaptive scenarios a potential reduction relative to clinical practice was evaluated. The use of a trolley-mounted PGI system for online treatment verification to trigger an adaptation reduced the current range margins from 7 mm to 3 mm. In a case example, the dose reduction due to reduced range margins was substantially larger compared to reduced setup margins when using pre-treatment volumetric imaging., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: OncoRay has an institutional research agreement with Ion Beam Applications S.A. (IBA). G. Janssens and J. Smeets are employees of IBA. For the present study, the authors received no financial support involved in the study design or materials used, nor in the collection, analysis and interpretation of data nor in the writing of the publication. The other authors report no conflict of interest., (© 2023 The Author(s).)

Objectives. The energy deposited in a medium by a pulsed proton beam results in the emission of thermoacoustic waves, also called ionoacoustics (IA). The proton beam stopping position (Bragg peak) can be retrieved from a time-of-flight analysis (ToF) of IA signals acquired at different sensor locations (multilateration). This work aimed to assess the robustness of multilateration methods in proton beams at pre-clinical energies for the development of a small animal irradiator. Approach. The accuracy of multilateration performed using different algorithms; namely, time of arrival and time difference of arrival, was investigated in-silico for ideal point sources in the presence of realistic uncertainties on the ToF estimation and ionoacoustic signals generated by a 20 MeV pulsed proton beam stopped in a homogeneous water phantom. The localisation accuracy was further investigated experimentally based on two different measurements with pulsed monoenergetic proton beams at energies of 20 and 22 MeV. Main results. It was found that the localisation accuracy mainly depends on the position of the acoustic detectors relative to the proton beam due to spatial variation of the error on the ToF estimation. By optimally positioning the sensors to reduce the ToF error, the Bragg peak could be located in-silico with an accuracy better than 90 μ m (2% error). Localisation errors going up to 1 mm were observed experimentally due to inaccurate knowledge of the sensor positions and noisy ionoacoustic signals. Significance. This study gives a first overview of the implementation of different multilateration methods for ionoacoustics-based Bragg peak localisation in two- and three-dimensions at pre-clinical energies. Different sources of uncertainty were investigated, and their impact on the localisation accuracy was quantified in-silico and experimentally., (Creative Commons Attribution license.)

Background: Proton range uncertainty has been the main factor limiting the ability of proton therapy to concentrate doses to tumors to their full potential. Ionoacoustic (IA) range verification is an approach to reducing this uncertainty by detecting thermoacoustic waves emitted from an irradiated volume immediately following a pulsed proton beam delivery; however, the signal weakness has been an obstacle to its clinical application. To increase the signal-to-noise ratio (SNR) with the conventional piezoelectric hydrophone (PH), the detector-sensitive volume needs to be large, but it could narrow the range of available beam angles and disturb real-time images obtained during beam delivery., Purpose: To prevent this issue, we investigated a millimeter-sized optical hydrophone (OH) that exploits the laser interferometric principle. For two types of IA waves [γ-wave emitted from the Bragg peak (BP) and a spherical IA wave with resonant frequency (SPIRE) emitted from the gold fiducial marker (GM)], comparisons were made with PH in terms of waveforms, SNR, range detection accuracy, and signal intensity robustness against the small detector misalignment, particularly for SPIRE., Methods: A 100-MeV proton beam with a 27 ns pulse width and 4 mm beam size was produced using a fixed-field alternating gradient accelerator and was irradiated to the water phantom. The GM was set on the beam's central axis. Acrylic plates of various thicknesses, up to 12 mm, were set in front of the phantoms to shift the proton range. OH was set distal and lateral to the beam, and the range was estimated using the time-of-flight method for γ-wave and by comparing with the calibration data (SPIRE intensity versus the distance between the GM and BP) derived from an IA wave transport simulation for SPIRE. The BP dose per pulse was 0.5-0.6 Gy. To measure the variation in SPIRE amplitude against the hydrophone misalignment, the hydrophone was shifted by ± 2 mm at a maximum in lateral directions., Results: Despite its small size, OH could detect γ-wave with a higher SNR than the conventional PH (diameter, 29 mm), and a single measurement was sufficient to detect the beam range with a submillimeter accuracy in water. In the SPIRE measurement, OH was far more robust against the detector misalignment than the focused PH (FPH) used in our previous study [5%/mm (OH) versus 80%/mm (FPH)], and the correlation between the measured SPIRE intensity and the distance between the GM and BP agreed well with the simulation results. However, the OH sensitivity was lower than the FPH sensitivity, and about 5.6-Gy dose was required to decrease the intensity variation among measurements to less than 10%., Conclusion: The miniature OH was found to detect weak IA signals produced by proton beams with a BP dose used in hypofractionated regimens. The OH sensitivity improvement at the MHz regime is worth exploring as the next step., (© 2022 American Association of Physicists in Medicine.)

