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Abstract:

While novel radiotherapy modalities such as VHEE (Very High Energy Electron) and FLASH are being developed as effective potential cancer treatments, exposure of healthy cells to dose during radiotherapy remains a major challenge. Use of high-Z nanoparticles, in particular gold nanoparticles (AuNPs) has been identified as a method of radiosensitisation - increasing the toxicity of ionising radiation in a localised tumour region while avoiding dose increase to healthy tissue. This study focuses on AuNP radiosensitisation in VHEE irradiation with an investigation into dose enhancement through physical mechanisms. pBR322 plasmid DNA in solution with AuNPs was irradiated with VHEE beams at the CLEAR facility (CERN), with resulting lethal double-strand break (DSB) yields measured. AuNP size and beam energy were varied, in addition to dose rate to determine if a FLASH effect on DSB yield was observed. Significant increases in DSB yield were observed for samples containing 10 nm or 40 nm AuNPs, with dose enhancement factors of 1.21-1.34 and 1.27-1.50 for 10 and 40 nm AuNPs respectively. Such dose enhancement was found to be independent of electron beam energy across the range of 106-201 MeV. No significant variation in dose enhancement factor was observed between low and ultra-high dose rate irradiation. This study, having indicated significant increases in physical radiation effects through inclusion of AuNPs, highlights the potential for incorporating AuNPs in VHEE radiotherapy to increase the subsequent biological effects and improve clinical outcomes in addition to its potential to improve image contrasting.

Abstract:

Objective.Very high-energy electrons (VHEEs) offer deep penetration, low scattering, and the potential for ultra-high dose rate delivery, making them promising candidates for future radiotherapy. However, the collimation of VHEE beams to achieve sharp beam penumbra remains poorly characterized. This study experimentally and computationally investigates how collimator material, thickness, and beam characteristics affect penumbra and out-of-field dose for VHEEs and establishes an initial foundation for the design of clinically feasible VHEE collimators.Approach.Tungsten, lead, and brass 5 mm diameter collimators were evaluated using film dosimetry with a 200 MeV electron beam delivered at the CERN Linear Electron Accelerator for Research and validated through Monte Carlo (MC) simulations. Experimental measurements of penumbra and out-of-field dose were compared with simulations that systematically varied material (tungsten, lead, brass), thickness (20-80 mm), and beam energy (150-250 MeV). Additional sensitivity tests quantified the impact of beam instability on field shaping.Main results.For measurements in air, penumbrae increased linearly with distance from the collimator and was smallest for tungsten. Out-of-field dose decreased with increasing thickness, falling below 0.5% for a 40 mm thick tungsten collimator. Brass exhibited the highest out-of-field dose (up to 4.8%) and broadest penumbra. MC models reproduced experimental trends within 5% for penumbrae but underestimated out-of-field dose, particularly for brass. The simulations indicated that VHEE beam divergence, beam size and collimator misalignment strongly influence beam penumbra and out-of-field dose.Significance.The presented work demonstrates that collimator material and geometry play a critical role in defining VHEE beam quality. Tungsten provided optimal attenuation and sharpness compared to brass and lead. These results establish quantitative benchmarks for VHEE collimator design and emphasize the importance of beam stability.

Abstract:

This article describes the design and implementation of the first known prototype of a dual-scattering system for the delivery of a uniform VHEE beam with transverse dimensions suitable for pre-clinical and potential future clinical use. The results presented in this article are the first experimental characterisation of beam flattening with dual-scattering foils in the VHEE regime, confirmed with both profile measurements with a YAG screen and radiochromic EBT3 films. Polylactic acid and aluminium dual-scattering systems were designed using TOPAS Monte-Carlo simulations and multi-objective minimisation methods. Studies to test the success of the scattering systems in providing beam magnification and uniformity were carried out at the 200 MeV CERN Linear Electron Accelerator for Research (CLEAR) facility. A generalised super-Gaussian function was used to model the final beam, and comparisons were made with the simulations used for the design. Transverse profiles with uniform components were measured with each of the scattering systems and quantified with super-Gaussian fitting. The uniformity of the in-air profiles suggested that the superficial dose contributions from X-rays were low. This study demonstrated that magnified VHEE beam profiles with uniform components could be generated and measured at CLEAR. The results from this study were used as a basis for the design of future experiments. Similar systems and design methods could be employed by future clinical VHEE facilities to provide conformal treatment.

Abstract:

Objective. The FLASH effect holds significant potential in improving radiotherapy treatment outcomes. Very high energy electrons (VHEEs) with energies in the range of 50–250 MeV can effectively target tumors deep in the body and can be accelerated to achieve ultra-high dose rates (UHDR), making them a promising modality for delivering FLASH radiotherapy in the clinic. However, apart from suitable VHEE sources, clinical translation requires accurate dosimetry, which is challenging due to the limitation of standard dosimeters under UHDR conditions. In this study, water-equivalent and real-time plastic scintillation dosimeters (PSDs) are tested to evaluate their viability for FLASH VHEE dosimetry. Approach. A 4-channel PSD, consisting of polystyrene-based BCF12 and Medscint proprietary scintillators, polyvinyltoluene-based EJ-212 and a blank plastic fiber channel for Cherenkov subtraction was exposed to the 200 MeV VHEE UHDR beam at the CLEAR CERN facility. The Hyperscint RP200 platform was used to assess linearity to dose pulses of up to 90 Gy and dose rates up to 4.6×109 Gy s−1, and to investigate radiation damage and recovery after dose accumulation of 37.2 kGy. Main results. While blank fiber response was linear across the entire dose range studied, light output saturated above 45 Gy/pulse for scintillators. Despite radiation damage, linearity was preserved, though it resulted in a decrease of scintillator and blank fiber light output of <1.87%/kGy and a shift in spectra towards longer wavelengths. Short-term recovery ( <100 h) of these changes was observed and depended on rest duration and accumulated dose. After long-term rest ( <172 days), light output recovery was partial, with 6%–22% of residual permanent damage remaining, while spectral recovery was complete. Significance. We showed that PSDs are sensitive to radiation damage, but maintain dose linearity even after a total accumulated dose of 37.2 kGy, and exhibit significant response recovery. This work highlights the potential of PSDs for dosimetry in UHDR conditions.

Abstract:

Optical Beam-Loss Monitors (oBLMs) allow for cost-efficient and spatially continuous measurements of beam losses at accelerator facilities. A standard oBLM consists of several tens of metres of optical fibre aligned parallel to a beamline, coupled to photosensors at either or both ends. Using the timing information from loss signals, the loss positions can be reconstructed. This paper presents a novel oBLM system recently deployed at the CERN Linear Electron Accelerator for Research (CLEAR). Multiple methods of extracting timing and position information from measured waveforms with silicon photomultipliers (SiPM) and photomultiplier tubes (PMT) are investigated. For this installation, the optimal approach is determined to be applying a constant fraction discrimination (CFD) on the upstream readout. The position resolution is found to be similar for the tested SiPM and PMT. This work has resulted in the development of a user interface to aid operations by visualising the beam losses and their positions in real time.