M. Schürer

Dose-dependent biological damage of tumour cells by laser-accelerated proton beams

We report on the first irradiation of in vitro tumour cells with laser-accelerated proton pulses showing dose-dependent biological damage. This experiment, paving the way for future radiobiological studies with laser-accelerated protons, demonstrates the simultaneous availability of all the components indispensable for systematic radiobiological studies: a laser-plasma accelerator providing proton spectra with maximum energy exceeding 15MeV and applicable doses of a few Gy within a few minutes; a beam transport and filtering system; an in-air irradiation site; and a dosimetry system providing both online dose monitoring and absolute dose information applied to the cell sample and the full infrastructure for analysing radiation-induced damage in cells.

A dosimetric system for quantitative cell irradiation experiments with laser-accelerated protons

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.

A scintillator-based online detector for the angularly resolved measurement of laser-accelerated proton spectra.

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.

Radiobiological response to ultra-short pulsed megavoltage electron beams of ultra-high pulse dose rate.

Abstract Purpose: In line with the long-term aim of establishing the laser-based particle acceleration for future medical application, the radiobiological consequences of the typical ultra-short pulses and ultra-high pulse dose rate can be investigated with electron delivery. 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) for comparison with electron pulses at the ultra-high pulse dose rate of 1010 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 analyzed 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 rates of 1010 Gy min−1 and the low repetition rate of laser accelerated electrons have no statistically significant influence (within the 95% confidence intervals) on the radiobiological effectiveness of megavoltage electrons.

Irradiation system for pre-clinical studies with laser accelerated electrons

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 power laser-driven particle acceleration for radiotherapy

Radiation therapy is an important modality in cancer treatment. Compact electron linear accelerators are widely used to provide electron and photon beams with a maximum energy of about 20 MeV for tumor irradiation. Heavy charged particles (protons and heavier ions) due to their superior dose profile over photons and electrons, provide higher tumor dose conformity and healthy tissue sparing. But due to high costs and huge size of existing facilities, ion therapy is limited to few, large centers only.

Novel Approach to Utilize Proton Beams from High Power Laser Accelerators for Therapy

Protons provide superior radiotherapy benefits to patients, but immense size and cost of the system limits it to only few centers worldwide. Proton acceleration on μm scale via high intensity laser is promising to reduce size and costs of proton therapy, but associated beamlines are still big and massive. Also, in contrast to conventionally accelerated quasi-continuous mono-energetic pencil beams, laser-driven beams have distinct beam properties, i.e. ultra-intense pico-sec bunches with large energy spread and large divergences, and with low repetition rate. With new lasers with petawatt power, protons with therapy related energies could be achieved, however, the beam properties make it challenging to adapt them directly for medical applications. We will present our compact beamline solution including energy selection and divergence control, and a new beam scanning and dose delivery system with specialized 3D treatment planning system for laser-driven proton beams. The beamline is based on high field iron-less pulsed magnets and about three times smaller than the conventional systems, and can provide high quality clinical treatment plans.