The DRESDEN PLATFORM is a research hub for ultra-high dose rate radiobiology.

The recently observed FLASH effect describes the observation of normal tissue protection by ultra-high dose rates (UHDR), or dose delivery in a fraction of a second, at similar tumor-killing efficacy of conventional dose delivery and promises great benefits for radiotherapy patients. Dedicated studies are now necessary to define a robust set of dose application parameters for FLASH radiotherapy and to identify underlying mechanisms. These studies require particle accelerators with variable temporal dose application characteristics for numerous radiation qualities, equipped for preclinical radiobiological research. Here we present the DRESDEN PLATFORM, a research hub for ultra-high dose rate radiobiology. By uniting clinical and research accelerators with radiobiology infrastructure and know-how, the DRESDEN PLATFORM offers a unique environment for studying the FLASH effect. We introduce its experimental capabilities and demonstrate the platform's suitability for systematic investigation of FLASH by presenting results from a concerted in vivo radiobiology study with zebrafish embryos. The comparative pre-clinical study was conducted across one electron and two proton accelerator facilities, including an advanced laser-driven proton source applied for FLASH-relevant in vivo irradiations for the first time. The data show a protective effect of UHDR irradiation up to [Formula: see text] and suggests consistency of the protective effect even at escalated dose rates of [Formula: see text]. With the first clinical FLASH studies underway, research facilities like the DRESDEN PLATFORM, addressing the open questions surrounding FLASH, are essential to accelerate FLASH's translation into clinical practice.

Dosimetry for radiobiologicalin vivoexperiments at laser plasma-based proton accelerators.

Objective.Laser plasma-based accelerators (LPAs) of protons can contribute to research of ultra-high dose rate radiobiology as they provide pulse dose rates unprecedented at medical proton sources. Yet, LPAs pose challenges regarding precise and accurate dosimetry due to the high pulse dose rates, but also due to the sources' lower spectral stability and pulsed operation mode. Forin vivomodels, further challenges arise from the necessary small field dosimetry for volumetric dose distributions. For these novel source parameters and intended applications, a dosimetric standard needs to be established.Approach.In this work, we present a dosimetry and beam monitoring framework forin vivoirradiations of small target volumes with LPA protons, solving aforementioned challenges. The volumetric dose distribution in a sample (mean dose value and lateral/depth dose inhomogeneity) is provided by combining two independent dose measurements using radiochromic films (dose rate-independent) and ionization chambers (dose rate-dependent), respectively. The unique feature of the dosimetric setup is beam monitoring with a transmission time-of-flight spectrometer to quantify spectral fluctuations of the irradiating proton pulses. The resulting changes in the depth dose profile during irradiation of anin vivosample are hence accessible and enable pulse-resolved depth dose correction for each dose measurement.Main results.A first successful small animal pilot study using an LPA proton source serves as a testcase for the presented dosimetry approach and proves its performance in a realistic setting.Significance.With several facilities worldwide either setting up or already using LPA infrastructure for radiobiological studies with protons, the importance of LPA-adapted dosimetric frameworks as presented in this work is clearly underlined.

Ultra-short pulse laser acceleration of protons to 80 MeV from cryogenic hydrogen jets tailored to near-critical density.

Laser plasma-based particle accelerators attract great interest in fields where conventional accelerators reach limits based on size, cost or beam parameters. Despite the fact that particle in cell simulations have predicted several advantageous ion acceleration schemes, laser accelerators have not yet reached their full potential in producing simultaneous high-radiation doses at high particle energies. The most stringent limitation is the lack of a suitable high-repetition rate target that also provides a high degree of control of the plasma conditions required to access these advanced regimes. Here, we demonstrate that the interaction of petawatt-class laser pulses with a pre-formed micrometer-sized cryogenic hydrogen jet plasma overcomes these limitations enabling tailored density scans from the solid to the underdense regime. Our proof-of-concept experiment demonstrates that the near-critical plasma density profile produces proton energies of up to 80 MeV. Based on hydrodynamic and three-dimensional particle in cell simulations, transition between different acceleration schemes are shown, suggesting enhanced proton acceleration at the relativistic transparency front for the optimal case.

Enhanced ion acceleration from transparency-driven foils demonstrated at two ultraintense laser facilities.

