Andreas Hoffmann

Cancer treatment with radiotherapy aims to kill tumor cells while sparing healthy tissue. Therefore,the experimentally observed sparing of healthy tissue by the FLASH effect during ultra-high dose rate (UHDR) irradiations enables clinicians to extend the therapeutic window. However, the underlying chemical mechanisms are far from being understood. DNA is the main molecular targets for radiotherapy. Here radiation-damage to DNA depends strongly on solvent conditions. We irradiated plasmid DNA pUC19, with 18MeV electrons at conventional/low-dose-rates(LDR) and UHDR under tightly controlled ambient and physiological oxygen conditions in phosphate-buffered-saline (PBS). For the first time, a sparing effect of DNA strand-break induction between UHDR and LDR irradiated DNA under physiological oxygen, salt and pH7.4 is observed. Under physiological oxygen (physoxia≈5%O2,40mmHg), more single-strand-breaks(SSB) and double-strand-breaks(DSB) are observed when exposed with LDR than UHDR. This behaviour is absent for ambient oxygen (normoxia,≈21%O2,150-160mmHg). Additional Geant4/TOPAS-nBio based particle-scattering and radiation-chemical Monte-Carlo simulations helped to determine radical-yields and reactive-oxygen-species(ROS). A model for the observed DNA sparing under FLASH conditions at physoxia was proposed: The interplay of O2 with the •OH-induced hydrogen-abstraction at the sugar-phosphate-backbone, and the conversion of DNA-base-damage to SSB, under consideration of the dose-rate-dependent H3O+ yield via beta-elimination processes is accounted for,to explain the observed behavior.

The optimization of photoinjector brightness is crucial for achieving the highest performance at X-ray free-electron lasers. To this end, photocathode laser pulse shaping has been identified as a key technology for enhancing photon flux and lasing efficiency at short wavelengths. Supported by beam dynamics simulations, we identify transversely and longitudinally truncated Gaussian electron bunches as a beneficial bunch shape in terms of the projected emittance and 5D brightness. The realization of such pulses from chirped Gaussian pulses is studied for 514 nm and 257 nm wavelengths by inserting an amplitude mask in the symmetry plane of the pulse stretcher to achieve longitudinal shaping and an aperture for transverse beam shaping. Using this scheme, transversely and longitudinally truncated Gaussian pulses can be generated and later used for the production of up to 3 nC electron bunches in the photoinjector. The 3D pulse shape at a wavelength of 514 nm is characterized via imaging spectroscopy, and second-harmonic generation frequency-resolved optical gating (SHG FROG) measurements are also performed to analyze the shaping scheme’s efficacy. Furthermore, this pulse-shaping scheme is transferred to a UV stretcher, allowing for direct application of the shaped pulses to cesium telluride photocathodes.

We report on the operation of the first high peak and average power single-pass terahertz free-electron laser (THz FEL) based on a high-brightness photoinjector for developing a THz source for pump-probe experiments at advanced x-ray FELs (XFELs). Electron beams with 17 MeV / c momentum and charge up to 2.4 nC were used to generate narrow-band 3 THz radiation with pulse energies of more than 0.1 mJ. The novelty of the realized method is that the undulator radiation by electron beams is much longer than the radiation wavelength, with FEL starting from coherent beam contribution rather than shot noise. This proved to be not a simple scaling of the XFEL mechanism due to the significant role of the bunching factor in the considered case.

Objective. The photo injector test facility at DESY in Zeuthen (PITZ) is building up an R&D platform, known as FLASH lab @PITZ, for systematically studying the FLASH effect in cancer treatment with its high-brightness electron beams, which can provide a uniquely large dose parameter range for radiation experiments. In this paper, we demonstrate the capabilities by experiments with a reduced parameter range on a startup beamline and study the potential performance of the full beamline by simulations. Approach. To measure the dose, Gafchromic films are installed both in front of and after the samples; Monte Carlo simulations are conducted to predict the dose distribution during beam preparation and help understand the dose distribution inside the sample. Plasmid DNA is irradiated under various doses at conventional and ultra-high dose rate (UHDR) to study the DNA damage by radiations. Start-to-end simulations are performed to verify the performance of the full beamline. Main results. On the startup beamline, reproducible irradiation has been established with optimized electron beams and the delivered dose distributions have been measured with Gafchromic films and compared to FLUKA simulations. The functionality of this setup has been further demonstrated in biochemical experiments at conventional dose rate of 0.05 Gy s⁻¹ and UHDR of several 10⁵ Gy s⁻¹ and a varying dose up to 60 Gy, with the UHDR experiments finished within a single RF pulse (less than 1 millisecond); the observed conformation yields of the irradiated plasmid DNA revealed its dose-dependent radiation damage. The upgrade to the full FLASH lab @PITZ beamline is justified by simulations with homogeneous radiation fields generated by both pencil beam scanning and scattering beams. Significance. With the demonstration of UHDR irradiation and the simulated performance of the new beamline, FLASH lab @PITZ will serve as a powerful platform for studying the FLASH effects in cancer treatment.

