Search

Proton therapy has a substantial physical advantage over conventional cancer radiation treatment with X-rays. Proton therapy reduces the radiation dose to healthy tissues and therefore the toxicity and side effects to the patients. However, the current high capital cost and required space make proton therapy a very limited resource. In current proton therapy, the patient is fixed on a table and a gantry is used to bend the proton beam for treatment. We propose to change the model by precisely moving a patient relative to a fixed proton beam rather than moving the beam relative to the patient. This requires a robot to move the patient and a strong immobilization device to ensure that the patient’s body position remains accurate during movement. We introduce a solution to enable compact and affordable proton therapy using a parallel robot with real-time surface positioning feedback and an immobilization system made of soft robotic actuators. Immobilization experiments with healthy volunteers demonstrate that our prototype device can position and immobilize healthy volunteers in sitting position to clinical standards and correct slouching through a feedback loop. The soft robotic immobilization device is strong but soft and comfortable as well as adaptive to the body shape. The force that the immobilization device can exert on the body using negative pneumatic pressure was characterized. This new immobilization device and the robotic positioning system have great potential to significantly reduce the cost of proton radiation cancer treatment.

We present an open-source platform to aid medical dosimetrists in preventing collisions between gantry head and patient or couch during photon or particle beam therapy treatment planning. This generic framework uses the native scripting interface of the particular planning software to import STL files of the treatment machine elements. These are visualized in 3D together with the contoured or scanned patient surface. A graphical dialog with sliders allows the interactive rotation of the gantry and couch, with real-time feedback. To prevent a future replanning, treatment planners can assess in advance and exclude beam angles resulting in a potential risk of collision. The software platform is publicly available on GitHub and has been validated for RayStation with actual patient plans. Furthermore, the incorporation of the complete patient geometry was tested with a 3D surface scan of a full-body phantom performed with a handheld smartphone. With this study, we aim at minimizing the risk of replanning due to collisions and thus of treatment delays and unscheduled consumption of manpower. The clinical workflow can be streamlined at no cost already at the treatment planning stage. By ensuring a real-time verification of the plan feasibility, the script might boost the use of optimal couch angles that a planner might shy away from otherwise.

In proton therapy, patients benefit from the precise deposition of the dose in the tumor volume due to the interaction of charged particles with matter. Currently, the determination of the beam range in the patient’s body during the treatment is not a clinical standard. This lack causes broad safety margins around the tumor, which limits the potential of proton therapy. To overcome this obstacle, different methods are under investigation aiming at the verification of the proton range in real time during the irradiation. One approach is the prompt gamma-ray timing (PGT) method, where the range of the primary protons is derived from time-resolved profiles (PGT spectra) of promptly emitted gamma rays, which are produced along the particle track in tissue. After verifying this novel technique in an experimental environment but far away from treatment conditions, the translation of PGT into clinical practice is intended. Therefore, new hardware was extensively tested and characterized using short irradiation times of 70 ms and clinical beam currents of 2 nA. Experiments were carried out in the treatment room of the University Proton Therapy Dresden. A pencil beam scanning plan was delivered to a target without and with cylindrical air cavities of down to 5 mm thickness. The range shifts of the proton beam induced due to the material variation could be identified from the corresponding PGT spectra, comprising events collected during the delivery of a whole energy layer. Additionally, an assignment of the PGT data to the individual pencil beam spots allowed a spot-wise analysis of the variation of the PGT distribution mean and width, corresponding to range shifts produced by the different air cavities. Furthermore, the paper presents a comprehensive software framework which standardizes future PGT analysis methods and correction algorithms for technical limitations that have been encountered in the presented experiments., publishedVersion

Range uncertainties in proton therapy hamper treatment precision. Prompt gamma-rays were suggested 16 years ago for real-time range verification, and have already shown promising results in clinical studies with collimated cameras. Simultaneously, alternative imaging concepts without collimation are investigated to reduce the footprint and price of current prototypes. In this manuscript, a compact range verification method is presented. It monitors prompt gamma-rays with a single scintillation detector positioned coaxially to the beam and behind the patient. Thanks to the solid angle effect, proton range deviations can be derived from changes in the number of gamma-rays detected per proton, provided that the number of incident protons is well known. A theoretical background is formulated and the requirements for a future proof-of-principle experiment are identified. The potential benefits and disadvantages of the method are discussed, and the prospects and potential obstacles for its use during patient treatments are assessed. The final milestone is to monitor proton range differences in clinical cases with a statistical precision of 1 mm, a material cost of 25000 USD and a weight below 10 kg. This technique could facilitate the widespread application of in vivo range verification in proton therapy and eventually the improvement of treatment quality., Comment: 2469--7311 (c) 2019 IEEE Transactions on Radiation and Plasma Medical Sciences. Personal use is permitted, but republication/redistribution requires IEEE permission. This article has been accepted for publication in a future issue of this journal, but has not been fully edited. Content may change prior to final publication

