Ultra-high dose rate proton radiation has the potential to improve cancer treatment by reducing the normal tissue complication probability and, at the same time, reaching the tumor control probability known from conventional photon radiation therapy. Here, the ultra-high dose rate leads to normal tissue sparing via the FLASH effect. Before a clinical implementation is possible, the proton FLASH effect requires translational research via in-vivo irradiation studies with small animals.
Laser plasma-based accelerators (LPAs) for protons offer unique opportunities for studying the proton FLASH effect, since the proton dose rate at LAPs is in the order of 10^9 Gy/s, which is unreached at conventional medical proton accelerators. Different to medical proton accelerators, LPAs are operated in a pulsed mode and feature a lower beam stability caused by inherent pulse-to-pulse fluctuations of the acceleration process. To ensure successful in-vivo irradiation studies, advanced beam delivery, monitoring and dosimetry concepts for an online-monitored application of the 3D dose distribution in the target volume (TV) of the in-vivo sample are needed.
The detectors and dosimetric concept developed in this thesis enable the world wide frst pilot radiobiological in-vivo study with LPA protons, where mouse ear tumors are irradiated with ultra-high dose rate proton pulses. For performing the radiobiological study, the ALBUS-2S (Advanced Laser-driven Beamlines for User-specifc Studies - 2 Solenoids) beamline is used, which is installed at the compact petawatt (PW) laser system DRACO (Dresden laser acceleration source) at HZDR (Helmholtz-Zentrum Dresden-Rossendorf).
In this thesis, a scintillator-based time-of-fight (ToF) beam monitoring sytem (BMS) is developed, which records single-pulse proton energy spectra in transmission at the ALBUS-2S beamline. A relative energy uncertainty of 5.5 % (1σ) is reached for the ToF BMS, allowing for a Monte Carlo simulation-based prediction of depth dose profiles at the irradiation site. The ToF BMS is used for characterization of the ALBUS-2S LPA beamline for application-oriented parameters, in order to qualify the LPA proton source for radiobiological in-vivo studies.
Furthermore, a dosimetry and beam monitoring concept for in-vivo irradiations of small target volumes with LPA protons is presented in this thesis. With the overall relative dose uncertainty of 7.4 % (2σ) for the specifc mouse ear tumor irradiation scenario, the concept enables verifcation of accurate volumetric dose delivery to the mm-scale TVs.
In addition, tomography-based approaches with scintillators are investigated as detectors for online 3D dose measurement at LPAs. The miniature scintillator dosimeter (miniSCIDOM) detector, which is developed in the scope of this thesis, is used for online 3D dose measurements in 1 cm^3 volumes with < 1 mm^3 resolution at the irradiation site of the ALBUS-2S beamline. For online 3D dose measurements directly behind the LPA proton source of the DRACO PW laser system, the optical cone beam tomograph for proton online dosimetry (OCTOPOD) detector is developed. The OCTOPOD detector has a sensitive volume of 5 cm-diameter and water equivalent thickness of 4.3 cm, which is sufficient to stop 70 MeV protons. It is designed to reach a spatial resolution of 1 mm^3.
The detectors developed in this thesis are optimized tools for source-to-sample characterization of LPA beamlines and hence are an essential contribution for radiobiological in-vivo studies with LPA protons.
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:90792 |
| Date | 11 April 2024 |
| Creators | Reimold, Marvin |
| Contributors | Schramm, Ulrich, Cowan, Thomas, Schreiber, Jörg, Metzkes-Ng, Josefine, Technische Universität Dresden |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, doc-type:doctoralThesis, info:eu-repo/semantics/doctoralThesis, doc-type:Text |
| Rights | info:eu-repo/semantics/openAccess |
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