An R&D platform for electron FLASH radiation therapy and radiation biology is being prepared at the Photo Injector Test facility at DESY in Zeuthen (FLASHlab@PITZ). This platform is based on the unique beam parameters available at PITZ: ps scale electron bunches of up to 22 MeV with up to 5 nC bunch charge at MHz bunch repetition rate in bunch trains of up to 1 ms in length repeating at 1 to 10 Hz. It works together with the Technical University of Applied Sciences Wildau (TH Wildau) as partner in close vicinity for the biological resources. A startup beamline has been installed to allow dosimetry studies and irradiation experiments on chemical, biochemical and biological samples after a 60-degree dispersive arm. The measured dose and dose rates under different beam conditions and first experimental results will be reported in this paper. In addition, a dedicated beamline for FLASHlab@PITZhas been designed for better control of the high brightness electron beams. This includes a dogleg to translate the beam and a 2D kicker system to scan the tiny beam focused by quadrupoles across the samples within less than 1 ms. Simulation studies will be presented to demonstrate the extremely flexible dose parameters with various irradiation options for electron FLASH radiation therapy and radiation biology studies.

The high-brightness electron beam at the Photo Injector Test facility at DESY in Zeuthen (PITZ) is now also used for FLASHlab@PITZ: an R.&D platform for studying radiation biology and the FLASH effect in radiation therapy. The available parameter space of the electron beam with a momentum of 22 MeV/c allows bunch charges from 1 pC up to 5 nC, bunch durations of 0.160 ps and bunch train lengths up to 1 ms. The number of bunches in the single train can currently be varied between 1 and 1000 bunches, with an upgrade to 4500 foreseen in 2023. Radiation biology studies require accurate dose predic-tion, therefore Monte Carlo simulations based on the FLUKA code were performed. According to estimations, dose delivery of 0.002 Gy (low charge case 1 pC) and 10 Gy (high charge case 5 nC) is possible, if the beam is confined to a circular area with a radius of 5 mm with a lead collimator. For the Monte Carlo simulations, the experimental setup was accurately modelled, including the exit window, lead collimator, etc. Dose measurements were used to compare simulations with experiments. Dose profiles were experimentally measured with Gafchromic films and then compared with Monte Carlo simulations. The first experiments at FLASHlab@PITZ in 2023 have demonstrated flexible dose options for studying the FLASH effect and radiation biology studies.

Development of an accelerator-based tunable THz source prototype for pump-probe experiments at the European XFEL is ongoing at the Photo Injector Test facility at DESY in Zeuthen (PITZ). The proof-of-principle experiments on the THz SASE FEL are performed utilizing the LCLS-I undulator (on loan from SLAC) installed in the PITZ beamline. The first lasing at a center wavelength of 100 μm was observed in the summer of 2022. The lasing of the narrowband THz source was achieved using an electron beam with an energy of ∼17 MeV and a bunch charge up to several nC. Optimization of beam transport and matching resulted in the measurement of THz radiation with a pulse energy of tens of μJ, measured with pyroelectric detectors. The THz FEL gain curves were measured by means of specially designed short coils along the undulator. The results of the first characterization of the THz source at PITZ will be presented.

Research and development of an accelerator-based THz source prototype for pump-probe experiments at the European XFEL are ongoing at the Photo Injector Test Facility at DESY in Zeuthen (PITZ). Proof-of-principle experiments have been performed to generate a high-gain THz Free-electron Laser (FEL) based on the Self-Amplified Spontaneous Emission scheme. The FEL radiation pulses with a central wavelength of about 100 μm (3 THz) and single pulse energy of several tens μm can be generated. In this paper, we present and discuss the photon diagnostic setup for the THz FEL together with examples of diagnostic results, including pulse energy and an FEL gain curve. The upgraded photon diagnostic setup, capable of measuring pulse energy, transverse distribution, and spectral distribution, is expected to be operational in the spring of 2023.

Methodical studies to improve the existing e-beam Longitudinal Phase Space (LPS) tomography were performed at the Photo Injector Test facility at DESY in Zeuthen. Proof-of-principle simulations were done to address some core concerns e.g. booster phase range, space charge effects and noisy artefacts in results. Phase advance analysis was done with the help of an analytical model that determined the booster phase range and step size. A slit was introduced before the booster to truncate the beam and reduce space charge forces. The reconstruction method adopted was image space reconstruction algorithm owing to its assurance of non-negative solution. An initial scientific presumption of LPS from low energy momentum measurements was established to reduce artefacts in the phase space. This paper will explain the proof-of-principle simulations highlighting the key aspects to obtain accurate results. Reconstructed LPS for different experimental cases will be presented to demonstrate the diagnostic capability.