Range verification of particle beams in real time is considered a key for tapping the full potential of radio-oncological particle therapies. The novel technique of prompt gamma-ray timing (PGT), recently proposed and explored in first proof-of-principle experiments, promises range assessment at reasonable expense but challenges detectors, electronics, and data acquisition. Energy-selected time distributions have to be measured at very high throughput rates to obtain the statistics necessary for range verification with single pencil beam spots. Clinically applicable systems should provide a time resolution of about 200 ps, to be obtained with large (about 2” diameter) scintillators, detector loads in the few-Mcps range, and data acquisition rates around 1 Mcps, if possible with compact and inexpensive systems. Such requirements can be met best with ${\rm CeBr}_{3}$ scintillators read out with conventional photomultiplier tubes, coupled to commercial but customized electronics featuring high-resolution pulse digitization and fast digital signal processing. The paper deduces design parameters from the constraints given by typical treatment conditions, and presents first results obtained with prototype detectors and electronics developed in accordance with the derived specifications.

Range uncertainties in proton therapy pose a limitation on its benefits for cancer treatment. Robust planning and conservative safety margins of up to 1 cm are necessary for guaranteeing full tumor coverage, at the price of a larger dose to normal tissue. At the Massachusetts General Hospital, a full-scale prototype system for in vivo proton range verification is under development, based on spectroscopy of prompt gamma-rays emitted from proton-nuclear reactions with tissue. The aim is to verify the proton range during patient treatments with 1 mm precision. The system consists of eight LaBr3 detectors and a tungsten collimator that are mounted on a rotating frame. The electronics and data processing algorithms are designed to cope with the highly variable count rates that occur during pencil-beam scanning. The prototype was tested by irradiating a water phantom with a clinical dose of 0.9 Gy, a beam current of 2 nA and a field size of 10 cm x 10 cm. Energy- and time-resolved gamma-ray spectra were acquired during the irradiation and further analyzed to subtract the neutron background and to determine the prompt gamma-ray line magnitudes. A GPU-accelerated Monte Carlo model of the gamma-ray emissions was developed, which relies on measured nuclear reaction cross sections and the treatment plan CT. We reconstruct both the absolute proton range and the elemental concentrations of the irradiated tissue by minimizing the deviation between the measurement and the parameterized model. Range shifters and changes in the elemental composition were introduced in different parts of the water phantom to verify the precision and robustness of the range verification method. A statistical precision of 1.1 mm at 95% confidence level and a mean systematic error of 0.5 mm were obtained, when merging protons delivered to the two distal pencil-beam layers within a 10 mm radius. In an upcoming clinical study, the prototype will be tested during the treatment of brain cancer patients.

In-situ range verification of ion beams during dose delivery is a key for further improving the precision and reducing side effects of radiotherapy with particle beams. The detection and analysis of prompt gamma rays with respect to their emission points, emission time, and emission energy can provide corresponding means. Prompt gamma-ray imaging (PGI) has already been used for range verification in patient treatments with proton beams. The prompt gamma-ray timing (PGT) technique promises range verification at lower hardware expense with simpler detection systems superseding heavy collimators. After proving the principle, this technique is now being translated to the treatment room. The paper presents latest experimental results obtained with clinically applicable PGT hardware in irradiations of plexiglass targets in pencil beam scanning (PBS) mode with proton beams at clinical dose rates. The data were acquired with multiple PGT detection units while the distal layer of an artificial 1 Gy dose cube treatment plan was repeatedly delivered to a solid PMMA target that sometimes comprised a cylindrical air cavity of 5, 10, or 20 mm depth. The corresponding local range shifts were clearly detected and visualized by analyzing position or variance of the prompt gamma-ray timing peaks in PGT spectra assigned to the individual PBS spots. In this context, a major challenge concerning all prompt-gamma based techniques is examined and discussed: collecting the event statistics that is needed for range verification of single pencil beam spots at an accuracy level of a few millimeters.

We present a full-scale clinical prototype system for in vivo range verification of proton pencil-beams using the prompt gamma-ray spectroscopy method. The detection system consists of eight LaBr3 scintillators and a tungsten collimator, mounted on a rotating frame. Custom electronics and calibration algorithms have been developed for the measurement of energy- and time-resolved gamma-ray spectra during proton irradiation at a clinical dose rate. Using experimentally determined nuclear reaction cross sections and a GPU-accelerated Monte Carlo simulation, a detailed model of the expected gamma-ray emissions is created for each individual pencil-beam. The absolute range of the proton pencil-beams is determined by minimizing the discrepancy between the measurement and this model, leaving the absolute range of the beam and the elemental concentrations of the irradiated matter as free parameters. The system was characterized in a clinical-like situation by irradiating different phantoms with a scanning pencil-beam. A dose of 0.9 Gy was delivered to a 5x10x10 cm$^3$ target with a beam current of 2 nA incident on the phantom. Different range shifters and materials were used to test the robustness of the verification method and to calculate the accuracy of the detected range. The absolute proton range was determined for each spot of the distal energy layer with a mean statistical precision of 1.1 mm at a 95% confidence level and a mean systematic deviation of 0.5 mm, when aggregating pencil-beam spots within a cylindrical region of 10 mm radius and 10 mm depth. Small range errors that we introduced were successfully detected and even large differences in the elemental composition do not affect the range verification accuracy. These results show that our system is suitable for range verification during patient treatments in our upcoming clinical study., Comment: 33 pages, 10 figures, 5 tables. This is a peer-reviewed, un-copyedited version of an article accepted for publication in Physics in Medicine and Biology. IOP Publishing Ltd is not responsible for any errors or omissions in this version of the manuscript or any version derived from it. The Version of Record is available online at http://iopscience.iop.org/article/10.1088/1361-6560/aad513

