C. Golnik

Test of Compton camera components for prompt gamma imaging at the ELBE bremsstrahlung beam

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.

First test of the prompt gamma ray timing method with heterogeneous targets at a clinical proton therapy facility.

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.

Simulation and experimental verification of prompt gamma-ray emissions during proton irradiation

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 γ-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 γ-ray depth profile were assessed. Experiments were performed at the superconducting AGOR cyclotron at KVI-CART, University of Groningen. Properties of the γ-ray emissions were experimentally determined. The prompt γ-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 γ 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 γ-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.

Tests of a Compton imaging prototype in a monoenergetic 4.44 MeV photon field—a benchmark setup for prompt gamma-ray imaging devices

The finite range of a proton beam in tissue opens new vistas for the delivery of a highly conformal dose distribution in radiotherapy. However, the actual particle range, and therefore the accurate dose deposition, is sensitive to the tissue composition in the proton path. Range uncertainties, resulting from limited knowledge of this tissue composition or positioning errors, are accounted for in the form of safety margins. Thus, the unverified particle range constrains the principle benefit of proton therapy. Detecting prompt γ-rays, a side product of proton-tissue interaction, aims at an on-line and non-invasive monitoring of the particle range, and therefore towards exploiting the potential of proton therapy. Compton imaging of the spatial prompt γ-ray emission is a promising measurement approach. Prompt γ-rays exhibit emission energies of several MeV. Hence, common radioactive sources cannot provide the energy range a prompt γ-ray imaging device must be designed for. In this work a benchmark measurement-setup for the production of a localized, monoenergetic 4.44 MeV γ-ray source is introduced. At the Tandetron accelerator at the HZDR, the proton-capture resonance reaction 15N(p,α γ4.439)12C is utilized. This reaction provides the same nuclear de-excitation (and γ-ray emission) occurrent as an intense prompt γ-ray line in proton therapy. The emission yield is quantitatively described. A two-stage Compton imaging device, dedicated for prompt γ-ray imaging, is tested at the setup exemplarily. Besides successful imaging tests, the detection efficiency of the prototype at 4.44 MeV is derived from the measured data. Combining this efficiency with the emission yield for prompt γ-rays, the number of valid Compton events, induced by γ-rays in the energy region around 4.44 MeV, is estimated for the prototype being implemented in a therapeutic treatment scenario. As a consequence, the detection efficiency turns out to be a key parameter for prompt γ-rays Compton imaging limiting the applicability of the prototype in its current realization.

Scintillator-Based High-Throughput Fast Timing Spectroscopy for Real-Time Range Verification in Particle Therapy

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 CeBr3 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.

Compton Camera and Prompt Gamma Ray Timing: Two Methods for In Vivo Range Assessment in Proton Therapy

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.

Characterization of scintillator crystals for usage as prompt gamma monitors in particle therapy

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.

The use of prompt γ-rays for in-vivo dosimetry at therapeutic proton and ion beams

Radiation therapy is an important treatment modality in cancer therapy. New radiation species like protons and light ions have the potential of increasing tumor conformity of the irradiation. These particle beams offer advantages over conventional treatment modalities, such as photons. Because of the way particles deposit their energy on their path through tissue they allow for an increased dose deposition in the tumor volume and reduce the damage to the surrounding healthy tissue. However, the parameters of the ion beams must be calculated from X-ray CT data using a physical beam model. Minor inaccuracies of imaging and modeling and small changes in the irradiated volume will lead to a mismatch of the deposited dose maximum and the tumor. This causes missing dose in the tumor volume and potential damage to healthy tissue. Thus, to use the advantages of particle therapy to full capacity, proton and ion beam radiotherapy treatment requires efficient quality assurance techniques for dose delivery monitoring. Until now, the only clinically applied in-vivo dosimetry method for ion beams is PET. However, this method suffers from inherent physical limitations. Therefore, a new approach based on the detection of prompt gamma rays is under development. A Compton camera seems to be a feasible technical solution for monitoring proton and ion irradiation. Our project is aimed to design and construct such a camera, and evaluate if it could lead to clinical applications. This comprises the whole simulation process, i.e. simulating the expected gamma-emissions from the treatment plan, the reconstruction and the assembly of a prototype as well as the simulation of the detector efficiency.

Comparison of LSO and BGO block detectors for prompt gamma imaging in ion beam therapy

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.

Simulation Study of a Combined Pair Production – Compton Camera for In-Vivo Dosimetry During Therapeutic Proton Irradiation

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 patients 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 γ-rays emitted during therapy are under investigation for this purpose. Due to the energy spectrum of prompt γ-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.