Production of carbon-11 for PET preclinical imaging using a high-repetition rate laser-driven proton source.

Most advanced medical imaging techniques, such as positron-emission tomography (PET), require tracers that are produced in conventional particle accelerators. This paper focuses on the evaluation of a potential alternative technology based on laser-driven ion acceleration for the production of radioisotopes for PET imaging. We report for the first time the use of a high-repetition rate, ultra-intense laser system for the production of carbon-11 in multi-shot operation. Proton bunches with energies up to 10-14 MeV were systematically accelerated in long series at pulse rates between 0.1 and 1 Hz using a PW-class laser. These protons were used to activate a boron target via the 11 B(p,n) 11 C nuclear reaction. A peak activity of 234 kBq was obtained in multi-shot operation with laser pulses with an energy of 25 J. Significant carbon-11 production was also achieved for lower pulse energies. The experimental carbon-11 activities measured in this work are comparable to the levels required for preclinical PET, which would be feasible by operating at the repetition rate of current state-of-the-art technology (10 Hz). The scalability of next-generation laser-driven accelerators in terms of this parameter for sustained operation over time could increase these overall levels into the clinical PET range.

Development of a portable hypoxia chamber for ultra-high dose rate laser-driven proton radiobiology applications.

BACKGROUND: There is currently significant interest in assessing the role of oxygen in the radiobiological effects at ultra-high dose rates. Oxygen modulation is postulated to play a role in the enhanced sparing effect observed in FLASH radiotherapy, where particles are delivered at 40-1000 Gy/s. Furthermore, the development of laser-driven accelerators now enables radiobiology experiments in extreme regimes where dose rates can exceed 109 Gy/s, and predicted oxygen depletion effects on cellular response can be tested. Access to appropriate experimental enviroments, allowing measurements under controlled oxygenation conditions, is a key requirement for these studies. We report on the development and application of a bespoke portable hypoxia chamber specifically designed for experiments employing laser-driven sources, but also suitable for comparator studies under FLASH and conventional irradiation conditions. MATERIALS AND METHODS: We used oxygen concentration measurements to test the induction of hypoxia and the maintenance capacity of the chambers. Cellular hypoxia induction was verified using hypoxia inducible factor-1α immunostaining. Calibrated radiochromic films and GEANT-4 simulations verified the dosimetry variations inside and outside the chambers. We irradiated hypoxic human skin fibroblasts (AG01522B) cells with laser-driven protons, conventional protons and reference 225 kVp X-rays to quantify DNA DSB damage and repair under hypoxia. We further measured the oxygen enhancement ratio for cell survival after X-ray exposure in normal fibroblast and radioresistant patient- derived GBM stem cells. RESULTS: Oxygen measurements showed that our chambers maintained a radiobiological hypoxic environment for at least 45 min and pathological hypoxia for up to 24 h after disconnecting the chambers from the gas supply. We observed a significant reduction in the 53BP1 foci induced by laser-driven protons, conventional protons and X-rays in the hypoxic cells compared to normoxic cells at 30 min post-irradiation. Under hypoxic irradiations, the Laser-driven protons induced significant residual DNA DSB damage in hypoxic AG01522B cells compared to the conventional dose rate protons suggesting an important impact of these extremely high dose-rate exposures. We obtained an oxygen enhancement ratio (OER) of 2.1 ± 0.1 and 2.5 ± 0.1 respectively for the AG01522B and patient-derived GBM stem cells for X-ray irradiation using our hypoxia chambers. CONCLUSION: We demonstrated the design and application of portable hypoxia chambers for studying cellular radiobiological endpoints after exposure to laser-driven protons at ultra-high dose, conventional protons and X-rays. Suitable levels of reduced oxygen concentration could be maintained in the absence of external gassing to quantify hypoxic effects. The data obtained provided indication of an enhanced residual DNA DSB damage under hypoxic conditions at ultra-high dose rate compared to the conventional protons or X-rays.

Avoidance of different durations, colours and intensities of artificial light by adult seabirds.