Background: Proton radiography (PR) uses highly energetic proton beams to create images where energy loss is the main contrast mechanism. Water-equivalent path length (WEPL) measurements using flat panel PR (FP-PR) have potential for in vivo range verification. However, an accurate WEPL measurement via FP-PR requires irradiation with multiple energy layers, imposing high imaging doses., Purpose: A FP-PR method is proposed for accurate WEPL determination based on a patient-specific imaging field with a reduced number of energies (n) to minimize imaging dose., Methods: Patient-specific FP-PRs were simulated and measured for a head and neck (HN) phantom. An energy selection algorithm estimated spot-wise the lowest energy required to cross the anatomy (Emin) using a water-equivalent thickness map. Starting from Emin, n was restricted to certain values (n = 26, 24, 22, …, 2 for simulations, n = 10 for measurements), resulting in patient-specific FP-PRs. A reference FP-PR with a complete set of energies was compared against patient-specific FP-PRs covering the whole anatomy via mean absolute WEPL differences (MAD), to evaluate the impact of the developed algorithm. WEPL accuracy of patient-specific FP-PRs was assessed using mean relative WEPL errors (MRE) with respect to measured multi-layer ionization chamber PRs (MLIC-PR) in the base of skull, brain, and neck regions., Results: MADs ranged from 2.1 mm (n = 26) to 21.0 mm (n = 2) for simulated FP-PRs, and 7.2 mm for measured FP-PRs (n = 10). WEPL differences below 1 mm were observed across the whole anatomy, except at the phantom surfaces. Measured patient-specific FP-PRs showed good agreement against MLIC-PRs, with MREs of 1.3 ± 2.0%, -0.1 ± 1.0%, and -0.1 ± 0.4% in the three regions of the phantom., Conclusion: A method to obtain accurate WEPL measurements using FP-PR with a reduced number of energies selected for the individual patient anatomy was established in silico and validated experimentally. Patient-specific FP-PRs could provide means of in vivo range verification., (© 2023 The Authors. Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

Hadron therapy allows for highly conformal dose distributions and better sparing of organs-at-risk, thanks to the characteristic dose deposition as function of depth. However, the quality of hadron therapy treatments is closely connected with the ability to predict and achieve a given beam range in the patient. Currently, uncertainties in particle range lead to the employment of safety margins, at the expense of treatment quality. Much research in particle therapy is therefore aimed at developing methods to verify the particle range in patients.Non-invasive in-vivo monitoring of the particle range can be performed by detecting secondary radiation, emitted from the patient as a result of nuclear interactions of charged hadrons with tissue, including beta+ emitters, prompt photons, and charged fragments. The correctness of the dose delivery can be verified by comparing measured and pre-calculated distributions of the secondary particles. The reliability of Monte Carlo (MC) predictions is a key issue. Correctly modelling the production of secondaries is a non-trivial task, because it involves nuclear physics interactions at energies, where no rigorous theories exist to describe them. The goal of this review is to provide a comprehensive overview of various aspects in modelling the physics processes for range verification with secondary particles produced in proton, carbon, and heavier ion irradiation. We discuss electromagnetic and nuclear interactions of charged hadrons in matter, which is followed by a summary of some widely used MC codes in hadron therapy. Then we describe selected examples of how these codes have been validated and used in three range verification techniques: PET, prompt gamma, and charged particle detection. We include research studies and clinically applied methods. For each of the techniques we point out advantages and disadvantages, as well as clinical challenges still to be addressed, focusing on MC simulation aspects.

Purpose: Measurement of the arrival times of thermoacoustic waves induced by pulsed proton dose depositions (protoacoustics) may provide a proton range verification method. The goal of this study is to characterize the required dose and protoacoustic proton range (distance) verification accuracy in a homogeneous water medium at a hospital-based clinical cyclotron. Methods: Gaussian-like proton pulses with 17 µs widths and instantaneous currents of 480 nA (5.6×107 protons/pulse, 3.4 cGy/pulse at the Bragg peak) were generated by modulating the cyclotron proton source with a function generator. After energy degradation, the 190 MeV proton pulses irradiated a water phantom, and the generated protoacoustic emissions were measured by a hydrophone. The detector position and proton pulse characteristics were varied. The experimental results were compared to simulations. Different arrival time metrics derived from acoustic waveforms were compared, and the accuracy of protoacoustic time-of-flight distance calculations was assessed. Results: A 27 mPa noise level was observed in the treatment room during irradiation. At 5 cm from the proton beam, an average maximum pressure of 5.2 mPa/1×107 protons (6.1 mGy at the Bragg peak) was measured after irradiation with a proton pulse with 10%-90% rise time of 11 µs. Simulation and experiment arrival times agreed well, and the observed 2.4 µs delay between simulation and experiment is attributed to the difference between the hydrophone's acoustic and geometric centers. Based on protoacoustic arrival times, the beam axis position was measured to within (x,y) = (-2.0, 0.5)±1 mm. After deconvolution of the exciting proton pulse, the protoacoustic compression peak provided the most consistent measure of the distance to the Bragg peak, with an error distribution with mean = -4.5 mm and standard deviation = 2.0 mm. Conclusions: Based on water tank measurements at a clinical hospital-based cyclotron, protoacoustics is a potential method for measuring the beam's position (x and y within 2.0 mm) and Bragg peak range (2.0 mm standard deviation), although range verification will require simulation or experimental calibration to remove systematic error. Based on extrapolation, a protoacoustic arrival time reproducibility of 1.5 µs (2.2 mm) is achievable with 2 Gy of total deposited dose. Of the compared methods, deconvolution of the excitation proton pulse is the best technique for extracting protoacoustic arrival times, particularly if there is variation in the proton pulse shape. [ABSTRACT FROM AUTHOR]

