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 >10^{21} W/cm^{2}. 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.

Particle-in-cell (PIC) simulations are a widely-used tool to model kinetics-dominated plasmas in ultrarelativistic laser-solid interactions (dimensionless vectorpotential a0 > 1). However, interactions approaching subrelativistic laser intensities (a0 ≲ 1) are governed by correlated and collisional plasma physics, calling for benchmarks of available modeling capabilities and the establishment of standardized testbeds. Here, we propose such a testbed to experimentally benchmark PIC simulations of laser-solid interactions using a laser-irradiated micron-sized cryogenic hydrogen-jet target. Time-resolved optical shadowgraphy of the expanding plasma density, complemented by hydrodynamics and ray-tracing simulations, is used to determine the bulk-electron-temperature evolution after laser irradiation. We showcase our testbed by studying isochoric heating of solid hydrogen induced by laser pulses with a dimensionless vectorpotential of a0 ≈ 1. Our testbed reveals that the initial surface-density gradient of the target is decisive to reach quantitative agreement at 1 ps after the interaction, demonstrating its suitability to benchmark controlled parameter scans at subrelativistic laser intensities.

In this paper, we present an experiment that explores the plasma dynamics of a 7 μm diameter carbon wire after being irradiated with a near-relativistic-intensity short pulse laser. Using an x-ray free electron laser pulse to measure the small angle x-ray scattering signal, we observe that the scattering surface is bent and prone to instability over tens of picoseconds. The dynamics of this process are consistent with the presence of a sharp, propagating shock front inside the wire, moving at a speed close to the hole boring velocity or that expected from a thermal shock at a few tens of Mbar.

We report on electron beam collimation using a passive plasma lens, integrated directly and conveniently into a laser wakefield accelerator stage operating in the high charge regime. The lens is created by reshaping the gas density profile of a super-sonic jet at the beam's exit side through an obstacle mounted above the jet. It reduces the beam's divergence by a factor of two to below 1 mrad (root-mean-square), while preserving the total charge of 170 pC and maintaining the energy spread. The resulting spectral-charge density, here defined as the charge per energy bandwidth and emission angle, of up to 7 pC/(MeV·mrad) played a key role in the recent experimental demonstration of free-electron lasing. The presented simple and robust gas shaping technique holds the potential to generate specific density profiles, essential for the application of adiabatic focusing or staging of accelerators.

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.

The recently observed FLASH effect provides normal tissue protection at a similar tumor treatment efficacy via ultra-high dose rate (UHDR) irradiation 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 qualify the platform 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 three 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 10^5 Gy/s and suggests consistency of the protective effect even at escalated dose rates of 10^9 Gy/s. 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.

Article about Heating in multi-layered target upon UHI laser irradiation

The acoustic pulse emitted from the Bragg peak of a laser-accelerated proton bunch focused into water has recently enabled the reconstruction of the bunch energy distribution. By adding three ultrasonic transducers and implementing a fast data analysis of the filtered raw signals, I-BEAT (Ion-Bunch Energy Acoustic Tracing) 3D now provides the mean bunch energy and absolute lateral bunch position in real-time and for individual bunches. Relative changes in energy spread and lateral bunch size can also be monitored. Our experiments at DRACO with proton bunch energies between 10 and 30 MeV reveal sub-MeV and sub-mm resolution. In addition to this 3D bunch information, the signal strength correlates also with the absolute bunch particle number.

Plasma wakefield accelerators can be driven either by intense laser pulses (LWFA) or by intense particle beams (PWFA). A third approach that combines the complementary advantages of both types of plasma wakefield accelerator has been established with increasing success over the last decade and is called hybrid LWFA→PWFA. Essentially, a compact LWFA is exploited to produce an energetic, high-current electron beam as a driver for a subsequent PWFA stage, which, in turn, is exploited for phase-constant, inherently laser-synchronized, quasi-static acceleration over extended acceleration lengths. The sum is greater than its parts: the approach not only provides a compact, cost-effective alternative to linac-driven PWFA for exploitation of PWFA and its advantages for acceleration and high-brightness beam generation, but extends the parameter range accessible for PWFA and, through the added benefit of co-location of inherently synchronized laser pulses, enables high-precision pump/probing, injection, seeding and unique experimental constellations, e.g., for beam coordination and collision experiments. We report on the accelerating progress of the approach achieved in a series of collaborative experiments and discuss future prospects and potential impact.

The University Proton Therapy facility in Dresden (UPTD), Germany, is equipped with an experimental room with a beamline providing a static pencil beam. High proton beam currents can be achieved at this beamline which makes it suitable for FLASH experiments. However, the established experimental setup uses only the entrance channel of the proton Bragg curve. In this work, a set of 3D-printed range modulators designed to generate spread out Bragg peaks (SOBPs) for radiobiological experiments at ultra-high dose rate at this beamline is described. A new method to optimize range modulators specifically for the case of a static pencil beam based on the central depth dose profile is introduced. Modulators for two different irradiation setups were produced and characterized experimentally by measurements of lateral and depth dose distributions using different detectors. In addition, Monte Carlo simulations were performed to assess profiles of the dose averaged linear energy transfer. These newly produced range modulators will allow future proton FLASH experiments in the SOBP at UPTD with two different experimental setups.

Laser-plasma accelerated (LPA) proton bunches are now prepared and provided for research fields ranging from ultra-high dose rate radiobiology to material science and probing of extreme states of matter. Yet, the capabilities to fully characterize the spectrally and angularly broad LPA bunches lag behind the rapidly evolving applications. The Optical Cone beam TOmograph for Proton Online Dosimetry - short OCTOPOD - translates the angularly resolved spectral characterization of LPA proton bunches into the spatially resolved detection of the volumetric dose distribution deposited in a liquid scintillator. Up to 24 multi-pinhole arrays record projections of the volumetric scintillation light distribution and allow for tomographic reconstruction of the volumetric dose deposition pattern, from which proton spectra may be retrieved in arbitrary directions by spectral deconvolution.
Applying the OCTOPOD at a cyclotron, we show the reliable retrieval of various spatial dose deposition patterns and detector sensitivity over a broad dose range from less than 1 Gy to more than 100 Gy, as required for LPA proton bunch characterization. With a dedicated vacuum housing, the OCTOPOD was installed at a LPA proton source, providing real-time data on proton acceleration performance for various laser-target interaction parameters and attesting the system optimal performance in the harsh laser plasma environment.

We present a method extending scanning third-order correlator temporal pulse14
evolution measurement capabilities of high power short pulse lasers to spectral sensitivity within15
the spectral range exploited by typical chirped pulse amplification systems. Modelling of the16
spectral response achieved by angle tuning of the third harmonic generating crystal is applied17
and experimentally validated. Exemplary measurements of spectrally resolved pulse contrast of a18
Petawatt laser frontend illustrate the importance of full bandwidth coverage for the interpretation19
of relativistic laser target interaction in particular for the case of solid targets.

Seeded free-electron laser driven by a compact laser plasma accelerator
Free-electron lasers generate high-brilliance coherent radiation at
wavelengths spanning from the infrared to the X-ray domains. The recent
development of short-wavelength seeded free-electron lasers now allows
for unprecedented levels of control on longitudinal coherence, opening
new scientific avenues such as ultra-fast dynamics on complex systems
and X-ray nonlinear optics. Although those devices rely on state-of-the-art
large-scale accelerators, advancements on laser-plasma accelerators, which
harness gigavolt-per-centimetre accelerating fields, showcase a promising
technology as compact drivers for free-electron lasers. Using such
footprint-reduced accelerators, exponential amplification of a shot-noise
type of radiation in a self-amplified spontaneous emission configuration
was recently achieved. However, employing this compact approach for the
delivery of temporally coherent pulses in a controlled manner has remained
a major challenge. Here we present the experimental demonstration
of a laser-plasma accelerator-driven free-electron laser in a seeded
configuration, where control over the radiation wavelength is accomplished.
Furthermore, the appearance of interference fringes, resulting from the
interaction between the phase-locked emitted radiation and the seed,
confirms longitudinal coherence. Building on our scientific achievements,
we anticipate a navigable pathway to extreme-ultraviolet wavelengths,
paving the way towards smaller-scale free-electron lasers, unique tools for a
multitude of applications in industry, laboratories and universities.

In ultra-short laser pulses, small changes in dispersion properties before the final focusing mirror can
lead to severe pulse distortions around the focus and therefore to very different pulse properties at the
point of laser-matter interaction yielding unexpected interaction results. The mapping between far and
near-field laser properties intricately depends on the spatial and angular dispersion properties as well as the
focal geometry. For a focusing Gaussian laser pulse subject to angular, spatial, and group delay dispersion,
we derive analytical expressions for its pulse-front tilt, duration, and width from a fully analytic expression
for its electric field in time-space domain. This expression is not only valid in and near the focus but along
the entire propagation distance from the focusing mirror to the focus. Together with expressions relating
angular, spatial, and group delay dispersion before focusing at an off-axis parabola to the respective values
in the pulse’s focus, these formulas are used to show in example setups that pulse-front tilts of lasers
with small initial dispersion can become several ten degrees large in the vicinity of the focus while being
small directly in the focus. The formulas derived here provide the analytical foundation for observations
previously made in numerical experiments. By numerically simulating Gaussian pulse propagation and
measuring properties of the pulse at distances several Rayleigh lengths off the focus we verified the analytic
expressions.

For high-intensity laser-solid interactions, the absolute density and surface density gradients of the target at the arrival of the ultra-relativistic laser peak are critical parameters. Accurate modeling of the leading edge-driven target pre-expansion is desired to strengthen the predictive power of associated computer simulations. The transition from an initial solid state to a plasma state, i.e., the breakdown of the solid, defines the starting point of the subsequent target pre-expansion. In this work, we report on the time-resolved observation of transient laser-induced breakdown (LIB) during the leading edge of high-intensity petawatt-class laser pulses with peak intensities of up to 5.7 × 10^21 W/cm^2 in interaction with dielectric cryogenic hydrogen jet targets. LIB occurs much earlier than what is typically expected following the concept of barrier suppression ionization. The observation is explained by comparing a characterization study of target
specific LIB thresholds with laser contrast measurements. The results demonstrate the relevance of the laser pulse duration dependence of LIB for high-intensity laser-solid interactions. We provide an effective approach to determine the onset of LIB and thereby the starting point of target pre-expansion in other laser-target systems.

Laser plasma-based proton accelerators (LPA) 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 dosimetry due to the high pulse dose rates, but also due to the sources' lower spectral stability and pulsed operation mode. For in-vivo models, further challenges arise from the necessary small field dosimetry for volumetric dose distributions.
In this work, we present a dosimetry and beam monitoring concept for in-vivo irradiations 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 an in-vivo sample are hence accessible and enable pulse-resolved depth dose correction for each dose measurement.
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.

Böhlen et al. [1] recently proposed a model that describes the magnitude of the normal tissue sparing Flash effect as a function of dose based on available in vivo data. The newly introduced flash modifying factor FMF translates doses applied at ultra-high dose rate to equivalent doses at conventional dose rate similar to the concept of relative biological effectiveness [1]. Primarily founded on rodent data, the model [1] includes only one study that demonstrated a dose-dependent Flash effect by length differences measured at 5 days-old zebrafish embryo (ZFE) after irradiation with electron doses of 5 – 12 Gy [2]. We studied this systematic overview about the available Flash data with great interest and acknowledged it as a very useful guidance for future Flash research. Coincidentally, we have just recently measured ZFE data in the high dose range (15 – 50 Gy) that appear to match very well with the existing rodent data.
Comparable to our previous studies at the ELBE accelerator [3, 4], one day-old ZFE were irradiated using electron beams of reference (mean dose rate 0.11 Gy/s) and ultra-high dose rate (UHDR; mean dose rate 0.9×105 Gy/s) (Fig. 1a). Normal tissue toxicity was quantified by analyzing the length deficit of the 5 days-old embryos compared to unirradiated controls. Since the controls grew on average 30% from irradiation to analysis this is the maximum length deficit that can be caused by irradiation. The derived FMF values extend the available ZFE data [2] and cover in a single experiment almost the entire dose range applied in the rodent studies for different tissues. Comparable to the rodent data (Fig. 1b) the ZFE FMF increases with dose.
The good agreement of our ZFE data with the rodent data [1] demonstrates the feasibility of the ZFE model for basic Flash effect studies, e.g., on the influence of physical beam parameters [3–6]. Hence, the ZFE model could be deployed as a high-throughput alternative to rodent studies at this translational level [5] promising the exploration of a large dose and dose rate range of clinically relevant beams.

We present EZ, a novel Current Deposition algorithm for particle-in-cell simulations, which calculates the current density field due to macro-particle motion within a time step by solving the electrodynamic continuity equation.
Being a charge conserving hybridization of \textbf{E}sirkepov's method and \textbf{Z}igZag, we refer to it as ``EZ'' as shorthand for ``Esirkepov meets ZigZag''.
EZ achieves the same level of charge conservation as the commonly used method by Esirkepov, yet reaches higher performance for macro-particle assignment-functions up to third-order.
Key considerations of its implementation in PIConGPU, an open source, C++, performance portable, fully relativistic 3D3V particle-in-cell code, are outlined in addition to the detailed description of EZ along with remarks on its optimization and customization.

Comprehending cellular changes of radiation-induced brain injury is crucial to prevent and treat the pathology. We provide a unique open dataset of proton-irradiated mouse brains consisting of medical imaging, radiation dose simulations, and large-scale microscopy images, all registered into a common coordinate system. This allows dose-dependent analyses on single-cell level.

The investigation of spatio-temporal couplings (STCs) of broadband light beams is
becoming a key topic for the optimization as well as applications of ultrashort laser systems.
This calls for accurate measurements of STCs. Yet, it is only recently that such complete
spatio-temporal or spatio-spectral characterization has become possible, and it has so far mostly
been implemented at the output of the laser systems, where experiments take place. In this survey,
we present for the first time STC measurements at different stages of a collection of high-power
ultrashort laser systems, all based on the chirped-pulse amplification (CPA) technique, but with
very different output characteristics. This measurement campaign reveals spatio-temporal effects
with various sources, and motivates the expanded use of STC characterization throughout CPA
laser chains, as well as in a wider range of types of ultrafast laser systems. In this way knowledge
will be gained not only about potential defects, but also about the fundamental dynamics and
operating regimes of advanced ultrashort laser systems.

We report on the design and characterization of the plasma mirror system installed on the J-KAREN-P laser at the Kansai
Photon Science Institute, National Institutes for Quantum Science and Technology. The reflectivity of the single plasma
mirror system exceeded 80%. In addition, the temporal contrast was improved by two orders of magnitude at 1 ps before
the main pulse. Furthermore, the laser near-field spatial distribution after the plasma mirror was kept constant at plasma
mirror fluence of less than 100 kJ/cm2. We also present the results of investigating the difference and the fluctuation in
energy, pulse width and pointing stability with and without the plasma mirror system.

Pathological complete response (pCR) has been correlated with overall survival in several
cancer entities including colorectal cancer. Novel total neoadjuvant treatment (TNT) in rectal cancer
has achieved pathological complete response in one‐third of the patients. To define better treatment
options for nonresponding patients, we used patient‐derived organoids (PDOs) as avatars of the
patient´s tumor to apply both photon‐ and proton‐based irradiation as well as single and combined
chemo(radio)therapeutic treatments. While response to photon and proton therapy was similar,
PDOs revealed heterogeneous responses to irradiation and different chemotherapeutic drugs.
Radiotherapeutic response of the PDOs was significantly correlated with their ability to repair
irradiation‐induced DNA damage. The classical combination of 5‐FU and irradiation could not
sensitize radioresistant tumor cells. Ataxia‐telangiectasia mutated (ATM) kinase was activated
upon radiation, and by inhibition of this central sensor of DNA damage, radioresistant PDOs were
resensitized. The study underlined the capability of PDOs to define nonresponders to irradiation
and could delineate therapeutic approaches for radioresistant patients.

