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A general procedure is described to calculate the intensity and Strehl ratio, at a generic plane in the focal region, of a beam focused by an off-axis parabolic mirror in the presence of small misalignments. The general theoretical framework is first developed, which allows a full vector diffraction treatment in the case of general misalignments. Then, a parametric numerical study is reported, aimed at highlighting the tolerances of both the intensity and Strehl ratio for small misalignments, for different focusing and off-axis parabola parameters. A set of experimental measurements aimed at validating the theoretical model is also discussed.
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PURPOSE: Flash radiotherapy (FLASH-RT) is currently being regarded as the next breakthrough in radiation treatment of cancer, delivering ultrahigh radiation doses in a very short time, and sparing normal tissues from detrimental injury. Here we review the current evidence on the preclinical findings as well as the radiobiological mechanisms underlying the FLASH effect. We also briefly examine the scenario of available technologies for delivering FLASH dose-rates for research and their implications for future clinical use. CONCLUSIONS: Preclinical studies report that the FLASH-RT reduces radiation-induced toxicity whilst maintaining an equivalent tumor response across different animal models. However, the molecular radiobiology underlying FLASH effect is not fully understood and further experiments are necessary to understand the biological response. Future studies also includes the design of a FLASH delivery system able to produce beams appropriate for treatment of tumors with ultra-high dose rates. All these research activities will greatly benefit from a multidisciplinary collaboration across biology, physics and clinical oncology, increasing the potential of a rapid clinical translation of FLASH-RT.
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Neoplasias , Oncología por Radiación , Animales , Protocolos Clínicos , Neoplasias/radioterapia , Radiobiología , Radioterapia , Dosificación RadioterapéuticaRESUMEN
The interaction of ultraintense laser pulses with solids is largely affected by the plasma gradient at the vacuum-solid interface, which modifies the absorption and ultimately, controls the energy distribution function of heated electrons. A micrometer scale-length plasma has been predicted to yield a significant enhancement of the energy and weight of the fast electron population and to play a major role in laser-driven proton acceleration with thin foils. We report on recent experimental results on proton acceleration from laser interaction with foil targets at ultra-relativistic intensities. We show a threefold increase of the proton cut-off energy when a micrometer scale-length pre-plasma is introduced by irradiation with a low energy femtosecond pre-pulse. Our realistic numerical simulations agree with the observed gain of the proton cut-off energy and confirm the role of stochastic heating of fast electrons in the enhancement of the accelerating sheath field.
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Radiotherapy with very high energy electrons has been investigated for a couple of decades as an effective approach to improve dose distribution compared to conventional photon-based radiotherapy, with the recent intriguing potential of high dose-rate irradiation. Its practical application to treatment has been hindered by the lack of hospital-scale accelerators. High-gradient laser-plasma accelerators (LPA) have been proposed as a possible platform, but no experiments so far have explored the feasibility of a clinical use of this concept. We show the results of an experimental study aimed at assessing dose deposition for deep seated tumours using advanced irradiation schemes with an existing LPA source. Measurements show control of localized dose deposition and modulation, suitable to target a volume at depths in the range from 5 to 10 cm with mm resolution. The dose delivered to the target was up to 1.6 Gy, delivered with few hundreds of shots, limited by secondary components of the LPA accelerator. Measurements suggest that therapeutic doses within localized volumes can already be obtained with existing LPA technology, calling for dedicated pre-clinical studies.
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Electrones/uso terapéutico , Rayos Láser , Dosificación Radioterapéutica , Radioterapia de Intensidad Modulada/instrumentación , Radioterapia de Intensidad Modulada/métodos , Estudios de Factibilidad , Humanos , Aceleradores de PartículasRESUMEN
Accurate dynamic three-dimensional (4D) imaging of the heart of small rodents is required for the preclinical study of cardiac biomechanics and their modification under pathological conditions, but technological challenges are met in laboratory practice due to the very small size and high pulse rate of the heart of mice and rats as compared to humans. In 4D X-ray microtomography (4D µCT), the achievable spatio-temporal resolution is hampered by limitations in conventional X-ray sources and detectors. Here, we propose a proof-of-principle 4D µCT platform, exploiting the unique spatial and temporal features of novel concept, all-optical X-ray sources based on Thomson scattering (TS). The main spatial and spectral properties of the photon source are investigated using a TS simulation code. The entire data acquisition workflow has been also simulated, using a novel 4D numerical phantom of a mouse chest with realistic intra- and inter-cycle motion. The image quality of a typical single 3D time frame has been studied using Monte Carlo simulations, taking into account the effects of the typical structure of the TS X-ray beam. Finally, we discuss the perspectives and shortcomings of the proposed platform.
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Tomografía Computarizada Cuatridimensional/métodos , Corazón/diagnóstico por imagen , Microtomografía por Rayos X/métodos , Animales , Simulación por Computador , Humanos , Ratones , Método de Montecarlo , Fantasmas de Imagen , Fotones , Ratas , Roedores , Relación Señal-RuidoRESUMEN
Laser-driven electron accelerators are capable of producing high-energy electron bunches in shorter distances than conventional radiofrequency accelerators. To date, our knowledge of the radiobiological effects in cells exposed to electrons using a laser-plasma accelerator is still very limited. In this study, we compared the dose-response curves for micronucleus (MN) frequency and telomere length in peripheral blood lymphocytes exposed to laser-driven electron pulse and X-ray radiations. Additionally, we evaluated the effects on cell survival of in vitro tumor cells after exposure to laser-driven electron pulse compared to electron beams produced by a conventional radiofrequency accelerator used for intraoperative radiation therapy. Blood samples from two different donors were exposed to six radiation doses ranging from 0 to 2 Gy. Relative biological effectiveness (RBE) for micronucleus induction was calculated from the alpha coefficients for electrons compared to X rays (RBE = alpha laser/alpha X rays). Cell viability was monitored in the OVCAR-3 ovarian cancer cell line using trypan blue exclusion assay at day 3, 5 and 7 postirradiation (2, 4, 6, 8 and 10 Gy). The RBE values obtained by comparing the alpha values were 1.3 and 1.2 for the two donors. Mean telomere length was also found to be reduced in a significant dose-dependent manner after irradiation with both electrons and X rays in both donors studied. Our findings showed a radiobiological response as mirrored by the induction of micronuclei and shortening of telomere as well as by the reduction of cell survival in blood samples and cancer cells exposed in vitro to laser-generated electron bunches. Additional studies are needed to improve preclinical validation of the radiobiological characteristics and efficacy of laser-driven electron accelerators in the future.