Ion beam therapy promises enhanced tumour coverage compared to conventional radiotherapy, but particle range uncertainties significantly blunt the achievable precision. Experimental tools for range verification in real-time are not yet available in clinical routine. The prompt gamma ray timing method has been recently proposed as an alternative to collimated imaging systems. The detection times of prompt gamma rays encode essential information about the depth-dose profile thanks to the measurable transit time of ions through matter. In a collaboration between OncoRay, Helmholtz-Zentrum Dresden-Rossendorf and IBA, the first test at a clinical proton accelerator (Westdeutsches Protonentherapiezentrum Essen, Germany) with several detectors and phantoms is performed. The robustness of the method against background and stability of the beam bunch time profile is explored, and the bunch time spread is characterized for different proton energies. For a beam spot with a hundred million protons and a single detector, range differences of 5 mm in defined heterogeneous targets are identified by numerical comparison of the spectrum shape. For higher statistics, range shifts down to 2 mm are detectable. A proton bunch monitor, higher detector throughput and quantitative range retrieval are the upcoming steps towards a clinically applicable prototype. In conclusion, the experimental results highlight the prospects of this straightforward verification method at a clinical pencil beam and settle this novel approach as a promising alternative in the field of in vivo dosimetry.

Irradiation with protons and light ions offers new possibilities for tumor therapy but has a strong need for novel imaging modalities for treatment verification. The development of new detector systems, which can provide an in vivo range assessment or dosimetry, requires an accurate knowledge of the secondary radiation field and reliable Monte Carlo simulations. This paper presents multiple measurements to characterize the prompt gamma-ray emissions during proton irradiation and benchmarks the latest Geant4 code against the experimental findings. Within the scope of this work, the total photon yield for different target materials, the energy spectra as well as the gamma-ray depth profile were assessed. Experiments were performed at the superconducting AGOR cyclotron at KVI-CART, University of Groningen. Properties of the gamma-ray emissions were experimentally determined. The prompt gamma-ray emissions were measured utilizing a conventional HPGe detector system (Clover) and quantitatively compared to simulations. With the selected physics list QGSP_BIC_HP, Geant4 strongly overestimates the photon yield in most cases, sometimes up to 50%. The shape of the spectrum and qualitative occurrence of discrete gamma lines is reproduced accurately. A sliced phantom was designed to determine the depth profile of the photons. The position of the distal fall-off in the simulations agrees with the measurements, albeit the peak height is also overestimated. Hence, Geant4 simulations of prompt gamma-ray emissions from irradiation with protons are currently far less reliable as compared to simulations of the electromagnetic processes. Deviations from experimental findings were observed and quantified. Although there has been a constant improvement of Geant4 in the hadronic sector, there is still a gap to close.

To ensure the optimal outcome of proton therapy, in vivo range verification is highly desired. Prompt γ-ray imaging (PGI) is a possible approach for in vivo range monitoring. For PGI, dedicated detection systems, e.g. Compton cameras, are currently under investigation. The presented paper deals with substantial requirements regarding hardware and software that a Compton camera used in clinical routine has to meet. By means of GEANT4 simulations, we investigate the load on the detectors and the percentage of background expected in a realistic irradiation and we simulate γ-ray detections subsequently used as input data for the reconstruction. By reconstructing events from simulated sources of well-defined geometry, we show that large-area detectors are favourable. We investigate reconstruction results in dependence of the number of events. Finally, an end-to-end test for a realistic patient scenario is presented: starting with a treatment plan, the γ-ray emissions are calculated, the detector response is modelled, and the image reconstruction is performed. By this, the complexity of the system is shown, and requirements and limitations regarding precision and costs are determined.