Seeded free-electron laser driven by a compact laser plasma accelerator
Free-electron lasers generate high-brilliance coherent radiation at
wavelengths spanning from the infrared to the X-ray domains. The recent
development of short-wavelength seeded free-electron lasers now allows
for unprecedented levels of control on longitudinal coherence, opening
new scientific avenues such as ultra-fast dynamics on complex systems
and X-ray nonlinear optics. Although those devices rely on state-of-the-art
large-scale accelerators, advancements on laser-plasma accelerators, which
harness gigavolt-per-centimetre accelerating fields, showcase a promising
technology as compact drivers for free-electron lasers. Using such
footprint-reduced accelerators, exponential amplification of a shot-noise
type of radiation in a self-amplified spontaneous emission configuration
was recently achieved. However, employing this compact approach for the
delivery of temporally coherent pulses in a controlled manner has remained
a major challenge. Here we present the experimental demonstration
of a laser-plasma accelerator-driven free-electron laser in a seeded
configuration, where control over the radiation wavelength is accomplished.
Furthermore, the appearance of interference fringes, resulting from the
interaction between the phase-locked emitted radiation and the seed,
confirms longitudinal coherence. Building on our scientific achievements,
we anticipate a navigable pathway to extreme-ultraviolet wavelengths,
paving the way towards smaller-scale free-electron lasers, unique tools for a
multitude of applications in industry, laboratories and universities.

We present experimental results on a plasma wakefield accelerator (PWFA) driven by high-current
electron beams from a laser wakefield accelerator (LWFA). In this staged setup stable and high-quality
(low-divergence and low energy spread) electron beams are generated at an optically generated hydro-
dynamic shock in the PWFA. The energy stability of the beams produced by that arrangement in the PWFA
stage is comparable to both single-stage laser accelerators and plasma wakefield accelerators driven by
conventional accelerators. Simulations support that the intrinsic insensitivity of PWFAs to driver energy
fluctuations can be exploited to overcome stability limitations of state-of-the-art laser wakefield
accelerators when adding a PWFA stage. Furthermore, we demonstrate the generation of electron bunches
with energy spread and divergence superior to single-stage LWFAs, resulting in bunches with dense phase
space and an angular-spectral charge density beyond the initial drive beam parameters. These results
unambiguously show that staged LWFA-PWFA can help to tailor the electron-beam quality for certain
applications and to reduce the influence of fluctuating laser drivers on the electron-beam stability. This
encourages further development of this new class of staged wakefield acceleration as a viable scheme
toward compact, high-quality electron beam sources.

We report on experimental investigations of plasma wave structures in a plasma wakefield acceleration (PWFA) stage which is driven by electron beams from a preceding laser plasma accelerator. Femtosecond optical probing is utilized to allow for direct visualization of the plasma dynamics inside the target. We compare two regimes in which the driver propagates either through an initially neutral gas, or a preformed plasma. In the first case, plasma waves are observed that quickly damp after a few oscillations and are located within a narrow plasma channel ionized by the driver, having about the same transverse size as the plasma wakefield cavities. In contrast, for the latter robust cavities are recorded sustained over many periods. Furthermore, here an elongation of the first cavity is measured, which becomes stronger with increasing driver beam charge. Since the cavity length is linked to the maximum accelerating field strength, this elongation implies an increased field strength. This observation is supported by 3D particle-in-cell simulations performed with PIConGPU. This work can be extended for the investigation of driver depletion by probing at different propagation distances inside the plasma, which is essential for the development of high energy efficiency PWFAs.

To optimize neoadjuvant radiochemotherapy of pancreatic ductal adenocarcinoma (PDAC),
the value of new irradiation modalities such as proton therapy needs to be investigated in relevant
preclinical models. We studied individual treatment responses to RCT using patient-derived PDAC
organoids (PDO). Four PDO lines were treated with gemcitabine, 5-fluorouracile (5FU), photon and
proton irradiation and combined RCT. Therapy response was subsequently measured via viability
assays. In addition, treatment-naive PDOs were characterized via whole exome sequencing and
tumorigenicity was investigated in NMRI Foxn1nu/nu mice. We found a mutational pattern con-
taining common mutations associated with PDAC within the PDOs. Although we could unravel
potential complications of the viability assay for PDOs in radiobiology, distinct synergistic effects
of gemcitabine and 5FU with proton irradiation were observed in two PDO lines that may lead to further mechanistical studies. We could demonstrate that PDOs are a powerful tool for translational
proton radiation research.

The influence of different average and bunch dose rates in electron beams on the FLASH effect was investigated. The present study measures O2 content in water at different beam pulse patterns and finds strong correlation with biological data, strengthening the hypothesis of radical-related mechanisms as a reason for the FLASH effect.

The influence of a transverse magnetic field on the formation and evolution of supersonic plasma jets and shocks was studied experimentally, and compared with 3D numerical simulations. An improved jet collimation was seen due to the change in the magnetic field topology restricting the radial expansion of the ablated plasma. The magnetic field was also shown to strongly affect the shock structures, both indirectly through the modified jet geometry, as well as due to a compression of the field lines in the shock region. The interaction characteristics were found to depend on the relative contribution of the magnetic and plasma pressure in balancing the ram pressure of the jet.

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 % (1σ) 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.

Background and purpose: Proton therapy has become a popular treatment modality in the field of radiooncology due to higher spatial dose conformity compared to conventional radiotherapy, which holds the potential to spare normal tissue. Nevertheless, unresolved research questions, such as the much debated relative biological effectiveness (RBE) of protons, call for preclinical research, especially regarding in vivo studies. To mimic clinical workflows, high-precision small animal irradiation setups with image-guidance are needed.

Material and methods: A preclinical experimental setup for small animal brain irradiation using proton radiographies was established to perform planning, repositioning, and irradiation of mice. The image quality of proton radiographies was optimized regarding the resolution, contrast-to-noise ratio (CNR), and minimal dose deposition in the animal. Subsequently, proof-of-concept histological analysis was conducted by staining for DNA double-strand breaks that were then correlated to the delivered dose.

Results: The developed setup and workflow allow precise brain irradiation with a lateral target positioning accuracy of <0.26mm for in vivo experiments at minimal imaging dose of <23mGy per mouse. The custom-made software for image registration enables the fast and precise animal positioning at the beam with low observer-variability. DNA damage staining validated the successful positioning and irradiation of the mouse hippocampus.

Conclusion: Proton radiography enables fast and effective high-precision lateral alignment of proton beam and target volume in mouse irradiation experiments with limited dose exposure. In the future, this will enable irradiation of larger animal cohorts as well as fractionated proton irradiation.

We report the development of a multipurpose differential X-ray calorimeter with a broad energy bandwidth. The absorber architecture is combined with a Bayesian unfolding algorithm to unfold high-energy X-ray spectra generated in high-intensity laser-matter interactions. Particularly, we show how to extract absolute energy spectra and how our unfolding algorithm can reconstruct features not included in the initial guess. The performance of the calorimeter is evaluated via Monte Carlo generated data. The method accuracy to reconstruct electron temperatures from bremsstrahlung is shown to be 5 % for electron temperatures from 1 MeV to 50 MeV. We study bremsstrahlung generated in solid target interaction showing an electron temperature of 0.56±0.04MeV for a 700 µm Ti titanium target and 0.53±0.03MeV for a 50 µm target. We investigate bremsstrahlung from a target irradiated by laser wakefield accelerated electrons showing an endpoint energy of 551 ± 5 MeV, inverse Compton generated X-rays with a peak energy of 1.1 MeV and calibrated radioactive sources. The total energy range covered by all these sources ranges from 10 keV to 551 MeV.

Background and purpose
Continuing recent experiments at the research electron accelerator ELBE at the Helmholtz-Zentrum Dresden-Rossendorf the influence of beam pulse time structure on the Flash effect should be investigated in a zebrafish embryo model.
Materials and methods
The pulse structures of an isochronous and a synchrocyclotron were mimicked at ELBE with mean dose rates of 287 Gy/s and 177 Gy/s and pulse dose rates of 106 Gy/s and 109 Gy/s, respectively; and a macro pulsing for the latter. For comparison, a maximum (mean dose rate 2.5 x 105 Gy/s, pulse dose rate ~109 Gy/s) and a reference (mean dose rate of ~8 Gy/min) regime were applied. Radiation induced changes were assessed in zebrafish embryos over four days post irradiation.
Results
A significant protecting Flash effect with a clear dependence on mean dose rate was revealed for almost all endpoints and all electron pulse regimes relative to the reference. The macro pulse dependent prolongation of treatment time of the synchrotron-like regime reduce the protecting effect compared to the maximum regime delivered at same pulse but higher mean dose rate. The protecting Flash effect of the cyclotron-like regime was confirmed at a clinical isochronous proton cyclotron comparing the effects induced by 300 Gy/s relative to conventional proton beam delivery.
Conclusion
The mean dose rate or treatment time are more important than pulse dose rate for the extent of the normal tissue protecting Flash effect.

Background and purpose: Radiomics analyses have been shown to allow for the prediction of clinical outcomes of radiotherapy based on medical imaging-derived biomarkers. However, the biological meaning attached to such image features often remains unclear, thus hindering the clinical translation of radiomics analysis. In this manuscript, we describe a preclinical radiomics trial, which attempts to establish correlations between the expression of histological tumor microenvironment (TME)- and magnetic resonance imaging (MRI)-derived image features.
Materials & Methods: 114 mice were transplanted with the radioresistant and radiosensitive head and neck squamous cell carcinoma cell lines SAS and UT-SCC-14, respectively. The models were irradiated with five fractions of protons or photons using different doses. Post-treatment T1-weighted MRI and histopathological evaluation of the TME was conducted to extract quantitative features. We performed radiomics analysis with leave-one-out cross validation to identify the features most strongly associated with the tumor’s phenotype. Performance was assessed using the area under the curve (AUCValid) and F1-score. Furthermore, we analyzed correlations between TME- and MRI features using the Spearman correlation coefficient ρ.
Results: TME and MRI-derived features showed good performance (AUCValid, TME = 0.72, AUCValid, MRI = 0.85, AUCValid, Combined = 0.85) individual tumor phenotype prediction. We found correlation coefficients of ρ = - 0.46 between hypoxia-related TME features and texture-related MRI features. Tumor volume was a strong confounder for MRI feature expression.
Conclusion: We demonstrated a preclinical radiomics implementation and notable correlations between MRI- and TME hypoxia-related features. Developing additional TME features may help to further unravel the underlying biology.

Novel particle therapy was implemented into standard-of-care for cancer patients during the
last years. However, experimental studies investigating cellular and molecular mechanisms
are lacking and prognostic biomarker are urgently needed. Cancer stem cell
(CSC)-related biomarkers such as aldehyde dehydrogenase (ALDH) are known to cellular radiosensitivity by affecting defense against reactive
oxygen species, DNA damage repair and cell survival. Within a previous study, we found that ionizing radiation itself enriches for
ALDH-positive CSCs.
Within the present study, we investigated CSC marker dynamics in prostate cancer, head and neck cancer and glioblastoma cells upon proton beam irradiation. We found that proton irradiation has an increased CSC targeting potential, reduced methylation of activating histone marks and
a lower induction of cellular senescence compared to conventional photon irradiation. Interestingly, mathematical modeling
indicated to differences in plasticity rates among ALDH-positive CSCs and ALDH-negative cancer cells between the two irradiation types.

Due to the non-linear nature of relativistic laser induced plasma processes, the development of laser-plasma accelerators requires precise numerical modeling. Especially high intensity laser-solid interactions are sensitive to the temporal laser rising edge and the predictive capability of simulations suffers from incomplete information on the plasma state at the onset of the relativistic interaction. Experimental diagnostics utilizing ultra-fast optical backlighters can help to ease this challenge by providing temporally resolved inside into the plasma density evolution. We present the successful implementation of an off-harmonic optical probe laser setup to investigate the interaction of a high-intensity laser at 5.4E21 W / cm^2 peak intensity with a solid-density cylindrical cryogenic hydrogen jet target of 5 um diameter as a target test bed. The temporal synchronization of pump and probe laser, spectral filtering and spectrally resolved data of the parasitic plasma self-emission are discussed. The probing technique mitigates detector saturation by self-emission and allowed to record a temporal scan of shadowgraphy data revealing details of the target ionization and expansion dynamics that were so far not accessible for the given laser intensity. Plasma expansion speeds of up to (2.3+-0.4)E7 m / s followed by full target transparency at 1.4 ps after the high intensity laser peak are observed. A three dimensional particle-in-cell simulation initiated with the diagnosed target pre-expansion at -0.2 ps and post processed by ray tracing simulations supports the experimental observations and demonstrates the capability of time resolved optical diagnostics to provide quantitative input and feedback to the numerical treatment within the time frame of the relativistic laser-plasma interaction.

In the effort of achieving high-energetic ion beams from the interaction of ultrashort laser pulses with a plasma, volumetric acceleration mechanisms beyond Target Normal Sheath Acceleration have gained attention.
A relativisticly intense laser can turn a near critical density plasma slowly transparent, facilitating a synchronized acceleration of ions at the moving relativistic critical density front. While simulations promise extremely high ion energies in in this regime, the challenge resides in the realization of a synchronized movement of the ultra-relativistic laser pulse ($a_0\gtrsim 30$) driven reflective relativistic electron front and the fastest ions, which imposes a narrow parameter range on the laser and plasma parameters. We present an analytic model for the relevant processes, confirmed by a broad parameter simulation study in 1D- and 3D-geometry. By tayloring the pulse length and plasma density profile at the front side, we can optimize the proton acceleration performance and extend the regions in parameter space of efficient ion acceleration at the relativistic relativistic density surface.

Recent oncological studies identified beneficial properties of radiation applied at ultra-high dose rates several orders of magnitude higher than the clinical standard of the order of Gy/min. Sources capable of providing these ultra-high dose rates are under investigation. Here, we show that a stable, compact laser-driven proton source with energies greater than 60 MeV enables radiobiological in vivo studies. We performed a pilot irradiation study on human tumors in a mouse model, showing the concerted preparation of mice and laser accelerator, the dose-controlled, tumor-conform irradiation using a laser-driven as well as a clinical reference proton source, and the radiobiological evaluation of irradiated and unirradiated mice for radiation-induced tumor growth delay. The prescribed homogeneous dose of 4 Gy was precisely delivered at the laser-driven source. The results demonstrate a complete laser-driven proton research platform for diverse user-specific small animal models, able to deliver tunable single-shot doses up to around 20 Gy to millimeter-scale volumes on nanosecond time scales, equivalent to around 1E9 Gy/s, spatially homogenized and tailored to the sample. The platform provides a unique infrastructure for translational research with protons at ultra-high dose rate.

We present design and realization of an ultra-broadband optical spectrometer capable of measuring the spectral intensity of multi-octave-spanning light sources on a single-pulse basis with a dynamic range of up to 8 orders of magnitude. The instrument is optimized for the characterization of the temporal structure of femtosecond long electron bunches by analyzing the emitted coherent transition radiation (CTR) spectra. The spectrometer operates within the spectral range of 250nm to 11.35µm, corresponding to 5.5 optical octaves. This is achieved by dividing the signal beam into three spectral groups, each analyzed
by a dedicated spectrometer and detector unit. The complete instrument was characterized with regard to wavelength, relative spectral sensitivity, and absolute photo-metric sensitivity, always accounting for the light polarization and comparing different calibration methods. Finally, the capability of the spectrometer is demonstrated with a CTR measurement of a laser wakefield accelerated electron bunch, enabling to determine temporal pulse structures at unprecedented resolution.

The authors wish to make the following corrections to this paper [...].

High-energy and high-intensity lasers are essential for pushing the boundaries of science. Their development has allowed leaps forward in basic research areas, including laser–plasma interaction, high-energy density science, metrology, biology and medical technology. The Helmholtz International Beamline for Extreme Fields user consortium contributes and operates two high-peak-power optical lasers using the high energy density instrument at the European X-ray free electron laser (EuXFEL) facility. These lasers will be used to generate transient extreme states of density and temperature to be probed by the X-ray beam. This paper introduces the ReLaX laser, a short-pulse high-intensity Ti:Sa laser system, and discusses its characteristics as available for user experiments. It will also present the first experimental commissioning results validating its successful integration into the EuXFEL infrastructure and viability as a relativistic-intensity laser driver.

