Search

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.

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.

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.

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.

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.

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.

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.