Christian Golnik

Range assessment in particle therapy based on prompt γ-ray timing measurements

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 patients 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.

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 protons 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.

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 1.1u2009mm (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 2-5u2009mm 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.

An Image Reconstruction Framework and Camera Prototype Aimed for Compton Imaging for In-vivo Dosimetry of Therapeutic Ion Beams

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Compton imaging in a high energetic photon field

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A compton imaging prototype for range verification in particle therapy

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OC-0456: Translation of a prompt gamma based proton range verification system to first clinical application

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Scintillator characterization at energies relevant for a prompt gamma detection system in particle therapy

</tex-math></inline-formula>-rays emitted during therapeutic irradiation in the order of MeV, Compton imaging is a feasible method. In this work, an imaging prototype together with the corresponding data handling and an image reconstruction framework are presented. Data and reconstructed images from laboratory measurements are shown and evaluated. A spatial resolution of 7 mm full width at half maximum in a distance of 7 cm has been achieved. More importantly, current limitations were identified for further work. It has been shown that an assumption on the unknown initial photon energy can considerably improve the imaging result.

Particle range retrieval in heterogeneous phantoms with the prompt gamma ray timing method at a clinical proton accelerator

Through the well defined range of charged particles in matter, cancer irradiation by means of ions can be very tumor conformal. However, external range verification is needed to fully exploit the advantages of ion beam therapy. Nuclear interactions between the projectiles and targets result in excited nuclei which emit photons in the MeV energy range during deexcitation. With a Compton camera, it should be possible to image the origin of these photons which is correlated to the beam position. A prototype Compton camera comprising CdZnTe layers and scintillation detectors has been developed and tested with radioactive point sources. In this work, the performance of the camera is tested at a tandetron beam line in a clean radiation field of 4.44 MeV photons. It was shown that Compton imaging at this energy is feasible.

Timing of pulsed prompt gamma rays for background discrimination

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.