Extreme states of matter exist throughout the universe e.g. inside planetary cores, stars or astrophysical jets. Such conditions can be generated in the laboratory in the interaction of powerful lasers with solids.
Yet, the measurement of the subsequent plasma dynamics with regard to density, temperature and ionization is a major experimental challenge. However, ultra-short X-ray pulses provided by X-ray free electron lasers (XFELs) allow for dedicated studies, which are highly relevant to study laboratory astrophysics, laser-fusion research or laser-plasma-based particle acceleration.
Here, we report on experiments that employ a novel ultrafast method, which allows to simultaneously access temperature, ionization state and nanometer scale expansion dynamics in high-intensity laser-driven solid-density plasmas with a single X-ray detector.
Using this method, we gain access to the expansion dynamics of a buried layer in compound samples, and we measure opacity changes arising from bound-bound resonance transitions in highly ionized copper. The presence of highly ionized copper leads to a temperature estimate of at least 2 million Kelvin already after the first 100 femtoseconds following the high-intensity laser irradiation.
More specifically, we make use of asymmetries in small-angle X-ray scattering (SAXS) patterns, which arise from different spatial distributions of absorption and scattering cross sections in nanostructured grating samples when we tune an XFEL to atomic resonant energies of copper.
Thereby, changes in asymmetry can be connected with the evolution of the plasma expansion and ionization dynamics.
The potential of XFEL-based resonant SAXS to obtain three-dimensional ultrafast, nanoscopic information on density and opacity may offer a unique path for the characterization of dynamic processes in High Energy Density plasmas.

We present the experimental demonstration of density downramp injection at a gas-dynamic shock in a beam-driven plasma accelerator.
The ultrashort driver electron beam with a peak-current exceeding 10 kA allows operation in the blowout regime and enables injection of electron witness bunches at gentle density ramps, i.e. longer than the plasma wavelength, which nurtures prospects for ultralow bunch emittance.
By precision control over the position of injection we show that these bunches can be energy-tuned in acceleration gradients of near 120 GV/m.

Matched beam loading in laser wakefield acceleration (LWFA), characterizing the state of flattening the accelerating electric field along the bunch, leads to the minimization of energy spread at high bunch charges. Here, we experimentally demonstrate by independently controlling injected charge and accelerating gradients, using the self-truncated ionization injection scheme, that minimal energy spread coincides with a reduction of the normalized beam divergence. With the simultaneous confirmation of the micrometer-small beam radius at the plasma exit, deduced from betatron radiation spectroscopy, we attribute this effect to the minimization of chromatic betatron decoherence. These findings are supported by rigorous three-dimensional particle-in-cell simulations tracking self-consistently particle trajectories from injection, acceleration until beam extraction to vacuum. We conclude that beam-loaded LWFA enables highest longitudinal and transverse phase space densities.

The interaction between intense 30 fs laser pulses and foam-coated 1.5 μm-thick Al foils in the relativistic regime (up to
5x10²⁰ W/cm2) is studied to optimize the laser energy conversion into laser-accelerated protons. A significant enhancement is
observed for foam targets in terms of proton cut-off energy (18.5 MeV) and number of protons above 4.7 MeV (4x10⁹
protons/shot) with respect to uncoated foils (9.5 MeV, 1x10⁹ protons/shot), together with a sixfold increase in the
Bremsstrahlung yield. This enhancement is attributed to increased laser absorption and electron generation in the foam meso-
and nanostructure.

We reconstruct spectra of secondary X‑rays from a tunable 250–350 MeV laser wakefield electron accelerator from single‑shot X‑ray depth‑energy measurements in a compact (7.5 × 7.5 × 15 cm), modular X‑ray calorimeter made of alternating layers of absorbing materials and imaging plates. X‑rays range from few‑keV betatron to few‑MeV inverse Compton to > 100 MeV bremsstrahlung emission, and are characterized both individually and in mixtures. Geant4 simulations of energy deposition of single‑energy X‑rays in the stack generate an energy‑vs‑depth response matrix for a given stack configuration. An iterative reconstruction algorithm based on analytic models of betatron, inverse Compton and bremsstrahlung photon energy distributions then unfolds X‑ray spectra,
typically within a minute. We discuss uncertainties, limitations and extensions of both measurement and reconstruction methods.

The interaction of supersonic laser-generated plasma jets with a secondary gas target was studied experimentally. The plasma parameters of the jet, and the resulting shock, were characterized using a combination of multi-frame interferometry/shadowgraphy, and x-ray diagnostics, allowing for a detailed study of their structure and evolution. The velocity was obtained with an x-ray streak camera, and filtered x-ray pinhole imaging was used to infer the electron temperature of the jet and shock. The topology of the ambient plasma density was found to have a significant effect on the jet and shock formation, as well as on their radiation characteristics. The experimental results were compared with radiation hydrodynamic simulations, thereby providing further insights into the underlying physical processes of the jet and shock formation and evolution.

Plasma wakefield accelerators are capable of sustaining gigavolt-per-centimeter accelerating
fields, surpassing the electric breakdown threshold in state-of-the-art accelerator modules by
3-4 orders of magnitude. Beam-driven wakefields offer particularly attractive conditions for
the generation and acceleration of high-quality beams. However, this scheme relies on
kilometer-scale accelerators. Here, we report on the demonstration of a millimeter-scale
plasma accelerator powered by laser-accelerated electron beams. We showcase the acceleration
of electron beams to 128 MeV, consistent with simulations exhibiting accelerating
gradients exceeding 100 GVm⁻¹. This miniaturized accelerator is further explored by
employing a controlled pair of drive and witness electron bunches, where a fraction of the
driver energy is transferred to the accelerated witness through the plasma. Such a hybrid
approach allows fundamental studies of beam-driven plasma accelerator concepts at widely
accessible high-power laser facilities. It is anticipated to provide compact sources of energetic
high-brightness electron beams for quality-demanding applications such as free-electron
lasers.

We report on experimental investigations of proton acceleration from solid foils irradiated with PW‑class laser‑pulses, where highest proton cut‑off energies were achieved for temporal pulse parameters that varied significantly from those of an ideally Fourier transform limited (FTL) pulse. Controlled spectral phase modulation of the driver laser by means of an acousto‑optic programmable dispersive filter enabled us to manipulate the temporal shape of the last picoseconds around the main pulse and to study the effect on proton acceleration from thin foil targets. The results show that applying positive third order dispersion values to short pulses is favourable for proton acceleration and can lead to maximum energies of 70 MeV in target normal direction at 18 J laser energy for thin plastic foils, significantly enhancing the maximum energy compared to ideally compressed FTL pulses. The paper further proves the robustness and applicability of this enhancement effect for the use of different target materials and thicknesses as well as laser energy and temporal intensity contrast settings. We demonstrate that application relevant proton beam quality was reliably achieved over many months of operation with appropriate control of spectral phase and temporal contrast conditions using a state‑of‑the‑art high‑repetition rate PW laser system.

Plasma-based accelerators use the strong electromagnetic fields that can be supported by plasmas to accelerate charged particles to high energies. Accelerating field structures in plasma can be generated by powerful laser pulses or charged particle beams. This research field has recently transitioned from involving a few small-scale efforts to the development of national and international networks of scientists supported by substantial investment in large-scale research infrastructure. In this New Journal of Physics 2020 Plasma Accelerator Roadmap, perspectives from experts in this field provide a summary overview of the field and insights into the research needs and developments for an international audience of scientists, including graduate students and researchers entering the field.

Purpose: To investigate experimentally, if FLASH irradiation depletes oxygen within water for different radiation types such as photons, protons and carbon ions.
Methods: This study presents measurements of the oxygen consumption in sealed, 3D printed water phantoms during irradiation with X-rays, protons and carbon ions at varying dose rates up to 340Gy/s. The oxygen measurement was performed using an optical sensor allowing for non-invasive measurements.
Results: Oxygen consumption in water only depends on dose, dose-rate and linear energy transfer (LET) of the irradiation. The total amount of oxygen depleted per 10Gy was found to be 0.04 - 0.18% atm for 225 kV photons, 0.04 - 0.25% atm for 224 MeV protons and 0.09 - 0.17% atm for carbon ions. Consumption depends on dose-rate by an inverse power law and saturates for higher dose rates because of self-interactions of radicals. Higher dose rates yield lower oxygen consumption. No total depletion of oxygen was found for clinical doses.
Conclusions: FLASH irradiation does consume oxygen, but not enough to deplete all the oxygen present. For higher dose rates, less oxygen was consumed than at standard radiotherapy dose rates. No total depletion was found for any of the analyzed radiation types for 10Gy dose delivery using FLASH.

Background and purpose
In consequence of a previous study, where no protecting proton Flash effect was found for zebrafish embryos, potential reasons and requirements for inducing a Flash effect should be investigated with the beam pulse structure and the partial oxygen pressure (pO2) as relevant parameters.
Materials and methods
The experiments were performed at the research electron accelerator ELBE, whose variable pulse structure enables dose delivery as electron Flash and quasi-continuously (reference). Zebrafish embryos were irradiated with ~26 Gy either continuously with a dose rate of ~6.7 Gy/min or in one 111 µs long pulse with a pulse dose rate of 109 Gy/s and a mean dose rate of 105 Gy/s, respectively. Using the OxyLite system to measure the pO2 a low- (pO2 ≤ 5 mmHg) and a high-pO2 group were defined on basis of the oxygen depletion kinetics in sealed embryo samples.
Results
A protective Flash effect was seen for most endpoints ranging from 4 % less reduction in embryo length to about 20 – 25 % less embryos with spinal curvature and pericardial edema, relative to reference irradiation. The reduction of pO2 below atmospheric levels (148 mmHg) resulted in higher protection, which was however more pronounced in the low-pO2 group.
Conclusion
The Flash experiment at ELBE showed that the zebrafish embryo model is appropriate for studying the radiobiological response of high dose rate irradiation. Pulse dose and pulse dose rate as important beam parameters were confirmed as well as the pivotal role of pO2 during irradiation.

Radiation induced late side effects such as cognitive decline and normal tissue complications can severely affect quality of life and outcome in long-term survivors of brain tumors. Proton therapy offers a favorable depth-dose deposition with the potential to spare tumor-surrounding normal tissue, thus potentially reducing such side effects. In this study, we describe a preclinical model to reveal underlying biological mechanisms caused by precise high-dose proton irradiation of a brain subvolume.
We studied the dose- and time-dependent radiation response of mouse brain tissue, using a high-precision image-guided proton irradiation setup for small animals established at the University Proton Therapy Dresden. The right hippocampal area of ten C57BL/6 and ten C3H/He mice was irradiated. Both strains consisted of four groups treated with increasing doses (0 – 85 Gy and 0 – 80 Gy, respectively). Follow-ups were performed up to six months, including longitudinal monitoring of general health status and regular contrast-enhanced magnetic resonance imaging (MRI) of mouse brains. These findings were related to comprehensive final histological analysis.
In mice of the highest dose group, first symptoms of blood-brain barrier (BBB) damage appeared one week after irradiation, while a dose-dependent delay in onset was observed for lower doses. MRI contrast agent leakage occurred in the irradiated brain areas and was progressive in the higher dose groups. Mouse health status and survival corresponded to the extent of contrast agent leakage. Histological analysis revealed tissue changes such as vessel abnormalities, gliosis, and granule cell dispersion, which also partly affected the non-irradiated contralateral hippocampus.
All observed effects depended strongly on the prescribed radiation doses and the outcome, i.e. survival, image changes and tissue alterations, within an experimental dose cohort was very consistent. A derived dose-response model will determine doses in future experiments and may support the formulation of clinical hypotheses on brain toxicity after proton therapy.

We report on a compact diode-pumped, chirped pulse regenerative amplifier system with a pulse duration of 162 fs and an output pulse energy of 1 mJ before as well as 910 µJ after compression optimized for the probing of ultrafast relativistic laser-plasma processes. A chirped volume Bragg grating (CVBG) acts as a combined pulse stretcher/compressor representing a robust solution for a CPA laser system in the millijoule range. Yb3+:CaF2 is used as gain medium to support a large bandwidth of 16 nm (FWHM) when spectral gain shaping is applied. Chirped mirrors compensate for any additional dispersion introduced to the system.

Ultra-high intensity femtosecond lasers have now become excellent scientific tools for the study of extreme material states in small-scale laboratory settings. The invention of chirped-pulse amplification (CPA) combined with titanium-doped sapphire (Ti:sapphire) crystals have enabled realization of such lasers. The pursuit of ultra-high intensity science and applications is driving worldwide development of new capabilities. A petawatt (PW = 1015 W), femtosecond (fs = 10−15 s), repetitive (0.1 Hz), high beam quality J-KAREN-P (Japan Kansai Advanced Relativistic ENgineering Petawatt) Ti:sapphire CPA laser has been recently constructed and used for accelerating charged particles (ions and electrons) and generating coherent and incoherent ultra-short-pulse, high-energy photon (X-ray) radiation. Ultra-high intensities of 1022 W/cm2 with high temporal contrast of 10−12 and a minimal number of pre-pulses on target has been demonstrated with the J-KAREN-P laser. Here, worldwide ultra-high intensity laser development is summarized, the output performance and spatiotemporal quality improvement of the J-KAREN-P laser are described, and some experimental results are briefly introduced.

High power laser systems are an attractive driver for compact energetic ion sources. We demonstrate repetitive
acceleration at 0.1 Hz of proton beams up to 40 MeV from a reeled tape target irradiated by ultra-high intensities
up to 5 × 1021 Wcm 2 and laser energies ≈ 15 J using the J-KAREN-P laser system. We investigate the stability
of the source and its behaviour with laser spot focal size. We compare the scaling of proton energy with laser
energy to a recently developed analytical model, and also demonstrate that it is possible to reach energies up to
50 MeV on a single shot with a lower laser energy ≈ 10 J by using a thinner target, motivating development of
high repetition targetry suitable for thinner targets.

Motivated by the development of next-generation heavy-ion sources, we have investigated the ionization and acceleration dynamics of an ultraintense laser-driven high-Z silver target, experimentally, numerically, and analytically. Using a novel ion measurement technique allowing us to uniquely identify silver ions, we experimentally demonstrate generation of highly charged silver ions (Z= 45+2−2 ) with energies of >20 MeV/nucleon (>2.2 GeV) from submicron silver targets driven by a laser with intensity 5 × 1021 W/cm 2 , with increasing ion energy and charge state for decreasing target thickness. We show that although target pre-expansion by the unavoidable rising edge of state-of-the-art high-power lasers can limit proton energies, it is advantageous for heavy-ion acceleration. Two-dimensional particle-in-cell simulations show that the Joule heating in the target bulk results in a high temperature (∼10 keV) solid density plasma, leading to the generation of high flux highly charged ions (Z= 40−2 +2, 10 MeV/nucleon) via electron collisional ionization, which are extracted and accelerated with a small divergence by an extreme sheath field at the target rear. However, with reduced target thickness this favorable acceleration is degraded due to the target deformation via laser hole boring, which accompanies higher energy ions with higher charge states but in an uncontrollable manner.
Our elucidation of the fundamental processes of high-intensity laser-driven ionization and ion acceleration provides a path for improving the control and parameters of laser-driven heavy-ion sources, a key component for next-generation heavy-ion accelerators.

This paper provides an up-to-date review of the problems related to the generation, detection and mitigation of strong electromagnetic pulses created in the interaction of high-power, high-energy laser pulses with different types of solid targets. It includes new experimental data obtained independently at several international laboratories. The mechanisms of electromagnetic field generation are analyzed and considered as a function of the intensity and the spectral range of emissions they produce. The major emphasis is put on the GHz frequency domain, which is the most damaging for electronics and may have important applications. The physics of electromagnetic emissions in other spectral domains, in particular THz and MHz, is also discussed. The theoretical models and numerical simulations are compared with the results of experimental measurements, with special attention to the methodology of measurements and complementary diagnostics. Understanding the underlying physical processes is the basis for developing techniques to mitigate the electromagnetic threat and to harness electromagnetic emissions, which may have promising applications.

This protocol presents a detailed procedure for the operation of continuous, micron-sized cryogenic cylindrical and planar liquid jets. When operated as described here, the jet exhibits high laminarity and stability for centimeters. Successful operation of a cryogenic liquid jet in the Rayleigh regime requires a basic understanding of fluid dynamics and thermodynamics at cryogenic temperatures. Theoretical calculations and typical empirical values are provided as a guide to design a comparable system. This report identifies the importance of both cleanliness during cryogenic source assembly and stability of the cryogenic source temperature once liquefied. The system can be used for high repetition rate laser-driven proton acceleration, with an envisioned application in proton therapy. Other applications include laboratory astrophysics, materials science, and next-generation particle accelerators.

