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

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

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

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

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

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

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

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

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

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

Off-harmonic optical probing of high intensity laser plasma expansion dynamics in solid density hydrogen jets.

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 [Formula: see text] peak intensity with a solid-density cylindrical cryogenic hydrogen jet target of [Formula: see text] 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 [Formula: see text] followed by full target transparency at [Formula: see text] after the high intensity laser peak are observed. A three dimensional particle-in-cell simulation initiated with the diagnosed target pre-expansion at [Formula: see text] 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.

Publisher Correction: Spectral and spatial shaping of laser-driven proton beams using a pulsed high-field magnet beamline.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Spectral and spatial shaping of laser-driven proton beams using a pulsed high-field magnet beamline.

Intense 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.

I-BEAT: Ultrasonic method for online measurement of the energy distribution of a single ion bunch.

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.

All-optical structuring of laser-driven proton beam profiles.

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.

Efficient laser-driven proton acceleration from cylindrical and planar cryogenic hydrogen jets.

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 (∅ 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.

Persurf, a new method to improve surfactant delivery: a study in surfactant depleted rats.

PURPOSE: Exogenous surfactant is not very effective in adults with ARDS, since surfactant does not reach atelectatic alveoli. Perfluorocarbons (PFC) can recruit atelectatic areas but do not replace impaired endogenous surfactant. A surfactant-PFC-mixture could combine benefits of both therapies. The aim of the proof-of-principal-study was to produce a PFC-in-surfactant emulsion (Persurf) and to test in surfactant depleted Wistar rats whether Persurf achieves I.) a more homogenous pulmonary distribution and II.) a more homogenous recruitment of alveoli when compared with surfactant or PFC alone. METHODS: Three different PFC were mixed with surfactant and phospholipid concentration in the emulsion was measured. After surfactant depletion, animals either received 30 ml/kg of PF5080, 100 mg/kg of stained (green dye) Curosurf™ or 30 ml/kg of Persurf. Lungs were fixated after 1 hour of ventilation and alveolar aeration and surfactant distribution was estimated by a stereological approach. RESULTS: Persurf contained 3 mg/ml phospholipids and was stable for more than 48 hours. Persurf-administration improved oxygenation. Histological evaluation revealed a more homogenous surfactant distribution and alveolar inflation when compared with surfactant treated animals. CONCLUSIONS: In surfactant depleted rats administration of PFC-in-surfactant emulsion leads to a more homogenous distribution and aeration of the lung than surfactant alone.

Experimental investigation of ultracold atom-molecule collisions.

Ultracold collisions between Cs atoms and Cs2 dimers in the electronic ground state are observed in an optically trapped gas of atoms and molecules. The Cs2 molecules are formed in the triplet ground state by cw photoassociation through the outer well of the 0-(g) (P3/2) excited electronic state. Inelastic atom-molecule collisions converting internal excitation into kinetic energy lead to a loss of Cs2 molecules from the dipole trap. Rate coefficients are determined for collisions involving Cs atoms in either the F=3 or F=4 hyperfine ground state, and Cs2 molecules in either highly vibrationally excited states (nu'=32-47) or in low vibrational states (nu'=4-6) of the a3 summation(u)+ triplet ground state. The rate coefficients beta approximately 10(-10) cm3/s are found to be largely independent of the vibrational and rotational excitation indicating unitary limited cross sections.

Uncommon synovial cysts in children.

UNLABELLED: Popliteal synovial cysts (Baker's cysts) are a common occurrence in children and adults. Synovial cysts in other locations and/or with atypical extension are less common and may be confounded with tumors or other medical conditions. In this article we describe the underlying disease, clinical presentation and clinical course in six children with a sudden onset of paraarticular soft tissue masses or non-specific chronic pain. Ultrasound was the initial imaging method used in all cases; this was supplemented by MRI in three patients. Four children were diagnosed to be suffering from juvenile idiopathic arthritis (JIA), one child from Lyme Arthritis, whereas in one child no underlying disease was identified. Well-demarcated hypoechogenic lesions without signs of perfusion extending from the shoulder (two patients), elbow (one patient), hip (one patient), knee (1) or ankle (one patient) far into the adjacent musculature were detected on ultrasonography. A direct connection to the joint was demonstrated in all cases. All synovial cysts in the five arthritic patients resolved rapidly with medical treatment for arthritis, whereas the cyst persisted in the non-JIA patient. CONCLUSION: Uncommon synovial cysts occur in particular as a complication of arthritis. Ultrasonography is the initial and follow-up imaging method of choice, which can be supplemented by MRI in unusual cases. Apart from treatment for arthritis, no specific therapeutic interventions were required in the present cases.

Airway management under general anaesthesia in pigs using the LMA-ProSeal: a pilot study.

OBJECTIVE: Evaluation of the LMA-ProSeal for positive pressure ventilation (PPV) in the pig. STUDY DESIGN: Prospective observational study. ANIMALS: Twelve German country pigs, weighing 25-62 kg. METHOD: Lungs of pigs were mechanically ventilated under general anaesthesia using the LMA-ProSeal. The ease of insertion, number of attempts and total time until placement of the LMA-ProSeal and gastric tube were recorded. Bronchoscopy was performed to determine the position of the LMA-ProSeal and to detect signs of aspiration. Ventilation variables and the leak airway pressure (P(leak)) were measured. An arterial blood gas sample was taken to determine the adequacy of ventilation. RESULTS: The airway was secured in all pigs within 39 +/- 19 seconds (27-51). Different sizes of LMA-ProSeal were used; up to 30 kg: size 3, up to 43 kg: size 4; and above 43 kg: size 5. In all but one animal the P-LMA and gastric tube were inserted at the first attempt. In nine animals gastric fluid was drained through the gastric tube. There was no evidence of aspiration in any animal. The mean [+/-SD (95%CI)]P(leak) was 28.8 +/- 7.5 cm H(2)O (24.06-33.60) and normal ventilation was achieved in all animals. CONCLUSIONS: The results of this study indicate that the airway of pigs weighing 25-62 kg can be secured safely and reliably with the sizes 3, 4 and 5 LMA-ProSeal. CLINICAL RELEVANCE: Endotracheal intubation in pigs can be difficult so there is a risk of hypoxemia in the apnoeic animal. With the LMA-ProSeal the airway can be secured rapidly, safely and reliably. Use of the Standard-LMA under PPV can be associated with gas leakage into the stomach and the subsequent risk of gastric distension and regurgitation. Both the ability to drain the stomach and the high P(leak) of the LMA-ProSeal could contribute to improved protection against aspiration under PPV.