There is increasing evidence for impacts of light pollution on the physiology and behaviour of wild animals. Nocturnally active Procellariiform seabirds are often found grounded in areas polluted by light and struggle to take to the air again without human intervention. Hence, understanding their responses to different wavelengths and intensities of light is urgently needed to inform mitigation measures. Here, we demonstrate how different light characteristics can affect the nocturnal flight of Manx shearwaters Puffinus puffinus by experimentally introducing lights at a colony subject to low levels of light pollution due to passing ships and coastal developments. The density of birds in flight above the colony was measured using a thermal imaging camera. We compared number of flying shearwaters under dark conditions and in response to an artificially introduced light, and observed fewer birds in flight during 'light-on' periods, suggesting that adult shearwaters were repelled by the light. This effect was stronger with higher light intensity, increasing duration of 'light-on' periods and with green and blue compared to red light. Thus, we recommend lower light intensity, red colour, and shorter duration of 'light-on' periods as mitigation measures to reduce the effects of light at breeding colonies and in their vicinity.

High energy implementation of coil-target scheme for guided re-acceleration of laser-driven protons.

Developing compact ion accelerators using intense lasers is a very active area of research, motivated by a strong applicative potential in science, industry and healthcare. However, proposed applications in medical therapy, as well as in nuclear and particle physics demand a strict control of ion energy, as well as of the angular and spectral distribution of ion beam, beyond the intrinsic limitations of the several acceleration mechanisms explored so far. Here we report on the production of highly collimated ([Formula: see text] half angle divergence), high-charge (10s of pC) and quasi-monoenergetic proton beams up to [Formula: see text] 50 MeV, using a recently developed method based on helical coil targetry. In this concept, ions accelerated from a laser-irradiated foil are post-accelerated and conditioned in a helical structure positioned at the rear of the foil. The pencil beam of protons was produced by guided post-acceleration at a rate of [Formula: see text] 2 GeV/m, without sacrificing the excellent beam emittance of the laser-driven proton beams. 3D particle tracing simulations indicate the possibility of sustaining high acceleration gradients over extended helical coil lengths, thus maximising the gain from such miniature accelerating modules.

Laser-driven high-quality positron sources as possible injectors for plasma-based accelerators.

The intrinsic constraints in the amplitude of the accelerating fields sustainable by radio-frequency accelerators demand for the pursuit of alternative and more compact acceleration schemes. Among these, plasma-based accelerators are arguably the most promising, thanks to the high-accelerating fields they can sustain, greatly exceeding the GeV/m. While plasma-based acceleration of electrons is now sufficiently mature for systematic studies in this direction, positron acceleration is still at its infancy, with limited projects currently undergoing to provide a viable test facility for further experiments. In this article, we study the feasibility of using a recently demonstrated laser-driven configuration as a relatively compact and inexpensive source of high-quality ultra-relativistic positrons for laser-driven and particle-driven plasma wakefield acceleration studies. Monte-Carlo simulations show that near-term high-intensity laser facilities can produce positron beams with high-current, femtosecond-scale duration, and sufficiently low normalised emittance at energies in the GeV range to be injected in further acceleration stages.

Evaluating laser-driven Bremsstrahlung radiation sources for imaging and analysis of nuclear waste packages.

A small scale sample nuclear waste package, consisting of a 28mm diameter uranium penny encased in grout, was imaged by absorption contrast radiography using a single pulse exposure from an X-ray source driven by a high-power laser. The Vulcan laser was used to deliver a focused pulse of photons to a tantalum foil, in order to generate a bright burst of highly penetrating X-rays (with energy >500keV), with a source size of <0.5mm. BAS-TR and BAS-SR image plates were used for image capture, alongside a newly developed Thalium doped Caesium Iodide scintillator-based detector coupled to CCD chips. The uranium penny was clearly resolved to sub-mm accuracy over a 30cm(2) scan area from a single shot acquisition. In addition, neutron generation was demonstrated in situ with the X-ray beam, with a single shot, thus demonstrating the potential for multi-modal criticality testing of waste materials. This feasibility study successfully demonstrated non-destructive radiography of encapsulated, high density, nuclear material. With recent developments of high-power laser systems, to 10Hz operation, a laser-driven multi-modal beamline for waste monitoring applications is envisioned.