Laser-plasma proton acceleration was investigated in the target normal sheath acceleration regime with a target composed of a gas layer and a thin foil. The laser's shape, duration, energy and frequency are modified as it propagates in the gas, altering the laser-solid interaction leading to proton acceleration. The modified properties of the laser were assessed by both numerical simulations and by measurements. The 3D particle-in-cell simulations have shown that a nearly seven-fold increase in peak intensity at the foil plane is possible. In the experiment, maximum proton energies showed high dependence on the energy transmission of the laser through the gas and a lesser dependence on the size and shape of the pulse. At high gas densities, where high intensity was expected, laser energy depletion and pulse distortion suppressed proton energies. At low densities, with the laser focused far behind the foil, self-focusing was observed and the gas showed a positive effect on proton energies. The promising results of this first exploration motivate further study of the target.

The current filamentation instability is a key phenomenon underpinning various processes in astrophysics, laboratory laser-plasma, and beam-plasma experiments. Here we show that the ultrafast dynamics of this instability can be explored in the context of relativistic laser-solid interactions through deflectometry by low-emittance, highly relativistic electron bunches from a laser wakefield accelerator. We present experimental measurements of the femtosecond timescale generation of strong magnetic-field fluctuations, with a measured line-integrated B field of 2.70±0.39kTμm. Three-dimensional, fully relativistic particle-in-cell simulations demonstrate that such fluctuations originate from the current filamentation instability arising at submicron scales around the irradiated target surface, and that they grow to amplitudes strong enough to broaden the angular distribution of the probe electron bunch a few tens of femtoseconds after the laser pulse maximum. Our results open a branch of physics experiments investigating the femtosecond dynamics of laser-driven plasma instabilities by means of synchronized, wakefield-accelerated electron beams.

Thomson scattering sources with their hard x-ray pencil beams represent a promising candidate to drive high-resolution X-ray Fluorescence Imaging (XFI). As XFI is a scanning imaging modality, it specifically requires pencil-beam geometries along with a high beam mobility. In combination with laser-wakefield acceleration (LWFA) such sources could provide the compactness needed for a future transition into clinical application. A sufficient flux within a small bandwidth could enable in-vivo high-sensitivity XFI for early cancer diagnostics and pharmacokinetic imaging. We thus report on a specific all-laser driven source design directed at increasing the photon number within the bandwidth and opening angle defined by XFI conditions. Typical parameters of driver lasers and electron bunches from LWFA are utilized and controlled within realistic parameter regions on the basis of appropriate beam optics. An active plasma lens is implemented for chromatic focal control of the bunch. Source performance limits are identified and compared to existing x-ray sources with regard to their potential to be implemented in future clinical XFI.

The interaction of high-intensity laser pulses with solid targets can be used as a highly charged, energetic heavy ion source. Normally, intrinsic contaminants on the target surface suppress the performance of heavy ion acceleration from a high-intensity laser–target interaction, resulting in preferential proton acceleration. Here, we demonstrate that CW laser heating of 5 µm titanium tape targets can remove contaminant hydrocarbons in order to expose a thin oxide layer on the metal surface, ideal for the generation of energetic oxygen beams. This is demonstrated by irradiating the heated targets with a PW class high-power laser at an intensity of 5 x 10^21 W/cm^2, showing enhanced acceleration of oxygen ions with a non-thermal-like distribution. Our new scheme using a CW laser-heated Ti tape target is promising for use as a moderate repetition energetic oxygen ion source for future applications.

In this study, a detailed investigation of the dynamics of the generation of pre-pulse bypost-pulses is presented, using single-shot self-referenced spectral interferometry (SRSI). The capabilityof SRSI in terms of the single-shot measurement of the temporal contrast of high-power lasersystems has been experimentally demonstrated. The results confirm that the energy levels of thepre-pulses increase proportional to the square of the B-integral parametrizing the nonlinearity of theamplifier chain.

We report on a new approach to measure the accumulated B-integral in the regenerative and multipass amplifier stages of ultrashort-pulse high-power laser systems by B-integral-induced coupling between delayed test post-pulses and the main pulse. A numerical model for such non-linear pulse coupling is presented and compared to data taken at the high-power laser Draco with self-referenced spectral interferometry (SRSI). The dependence of the B-integral accumulated in the regenerative amplifier on its operation mode enables optimization strategies for extracted energy vs. collected B-integral. The technique presented here can, in principle, be applied to characterize any type of ultrashort pulse laser system and is essential for pre-pulse reduction.

We report observations of coherent optical transition radiation interferometry (COTRI) patterns generated by microbunched∼200-MeV electrons as they emerge from a laser-driven plasma accelerator. The divergence of the microbunched portion of electrons, deduced by comparison to a COTRI model, is ∼9× smaller than the ∼3 mrad ensemble beam divergence, while the radius of the microbunched beam, obtained from COTR images on the same shot, is <3 μm. The combined results show that the microbunched distribution has estimated transverse normalized emittance∼0.4mm mrad.

With the rapid development of short-pulse intense laser sources, studies of matter under extreme irradiation conditions enter further unexplored regimes. In addition, an application of X-ray Free-Electron Lasers (XFELs) delivering intense femtosecond X-ray pulses, allows to investigate sample evolution in IR pump - X-ray probe experiments with an unprecedented time resolution. Here we present a detailed study of the periodic plasma created from the colloidal crystal. Both experimental data and theory modeling show that the periodicity in the sample survives to a large extent the extreme excitation and shock wave propagation inside the colloidal crystal. This feature enables probing the excited crystal, using the powerful Bragg peak analysis, in contrast to the conventional studies of dense plasma created from bulk samples for which probing with Bragg diffraction technique is not possible. X-ray diffraction measurements of excited colloidal crystals may then lead towards a better understanding of matter phase transitions under extreme irradiation conditions.

ntense laser-driven proton pulses, inherently broadband and highly divergent, pose a challenge to established beamline concepts on the path to application-adapted irradiation field formation, particularly for 3D. Here we experimentally show the successful implementation of a highly efficient (50% transmission) and tuneable dual pulsed solenoid setup to generate a homogeneous (laterally and in depth) volumetric dose distribution (cylindrical volume of 5 mm diameter and depth) at a single pulse dose of 0.7 Gy via multi-energy slice selection from the broad input spectrum. The experiments were conducted at the Petawatt beam of the Dresden Laser Acceleration Source Draco and were aided by a predictive simulation model verified by proton transport studies. With the characterised beamline we investigated manipulation and matching of lateral and depth dose profiles to various desired applications and targets. Using an adapted dose profile, we performed a first proof-of-technical-concept laser-driven proton irradiation of volumetric in-vitro tumour tissue (SAS spheroids) to demonstrate concurrent operation of laser accelerator, beam shaping, dosimetry and irradiation procedure of volumetric biological samples.

Small angle x-ray scattering (SAXS) is a well established technique to detect nanometer scale structure in matter. In typical setup, this diagnostics has an detector directly opened towards the scattering target. However, in a harsh environment of high intensity laser interaction, many high energetic particles and strong radiation are emerging from the laser target interaction. Such setup would therefore suffer a significant increase of noise due to this background which could eventually disable this measurement. In this paper, we present a novel tool consisting of mosaic graphite crystal which works as a mirror for the SAXS signal and allows to hide the detector behind proper shielding. This paper studies the performance of such mirror both by experiment at the European XFEL laboratory and by simulations.

Laser-ion acceleration with ultra-short pulse, PW-class lasers is dominated by non-thermal, intra-pulse plasma dynamics. The presence of multiple ion species or multiple charge states in targets leads to characteristic modulations and even mono-energetic features, depending on the choice of target material. As spectral signatures of generated ion beams are frequently used to characterize underlying acceleration mechanisms, thermal, multi-fluid descriptions require a revision for predictive capabilities and control in next-generation particle beam sources. We present an analytical model with explicit inter-species interactions, supported by extensive ab initio simulations. This enables us to derive important ensemble properties from the spectral distribution resulting from those multi-species effects for arbitrary mixtures. We further propose a potential experimental implementation with a novel cryogenic target, delivering jets with variable mixtures of hydrogen and deuterium. Free from contaminants and without strong influence of hardly controllable processes such as ionization dynamics, this would allow a systematic realization of our predictions for the multi-species effect.

Microbeam radiation therapy (MRT), a preclinical form of spatially fractionated radiotherapy, uses an array of microbeams of hard synchrotron X-ray radiation. Recently, compact synchrotron X-ray sources got more attention as they provide essential prerequisites for the translation of MRT into clinics while overcoming the limited access to synchrotron facilities. At the Munich Compact Light Source (MuCLS), a beamline at one of these novel compact X-ray sources, a proof of principle experiment was conducted applying MRT to a xenograft tumor mouse model. First, subcutaneous tumors derived from the established squamous carcinoma cell line FaDu were irradiated at a conventional X-ray tube using broadbeam geometry to determine a suitable dose range for the tumor growth delay.
For irradiations at the MuCLS, FaDu tumors were irradiated with broadbeam and microbeam irradiation at integral doses of either 3 or 5 Gy and tumor growth delay was measured. Microbeams had a width of 50 µm and a center-to-center distance of 350 µm with peak doses of either 21 or 35 Gy. A dose rate of up to 5 Gy/min was delivered to the tumor. Both doses and modalities delayed the tumor growth compared to a sham-irradiated tumor. The irradiated area and microbeam pattern were verified by staining of the DNA double-strand break marker γH2AX. This study demonstrates for the first time that microbeam radiation therapy can be successfully performed in vivo at the MuCLS.

Purpose/Objective: The laser-driven ionizing (LDI) beams have unique property of ultra-high dose rate, ultra-short pulses and carry the potential toward special clinical application. Our aim was to establish an in vivo zebrafish model for radiobiological research on later LDI radiation.
Material/methods: 24 hours post-fertilization (hpf) zebrafish (Danio rerio) embryos were irradiated at the University Proton Therapy Dresden with escalated doses (5, 10, 15, 20 and 30 Gy) at two positions along the proton depth-dose curve, at the plateau and at the middle of Spread Out Bragg Peak, and with reference 6 MV photon beams from a clinical linac (n=96 in each group). The experiment was 3 times repeated under the same conditions. On the 3th (96 hpf) and 4th (120 hpf) days after irradiation morphological malformations were documented (photo) and determined quantitatively. Two independent observers measured the length of the embryos, the degree of the yolk sac edema and the diameter of the eyes. Additionally, we have detected the DNA double-strand breaks immunohistochemically (gamma-H2AX foci) after 30 min of the irradiation at the two positions of the proton (mSOBP and plateau) and photon beams, at 5 Gy dose level.
Results: Dose-dependent organ developmental deteriorations could be detected morphologically at >10 Gy dose levels. The length of the embryo and the size of the eyes reduced, while the yolk sac edema increased significantly in dose dependent degree after 10 Gy, 15 Gy, 20 Gy and 30 Gy irradiation, at both developmental stages. At 5 Gy dose irradiation we have found significant elevation in the number of DNA double-strand breaks, as compared to the unirradiated control groups. Furthermore, data showed that after proton irradiation the degree of the DNA damage was higher, as compared to the photon irradiation.
Conclusion: We could establish a reliable quantitative morphological analysis of dose-dependent organ malformations using an in vivo vertebrate system. The zebrafish embryo model proved to be appropriate for complex evaluation of the irradiation-caused damages, molecular changes and for comparison of the biological effects of different radiation qualities. We could define the optimal parameters for future radiobiological experiments with the LDI beams.
Supported by: The ELI-ALPS project (GINOP-2.3.6-15-2015-00001) is supported by the European Union and co-financed by the European Regional Development Fund. The project has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement no 654148 Laserlab-Europe and by the German BMBF, grant no. 03Z1N511.

As a basic diagnostic tool, scintillation screens are employed in particle accelerators to detect charged particles. In extension to the recent revision on the calibration of scintillation screens commonly applied in the context of plasma acceleration [T. Kurz et al., Rev. Sci. Instrum. 89 (2018) 093303], here we present the charge calibration of three DRZ screens (Std, Plus, High), which promise to offer similar spatial resolution to other screen types whilst reaching higher conversion efficiencies. The calibration was performed at the Electron Linac for beams with high Brilliance and low Emittance (ELBE) at the Helmholtz-Zentrum Dresden-Rossendorf, which delivers picosecond-long beams of up to 40 MeV energy. Compared to the most sensitive screen, Kodak BioMAX MS, of the aforementioned recent investigation by Kurz et al., the sample with highest yield in this campaign, DRZ High, revealed a 30% increase in light yield. The detection threshold with these screens was found to be below 10 pC/mm². For higher charge-densities (several nC/mm²) saturation effects were observed. In contrast to the recent reported work, the DRZ screens were more robust, demonstrating higher durability under the same high level of charge deposition.

Fundamental similarities and differences between laser-driven plasma wakefield acceleration (LWFA) and particle-driven plasma wakefield acceleration (PWFA) are discussed.
The complementary features enable the conception and development of novel hybrid plasma accelerators, which allow previously not accessible compact solutions for high quality electron bunch generation and arising applications. Very high energy gains can be realized by electron beam drivers even in single stages because PWFA is practically dephasing-free and not diffraction-limited.
These electron driver beams for PWFA in turn can be produced in compact LWFA stages. In various hybrid approaches, these PWFA systems can be spiked with ionizing laser pulses to realize tunable and high-quality electron sources via optical density downramp injection (also known as plasma torch) or plasma photocathodes (also known as Trojan Horse) and via wakefield-induced injection (also known as WII). These hybrids can act as beam energy, brightness and quality transformers, and partially have built-in stabilizing features. They thus offer compact pathways towards beams with unprecedented emittance and brightness, which may have transformative impact for light sources and photon science applications. Furthermore, they allow the study of PWFA-specific challenges in compact setups in addition to large linac-based facilities, such as fundamental beam–plasma interaction physics, to develop novel diagnostics, and to develop contributions such as ultralow emittance test beams or other building blocks and schemes which support future plasma-based collider concepts.

Abstract: The development of new radiotherapy technologies is a long-term process, which requires proving the general concept although clinical requirements with respect to beam quality and controlled dose delivery may not yet be fulfilled. Exemplarily, the necessary radiobiological experiments with laser-accelerated ion beams are challenged by fluctuating beam intensities. Based on tumour-growth data and dose values obtained in an in-vivo trial comparing the biological efficacy of laser-driven and conventional Linac electrons [2], different statistical approaches for analysis were compared. In addition to the classical averaging per dose point, which excludes animals with high dose deviations, multivariable linear regression, Cox regression and a Monte-Carlo-based approach were tested as alternatives that include all animals in statistical analysis. The four methods were compared based on experimental and simulated data. All applied statistical approaches revealed a comparable radiobiological efficacy of laser-driven and conventional Linac electrons, confirming the experimental conclusion. However, in the simulation study, significant differences in dose-response were observed by all methods except for the conventional method. Thereby, these statistical approaches may allow for reducing the total number of required animals in future pre-clinical trials.

We present a conceptual design for a hybrid laserdriven plasma wakefield accelerator (LWFA) to beam-driven plasma wakefield accelerator (PWFA). In this set-up, the output beams from an LWFA stage are used as input beams of a new PWFA stage. In the PWFA stage, a new witness beam of largely increased quality can be produced and accelerated to higher energies. The feasibility and the potential of this concept is shown through exemplary particle-in-cell simulations.
In addition, preliminary simulation results for a proof-of-concept experiment in Helmholtz-Zentrum Dresden-Rossendorf (Germany) are shown.

the shape of a wave carries all information about the spatial and temporal structure of its source, given that the medium and its properties are known. Most modern imaging methods seek to utilize this nature of waves originating from Huygens’ principle. We discuss the retrieval of the complete kinetic energy distribution from the acoustic trace that is recorded when a short ion bunch deposits its energy in water. this novel method, which we refer to as Ion-Bunch energy Acoustic tracing (I-BeAt), is a refinement of the ionoacoustic approach. With its capability of completely monitoring a single, focused proton bunch with prompt readout and high repetition rate, I-BeAt is a promising approach to meet future requirements of experiments and applications in the field of laser-based ion acceleration. We demonstrate its functionality at two laser-driven ion sources for quantitative online determination of the kinetic energy distribution in the focus of single proton bunches

Plasma wakefield acceleration (PWFA) is a novel acceleration technique with promising prospects for both particle colliders and light sources. However, PWFA research has so far been limited to a few large-scale accelerator facilities worldwide. Here, we present first results on plasma wakefield generation using electron beams accelerated with a 100-TW-class Ti:sapphire laser. Because of their ultrashort duration and high charge density, the laser-accelerated electron bunches are suitable to drive plasma waves at electron densities in the order of 1019  cm−3. We capture the beam-induced plasma dynamics with femtosecond resolution using few-cycle optical probing and, in addition to the plasma wave itself, we observe a distinctive transverse ion motion in its trail. This previously unobserved phenomenon can be explained by the ponderomotive force of the plasma wave acting on the ions, resulting in a modulation of the plasma density over many picoseconds. Because of the scaling laws of plasma wakefield generation, results obtained at high plasma density using high-current laser-accelerated electron beams can be readily scaled to low-density systems. Laser-driven PWFA experiments can thus act as miniature models for their larger, conventional counterparts. Furthermore, our results pave the way towards a novel generation of laser-driven PWFA, which can potentially provide ultralow emittance beams within a compact setup.

