J. Petzoldt

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.

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.

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.

Prompt Gamma Rays Detected With a BGO Block Compton Camera Reveal Range Deviations of Therapeutic Proton Beams

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 Universitäts 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.

Prompt Gamma Timing range verification for scattered proton beams

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.

Studies of a proton bunch phase monitor for range verification in proton therapy

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.

Fast timing with BGO (and other scintillators) on digital silicon photomultipliers for Prompt Gamma Imaging

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 time 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. 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 HZDR (Germany) were performed using digital silicon photomultiplier (dSiPM) from Philips with monolithic BGO and LYSO crystals, and for completeness with GAGG, CeBr3, CsI, CaF2, and GSO. The time resolution of BGO compared to the other scintillators will be presented for a wide range of trigger- and validation levels as well as validation lengths of the dSiPM. Timing resolutions below 220 ps are obtained for BGO, while LYSO and CeBr3 achieve about 170 ps.