Requirements for a Compton camera for in vivo range verification of proton therapy.

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.

Towards clinical application: prompt gamma imaging of passively scattered proton fields with a knife-edge slit camera.

Prompt γ-ray imaging with a knife-edge shaped slit camera provides the possibility of verifying proton beam range in tumor therapy. Dedicated experiments regarding the characterization of the camera system have been performed previously. Now, we aim at implementing the prototype into clinical application of monitoring patient treatments. Focused on this goal of translation into clinical operation, we systematically addressed remaining challenges and questions. We developed a robust energy calibration routine and corresponding quality assurance protocols. Furthermore, with dedicated experiments, we determined the positioning precision of the system to 1.1 mm (2σ). For the first time, we demonstrated the application of the slit camera, which was intentionally developed for pencil beam scanning, to double scattered proton beams. Systematic experiments with increasing complexity were performed. It was possible to visualize proton range shifts of 2-5 mm with the camera system in phantom experiments in passive scattered fields. Moreover, prompt γ-ray profiles for single iso-energy layers were acquired by synchronizing time resolved measurements to the rotation of the range modulator wheel of the treatment system. Thus, a mapping of the acquired profiles to different anatomical regions along the beam path is feasible and additional information on the source of potential range shifts can be obtained. With the work presented here, we show that an application of the slit camera in clinical treatments is possible and of potential benefit.

Characterization of the microbunch time structure of proton pencil beams at a clinical treatment facility.

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.

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.

Development of miniaturized potentiometric nitrate- and ammonium selective electrodes for applications in water monitoring.

Mobile analysis with potentiometric sensors is well suited for field measurements. Ion-selective electrodes (ISE) based on polymeric membranes for in-situ determination of nitrate and ammonium contents in ground water, drinking water and surface water have been developed. The ISE are integrated in a multisensor module (MSM) for monitoring these ions over longer time intervals. The receptor is a PVC-membrane with tridodecylammonium nitrate (TDDA) for nitrate- and nonactine for ammonium-electrodes as ionophores. As plasticizer dibutylphthalate (DBT) was used. The main parameters for assessing the efficiency of these ISE are presented.

Multifractal analysis of the 137Cs fallout pattern in Austria resulting from the Chernobyl accident.

The cumulative deposition of the 137Cs fallout in Austria resulting from the passage of the Chernobyl cloud has been investigated by applying correlation dimension and hyperbolic frequency distribution methods. For the analysis, a total of 1,881 deposition values were used, which were collected by the Federal Environmental Agency of Austria and the Federal Ministry of Health, representing all available measurements of 137Cs in soil made in Austria after the Chernobyl accident. From these data a hyperbolic exponent for the frequency distribution of 4.0 and a set of fractal correlation dimensions, which decrease from 1.426 +/- 0.022 (for the whole network) to 0.706 +/- 0.047 (for 137Cs values > or = 100 kBq m(-2)), were derived, thus confirming that the fallout pattern can be described as a multifractal.

Gangliosides in meningiomas: correlation of Glac2 to intermediary filament.

Human meninges and 29 meningiomas were analyzed as to their glycosphingolipid composition. In the neutral fraction GSL, a mostly even distribution of mono-, di-, tri-and tetrahexoside was demonstrated. In the group of the gangliosides, Glac1 in one broad band in chromatograms occurred in almost all meningiomas; Glac2 was present in 84% of tumours. Members of the Gtn-family were only found in a small minority of tumours while various Gtet-gangliosides were detectable in nearly half of them. No constant pattern or patterns emerged and no correlation to either morphological subtype or malignancy grade could be established. Immunohistochemistry revealed focal presence of Glac2 in a pattern similar to that of vimentin expression. Semiquantitative evaluation showed good correlation between both parameters.