Microbeam radiation therapy (MRT), a preclinical form of spatially fractionated radiotherapy, uses an array of microbeams of hard synchrotron X-ray radiation. Recently, compact synchrotron X-ray sources got more attention as they provide essential prerequisites for the translation of MRT into clinics while overcoming the limited access to synchrotron facilities. At the Munich Compact Light Source (MuCLS), a beamline at one of these novel compact X-ray sources, a proof of principle experiment was conducted applying MRT to a xenograft tumor mouse model. First, subcutaneous tumors derived from the established squamous carcinoma cell line FaDu were irradiated at a conventional X-ray tube using broadbeam geometry to determine a suitable dose range for the tumor growth delay.
For irradiations at the MuCLS, FaDu tumors were irradiated with broadbeam and microbeam irradiation at integral doses of either 3 or 5 Gy and tumor growth delay was measured. Microbeams had a width of 50 µm and a center-to-center distance of 350 µm with peak doses of either 21 or 35 Gy. A dose rate of up to 5 Gy/min was delivered to the tumor. Both doses and modalities delayed the tumor growth compared to a sham-irradiated tumor. The irradiated area and microbeam pattern were verified by staining of the DNA double-strand break marker γH2AX. This study demonstrates for the first time that microbeam radiation therapy can be successfully performed in vivo at the MuCLS.

Background and purpose
Motivated by first animal trials showing the normal tissue protecting effect of electron and photon Flash irradiation relative to conventional continuous beam delivery, the feasibility of proton Flash should be assessed.
Materials and methods
A setup and beam parameter settings for the treatment of zebrafish embryo with proton Flash and proton beam of conventional dose rate were established at the University Proton Therapy Dresden. Zebrafish embryos were treated with graded doses and the differential effect on embryonic survival and the induction of morphological malformations was followed for up to four days after irradiation.
Results
Beam parameters for the realization of proton Flash were set and tested with respect to controlled dose delivery to biological samples. The dose dependent embryonic survival data obtained for protons delivered as Flash and with a beam of conventional dose rate of 5 Gy/min show not significant influence of proton dose rate. Similarly, just a trend towards a protective effect of proton Flash was revealed for the induction of pericardial oedema as one type of acute radiation effect and spinal curvature as a developmental abnormality.
Conclusion
The feasibility of Flash proton irradiation was successfully shown, whereas more experiments are required to understand the absence of a clear protecting effect and therefore to figure out the limits and requirements for the Flash effect.

We show how optical free-electron lasers and enhanced incoherent Thomson scattering radiation sources can be realized with Traveling-Wave Thomson-Scattering (TWTS) today. Emphasis is put on the realization of optical free-electron lasers (OFELs) with existing state-of-the-art technology for laser systems and electron accelerators. The conceptual design of optical setups for the preparation of laser pulses suitable for TWTS OFELs and enhanced Thomson sources is presented. We further provide expressions to estimate the acceptable alignment tolerances of optical components for TWTS OFEL operation. Examples of TWTS OFELs radiating at 100 nm, 13.5 nm and 1.5 Å as well as an incoherent source at 40 pm highlight the feasibility of the concept and detail the procedure to determine the optical components parameters of a TWTS setup.

We examine the experimental requirements for realizing a high-gain Quantum free-electron laser (Quantum FEL). Beyond fundamental constraints on electron beam and undulator, we discuss optimized interaction geometries, include coherence properties along with the impact of diffraction, space-charge and spontaneous emission.
Based on desired Quantum FEL properties, as well as current experimental capabilities, we provide a procedure for determining a corresponding set of experimental parameters.
Even for an idealized situation, the combined constraints on space-charge and spontaneous emission put strong limits on sustaining the quantum regime over several gain lengths. Guided by these results we propose to shift the focus towards seeded Quantum FELs instead of continuing to aim for self-amplified spontaneous emission (SASE). Moreover, we point out the necessity of a rigorous quantum theory for spontaneous emission as well as for space-charge in order to identify possible loopholes in our line of argument.

Compact electron accelerators are paramount to next generation synchrotron light sources and free-electron lasers, as well as for advanced accelerators at the TeV energy frontier. Recent progress in laser-plasma driven accelerators (LPA) has extended their electron energies to the multi-GeV range and improved beam stability for insertion devices.
However, the sub-luminal group-velocity of plasma waves limits the final electron energy which can be achieved in a single LPA accelerator stage, also known as the dephasing limit.
Here we present the first laser-plasma driven electron accelerator concept without electrons outrunning the wakefield. Our scheme is robust against parasitic self-injection and self-phase modulation as well as drive-laser depletion and defocusing along the accelerated electron beam. It works for a broad range of plasma densities in gas targets.
This opens the way for scaling up electron energies towards TeV scale electron beams without the need for multiple laser-accelerator stages.

Extreme field gradients intrinsic to relativistic laser-interactions with thin solid targets enable compact MeV proton accelerators with unique bunch characteristics. Yet, direct control of the proton beam profile is usually not possible. Here we present a readily applicable all-optical approach to imprint detailed spatial information from the driving laser pulse onto the proton bunch. In a series of experiments, counter-intuitively, the spatial profile of the energetic proton bunch was found to exhibit identical structures as the fraction of the laser pulse passing around a target of limited size.
Such information transfer between the laser pulse and the naturally delayed proton bunch is attributed to the formation of quasi-static electric fields in the beam path by ionization of residual gas. Essentially acting as a programmable memory, these fields provide access to a higher level of proton beam manipulation.

Plasma-based accelerators that impart energy gain as high as several GeV to electrons or positrons within a few centimeters have engendered a new class of diagnostic techniques very different from those used in connection with conventional radio-frequency (rf) accelerators. The need for new diagnostics stems from the micrometer scale and transient, dynamic structure of plasma accelerators, which contrasts with the meter scale and static structure of conventional accelerators. Because of this micrometer source size, plasma-accelerated electron bunches can emerge with smaller normalized transverse emittance (εn<0.1  mm mrad) and shorter duration (τb∼1  fs) than bunches from rf linacs. Single-shot diagnostics are reviewed that determine such small εn and τb noninvasively and with high resolution from wide-bandwidth spectral measurement of electromagnetic radiation the electrons emit: εn from x rays emitted as electrons interact with transverse internal fields of the plasma accelerator or with external optical fields or undulators; τb from THz to optical coherent transition radiation emitted upon traversing interfaces. The duration of ∼1  fs bunches can also be measured by sampling individual cycles of a copropagating optical pulse or by measuring the associated magnetic field using a transverse probe pulse. Because of their luminal velocity and micrometer size, the evolving structure of plasma accelerators, the key determinant of accelerator performance, is exceptionally challenging to visualize in the laboratory. Here a new generation of laboratory diagnostics is reviewed that yield snapshots, or even movies, of laser- and particle-beam-generated plasma accelerator structures based on their phase modulation or deflection of femtosecond electromagnetic or electron probe pulses. Spatiotemporal resolution limits of these imaging techniques are discussed, along with insight into plasma-based acceleration physics that has emerged from analyzing the images and comparing them to simulated plasma structures.

During the last decade, the increasing application of proton radiotherapy and the rising number of long-term survivors gave rise to a vital discussion on potential effects on normal tissue. So far, deviations from clinically applied generic RBE (relative biological effectiveness) of 1.1 were just obtained by in vitro studies, whereas indications from in vivo trials and clinical studies are rare. In the present work, wildtype zebrafish embryos (Danio rerio) were applied to characterize effects of plateau and mid-SOBP proton radiation relative to that induced by clinical MV photon beam reference.
Based on embryonic survival data, RBE values of 1.13 ± 0.08 and of 1.20 ± 0.04 were determined four days after irradiations with 20 Gy plateau and SOBP protons relative to 6 MV photon beams. These RBE values were confirmed by relating the rates of embryos with morphological abnormalities for the respective radiation qualities and doses. Besides survival, the rate of spine bending, as one type of developmental abnormality, and of pericardial edema, as an example for acute radiation effects, were assessed. The results revealed that independent on radiation quality both rates increased with time approaching almost 100 % at the 4th day post irradiation with doses higher than 15 Gy.
To sum up, the applicability of the zebrafish embryo as a robust and simple alternative model for in vivo characterization of radiobiological effects in normal tissue was validated and the obtained RBE values are comparable to previous finding in animal trials.

Often, the interpretation of experiments concerning the manipulation of the energy distribution of laser-accelerated ion bunches is complicated by the multitude of competing dynamic processes simultaneously contributing to recorded ion signals. Here we demonstrate experimentally the acceleration of a clean proton bunch. This was achieved with a microscopic and three-dimensionally confined near critical density plasma, which evolves from a 1μm diameter plastic sphere, which is levitated and positioned with micrometer precision in the focus of a Petawatt laser pulse. The emitted proton bunch is reproducibly observed with central energies between 20 and 40 MeV and narrow energy spread (down to 25%) showing almost no low-energetic background. Together with three-dimensional particle-in-cell simulations we track the complete acceleration process, evidencing the transition from organized acceleration to Coulomb repulsion. This reveals limitations of current high power lasers and viable paths to optimize laser-driven ion sources.

The spatial distribution of protons accelerated from submicron-thick plastic foil targets using multi-terawatt, frequency-doubled laser pulses with ultra-high temporal contrast has been investigated experimentally. A very stable, ring-like beam profile of the accelerated protons, oriented around the target's normal direction has been observed. The ring's opening angle has been found to decrease with increasing foil thicknesses. Two-dimensional particle-in-cell simulations reproduce our results indicating that the ring is formed during the expansion of the proton density distribution into the vacuum as described by the mechanism of target-normal sheath acceleration. Here - in addition to the longitudinal electric fields responsible for the forward acceleration of the protons - a lateral charge separation leads to transverse field components accelerating the protons in the lateral direction.

In this article we revise the calibration measurements of different scintillation screens commonly used for the detection of relativistic electrons, extending previous reference work towards higher charge density and new types of screens. Electron peak charge densities up to 10 nC/mm² were provided by focused picosecond-long electron beams delivered by the ELBE linear accelerator at the Helmholtz-Zentrum Dresden-Rossendorf.
At low charge densities, a linear scintillation response was found, followed by the onset of saturation in the range of nC/mm². The absolute calibration factor (photons/sr/pC) in this linear regime was measured to be almost a factor of 2 lower than reported by Buck et al. retrospectively implying a higher charge in charge measurements performed with the old calibration. A good agreement was found with the results by Glinec et al.. Furthermore long-term irradiation tests with an integrated dose of approximately 50 nC/mm² indicate a significant decrease of the scintillation efficiency over time.
Finally, in order to enable the transfer of the absolute calibration between laboratories, a new constant reference has been developed.

Purpose: In order to take full advantage of proton radiotherapy the biological effect of protons in normal and tumor tissue as well as the interaction with concomitant therapies should be investigated and understood in detail. Dedicated and systematic in vitro trials are needed to resolve the underlying mechanisms and processes that are necessary to prepare the translation into the clinics. For this purpose, a setup for radiobiological studies and the corresponding dosimetry should be established that enables in vitro experiments at a horizontal proton beam and, as a reference, a clinical 6 MV photon linear accelerator (Linac).
Methods and results: The experimental proton beam is characterized by high beam availability and reliability throughout the day in parallel to patient treatment. For cell irradiation, a homogeneous 10 × 10 cm² proton field with an optional spread-out Bragg-peak can be formed. A water-filled phantom was installed that allows for precise positioning of different cell sample geometries along the proton path. The depth-dose profiles within the phantom and the dose homogeneity over different cell samples were characterized for the proton beam and the photon reference source. A daily quality assurance protocol was implemented that provides absolute dose information required for significant and reproducible in vitro trials.
Conclusion: In the experimental room of the University Proton Therapy Dresden, clinically relevant conditions for proton in vitro experiments have been realized. The established cell phantom and dosimetry, which facilitate irradiation in an aqueous environment, could easily be transferred to other proton, photon or even ion accelerators. Precise positioning and easy exchange of cell samples, monitor unit-based dose delivery, and high beam availability allow for systematic in vitro trials. The close vicinity to the radiotherapy and radiobiology departments provides access to a clinical linacs as well as the interdisciplinary basis for further translational steps.

We report on tailoring ionization-induced injection in laser wakefield acceleration so that the electron injection process is self-truncating following the evolution of the plasma bubble. Robust generation of high-quality electron beams with shot-to-shot fluctuations of the beam parameters better than 10% is presented in detail. As a novelty, the scheme was found to enable well-controlled yet simple tuning of the injected charge while preserving acceleration conditions and beam quality. Quasimonoenergetic electron beams at several 100MeV energy and 15% relative energy spread were routinely demonstrated with a total charge of the monoenergetic feature reaching 0.5 nC. Finally these unique beam parameters, suggesting unprecedented peak currents of several 10 kA, are systematically related to published data on alternative injection schemes.

We show efficient laser driven proton acceleration up to 14\,MeV from a 50\,$\mu$m thick cryogenic hydrogen ribbon. Pulses of the short pulse laser ELFIE at LULI with a pulse length of $\approx 350$\,fs at an energy of 8\,J per pulse are directed onto the target. The results are compared to proton spectra from metal and plastic foils with different thicknesses and show a similar good performance both in maximum energy as well as in proton number. Thus, this target type is a promising candidate for experiments with high repetition rate laser systems.

We report on the setup and commissioning of a compact recollimating single plasma mirror (PM) for temporal contrast enhancement at the Draco 150 TW laser during laser-proton acceleration experiments. The temporal contrast with and without PM is characterized single-shot by means of self-referenced spectral interferometry with extended time excursion at unprecedented dynamic and temporal range. This allows for the first single-shot measurement of the PM trigger point, which is interesting for the quantitative investigation of the complex pre-plasma formation process at the surface of the target used for proton acceleration. As a demonstration of high contrast laser plasma interaction we present proton acceleration results with ultra-thin liquid crystal targets of similar to 1 mu m down to 10 nm thickness. Focus scans of different target thicknesses show that highest proton energies are reached for the thinnest targets at best focus. This indicates that the contrast enhancement is effective such that the acceleration process is not limited by target pre-expansion induced by laser light preceding the main laser pulse.

Probing the rapid dynamics of plasma evolution in laser-driven plasma interactions provides deeper understanding of experiments in the context of laser-driven ion acceleration and facilitates the interplay with complementing numerical investigations. Besides the microscopic scales involved, strong plasma (self-)emission, predominantly around the harmonics of the driver laser, often complicates the data analysis. We present the concept and the implementation of a stand-alone probe laser system that is temporally synchronized to the driver laser, providing probing wavelengths beyond the harmonics of the driver laser. The capability of this system is shown during a full-scale laser proton acceleration experiment using renewable cryogenic hydrogen jet targets. For further improvements, we studied the influence of probe color, observation angle of the probe and temporal contrast of the driver laser on the probe image quality.

We present an experimental study investigating laser-driven proton acceleration via Target Normal Sheath Acceleration (TNSA) over a target thickness range spanning the typical TNSA-dominant region (~1 μm) down to below the relativistic laser-transparency regime (< 40 nm), enabled by freely adjustable target film thickness using liquid crystals along with high contrast (via plasma mirror) laser interaction (~ 2.65 J, 30 fs, I > 1 × 10^21 W/cm^2). Thickness dependent maximum proton energies scale well with TNSA models down to the thinnest targets, while those under ~ 40 nm indicate transparency-enhanced TNSA via differences in light transmission, maximum proton energy, and proton beam spatial profile. Oblique laser incidence (45°) allowed additional diagnostics to be fielded to diagnose the interaction quality: a suite of ion energy and spatial distribution diagnostics in the laser axis and both front and rear target normal directions as well as reflected and transmitted light measurements on-shot collectively verify the dominant acceleration mechanism as TNSA from high contrast interaction, even for ultra-thin targets. Additionally, 3D particle-in-cell simulations support the experimental observations of target-normal-directed proton acceleration from ultra-thin films.