The dose deposition profile of protons is interesting for tumour treatment due to the increased ionization density at the end of their track. However, the inaccurate knowledge of the proton stopping point limits the precision of the therapy. Prompt gamma rays, a by-product of the irradiation, are candidates for an indirect measurement of the particle range. Compton cameras have been proposed for prompt gamma ray imaging, but struggle with high trigger rates and low coincident efficiency. The feasibility in a clinical environment has yet to be proved. At Universitats Protonen Therapie Dresden, two bismuth germanate (BGO) block detectors arranged face-to-face are deployed for imaging tests with a homogeneous target irradiated by a proton pencil beam. Shifts of the target, increase of its thickness and beam energy variation experiments are conducted. Each measurement lasts about 15 minutes at a low proton beam current. The effect of one centimetre proton range deviations on the backprojected images is analysed. The number of valid Compton events as well as the trigger rate expected in a realistic treatment plan with pencil beam scanning are estimated. The results support the use of a high density material despite its moderate energy resolution, in order to maximize the coincident efficiency. Nevertheless, they discourage the applicability of a two-plane Compton camera in a clinical scenario with usual beam currents.

Purpose RayStretch is a simple algorithm proposed for heterogeneity corrections in low-dose–rate brachytherapy. It is built on top of TG-43 consensus data, and it has been validated with Monte Carlo (MC) simulations. In this study, we take a real clinical prostate implant with 71 125I seeds as reference and we apply RayStretch to analyze its performance in worst-case scenarios. Methods and Materials To do so, we design two cases where large calcifications are located in the prostate lobules. RayStretch resilience under various calcification density values is also explored. Comparisons against MC calculations are performed. Results Dose–volume histogram–related parameters like prostate D90, rectum D2cc, or urethra D10 obtained with RayStretch agree within a few percent with the detailed MC results for all cases considered. Conclusions The robustness and compatibility of RayStretch with commercial treatment planning systems indicate its applicability in clinical practice for dosimetric corrections in prostate calcifications. Its use during intraoperative ultrasound planning is foreseen.

Proton and ion beams open up new vistas for the curative treatment of tumors, but adequate technologies for monitoring the compliance of dose delivery with treatment plans in real time are still missing. Range assessment, meaning the monitoring of therapy-particle ranges in tissue during dose delivery (treatment), is a continuous challenge considered a key for tapping the full potential of particle therapies. In this context the paper introduces an unconventional concept of range assessment by prompt-gamma timing (PGT), which is based on an elementary physical effect not considered so far: therapy particles penetrating tissue move very fast, but still need a finite transit time-about 1-2 ns in case of protons with a 5-20 cm range-from entering the patient's body until stopping in the target volume. The transit time increases with the particle range. This causes measurable effects in PGT spectra, usable for range verification. The concept was verified by proton irradiation experiments at the AGOR cyclotron, KVI-CART, University of Groningen. Based on the presented kinematical relations, we describe model calculations that very precisely reproduce the experimental results. As the clinical treatment conditions entail measurement constraints (e.g. limited treatment time), we propose a setup, based on clinical irradiation conditions, capable of determining proton range deviations within a few seconds of irradiation, thus allowing for a fast safety survey. Range variations of 2 mm are expected to be clearly detectable.

Proton therapy is an advantageous treatment modality compared to conventional radiotherapy. In contrast to photons, charged particles have a finite range and can thus spare organs at risk. Additionally, the increased ionization density in the so-called Bragg peak close to the particle range can be utilized for maximum dose deposition in the tumour volume. Unfortunately, the accuracy of the therapy can be affected by range uncertainties, which have to be covered by additional safety margins around the treatment volume. A real-time range and dose verification is therefore highly desired and would be key to exploit the major advantages of proton therapy. Prompt gamma rays, produced in nuclear reactions between projectile and target nuclei, can be used to measure the proton's range. The prompt gamma-ray timing (PGT) method aims at obtaining this information by determining the gamma-ray emission time along the proton path using a conventional time-of-flight detector setup. First tests at a clinical accelerator have shown the feasibility to observe range shifts of about 5 mm at clinically relevant doses. However, PGT spectra are smeared out by the bunch time spread. Additionally, accelerator related proton bunch drifts against the radio frequency have been detected, preventing a potential range verification. At OncoRay, first experiments using a proton bunch monitor (PBM) at a clinical pencil beam have been conducted. Elastic proton scattering at a hydrogen-containing foil could be utilized to create a coincident proton-proton signal in two identical PBMs. The selection of coincident events helped to suppress uncorrelated background. The PBM setup was used as time reference for a PGT detector to correct for potential bunch drifts. Furthermore, the corrected PGT data were used to image an inhomogeneous phantom. In a further systematic measurement campaign, the bunch time spread and the proton transmission rate were measured for several beam energies between 69 and 225 MeV as well as for variable momentum limiting slit openings. We conclude that the usage of a PBM increases the robustness of the PGT method in clinical conditions and that the obtained data will help to create reliable range verification procedures in clinical routine.

Compton camera prototype for a position-sensitive detection of prompt γ rays from proton-induced nuclear reactions is being developed in Garching. The detector system allows to track the Comptonscattered electrons. The camera consists of a monolithic LaBr3:Ce scintillation absorber crystal, read out by a multi-anode PMT, preceded by a stacked array of 6 double-sided silicon strip detectors acting as scatterers. The LaBr3:Ce crystal has been characterized with radioactive sources. Online commissioning measurements were performed with a pulsed deuteron beam at the Garching Tandem accelerator and with a clinical proton beam at the OncoRay facility in Dresden. The determination of the interaction point of the photons in the monolithic crystal was investigated.

