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.

From prompt gamma distribution to dose: a novel approach combining an evolutionary algorithm and filtering based on Gaussian-powerlaw convolutions.

Range verification and dose monitoring in proton therapy is considered as highly desirable. Different methods have been developed worldwide, like particle therapy positron emission tomography (PT-PET) and prompt gamma imaging (PGI). In general, these methods allow for a verification of the proton range. However, quantification of the dose from these measurements remains challenging. For the first time, we present an approach for estimating the dose from prompt γ-ray emission profiles. It combines a filtering procedure based on Gaussian-powerlaw convolution with an evolutionary algorithm. By means of convolving depth dose profiles with an appropriate filter kernel, prompt γ-ray depth profiles are obtained. In order to reverse this step, the evolutionary algorithm is applied. The feasibility of this approach is demonstrated for a spread-out Bragg-peak in a water target.

Detection of mixed-range proton pencil beams with a prompt gamma slit camera.

With increasing availability of proton and particle therapy centers for tumor treatment, the need for in vivo range verification methods comes more into the focus. Imaging of prompt gamma rays emitted during the treatment is one of the possibilities currently under investigation. A knife-edge shaped slit camera was recently proposed for this task and measurements proved the feasibility of range deviation detection in homogeneous and inhomogeneous targets. In the present paper, we concentrate on laterally inhomogeneous materials, which lead to range mixing situations when crossed by one pencil beam: different sections of the beam have different ranges. We chose exemplative cases from clinical irradiation and assembled idealized tissue equivalent targets. One-dimensional emission profiles were obtained by measuring the prompt gamma emission with the slit camera. It could be shown that the resulting range deviations can be detected by evaluation of the measured data with a previously developed range deviation detection algorithm. The retrieved value, however, strongly depends on the target composition, and is not necessarily in direct relation to the ranges of both parts of the beam. By combining the range deviation detection with an analysis of the slope of the distal edge of the measured prompt gamma profile, the origin of the detected range deviation, i.e. the mixed range of the beam, is also identified. It could be demonstrated that range mixed prompt gamma profiles exhibit less steep distal slopes than profiles from beams traversing laterally homogeneous material. For future application of the slit camera to patient irradiation with double scattered proton beams, situations similar to the range mixing cases are present and results could possibly apply.

Experimental investigation of irregular motion impact on 4D PET-based particle therapy monitoring.

Particle therapy positron emission tomography (PT-PET) is an in vivo and non-invasive imaging technique to monitor treatment delivery in particle therapy. The inevitable patient respiratory motion during irradiation causes artefacts and inaccurate activity distribution in PET images. Four-dimensional (4D) maximum likelihood expectation maximisation (4D MLEM) allows for a compensation of these effects, but has up to now been restricted to regular motion for PT-PET investigations. However, intra-fractional motion during treatment might differ from that during acquisition of the 4D-planning CT (e.g. amplitude variation, baseline drift) and therefore might induce inaccurate 4D PET reconstruction results. This study investigates the impact of different irregular analytical one-dimensional (1D) motion patterns on PT-PET imaging by means of experiments with a radioactive source and irradiated moving phantoms. Three sorting methods, namely phase sorting, equal amplitude sorting and event-based amplitude sorting, were applied to manage the PET list-mode data. The influence of these sorting methods on the motion compensating algorithm has been analysed. The event-based amplitude sorting showed a superior performance and it is applicable for irregular motions with ⩽ 4 mm amplitude elongation and drift. For motion with 10 mm baseline drift, the normalised root mean square error was as high as 10.5% and a 10 mm range deviation was observed.

Measurement of prompt gamma profiles in inhomogeneous targets with a knife-edge slit camera during proton irradiation.

Proton and ion beam therapies become increasingly relevant in radiation therapy. To fully exploit the potential of this irradiation technique and to achieve maximum target volume conformality, the verification of particle ranges is highly desirable. Many research activities focus on the measurement of the spatial distributions of prompt gamma rays emitted during irradiation. A passively collimating knife-edge slit camera is a promising option to perform such measurements. In former publications, the feasibility of accurate detection of proton range shifts in homogeneous targets could be shown with such a camera. We present slit camera measurements of prompt gamma depth profiles in inhomogeneous targets. From real treatment plans and their underlying CTs, representative beam paths are selected and assembled as one-dimensional inhomogeneous targets built from tissue equivalent materials. These phantoms have been irradiated with monoenergetic proton pencil beams. The accuracy of range deviation estimation as well as the detectability of range shifts is investigated in different scenarios. In most cases, range deviations can be detected within less than 2 mm. In close vicinity to low-density regions, range detection is challenging. In particular, a minimum beam penetration depth of 7 mm beyond a cavity is required for reliable detection of a cavity filling with the present setup. Dedicated data post-processing methods may be capable of overcoming this limitation.

Experimental verification of a 4D MLEM reconstruction algorithm used for in-beam PET measurements in particle therapy.

In-beam positron emission tomography (PET) has been proven to be a reliable technique in ion beam radiotherapy for the in situ and non-invasive evaluation of the correct dose deposition in static tumour entities. In the presence of intra-fractional target motion an appropriate time-resolved (four-dimensional, 4D) reconstruction algorithm has to be used to avoid reconstructed activity distributions suffering from motion-related blurring artefacts and to allow for a dedicated dose monitoring. Four-dimensional reconstruction algorithms from diagnostic PET imaging that can properly handle the typically low counting statistics of in-beam PET data have been adapted and optimized for the characteristics of the double-head PET scanner BASTEI installed at GSI Helmholtzzentrum Darmstadt, Germany (GSI). Systematic investigations with moving radioactive sources demonstrate the more effective reduction of motion artefacts by applying a 4D maximum likelihood expectation maximization (MLEM) algorithm instead of the retrospective co-registration of phasewise reconstructed quasi-static activity distributions. Further 4D MLEM results are presented from in-beam PET measurements of irradiated moving phantoms which verify the accessibility of relevant parameters for the dose monitoring of intra-fractionally moving targets. From in-beam PET listmode data sets acquired together with a motion surrogate signal, valuable images can be generated by the 4D MLEM reconstruction for different motion patterns and motion-compensated beam delivery techniques.

In-beam PET measurement of 7Li3+ irradiation induced beta+-activity.

At present positron emission tomography (PET) is the only feasible method of an in situ and non-invasive monitoring of patient irradiation with ions. At the experimental carbon ion treatment facility of the Gesellschaft für Schwerionenforschung (GSI) Darmstadt an in-beam PET scanner has been integrated into the treatment site and lead to a considerable quality improvement of the therapy. Since ions other than carbon are expected to come into operation in future patient treatment facilities, it is highly desirable to extend in-beam PET also to other therapeutic relevant ions, e.g. (7)Li. Therefore, by means of the in-beam PET scanner at GSI the beta(+)-activity induced by (7)Li(3+) ions has been investigated for the first time. Targets of PMMA, water, graphite and polyethylene were irradiated with monoenergetic, pencil-like beams of (7)Li(3+) with energies between 129.1 A MeV and 205.3 A MeV and intensities ranging from 3.0 x 10(7) to 1.9 x 10(8) ions s(-1). This paper presents the measured beta(+)-activity profiles as well as depth dependent thick target yields which have been deduced from the experimental data. The beta(+)-activity induced by (7)Li ions was found to be a factor of 1.76 higher than the one induced by (12)C ions at the same physical dose and particle range.