Interaction of relativistic electron beams with high power lasers can both serve as a secondary light source and as a novel diagnostic tool for various beam parameters. For both applications, it is important to understand the dynamics of the inverse Compton scattering mechanism and the dependence of the scattered light’s spectral properties on the interacting laser and electron beam parameters. Measurements are easily misinterpreted due to the complex interplay of the interaction parameters. Here we report the potential of inverse Compton scattering as an advanced diagnostic tool by investigating two of the most influential interaction parameters, namely the laser intensity and the electron beam emittance. Established scaling laws for the spectral bandwidth and redshift of the mean scattered photon energy are refined. This allows for a quantitatively well matching prediction of the spectral shape. Driving the interaction to a nonlinear regime, we spectrally resolve the rise of higher harmonic radiation with increasing laser intensity. Unprecedented agreement with 3D radiation simulations is found, showing the good control and characterization of the interaction. The findings advance the interpretation of inverse Compton scattering measurements into a diagnostic tool for electron beams from laser plasma acceleration.

Quantitative predictions from synthetic radiation diagnostics often have to consider all accelerated particles.
For particle-in-cell (PIC) codes, this not only means including all macro-particles but also taking into account the discrete electron distribution associated with them.
This paper presents a general form factor formalism that allows to determine the radiation from this discrete electron distribution in order to compute the coherent and incoherent radiation self-consistently.
Furthermore, we discuss a memory-efficient implementation that allows PIC simulations with billions of macro-particles.
The impact on the radiation spectra is demonstrated on a large scale LWFA simulation.

The complex physics of the interaction between short pulse high intensity lasers and solids is so far hardly accessible by experiments. As a result of missing experimental capabilities to probe the complex electron dynamics and competing instabilities, this impedes the development of compact laser-based next generation secondary radiation sources, e.g. for tumor therapy, laboratory-astrophysics, and fusion. At present, the fundamental plasma dynamics that occur at the nanometer and femtosecond scales during the laser-solid interaction can only be elucidated by simulations. Here we show experimentally that Small Angle X-ray Scattering (SAXS) of femtosecond X-ray free-electron laser (XFEL) pulses facilitates new capabilities for direct in-situ characterization of intense short-pulse laser plasma interaction at solid density that allows simultaneous nanometer spatial and femtosecond temporal resolution, directly verifying numerical simulations of the electron density dynamics during the short pulse high intensity laser irradiation of a solid density target. For laser-driven grating targets, we measure the solid density plasma expansion and observe the generation of a transient grating structure in front of the pre-inscribed grating, due to plasma expansion, which is an hitherto unknown effect. We expect that our results will pave the way for novel time-resolved studies, guiding the development of future laser-driven particle and photon sources from solid targets.

For laser-driven ion acceleration from thin foils (~10 µm- 100 nm) in the target normal sheath acceleration (TNSA) regime, the hydro-carbon contaminant layer at the target surface generally serves as the ion source and hence determines the accelerated ion species, i.e. mainly protons, carbon and oxygen ions. The specific characteristics of the source layer - thickness and relevant lateral extent - as well as its manipulation have both been investigated since the first experiments on laser-driven ion acceleration using a variety of techniques from direct source imaging to knife-edge or mesh imaging.
In this publication, we present an experimental study in which laser ablation in two fluence regimes (low: F~0.6 J/cm², high: F~4 J/cm²) was applied to characterize and manipulate the hydro-carbon source layer. The high-fluence ablation in combination with a timed laser pulse for particle acceleration allowed for an estimation of the relevant source layer thickness for proton acceleration. Moreover, from these data and independently from the low-fluence regime, the lateral extent of the ion source layer became accessible.

Intense and energetic electron currents can be generated by ultra-intense lasers interacting with solid density targets.
Especially for ultra-short laser pulses their temporal evolution needs to be taken into account for many non-linear processes as instantaneous currents may differ significantly from the average.
Hence, a dynamic model including the temporal variation of the electron currents which goes beyond a simple bunching with twice the laser frequency but otherwise constant current is needed.
Here we present a new time-dependent model to describe the laser generated currents and obtain simple expressions for the temporal evolution and resulting corrections of averages.
To exemplify the model and its predictive capabilities we show the impact of temporal evolution, spectral distribution and spatial modulations on Ohmic heating of the bulk target material.

We present an experimental study investigating laser-driven proton acceleration via Target Normal Sheath Acceleration (TNSA) over a target thickness range spanning the typical TNSA-dominant region (~1 μm) down to below the relativistic laser-transparency regime (< 40 nm), enabled by freely adjustable target film thickness using liquid crystals along with high contrast (via plasma mirror) laser interaction (~ 2.65 J, 30 fs, I > 1 × 10^21 W/cm^2). Thickness dependent maximum proton energies scale well with TNSA models down to the thinnest targets, while those under ~ 40 nm indicate transparency-enhanced TNSA via differences in light transmission, maximum proton energy, and proton beam spatial profile. Oblique laser incidence (45°) allowed additional diagnostics to be fielded to diagnose the interaction quality: a suite of ion energy and spatial distribution diagnostics in the laser axis and both front and rear target normal directions as well as reflected and transmitted light measurements on-shot collectively verify the dominant acceleration mechanism as TNSA from high contrast interaction, even for ultra-thin targets. Additionally, 3D particle-in-cell simulations support the experimental observations of target-normal-directed proton acceleration from ultra-thin films.

We study the feasibility of using small angle X-ray scattering (SAXS) as a new experimental diagnostic for intense laser-solid interactions. By using X-ray pulses from a hard X-ray free electron laser, we can simultaneously achieve nanometer and femtosecond resolution of laser-driven samples. This is an important new capability for the Helmholtz international beamline for extreme fields at the high energy density endstation currently built at the European X-ray free electron laser. We review the relevant SAXS theory and its application to transient processes in solid density plasmas and report on first experimental results that confirm the feasibility of the method. We present results of two test experiments where the first experiment employs ultra-short laser pulses for studying relativistic laser plasma interactions, and the second one focuses on shock compression studies with a nanosecond laser system.

We report on a high repetition rate proton source produced by high-intensity laser irradiation of a continuously flowing, cryogenic hydrogen jet. The proton energy spectra are recorded at 1Hz for Draco laser powers of 6, 20, 40, and 100 TW. The source delivers ca. 10^13 protons/MeV/sr/min. We find that the average proton number over one minute, at energies sufficiently far from the cut-off energy, is robust to laser-target overlap and nearly constant. This work is therefore a first step towards pulsed laser-driven proton sources for time-resolved radiation damage studies and applications which require quasi-continuous doses at MeV energies.

The Horizon 2020 Project EuPRAXIA ("European Plasma Research Accelerator with eXcellence In Applications") is preparing a conceptual design report of a highly compact and cost-effective European facility with multi-GeV electron beams using plasma as the acceleration medium. The accelerator facility will be based on a laser and/or a beam driven plasma acceleration approach and will be used for photon science, high-energy physics (HEP) detector tests, and other applications such as compact X-ray sources for medical imaging or material processing. EuPRAXIA started in November 2015 and will deliver the design report in October 2019. EuPRAXIA aims to be included on the ESFRI roadmap in 2020.

Only few ten radiotherapy facilities worldwide provide ion beams, in spite of their physical advantage of better achievable tumor conformity of the dose compared to conventional photon beams. Since, mainly the large size and high costs hinder their wider spread, great efforts are ongoing to develop more compact ion therapy facilities.
One promising approach for smaller facilities is the acceleration of ions on micrometre scale by high intensity lasers. Laser accelerators deliver pulsed beams with a low pulse repetition rate, but a high number of ions per pulse, broad energy spectra and high divergences. A clinical use of a laser based ion beam facility requires not only a laser accelerator providing beams of therapeutic quality, but also new approaches for beam transport, dosimetric control and tumor conformal dose delivery procedure together with the knowledge of the radiobiological effectiveness of laser-driven beams.
Over the last decade research was mainly focused on protons and progress was achieved in all important challenges. Although currently the maximum proton energy is not yet high enough for patient irradiation, suggestions and solutions have been reported for compact beam transport and dose delivery procedures, respectively, as well as for precise dosimetric control. Radiobiological in vitro and in vivo studies show no indications of an altered biological effectiveness of laser-driven beams.
Laser based facilities will hardly improve the availability of ion beams for patient treatment in the next decade. Nevertheless, there are possibilities for a need of laser based therapy facilities in future.

Laser-plasma wakefield accelerators have seen tremendous progress, now capable of producing quasi-monoenergetic electron beams in the GeV energy range with few-femtoseconds bunch duration. Scaling these accelerators to the nanocoulomb range would yield hundreds of kiloamperes peak-current and stimulate the next generation of radiation sources covering high-field THz, high-brightness X-ray and γ-ray sources, compact FELs and laboratory-size beam-driven plasma accelerators. However, accelerators generating such currents operate in the beam loading regime where the accelerating field is strongly modified by the self-fields of the injected bunch, potentially deteriorating key beam parameters.
Here we demonstrate that, if appropriately controlled, the beam loading effect can be employed to improve the accelerator's performance. Self-truncated ionization injection enabled loading of unprecedented charges of about 0.5 nC within a mono-energetic peak. As the energy balance is reached, we show that the accelerator operates at the theoretically predicted optimal loading condition and the final energy spread is minimized.

We report experimental evidence that multi-MeV protons accelerated in relativistic laser-plasma interactions are modulated by strong filamentary electromagnetic fields. Modulations are observed when a preplasma is developed on the rear side of a μm-scale solid-density hydrogen target. Under such conditions, electromagnetic fields are amplified by the relativistic electron Weibel instability and are maximized at the critical density region of the target. The analysis of the spatial profile of the protons indicates the generation of B>10  MG and E>0.1  MV/μm fields with a μm-scale wavelength. These results are in good agreement with three-dimensional particle-in-cell simulations and analytical estimates, which further confirm that this process is dominant for different target materials provided that a preplasma is formed on the rear side with scale length ≳0.13λ0√a0. These findings impose important constraints on the preplasma levels required for high-quality proton acceleration for multipurpose applications.

We report on recent experimental results deploying a continuous cryogenic hydrogen jet as a debris-free, renewable laser-driven source of pure proton beams generated at the 150 TW ultrashort pulse laser Draco. Efficient proton acceleration reaching cut-off energies of up to 20 MeV with particle numbers exceeding 109 particles per MeV per steradian is demonstrated, showing for the first time that the acceleration performance is comparable to solid foil targets with thicknesses in the micrometer range. Two different target geometries are presented and their proton beam deliverance characterized: cylindrical (diameter 5 μm) and planar (20 μm × 2 μm). In both cases typical Target Normal Sheath Acceleration emission patterns with exponential proton energy spectra are detected. Significantly higher proton numbers in laser-forward direction are observed when deploying the planar jet as compared to the cylindrical jet case. This is confirmed by two-dimensional Particle-in-Cell (2D3V PIC) simulations, which demonstrate that the planar jet proves favorable as its geometry leads to more optimized acceleration conditions.

A number of laser facilities coming on–line all over the world promise the capability of high–power laser experiments with shot repetition rates between 1 and 10 Hz. Target availability and technical issues related to the interaction environment could become a bottleneck for the exploitation of such facilities. In this paper, we report on target needs for three different classes of experiments: dynamic compression physics, electron transport and isochoric heating and laser–driven particle and radiation sources. We also review some of the most challenging issues in target fabrication and high repetition rate operation. Finally, we discuss current target supply strategies and future perspectives to establish a sustainable target provision infrastructure for advanced laser facilities.

We report on first commissioning results of the DRACO Petawatt ultra-short pulse laser system implemented at the ELBE center for high power radiation sources of Helmholtz-Zentrum Dresden-Rossendorf. Key parameters of the laser system essential for efficient and reproducible performance of plasma accelerators are presented and discussed with the demonstration of 40MeV proton acceleration under TNSA conditions as well as peaked electron spectra with unprecedented bunch charge in the 0.5 nC range.

Background: The long-term aim of developing laser based particle acceleration towards clinical application requires not only substantial technological progress, but also the radiobiological characterization of the resulting ultra-short and ultra-intensive particle beam pulses. Subsequent to comprehensive cell studies a mouse ear tumour model was established allowing for the penetration of low energy protons (~20 MeV) currently available at laser driven accelerators. The model was successfully applied for a first tumour growth delay study with laser driven electrons, whereby the need of improvements crop out .
Methods: To optimise the mouse ear tumour model with respect to a stable, high take rate and a lower number of secondary tumours MatrigelTM was introduced for tumour cell injection. Different concentrations of two human tumour cell lines (FaDu, LN229) and Matrigel were evaluated for stable tumour growth and fulfilling the allocation criteria for irradiation experiments. The originally applied cell injection with PBS was performed for comparison and to assess the long-term stability of the model. Finally, the optimum suspension of cells and Matrigel was applied to determine applicable dose ranges for tumour growth delay studies by 200 kV X-ray irradiation.
Results: Both human tumour models showed a high take rate and exponential tumour growth starting at a volume of ~10 mm3. As disclosed by immunofluorescence analysis these small tumours already interact with the surrounding tissue and activate endothelial cells to form vessels. The formation of delimited, solid tumours at irradiation size was shown by standard H&E staining and a realistic dose range for inducing tumour growth delay, but not tumour control, was obtained for both tumour entities.
Conclusion: The already established mouse ear tumour model was successfully upgraded now providing stable tumour growth with high take rate for two tumour entities (HNSCC, glioblastoma) that are of interest for future irradiation experiments at experimental accelerators.

For the relativistic Kelvin-Helmholtz instability (KHI) which occurs at shear interfaces between two plasma streams, we report results on the polarized radiation over all observation directions and frequencies emitted by the plasma electrons from ab-initio kinetic simulations. We find the polarization of the radiation to provide a clear signature for distinguishing the linear phase of the KHI from its other phases. During the linear phase, we predict the growth rate of the KHI radiation power to match the growth rate of the KHI to a high degree. Our predictions are based on a model of the vortex dynamics which describes the electron motion in the vicinity of the shear interface between the two streams. Albeit the complex and turbulent dynamics happening in the shear region, we find excellent agreement between our model and large-scale particle-in-cell simulations. Our findings pave the way for identifying the KHI linear regime and for measuring its growth rate in astrophysical jets observable on earth.

The dynamics of bulk heating and ionization is investigated both in simulations and theory, which determines the crucial plasma parameters such as plasma temperature and density in ultra-short relativistic laser-solid target interactions. During laser-plasma interactions, the solid density plasma absorbs a fraction of laser energy and converts it into kinetic energy of electrons. A portion of the electrons with relativistic kinetic energy goes through the solid density plasma and transfers energy into the bulk electrons, which results in bulk electron heating. The bulk electron heating is finally translated into the processes of bulk collisional ionization inside the solid target. A simple model based on the Ohmic heating mechanism indicates that the local and temporal profile of bulk return current is essential to determine the temporal evolution of bulk electron temperature. A series of particle-in-cell simulations showing the local heating model is robust in the cases of target with a preplasma and without a preplasma. Predicting the bulk electron heating is then benefit for understanding the collisional ionization dynamics inside the solid targets. The connection of the heating and ionization inside the solid target is further studied using Thomas-Fermi model.

In this paper, a scintillator-based online beam profile detector for the characterization of laser-driven proton beams is presented. Using a pixelated matrix with varying absorber thicknesses, the proton beam is spatially resolved in two spatial dimensions and simultaneously energy-resolved. A thin plastic scintillator placed behind the absorber and read out by a CCD camera is used as the active detector material. The spatial detector resolution reaches down to ~4mm and up to 9 energy ranges can be resolved with an energy resolution of ~1 MeV above 8 MeV proton energy. With these detector design parameters, the spatial characteristics of the proton distribution and its cut-off energy can be analyzed online and on-shot under vacuum conditions. The paper discusses the detector design, its characterization and calibration at a conventional proton source as well as the first detector application at a laser-driven proton source.

