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.

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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.

A: 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 15 N(p, α γ 4.439 ) 12 C is utilized. This reaction provides the same nuclear de-excitation (and γ-ray emission) occurrent as an intense prompt γray 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-ray Compton imaging limiting the applicability of the prototype in its current realization.

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