Hadron therapy offers the possibility of delivering a large amount of radiation dose to tumors with minimal absorption by the surrounding healthy tissue. In order to fully exploit the advantages of this technique, the use of real-time beam monitoring devices becomes mandatory. Compton imaging devices can be employed to map the distribution of prompt gamma emission during the treatment and thus assess its correct delivery. The Compton telescope prototype developed at IFIC-Valencia for this purpose is made of three layers of LaBr3 crystals coupled to silicon photomultipliers. The system has been tested in a 4.44 MeV gamma field at the 3 MV Tandetron accelerator at HZDR, Dresden. Images of the target with the system in three different positions separated by 10 mm were successfully reconstructed. This indicates the ability of MACACO for imaging the prompt gamma rays emitted at such energies.

Range verification is a very important point in order to fully exploit the physical advantages of protons compared to photons in cancer irradiation. Recently, a simple method has been proposed which makes use of the time of flight of protons in tissue and the promptly emitted secondary photons along the proton path (Prompt Gamma Timing, PGT). This has been considered so far for monoenergetic pencil beams only. In this work, it has been studied whether this technique can also be applied in passively formed irradiation fields with a so called spread out Bragg peak. Time correlated profiles could be recorded, which show a trend that is consistent with theoretical predictions.

A primary subject of the present research in particle therapy is to ensure the precise irradiation of the target volume. The prompt gamma timing (PGT) method provides one possibility for in vivo range verification during the irradiation of patients. Prompt gamma rays with high energies are emitted promptly due to nuclear reactions of protons with tissue. The arrival time of these gammas to the detector reflects the stopping process of the primary protons in tissue and is directly correlated to the range. Due to the time resolution of the detector and the proton bunch time spread, as well as drifts of the bunch phase with respect to the accelerator frequency, timing spectra are smeared out and compromise the accuracy of range information intended for future clinical applications. Nevertheless, counteracting this limitation and recovering range information from the PGT measured spectra, corrections using a bunch phase monitor can be performed. A first prototype of bunch phase monitor was tested at GSI Darmstadt, where measurements of the energy correlation profile of the ion bunches were performed. At the ELBE accelerator at Helmholtz-Zentrum Dresden-Rossendorf (HZDR), set up to provide bremsstrahlung photons in very short pulses, a constant fraction algorithm for the incoming digital signals was evaluated, which is used for optimizing the time resolution. Studies of scattering experiments with different thin targets and detector positions are accomplished at OncoRay Dresden, where a clinical proton beam is available. These experiments allow a basic characterization of the proton bunch structure and the detection yield.

In low energy brachytherapy, the presence of tissue heterogeneities contributes significantly to the discrepancies observed between treatment plan and delivered dose. In this work, we present a simplified analytical dose calculation algorithm for heterogeneous tissue. We compare it with Monte Carlo computations and assess its suitability for integration in clinical treatment planning systems. The algorithm, named as RayStretch, is based on the classic equivalent path length method and TG-43 reference data. Analytical and Monte Carlo dose calculations using Penelope2008 are compared for a benchmark case: a prostate patient with calcifications. The results show a remarkable agreement between simulation and algorithm, the latter having, in addition, a high calculation speed. The proposed analytical model is compatible with clinical real-time treatment planning systems based on TG-43 consensus datasets for improving dose calculation and treatment quality in heterogeneous tissue. Moreover, the algorithm is applicable for any type of heterogeneities.

Protons are excellent particles for tumour treatment due to the increased ionization density close to their stopping point. In practice, the uncertainty on the particle range compromises the achievable accuracy. Compton cameras imaging prompt gamma rays, a by-product of the irradiation, have been proposed for indirect range verification years since. At Universitäts Protonen Therapie Dresden, two BGO block detectors (from PET scanners) arranged as Compton camera are deployed for imaging tests with high energy prompt gamma rays produced in PMMA by a proton pencil beam. Target shifts, thickness increase and beam energy variation experiments are conducted. Each measurement lasts about 15 minutes at a low proton beam current. The effect of one centimetre proton range deviations on the backprojected images is analysed. In conclusion, the experimental results highlight the potential application of Compton cameras for high energy prompt gamma ray imaging of pencil beams, as a real-time and in vivo range verification method in proton therapy.

