Reichweiteverifikation ist ein Schlüsselelement auf dem Weg zur online-adaptiven Pro- tonentherapie. Das Prompt Gamma-Ray Timing ist hierfür ein vielversprechendes Verfah- ren, welches die Zeitverteilung der in der Therapie erzeugten Gammastrahlung nutzt, um Abweichungen zur Bestrahlungsplanung zu registrieren. Das Verfahren ist dabei auf eine präzise Zeitreferenz angewiesen. Am OncoRay wurde dafür bisher die Radiofrequenz des Beschleunigers verwendet, jedoch hat sich gezeigt, dass diese keine zuverlässige Größe zur Bestimmung der Ankunftszeit der Protonen ist. Protonen-Bunch-Monitore (PBM) sind Detektoren, die diese Zeiten direkt oder indirekt bestimmen können. In dieser Arbeit wurde das Monitorsignal Uφ des Zyklotrons dafür genutzt, um Phaseninsta- bilitäten in der Ankunftszeit unter realistischen Bedingungen zu detektieren. Dabei misst Uφ den Phasenunterschied der beschleunigenden Hochspannung zwischen beiden Duanten. Da Uφ nicht auf dem Nachweis von Einzelereignissen beruht, ist seine Genauigkeit unabhän- gig von der zur Verfügung stehenden Zählstatistik, was ihn zu einem idealen Kandidaten für einen klinisch einsetzbaren PBM macht. Weil es sich jedoch um eine indirekte Mess- methode handelt, wurden seine Ergebnisse durch zwei weitere PBM, die die Ankunftszeit der Protonen direkt messen können, verifiziert. Obwohl alle drei über große Zeitintervalle hinweg in sehr guter Übereinstimmung sind, zeigen sich Abweichungen innerhalb der ersten Sekunde nach Beginn der Bestrahlung.

The prompt gamma-ray timing (PGT) method offers a relatively simple approach for range verification in proton therapy. Starting from the findings of previous experiments, several steps toward a clinical application of PGT have been performed in this work. First of all, several scintillation materials have been investigated in the context of PGT. The time resolution was determined at high photon energies in the MeV-region. In conclusion, the fast and bright scintillator CeBr3 is the material of choice in combination with a timing photomultiplier tube as light detector. A second study was conducted at Universitäts Protonen Therapie Dresden (UPTD) to characterize the proton bunch structure of a clinical beam concerning its time width and relative arrival time. The data is mandatory as input for simulation studies and to correct for phase drifts. The obtained data could furthermore be used for the first 2D imaging of a heterogeneous phantom based on prompt gamma-rays. In a last step, a PGT prototype system was designed using the findings from the first two studies. The prototype system is based on a newly developed digital spectrometer and a CeBr3 detector. The device is characterized at the ELBE bremsstrahlung beam. It was verified that the prototype operates within the specifications concerning time and resolution as well as throughput rate. Finally, for the first time the PGT system was used under clinical conditions in the treatment room of UPTD. Here, PGT data was obtained from the delivery of a three-dimensional treatment plan onto PMMA phantoms. The spot-by-spot analysis helped to investigate the performance of the prototype device under clinical conditions. As a result, range variations of 5 mm could be detected for the first time with an uncollimated system at clinically relevant doses. To summarize, the obtained results help to bring PGT closer to a clinical application.

The prompt gamma-ray timing (PGT) method offers a relatively simple approach for range verification in proton therapy. Starting from the findings of previous experiments, several steps toward a clinical application of PGT have been performed in this work. First of all, several scintillation materials have been investigated in the context of PGT. The time resolution was determined at high photon energies in the MeV-region. In conclusion, the fast and bright scintillator CeBr3 is the material of choice in combination with a timing photomultiplier tube as light detector. A second study was conducted at Universitäts Protonen Therapie Dresden (UPTD) to characterize the proton bunch structure of a clinical beam concerning its time width and relative arrival time. The data is mandatory as input for simulation studies and to correct for phase drifts. The obtained data could furthermore be used for the first 2D imaging of a heterogeneous phantom based on prompt gamma-rays. In a last step, a PGT prototype system was designed using the findings from the first two studies. The prototype system is based on a newly developed digital spectrometer and a CeBr3 detector. The device is characterized at the ELBE bremsstrahlung beam. It was verified that the prototype operates within the specifications concerning time and resolution as well as throughput rate. Finally, for the first time the PGT system was used under clinical conditions in the treatment room of UPTD. Here, PGT data was obtained from the delivery of a three-dimensional treatment plan onto PMMA phantoms. The spot-by-spot analysis helped to investigate the performance of the prototype device under clinical conditions. As a result, range variations of 5 mm could be detected for the first time with an uncollimated system at clinically relevant doses. To summarize, the obtained results help to bring PGT closer to a clinical application.