Regarding the long term goal to develop and establish laser based particle accelerators for a future radiotherapeutic treatment of cancer the radiobiological consequences of the characteristic short intense particle pulses with ultra-high peak dose rate but low repetition rate of laser-driven beams have to be investigated. This work presents in vitro experiments performed at the radiation source ELBE (Electron Linac for beams with high Brilliance and low Emittance). This accelerator delivered 20 MeV electron pulses with ultra-high pulse dose rate of 10^10 Gy/min either at the low pulse frequency analogue to previous cell experiments with laser-driven electrons or at high frequency for minimizing the prolonged dose delivery and to perform comparison irradiation with a quasi-continuous electron beam analogue to a clinically used linear accelerator. The influence of the different electron beam pulse structures on the radiobiological response of the normal tissue cell line 184A1 and two primary fibroblasts were investigated regarding clonogenic survival and the number of DNA double strand breaks that remain 24 hours after irradiation. Thereby, no significant differences in radiation response were revealed for both biological endpoints and for all probed cell cultures. These results provide evidence that the radiobiological effectiveness of the pulsed electron beams is not affected by the ultra-high pulse dose rates alone.

In this paper, a reflective optical pump-probe technique for laser-driven plasmas at solid density target surfaces is presented. The technique is termed high depth-of-field time-resolved microscopy and it exploits the angular redistribution of the probe beam intensity after the probe’s reflection from an expanded and hence non-planar iso-density surface in the plasma. The main application of the robust technique, which uses simple imaging of the probe beam, is the spatio-temporal resolution of the plasma formation and expansion at the target rear surface. Analytic and numerical modeling of the experimental setup are applied for the analysis of the experimental results. The relevance and potential of the optical plasma probing method is highlighted by the application to targets of different geometries, helping to understand the target shape-related differences in the ion acceleration performance.

The design of an electron beam final focus system (FFS) aiming for high-flux laser-Thomson backscattering X-ray sources at ELBE is presented. A telescope system consisting of four permanent magnet based quadrupoles was found to have significantly less chromatic aberrations than a quadrupole doublet or triplet as commonly used. Focusing properties like the position of the focal plane and the spot size are retained for electron beam energies between 20 and 30 MeV by adjusting the position of the quadrupoles individually on a motorized stage. The desired ultra-short electron bunches require an increased relative energy spread up to a few percent and, thus, second order chromatic effects must be taken into account. We also present the design and test results of the permanent magnet quadrupoles. Adjustable shunts allow for correction of the field strength and compensation of deviations in the permanent magnet material.
For a beam emittance of 13 mm mrad, we predict focal spot sizes of about 40 μm (rms) and divergences of about 10 mrad using the FFS.

Laser wakefield acceleration (LWFA) has emerged as a promising concept for the next generation of high energy electron accelerators. The acceleration medium is provided by a target that creates a local well-defined gas-density profile inside a vacuum vessel. Target development and analysis of the resulting gas-density profiles is an important aspect in the further development of LWFA.
Gas-jet targets are widely used in regimes where relatively high electron densities over short interaction lengths are required (up to several millimetres interaction length, plasma densities down to ~10¹⁸ cm^-3).
In this paper we report a precise characterisation of such gas-jet targets by a laser interferometry technique. We show that phase shifts down to 4 mrad can be resolved. Tomographic phase reconstruction enables detection of non-axisymmetrical gas-density profiles which indicates defects in cylindrical nozzles, analysis of slit-nozzles and nozzles with an induced shock-wave density step. In a direct comparison between argon and helium jets we show that it cannot automatically be assumed, as is often done, that a nozzle measured with argon will provide the same gas density with helium.

Here we propose to exploit the low energy bandwidth, small wavelength and penetration power of ultrashort pulses from XFELs for resonant Small Angle Scattering (SAXS) on plasma structures in laser excited plasmas. Small angle scattering allows to detect nanoscale density fluctuations in forward scattering direction. Typically, the SAXS signal from laser excited plasmas is expected to be dominated by the free electron distribution. We propose that the ionic scattering signal becomes visible when the X-ray energy is in resonance with an electron transition between two bound states (Resonant coherent X-ray diffraction, RCXD). In this case the scattering cross-section dramatically increases so that the signal of X-ray scattering from ions silhouettes against the free electron scattering background which allows to measure the opacity and derived quantities with high spatial and temporal resolution, being fundamentally limited only by the X-ray wavelength and timing. Deriving quantities such as ion spatial distribution, charge state distribution and plasma temperature with such high spatial and temporal resolution will make a vast number of processes in shortpulse laser-solid interaction accessible for direct experimental observation e.g. hole-boring and shock propagation, filamentation and instability dynamics, electron transport, heating and ultrafast ionization dynamics.

The design of an electron beam final focus system (FFS) aiming for high-flux laser-Thomson backscattering X-ray sources at ELBE is presented. A telescope system consisting of four permanent magnet based quadrupoles was found to have significantly less chromatic aberrations than a quadrupole doublet or triplet as commonly used. Focusing properties like the position of the focal plane and the spot size are retained for electron beam energies between 20 and 30 MeV by adjusting the position of the quadrupoles individually on a motorized stage. The desired ultra-short electron bunches require an increased relative energy spread up to a few percent and, thus, second order chromatic effects must be taken into account. We also present the design and test results of the permanent magnet quadrupoles. Adjustable shunts allow for correction of the field strength and compensation of deviations in the permanent magnet material.
For a beam emittance of 13 mm mrad, we predict focal spot sizes of about 40 μm (rms) and divergences of about 10 mrad using the FFS.

The interaction of ultra-intense lasers with solid foils can be used to accelerate ions to high energies well exceeding 60MeV [Gaillard et al., Phys. Plasmas 18, 056710 (2011)]. The non-linear relativistic motion of electrons in the intense laser radiation leads to their acceleration and later to the acceleration of ions. Ions can be accelerated from the front surface, the foil interior region, and the foil rear surface (target normal sheath acceleration (TNSA), most widely used), or the foil may be accelerated as a whole if sufficiently thin (radiation pressure acceleration). Here, we focus on the most widely used mechanism for laser ion-acceleration of TNSA. Starting from perfectly flat foils, we show by simulations how electron filamentation at or inside the solid leads to spatial modulations in the ions. The exact dynamics depend very sensitively on the chosen initial parameters which has a tremendous effect on electron dynamics. In the case of step-like density gradients, we find evidence that suggests a two-surface-plasmon decay of plasma oscillations triggering a Raileigh-Taylor-like instability.

The long-term goal to integrate laser-based particle accelerators into radiotherapy clinics not only requires technological development of high-intensity lasers and new techniques for beam detection and dose delivery, but also characterization of the biological consequences of this new particle beam quality, i.e. ultra-short, ultra-intense pulses. In the present work, we describe successful in vivo experiments with laser-driven electron pulses by utilization of a small tumour model on the mouse ear for the human squamous cell carcinoma model FaDu. The already established in vitro irradiation technology at the laser system JETI was further enhanced for 3D tumour irradiation in vivo in terms of beam transport, beam monitoring, dose delivery and dosimetry in order to precisely apply a prescribed dose to each tumour in full-scale radiobiological experiments. Tumour growth delay was determined after irradiation with doses of 3 and 6 Gy by laser-accelerated electrons. Reference irradiation was performed with continuous electron beams at a clinical linear accelerator in order to both validate the dedicated dosimetry employed for laser-accelerated JETI electrons and above all review the biological results. No significant difference in radiation-induced tumour growth delay was revealed for the two investigated electron beams. These data provide evidence that the ultra-high dose rate generated by laser acceleration does not impact the biological effectiveness of the particles.

Purpose: In line with the long-term aim of establishing the laser based particle acceleration for future medical application the radiobiological consequences of electron delivery with the typical ultra-short pulses of ultra-high pulse dose rate have to be investigated.
Materials and methods: The radiation source ELBE (Electron Linac for beams with high Brilliance and low Emittance) was used to mimic the quasi-continuous electron beam of a clinical linear accelerator (LINAC) and to deliver electron pulses at the ultra-high pulse dose rate of 10^10 Gy min-1 either at the low frequency of a laser accelerator or at 13 MHz avoiding effects of prolonged dose delivery. The impact of pulse structure was analysed by clonogenic survival assay and by the number of residual DNA double-strand breaks remaining 24 h after irradiation of two human squamous cell carcinoma lines of differing radiosensitivity.
Results: The radiation response of both cell lines was found to be independent from electron pulse structure for the two endpoints under investigation.
Conclusions: The results reveal, that ultra-high pulse dose rate of 10^10 Gy min-1 and the low repetition rate of laser accelerated electrons have no additional influence on the radiobiological effectiveness of megavoltage electrons.

We present a fully analytic model of an all-optical free electron laser (OFEL) undulator based on the Traveling-Wave Thomson-Scattering (TWTS) scheme. The TWTS undulator provides for sub-mm undulator wavelengths, does not require any material or plasma to generate or contain the undulator field and allows for sub-meter saturation lengths.
Starting from a fully analytic description of the three-dimensional TWTS field we derive the OFEL pendulum equation for electrons in the TWTS field and discuss the constraints on laser and electron pulse parameters that have to be fulfilled for OFEL operation. We conclude in applying the TWTS OFEL to the realization of compact free electron laser sources at 13.5 nm and 0.2 nm using laser and electron sources in reach of present day technologies.

This paper reports on a systematic investigation of the ultrashort pulse laser driven acceleration of protons from thin targets of finite size, so-called reduced mass targets (RMTs). Reproducible series of targets, manufactured with lithographic techniques, and varying in size, thickness, and mounting geometry, were irradiated with ultrashort (30 fs) laser pulses of intensities of about 8 × 1020 Wcm−2. A robust maximum energy enhancement of almost a factor of two was found when comparing gold RMTs to reference irradiations of plain gold foils of the same thickness. Furthermore, a change of the thickness of these targets has less influence on the measured maximum proton energy when compared to standard foils, which, based on detailed particle-in-cell simulations, can be explained by the influence of the RMT geometry on the electron sheath. The performance gain was, however, restricted to lateral target sizes of greater than 50μm, which can be attributed to edge and mounting structure influences.

We report on the experimental observation of transverse modulations in proton beams accelerated from micrometer thick targets which were irradiated with ultra-short (30 fs) laser pulses of a peak intensity of 5·10^20 W/cm^2. The net-like proton beam modulations were recorded using radiochromic film and the data suggest a dependence on laser energy and target thickness for their onset and strength. Numerical simulations suggest that intensity-dependent instabilities in the laser-produced plasma at the target front side lead to electron beam break-up or filamentation, then serving as the source of the observed proton beam modulations.

The particle-in-cell code PIConGPU provides the feature of calculating angular resolved radiation spectra in the far field based on Liénard-Wiechert potentials for all macro particles of a plasma simulation. In order to verify the physics of our code we present a series of physics test scenarios, which compare numerical results to analytic solutions of nonlinear Thomson scattering at relativistic electrons. These scenarios range from single particle and electron bunch tests to full-scale laser-plasma simulations that include the collective effects of a plasma, as well as coherent and incoherent superposition of radiation of many particles. For the calculated test cases good agreement to the theoretical results with respect to absolute spectral intensities was found in all observation directions. In an electron density scan of a laser-plasma scenario, we reproduce a second-harmonic intensity scaling also observed in experiment.

We show that X-ray optical free-electron lasers (OFELs) can be realized using Traveling-Wave Thomson-Scattering (TWTS).
In TWTS pulse front tilted laser pulses are scattered off relativistic electron bunches in a side-scattering geometry.
The pulse-front tilt guarantees overlap between laser and electrons over distances in the meter range while both are traveling in different directions.
An interaction distance of 90 cm is obtained in a setup were 590 MeV electrons scatter off a petawatt class laser incident under an angle of 4.5°.
The amplification of the 1.5 Å radiation saturates at the end of the interaction.
In order to account for spatial and temporal dispersion introduced with the pulse front tilt, we develop an exact three-dimensional analytical description of TWTS pulses that can be used in three-dimensional simulations of the radiation amplification process.
The wave-optical formulation of the TWTS pulse includes dispersion to all orders and provides a general description of laser pulses diffracted at VLS gratings.

Background: The long-term aim of developing a laser based acceleration of protons and ions towards clinical application requires not only substantial technological progress, but also the radiobiological characterization of the resulting ultra-short pulsed particle beams. Recent in-vitro data showed similar effects of laser-accelerated versus “conventional” protons on clonogenic cell survival. As the proton energies currently achieved by laser driven acceleration are too low to penetrate standard tumour models on mice legs, the aim of the present work was to establish a tumour model allowing for the penetration of low energy protons (~ 20 MeV) to further verify their effects in vivo.
Methods: KHT mouse sarcoma cells were injected subcutaneously in the right ear of NMRI (nu/nu) mice and the growing tumours were characterized with respect to growth parameters, histology and radiation response. In parallel, the laser system JETI was prepared for animal experimentation, i.e. a new irradiation setup was implemented and the laser parameters were carefully adjusted. Finally, a proof-of-principle experiment with laser accelerated electrons was performed to validate the tumour model under realistic conditions, i.e. altered environment and horizontal beam delivery.
Results: KHT sarcoma on mice ears expressed a high take rate and showed continuous tumour growth after reaching a volume of ~ 5 mm³. The first irradiation experiment using laser accelerated electrons versus 200 kV X-rays was successfully performed and tumour growth delay was evaluated. Comparable tumour growth delay was found between X-ray and laser accelerated electron irradiation. Moreover, experimental influences, like anaesthesia and positioning at JETI, were found to be negligible.
Conclusion: A small animal tumour model suitable for the irradiation with low energy protons was established and validated at a laser based particle accelerator. For this reason, the translation from in vitro to in vivo experimentation was for the first time realized and an important milestone towards the clinical application of laser driven particle accelerators was achieved.

We demonstrate the potential of X-ray free-electron lasers (XFEL) to advancethe understanding of complex plasma dynamics by allowing for the first time nanometer and femtosecond resolution at the same time in plasma diagnostics. Plasma phenomena on such short timescales are of high relevance for many fields of physics, in particular in the ultra-intense ultra-short laser interaction with matter. Highly relevant yet only partially understood phenomena may become directly accessible in experiment. These include relativistic laser absorption at solid targets, creation of energetic electrons and electron transport in warm dense matter, including the seeding and development of surface and beam instabilities, ambipolar expansion, shock formation, and dynamics at the surfaces or at buried layers.
We demonstrate the potentials of XFEL plasma probing for high power laser matter interactions using exemplary the small angle X-ray scattering technique, focusing on general considerations for XFEL probing.

A Reply to the Comment by C. Thaury et al.

The particle-in-cell code PIConGPU provides the feature of calculating angular resolved radiation spectra in the far field based on Liénard-Wiechert potentials for all macro particles of a plasma simulation. In order to verify the physics of our code we present a series of physics test scenarios, which compare numerical results to analytic solutions of nonlinear Thomson scattering at relativistic electrons. These scenarios range from single particle and electron bunch tests to full-scale laser-plasma simulations that include the collective effects of a plasma, as well as coherent and incoherent superposition of radiation of many particles. For the calculated test cases good agreement to the theoretical results with respect to absolute spectral intensities was found in all observation directions. In an electron density scan of a laser-plasma scenario, we reproduce a second-harmonic intensity scaling also observed in experiment.

We investigate bulk ion heating in solid buried layer targets irradiated by ultra-short laser pulses of relativistic intensities using particle-in-cell simulations. Our study focuses on a CD2-Al-CD2 sandwich target geometry. We find enhanced deuteron ion heating in a layer compressed by the expanding aluminium layer. A pressure gradient created at the Al-CD2 interface pushes this layer of deuteron ions towards the outer regions of the target. During its passage through the target, deuteron ions are constantly injected into this layer. Our simulations suggest that the directed collective outward motion of the layer is converted into thermal motion inside the layer, leading to deuteron temperatures higher than those found in the rest of the target. This enhanced heating can already be observed at laser pulse durations as low as 100 fs. Thus, detailed experimental surveys at repetition rates of several ten laser shots per minute are in reach at current high-power laser systems, which would allow for probing and optimizing the heating dynamics.