Proton and light ion beams are applied to the therapeutic irradiation of cancer patients due to the favorable dose deposition of these particles in tissue. By means of accelerated ions, a high dose can be accurately deposited in the tumor while normal tissue is spared. Since minor changes in the patient’s tissue along the beam path can compromise the success of the treatment, an in-vivo monitoring of the dose deposition is highly desired. Cameras detecting the prompt $\gamma $ -rays emitted during therapy are under investigation for this purpose. Due to the energy spectrum of prompt $\gamma $ -rays with a range between a few keV and several MeV, it is reasonable to consider the utilization of electron-positron pair production events to reconstruct the origin of these prompt photons. The combined use as a pair production and Compton camera is expected to increase its efficiency. We evaluated if a pair production camera could be suitable in this context by means of Monte-Carlo simulations. Modelling of the pair production events taking place in a prototype detector dedicated to Compton imaging were performed. We analyzed the efficiency of the detector system regarding pair production and Compton events. The most crucial property of this pair production camera is the angular resolution. The results of this work indicate that the spatial resolution of the considered detection system used as pair production camera is, for principal reasons, insufficient for an application to range assessment in particle therapy. Furthermore, the efficiency of the pair production camera under study is one order of magnitude lower than the efficiency of the setup applied to the detection of Compton events.

The proton therapy in oncology requires instantaneous and reliable particle range verification, which can be achieved using prompt gamma emissions. The characteristic requirements of prompt gamma detection include the energy range of up to several MeV, increased background due to secondary emissions and high counting rates. Different concepts make use of the prompt gamma emissions for verification of dose deposition location, e.g. collimated systems or Compton cameras. Additionally to prompt gamma imaging, the prompt gamma timing method has been proposed, utilizing the proton transit time inside the body. Those approaches imply different needs on energy-, spatial- or timing-resolution of the detection system. Various scintillator materials with multiple shapes have been characterized with respect to those requirements using classical photomultiplier tubes (PMT) and different experimental setups and locations. The light output, non-linearity and energy resolution were measured using gamma sources. The timing was characterized at the ELBE facility at Helmholtz-Zentrum Dresden-Rossendorf (HZDR), using the bremsstrahlung beam with photons up to 12.5 MeV. Measurements at the 3 MV Tandetron accelerator at HZDR provided information of the energy resolution at therapy relevant energies of 4.4 MeV.

Proton therapy is supposed to be advantageous compared to classical radiation therapy in oncology. But range uncertainties can arise easily and have to be corrected for, preferably immediately during irradiation. Prompt gammas are a good means of instantaneous localization of the dose deposition. Detection systems have to cope with high counting rates, an energy region of up to several MeV and increased background due to secondary emissions, while providing reliable information on energy, timing and location of the detected gamma ray. Various concepts utilize these prompt gammas for dose verification like collimated systems, Compton cameras or prompt gamma timing method. The digital silicon photomultiplier (dSiPM), being a favorable alternative to PMTs because of good timing performances and no requirement of further electronics, has been modelled in order to understand the complex behavior when working with monolithic scintillation crystals. Especially the selection of trigger- and validation-parameters may lead to different spectrum shapes. This model will be helpful for finding best parameter settings for the required task, because it determines the photons lost in various processes as well as the trigger timing information. Comparison of modelled spectra and measured spectra are presented.

The characteristic dose profile of accelerated ions has opened up new horizons in the context of cancer treatment. However, particle range uncertainties strongly constrain the potentialities of ion beam therapy. In spite of worldwide efforts, a detector system for range and dose delivery assessment in real-time is not yet available for clinical routine.

Particle therapy is supposed to be an advanced treatment modality compared to conventional radiotherapy because of the well-defined range of the ions. Prompt gamma rays, produced in nuclear reactions between ion and nuclei, can be utilized for real-time range verification to exploit the full potential of particle therapy. Several devices have been investigated in the field of Prompt Gamma Imaging (PGI), like Slit and Compton Cameras. The latter need very high detection efficiency as well as good time and energy resolution, requiring a versatile scintillation detector. In positron emission tomography (PET), LSO and LYSO are known for their good timing resolution, while the lower cost alternative BGO shows worse performance. In PGI however, where gamma rays have energies up to 10 MeV, the light output of a scintillator is up to 20 times larger compared to PET with E gamma = 511 keV. This reduces the statistical contribution of the time resolution, which is the dominant part in case of BGO. Thus, BGO could be a reasonable alternative to LSO/LYSO for applications in PGI. Hence, experiments at the ELBE accelerator at Helmholtz-Zentrum Dresden Rossendorf (Germany) were performed using digital silicon photomultiplier (dSiPM) from Philips with monolithic BGO and LYSO crystals and for completeness with GAGG and CeBr3. The time resolution of BGO compared to the faster scintillators will be presented for a wide range of trigger- and validation levels as well as validation lengths of the dSiPM. Timing resolutions below 300 ps were obtained for BGO, while LYSO and CeBr3 achieve about 170 ps.

Through the well defined hrainge of chahrged pahrticles iin mattehr, caincehr ihrhradiatioin by meains of ioins cain be vehry tumohr coinfohrmal. Howevehr, extehrinal hrainge vehrifcatioin is ineeded to fully exploit the advaintages of ioin beam thehrapy. Nucleahr iintehractioins betweein the phrojectiles aind tahrgets hresult iin excited inuclei which emit photoins iin the MeV einehrgy hrainge duhriing deexcitatioin. With a Comptoin camehra, it should be possible to image the ohrigiin of these photoins which is cohrhrelated to the beam positioin. A phrototype Comptoin camehra comphrisiing CdZinTe layehrs aind sciintillatioin detectohrs has beein developed aind tested with hradioactive poiint souhrces. Iin this wohrk, the pehrfohrmaince of the camehra is tested at a taindethroin beam liine iin a cleain hradiatioin feld of 4.44 MeV photoins. It was showin that Comptoin imagiing at this einehrgy is feasible.