More and more camera concepts are being investigated to try and seize the opportunity of instantaneous range verification of proton therapy treatments offered by prompt gammas emitted along the proton tracks. Focusing on one-dimensional imaging with a passive collimator, the present study experimentally compared in combination with the first, clinically compatible, dedicated camera device the performances of instances of the two main options: a knife-edge slit (KES) and a multi-parallel slit (MPS) design. These two options were experimentally assessed in this specific context as they were previously demonstrated through analytical and numerical studies to allow similar performances in terms of Bragg peak retrieval precision and spatial resolution in a general context. Both collimators were prototyped according to the conclusions of Monte Carlo optimization studies under constraints of equal weight (40 mm tungsten alloy equivalent thickness) and of the specificities of the camera device under consideration (in particular 4 mm segmentation along beam axis and no time-of-flight discrimination, both of which less favorable to the MPS performance than to the KES one). Acquisitions of proton pencil beams of 100, 160, and 230 MeV in a PMMA target revealed that, in order to reach a given level of statistical precision on Bragg peak depth retrieval, the KES collimator requires only half the dose the present MPS collimator needs, making the KES collimator a preferred option for a compact camera device aimed at imaging only the Bragg peak position. On the other hand, the present MPS collimator proves more effective at retrieving the entrance of the beam in the target in the context of an extended camera device aimed at imaging the whole proton track within the patient. [ABSTRACT FROM AUTHOR]

Proton beams are promising means for treating tumors. Such charged particles stop at a defined depth, where the ionization density is maximum. As the dose deposit beyond this distal edge is very low, proton therapy minimizes the damage to normal tissue compared to photon therapy. Nevertheless, inherent range uncertainties cast doubts on the irradiation of tumors close to organs at risk and lead to the application of conservative safety margins. This constrains significantly the potential benefits of protons over photons. In this context, several research groups are developing experimental tools for range verification based on the detection of prompt gammas, a nuclear by-product of the proton irradiation. At OncoRay and Helmholtz-Zentrum Dresden-Rossendorf, detector components have been characterized in realistic radiation environments as a step toward a clinical Compton camera. On the one hand, corresponding experimental methods and results obtained during the ENTERVISION training network are reviewed. On the other hand, a novel method based on timing spectroscopy has been proposed as an alternative to collimated imaging systems. The first tests of the timing method at a clinical proton accelerator are summarized, its applicability in a clinical environment for challenging the current safety margins is assessed, and the factors limiting its precision are discussed. [ABSTRACT FROM AUTHOR]

Ion beam therapy is an emerging modality for high precision radiation treatment of cancer. In comparison to conventional radiation sources (photons, electrons), ion beams feature major dosimetric advantages due to their finite range with a localized dose deposition maximum, the Bragg peak, which can be selectively adjusted in depth. However, due to several sources of treatment uncertainties, full exploitation of these dosimetric advantages in clinical practice would require the possibility to visualize the stopping position of the ions in vivo, ideally in real-time. To this aim, different imaging methods have been proposed and investigated, either pre-clinically or even clinically, based on the detection of prompt or delayed radiation following nuclear interaction of the beam with the irradiated tissue. However, the chosen or ad-hoc developed instrumentation has often relied on technologies originally conceived for different applications, thus compromising on the achievable performances for the sake of cost-effectiveness. This contribution will review major examples of used instrumentation and related performances, identifying the most promising detector developments for next generation devices especially dedicated to on-line monitoring of ion beam treatment. Moreover, it will propose an original combination of different techniques in a hybrid detection scheme, aiming to make the most of complementary imaging methods and open new perspectives of image guidance for improved precision of ion beam therapy. [ABSTRACT FROM AUTHOR]