A tunable source of intense ultra-short hard X-ray pulses represents a novel tool for the structural analysis of complex systems with unprecedented temporal and spatial resolution. With the simultaneous availability of a high power short-pulse laser system this provides unique opportunities at the forefront of relativistic light–matter interactions. At Helmholtz-Zentrum Dresden-Rossendorf (HZDR) we demonstrated the principle of such a light source (PHOENIX – Photon Electron collider for Narrow bandwidth Intense X-Rays) by colliding picosecond electron bunches from the ELBE linear accelerator with counter-propagating femtosecond laser pulses from the 150 TW Draco Ti:Sapphire laser system. The generated narrowband X-rays are highly collimated and can be reliably adjusted from 12 keV to 20 keV by tuning the electron energy (24–30 MeV). Ensuring the spatial–temporal overlap at the interaction point and suppressing the Bremsstrahlung background a signal to noise ratio of greater than 300 was reached.

Thomson backscattering of intense laser pulses from relativistic electrons not only allows for the generation of bright X-ray pulses but also for the investigation of the complex particle dynamics at the interaction point. For this purpose a complete spectral characterization of a Thomson source powered by a compact linear electron accelerator was performed with unprecedented angular and energy resolution. A rigorous statistical analysis comparing experimental data to 3D simulations enabled, e.g., the extraction of the angular distribution of electrons with 1.5% accuracy and, in total, provides predictive capability for the future high brightness hard X-ray source PHOENIX (Photon electron collider for Narrow bandwidth Intense X-rays) and potential gamma-ray sources.

We show that X-ray optical free-electron lasers (OFELs) can be realized using Traveling-Wave Thomson-Scattering (TWTS).
In TWTS pulse front tilted laser pulses are scattered off relativistic electron bunches in a side-scattering geometry.
The pulse-front tilt guarantees overlap between laser and electrons over distances in the meter range while both are traveling in different directions.
An interaction distance of 90 cm is obtained in a setup were 590 MeV electrons scatter off a petawatt class laser incident under an angle of 4.5°.
The amplification of the 1.5 Å radiation saturates at the end of the interaction.
In order to account for spatial and temporal dispersion introduced with the pulse front tilt, we develop an exact three-dimensional analytical description of TWTS pulses that can be used in three-dimensional simulations of the radiation amplification process.
The wave-optical formulation of the TWTS pulse includes dispersion to all orders and provides a general description of laser pulses diffracted at VLS gratings.

Proton beams are a promising tool for the improvement of radiotherapy of cancer, and compact laserdriven proton radiation (LDPR) is discussed as an alternative to established large-scale technology acilitating wider clinical use. Yet, clinical use of LDPR requires substantial development in reliable beam generation and transport, but also in dosimetric protocols as well as validation in radiobiological studies. Here, we present the first dose-controlled direct comparison of the radiobiological effectiveness of intense proton pulses from a laser-driven accelerator with conventionally generated continuous proton beams, demonstrating a first milestone in translational research. Controlled dose delivery, precisely online and offline monitored for each out of *4,000 pulses, resulted in an unprecedented relative dose uncertainty of below 10 %, using approaches scalable to the next translational step toward radiotherapy application.

In recent years, a new generation of high repetition rate (∼10 Hz), high power (∼100 TW) laser systems has stimulated intense research on laser-driven sources for fast protons. Considering experimental instrumentation, this development requires online diagnostics for protons to be added to the established offline detection tools such as solid state track detectors or radiochromic films. In this article, we present the design and characterization of a scintillator-based online detector that gives access to the angularly resolved proton distribution along one spatial dimension and resolves 10 different proton energy ranges. Conceived as an online detector for key parameters in laser-proton acceleration, such as the maximum proton energy and the angular distribution, the detector features a spatial resolution of ∼1.3 mm and a spectral resolution better than 1.5 MeV for a maximum proton energy above 12 MeV in the current design. Regarding its areas of application, we consider the detector a useful complement to radiochromic films and Thomson parabola spectrometers, capable to give immediate feedback on the experimental performance. The detector was characterized at an electrostatic Van de Graaff tandetron accelerator and tested in a laser-proton acceleration experiment, proving its suitability as a diagnostic device for laser-accelerated protons.

In recent years, the new technology of laser based particle acceleration was developed at such a rate that medical application for cancer therapy could become feasible. Promising more compact and economic proton and ion accelerators the laser technology however results in specific properties, like ultra-short (~ps) and ultra-intensive particle beam pulses. The clinical applicability of such new beam qualities requires comprehensive translational research from basic investigations to cell and animal experiments, finally followed by clinical trials. For the first time, the new laser based irradiation technology was established for animal experiments by the German joint research project “onCOOPtics”. A complete irradiation facility for laser accelerated electrons was developed, set up, commissioned, tested and applied for radiobiological tumour irradiation experiments under usage of a mouse model at the high intensity laser system JETI. The integration of a magnet and a collimator system resulted in an optimized beam transport and efficient electron energy filtration. Moreover, a specific irradiation and dosimetry setup was integrated allowing for the formation of irradiation fields, the real-time control of beam parameters and dose delivery to the tumour. For an accurate and reproducible positioning of the tumour in the irradiation field the mice were fixed in a movable box and the tumour position was online verified by means of a CCD camera system. The combination of both, the advanced laser accelerator system and the newly implemented irradiation and dosimetry setup allowed the successful performance of systematic radiobiological studies over months. Moreover, the practicability and easy handling of the system results in a reasonable duration of about 15 min for the whole procedure of mouse preparation, positioning and irradiation. In conclusion, the successful establishment of all technical requirements for and the performance of systematic animal studies with laser accelerated electrons mark an important step towards the clinical application of laser accelerated particle beams.

High-intensity laser plasma-based ion accelerators provide unsurpassed field gradients in the megavolt-per-micrometer range. They represent promising candidates for next-generation applications such as ion beam cancer therapy in compact facilities. The weak scaling of maximum ion energies with the square-root of the laser intensity, established for large subpicosecond class laser systems, motivates the search for more efficient acceleration processes. Here we demonstrate that for ultrashort (pulse duration ~ 30 fs) highly relativistic (intensity ~ 10 21 W cm − 2 ) laser pulses, the intra-pulse phase of the proton acceleration process becomes relevant, yielding maximum energies of around 20 MeV. Prominent non-target-normal emission of energetic protons, reflecting an engineered asymmetry in the field distribution of promptly accelerated electrons, is used to identify this pre-thermal phase of the acceleration. The relevant timescale reveals the underlying physics leading to the near-linear intensity scaling observed for 100 TW class table-top laser systems.

Recent experiments in the Trident laser facility (Los Alamos National Laboratory) have shown that hollow conical targets with a flat top at the tip can enhance the maximum energy of proton beams created during the interaction of an ultra-intense short laser pulse with the target (Gaillard S A et al 2011 Phys. Plasmas 18 056710). The proton energies that have been seen in these experiments are the highest energies observed so far in laser-driven proton acceleration. This is attributed to a new acceleration mechanism, direct light pressure acceleration of electrons (DLLPA), which increases the number and energy of hot electrons that drive the proton acceleration. This acceleration process of protons due to a two-temperature sheath formed at the flat-top rear side is very robust and produces a large number of protons per shot, similar to what is regularly observed in target normal sheath acceleration (Hatchett S P et al 2000 Phys. Plasmas 7 2076, Maksimchuk A et al 2000 Phys. Rev. Lett. 84 4108, Snavely R A et al 2000 Phys. Rev. Lett. 85 2945) with flat foils. In this paper, we investigate the electron kinetics during DLLPA, showing that they are governed by two mechanisms, both of which lead to continuous electron acceleration along the inner cone wall. Based on our model, we predict the scaling of the hot electron temperature and ion maximum energy with both laser and target geometrical parameters. The scaling of T_e^{DLLPA}=m_e c_0 \frac {a_0^2} {4} with the laser strength parameter a0 leads to an ion energy scaling that surpasses that of some recently proposed acceleration mechanisms such as radiation pressure acceleration (RPA), while in addition the maximum electron energy is found to scale linearly with the length of the cone neck. We find that when optimizing parameters, high proton energies suitable for applications can be reached using compact short-pulse laser systems with pulse durations of only a few tens to hundreds of laser periods.

The notable progress in laser particle acceleration technology promises potential medical application in cancer therapy through compact and cost effective laser devices that are suitable for already existing clinics. Previously, consequences on the radiobiological response by laser driven particle beams characterised by an ultra high peak dose rate have to be investigated. Therefore, tumour and non-malignant cells were irradiated with pulsed laser accelerated electrons at the JETI facility for the comparison with continuous electrons of a conventional therapy LINAC. Dose response curves were measured for the biological endpoints clonogenic survival and residual DNA double strand breaks. The overall results show no significant differences in radiobiological response for in vitro cell experiments between laser accelerated pulsed and clinical used electron beams. These first systematic in vitro cell response studies with precise dosimetry to laser driven electron beams represent a first step toward the long term aim of the application of laser accelerated particles in radiotherapy.

Purpose: The use of laser accelerators in radiation therapy can perhaps increase the low number of proton and ion therapy facilities in some years due to the low investment costs and small size. The laser-based acceleration technology leads to a very high peak dose rate of about 1011 Gy/s. A first dosimetric task is the evaluation of dose rate dependence of clinical dosimeters and other detectors.
Methods: The measurements were done at ELBE, a superconductive linear electron accelerator which generates electron pulses with 5 ps length at 20 MeV. The different dose rates are reached by adjusting the number of electrons in one beam pulse. Three clinical dosimeters (TLD, OSL and EBT radiochromic films) were irradiated with four different dose rates and nearly the same dose. A faraday cup, an integrating current transformer and an ionization chamber were used to control the particle flux on the dosimeters. Furthermore two diamond detectors were testet.
Results: The dosimeters are dose rate independent up to 4•109 Gy/s within 2 % (OSL and TLD) and up to 15•109 Gy/s within 5 % (EBT films). The diamond detectors show strong dose rate dependence.
Conlusion: TLD, OSL dosimeters and EBT films are suitable for pulsed beams with a very high pulse dose rate like laser accelerated particle beams.

A precise knowledge of the temperature and number of hot electrons generated in the interaction of shortpulse high-intensity lasers with solids is crucial for harnessing the energy of a laser pulse in applications such as laser-driven ion acceleration or fast ignition. Nevertheless, present scaling laws tend to overestimate the hot electron temperature when compared to experiment and simulations. We present a novel approach that is based on a weighted average of the kinetic energy of an ensemble of electrons. We find that the scaling of electron energy with laser intensity can be derived from a general Lorentz invariant electron distribution ansatz that does not rely on a specific model of energy absorption. The scaling derived is in perfect agreement with simulation results and clearly follows the trend seen in recent experiments, especially at high laser intensities where other scalings fail to describe the simulations accurately.

Background: The development of the new technology of proton and ion acceleration by ultra-high intensity lasers for cancer therapy is the goal of the German joint research project “onCOOPtics”. The laser based acceleration promises compact and economic therapy facilities that are suitable for already existing clinics. In contrast to conventional particle acceleration the laser based method results in beams of very short pulses with ultra-high pulse dose and correspondingly peak dose rate. Within the project multidisciplinary issues like development and optimization of high-intensity laser systems, efficient proton acceleration schemes and proton beam transport are handled. Moreover, the physical and real-time dosimetric characterization as well as the investigation of radiobiological consequences of laser accelerated beams are essential. These imply translational investigations starting from in vitro cell irradiation.

Material and Methods: Systematic in vitro cell experiments were performed at the 150 terawatt laser facility DRACO at HZDR. Proton pulses up to 20MeV were accelerated, whereas the broad proton spectrum was downward limited to 6MeV using an energy-filter-system. An in-house developed integrated dosimetry and cell irradiation system (IDOCIS) was tested and calibrated allowing precise dosimetry as well as the exact positioning of each cell sample. Cell survival and residual DNA double strand breaks were determined after irradiation of the tumour cell line SKX in a dose range from 0.5Gy to 4.3Gy. Additionally, reference irradiation were performed with continuous proton beam at a conventional Tandem accelerator and with a 200 kVp X-ray tube.

Results: A stable and reproducible laser driven proton beam was achieved for experiments over weeks including real-time dose and energy spectrum monitoring as well as precise absolute dosimetry. The comparison of the radiobiological effectiveness of conventional and laser accelerated proton beams show no significant difference for in vitro cell irradiation.

Conclusions: These first systematic in vitro cell response studies with precise dosimetry of laser driven protons represent an important step toward the development of laser accelerated particles for radiotherapeutic application. Further experiments with other human cell lines and in vivo studies are under way.

The work was supported by the BMBF, grant no. 03ZIK445.

Over the past years, several in vitro studies have been performed on DNA damage induced by soft X-rays, especially in the energy range below 50 keV. Radiation effects originating from such low-energy photons are relevant in the context of medical diagnostics, e.g. mammography, or of accidental exposure to scattered radiation. The present study was initiated to investigate the X-ray energy dependent induction of stable and unstable chromosomal aberrations in the human mammary epithelial cell line 184A1. Three colour fluorescence in situ hybridisation was applied to identify chromosomal damage in chromosomes 1, 8 and 17, induced by 10 kV or 25 kV soft X-rays as well as by 200 kV X-rays as a reference quality.
Based on dose dependencies in the range of 0.5 to 5 Gy, RBE values of 0.84 ± 0.09 and 1.45 ± 0.18 were found for stable translocations induced by 25 kV and 10 kV X-rays, respectively, using 200 kV X-rays as reference. Moreover, the analysis of the minimum number of breaks, as required to form the visible chromosomal damage, resulted in similar RBE values of 0.93 ± 0.07 for 25 kV X-rays and 1.25 ± 0.10 for 10 kV X-rays relative to 200 kV X-rays. In addition, non-DNA-proportional contributions of chromosomes 8 and 17 to the whole DNA damage and deviations from the expected 1:1 ratio of translocations and dicentrics were revealed for the mammary epithelial cell line 184A1.

An Integrated DOsimetry and Cell Irradiation System (IDOCIS) with laser-accelerated proton beams was developed, characterized, calibrated and successfully used for systematic in vitro experiments. Due to the broad exponentially shaped energy spectrum, the low energy range of the protons (< 20 MeV) and the high pulse dose, the absolute dosimetry for this beam quality is challenging. Therefore, a dedicated Faraday cup is used as an energy and dose rate independent absolute dosimeter that has been calibrated consistently with three independent methods. A transmission ionization chamber providing online relative dose information is cross-calibrated against the Faraday cup. Providing both online and absolute dose information the IDOCIS allows for quantitative dosimetric and radiobiological studies at current low-energy laser-accelerated proton beams. Finally, first dosimetric characterizations of a laser-accelerated proton beam with the IDOCIS are presented.

This paper presents the concept of transport and filtering of laser-accelerated proton pulses used for the first cell irradiation experiments performed with the Dresden 150 TW laser DRACO. Based on a simple non-focusing magnetic dipole equipped with two apertures the concept makes use of an energy dependent angular asymmetry of the proton spectra. For micron thin target foils protons of interest with energies above 7 MeV are observed to be significantly oset from target normal where low energy emission is dominantly centered. As the eect can be controlled via the target rotation with respect to the incoming light, it can be used to optimize the transport efficiency for high energy protons while simultaneously suppressing background radiation.

This paper reports on simulations of solid mass-limited targets (MLT) via electrodynamic 2D3V particle-in-cell simulations. The interaction with long (300 fs) high intensity (10²⁰ W/cm²) laser pulses with targets of diameter down to 1 m is described in detail with respect to electron dynamics and proton and ion acceleration. Depending on the foil diameter, different effects consecutively arise. Electrons laterally recirculate within the target, smoothening the target rear accelerating sheath and increasing the hot electron density and temperature. Our results suggest that the most significant ion energy enhancement to should be expected for MLT with diameter below the laser focal spot size. The spread of energetic protons is decreased for medium sized foils while it is greatly increased for foils of size near the focal spot size.

A new scheme to efficiently accelerate protons by a single linear polarized high-intensity ultrashort laser pulse using multiple ultrathin foils is proposed. The foils are stacked at a spacing comparable to their thickness and subsequently irradiated by the same laser pulse. The foil thicknesses are chosen such that the laser light pressure can displace all electrons out of the foil. The authors present a simple, yet precise dynamical model of the acceleration process from which both optimum foil thickness and spacing can be derived. Extensive two-dimensional (2D) particle-in-cell simulations verify the model predictions and suggest an enhancement of the maximum proton kinetic energy by 30% for the two-foil case compared to a single foil.