In the context of particle therapy, particle range verification is a major challenge for the quality assurance of the treatment. One approach is the measurement of the prompt gamma rays resulting from the tissue irradiation. A Compton camera based on several position sensitive gamma ray detectors, together with an imaging algorithm, is expected to reconstruct the prompt gamma ray emission density map, which is correlated with the dose distribution. At Helmholtz-Zentrum Dresden-Rossendorf (HZDR) and OncoRay, a Compton camera setup has been developed consisting of two scatter planes (CdZnTe cross strip detectors) and an absorber (Lu 2 SiO 5 block detector). The data acquisition is based on VME electronics and handled by software developed on the ROOT framework. The setup was tested at the linear electron accelerator ELBE at HZDR, which was used to produce bunched bremsstrahlung photons with up to 12.5MeV. Their spectrum has similarities with the one expected from prompt gamma rays in the clinical case, and the flux is also bunched with the accelerator frequency. The spatial resolution for the CZT and LSO detector is analyzed and it showed a trend to improve for low and high energy depositions respectively. The time correlation between the pulsed prompt photons and the measured signals to be used for background discrimination exhibits a time resolution of 3 ns (2 ns) FWHM for the CZT (LSO) detector. A time walk correction and pixel calibration is applied for the LSO detector, whose resolution improved up to 630 ps. In conclusion, the detectors are suitable for time-resolved background suppression in pulsed clinical particle accelerators. Ongoing tasks are the test of the imaging algorithms and the quantitative comparison with simulations. Experiments at proton accelerators have been also performed and are now under analysis.

In the context of particle therapy, particle range verification is a major challenge for the quality assurance of the treatment. One approach is the measurement of the prompt gamma rays resulting from the tissue irradiation. A Compton camera based on several planes of position sensitive gamma ray detectors, together with an imaging algorithm, is expected to reconstruct the prompt gamma ray emission density profile, which is correlated with the dose distribution. At Helmholtz-Zentrum Dresden-Rossendorf (HZDR) and OncoRay, a camera prototype has been developed consisting of two scatter planes (CdZnTe cross strip detectors) and an absorber plane (Lu2SiO5 block detector). The data acquisition is based on VME electronics and handled by software developed on the ROOT platform. The prototype was tested at the linear electron accelerator ELBE at HZDR, which was set up to produce bunched bremsstrahlung photons. Their spectrum has similarities with the one expected from prompt gamma rays in the clinical case, and these are also bunched with the accelerator frequency. The time correlation between the pulsed prompt photons and the measured signals was used for background discrimination, achieving a time resolution of 3 ns (2 ns) FWHM for the CZT (LSO) detector. A timewalk correction was applied for the LSO detector and improved its resolution to 1 ns. In conclusion, the detectors are suitable for time-resolved background discrimination in pulsed clinical particle accelerators. Ongoing tasks are the test of the imaging algorithms and the quantitative comparison with simulations. Further experiments will be performed at proton accelerators.

Purpose: Tissue heterogeneities and calcifications have significant impact on the dosimetry of low energy brachytherapy (BT). RayStretch is an analytical algorithm developed in our institution to incorporate heterogeneity corrections in LDR prostate brachytherapy. The aim of this work is to study its application in clinical cases by comparing its predictions with the results obtained with TG-43 and Monte Carlo (MC) simulations. Methods: A clinical implant (71 I-125 seeds, 15 needles) from a real patient was considered. On this patient, different volumes with calcifications were considered. Its properties were evaluated in three ways by i) the Treatment planning system (TPS) (TG-43), ii) a MC study using the Penelope2009 code, and iii) RayStretch. To analyse the performance of RayStretch, calcifications located in the prostate lobules covering 11% of the total prostate volume and larger calcifications located in the lobules and underneath the urethra for a total occupied volume of 30% were considered. Three mass densities (1.05, 1.20, and 1.35 g/cm3) were explored for the calcifications. Therefore, 6 different scenarios ranging from small low density calcifications to large high density ones have been discussed. Results: DVH and D90 results given by RayStretch agree within 1% with the full MC simulations. Although no effort has been done to improve RayStretch numerical performance, its present implementation is able to evaluate a clinical implant in a few seconds to the same level of accuracy as a detailed MC calculation. Conclusion: RayStretch is a robust method for heterogeneity corrections in prostate BT supported on TG-43 data. Its compatibility with commercial TPSs and its high calculation speed makes it feasible for use in clinical settings for improving treatment quality. It will allow in a second phase of this project, its use during intraoperative ultrasound planning. This study was partly supported by a fellowship grant from the Spanish Ministry of Education, by the Generalitat Valenciana under Project PROMETEOII/2013/010, by the Spanish Government under Project No. FIS2013-42156 and by the European Commission within the SeventhFramework Program through ENTERVISION (grant agreement number 264552).