Laser-driven ion sources are a rapidly developing technology producing high energy, high peak current beams. Their suitability for applications, such as compact medical accelerators, motivates development of robust acceleration schemes using widely available repetitive ultraintense femtosecond lasers. These applications not only require high beam energy, but also place demanding requirements on the source stability and controllability. This can be seriously affected by the laser temporal contrast, precluding the replication of ion acceleration performance on independent laser systems with otherwise similar parameters. Here, we present the experimental generation of >60 MeV protons and >30 MeV u-1 carbon ions from sub-micrometre thickness Formvar foils irradiated with laser intensities >1021 Wcm2. Ions are accelerated by an extreme localised space charge field ≳30 TVm-1, over a million times higher than used in conventional accelerators. The field is formed by a rapid expulsion of electrons from the target bulk due to relativistically induced transparency, in which relativistic corrections to the refractive index enables laser transmission through normally opaque plasma. We replicate the mechanism on two different laser facilities and show that the optimum target thickness decreases with improved laser contrast due to reduced pre-expansion. Our demonstration that energetic ions can be accelerated by this mechanism at different contrast levels relaxes laser requirements and indicates interaction parameters for realising application-specific beam delivery.

Time-of-flight spectroscopy for laser-driven proton beam monitoring.

Application experiments with laser plasma-based accelerators (LPA) for protons have to cope with the inherent fluctuations of the proton source. This creates a demand for non-destructive and online spectral characterization of the proton pulses, which are for application experiments mostly spectrally filtered and transported by a beamline. Here, we present a scintillator-based time-of-flight (ToF) beam monitoring system (BMS) for the recording of single-pulse proton energy spectra. The setup's capabilities are showcased by characterizing the spectral stability for the transport of LPA protons for two beamline application cases. For the two beamline settings monitored, data of 122 and 144 proton pulses collected over multiple days were evaluated, respectively. A relative energy uncertainty of 5.5% (1[Formula: see text]) is reached for the ToF BMS, allowing for a Monte-Carlo based prediction of depth dose distributions, also used for the calibration of the device. Finally, online spectral monitoring combined with the prediction of the corresponding depth dose distribution in the irradiated samples is demonstrated to enhance applicability of plasma sources in dose-critical scenarios.

Detecting perturbations of a radiation field inside a head-sized phantom exposed to therapeutic carbon-ion beams through charged-fragment tracking.

PURPOSE: Noninvasive methods to monitor carbon-ion beams in patients are desired to fully exploit the advantages of carbon-ion radiotherapy. Prompt secondary ions produced in nuclear fragmentations of carbon ions are of particular interest for monitoring purposes as they can escape the patient and thus be detected and tracked to measure the radiation field in the irradiated object. This study aims to evaluate the performance of secondary-ion tracking to detect, visualize, and localize an internal air cavity used to mimic inter-fractional changes in the patient anatomy at different depths along the beam axis. METHODS: In this work, a homogeneous head phantom was irradiated with a realistic carbon-ion treatment plan with a typical prescribed fraction dose of 3 Gy(RBE). Secondary ions were detected by a mini-tracker with an active area of 2 cm2 , based on the Timepix3 semiconductor pixel detector technology. The mini-tracker was placed 120 mm behind the center of the target at an angle of 30 degrees with respect to the beam axis. To assess the performance of the developed method, a 2-mm thick air cavity was inserted in the head phantom at several depths: in front of as well as at the entrance, in the middle, and at the distal end of the target volume. Different reconstruction methods of secondary-ion emission profile were studied using the FLUKA Monte Carlo simulation package. The perturbations in the emission profiles caused by the air cavity were analyzed to detect the presence of the air cavity and localize its position. RESULTS: The perturbations in the radiation field mimicked by the 2-mm thick cavity were found to be significant. A detection significance of at least three standard deviations in terms of spatial distribution of the measured tracks was found for all investigated cavity depths, while the highest significance (six standard deviations) was obtained when the cavity was located upstream of the tumor. For a tracker with an eight-fold sensitive area, the detection significance rose to at least nine standard deviations and up to 17 standard deviations, respectively. The cavity could be detected at all depths and its position measured within 6.5 ± 1.4 mm, which is sufficient for the targeted clinical performance of 10 mm. CONCLUSION: The presented systematic study concerning the detection and localization of small inter-fractional structure changes in a realistic clinical setting demonstrates that secondary ions carry a large amount of information on the internal structure of the irradiated object and are thus attractive to be further studied for noninvasive monitoring of carbon-ion treatments.