Particle therapy in oncology is advantageous compared to classical radiotherapy due to its well-defined penetration depth. In the so-called Bragg peak, the highest dose is deposited; the tissue behind the cancerous area is not exposed. Different factors influence the range of the particle and thus the target area, e.g. organ motion, mispositioning of the patient or anatomical changes. In order to avoid over-exposure of healthy tissue and under-dosage of cancerous regions, the penetration depth of the particle has to be monitored, preferably already during the ongoing therapy session. The verification of the ion range can be performed using prompt gamma emissions, which are produced by interactions between projectile and tissue, and originate from the same location and time of the nuclear reaction. The prompt gamma emission profile and the clinically relevant penetration depth are correlated. Various imaging concepts based on the detection of prompt gamma rays are currently discussed: collimated systems with counting detectors, Compton cameras with (at least) two detector planes, or the prompt gamma timing method, utilizing the particle time-of-flight within the body. For each concept, the detection system must meet special requirements regarding energy, time, and spatial resolution. Nonetheless, the prerequisites remain the same: the gamma energy region (2 to 10 MeV), high counting rates and the stability in strong background radiation fields. The aim of this work is the comparison of different scintillation crystals regarding energy and time resolution for optimized prompt gamma detection.

A major weakness of ion beam therapy is the lack of tools for verifying the particle range in clinical routine. The application of the Compton camera concept for the imaging of prompt gamma rays, a by-product of the irradiation correlated to the dose distribution, is a promising approach for range assessment and even three-dimensional in vivo dosimetry.Multiple position sensitive gamma ray detectors arranged in scatter and absorber planes, together with an imaging algorithm, are required to reconstruct the prompt gamma emission density map. Conventional block detectors deployed in Positron Emission Tomography (PET), which are based on Lu2SiO5:Ce (LSO) and Bi4Ge3O12 (BGO) scintillators, are suitable candidates for the absorber of a Compton camera due to their high density and absorption efficiency with respect to the prompt gamma energy range (several MeV).We compare experimentally LSO and BGO block detectors in clinical-like radiation fields in terms of energy, spatial and time resolution. The high energy range compensates for the low light yield of the BGO material and boosts significantly its performance compared to the PET scenario. Notwithstanding the overall superiority of LSO, BGO catches up in the field of prompt gamma imaging and can be considered as a competitive alternative to LSO for the absorber plane due to its lower price and the lack of intrinsic radioactivity.

In the context of ion beam therapy, particle range verification is a major challenge for the quality assurance of the treatment. One approach is the measurement of the prompt gamma rays resulting from the tissue irradiation. A Compton camera based on several position sensitive gamma ray detectors, together with an imaging algorithm, is expected to reconstruct the prompt gamma ray emission density map, which is correlated with the dose distribution. At OncoRay and Helmholtz-Zentrum Dresden-Rossendorf (HZDR), a Compton camera setup is being developed consisting of two scatter planes: two CdZnTe (CZT) cross strip detectors, and an absorber consisting of one Lu2SiO5 (LSO) block detector. The data acquisition is based on VME electronics and handled by software developed on the ROOT framework. The setup has been tested at the linear electron accelerator ELBE at HZDR, which is used in this experiment to produce bunched bremsstrahlung photons with up to 12.5 MeV energy and a repetition rate of 13 MHz. Their spectrum has similarities with the shape expected from prompt gamma rays in the clinical environment, and the flux is also bunched with the accelerator frequency. The charge sharing effect of the CZT detector is studied qualitatively for different energy ranges. The LSO detector pixel discrimination resolution is analyzed and it shows a trend to improve for high energy depositions. The time correlation between the pulsed prompt photons and the measured detector signals, to be used for background suppression, exhibits a time resolution of 3 ns FWHM for the CZT detector and of 2 ns for the LSO detector. A time walk correction and pixel-wise calibration is applied for the LSO detector, whose resolution improves up to 630 ps. In conclusion, the detector setup is suitable for time-resolved background suppression in pulsed clinical particle accelerators. Ongoing tasks are the quantitative comparison with simulations and the test of imaging algorithms. Experiments at proton accelerators have also been performed and are currently under analysis.

During the 2012 AAPM Annual Meeting 33 percent of the delegates considered the range uncertainty in proton therapy as the main obstacle of becoming a mainstream treatment modality. Utilizing prompt gamma emission, a side product of particle tissue interaction opens the possibility of in-beam dose verification, due to the direct correlation between prompt gamma emission and particle dose deposition. Compton imaging has proven to be a technique to measure three dimensional gamma emission profiles ([1], [2]) and opens the possibility of adaptive dose monitoring and treatment correction.