Nanodosimetric effects of gold nanoparticles in megavoltage radiation therapy

Background and purpose: The addition of gold nanoparticles (GNPs) to tumours leads to an increase in dose due to their high density and energy absorption coefficient, making it a potential radiosensitiser. However, experiments have observed radiosensitisations significantly larger than the increase in dose alone, including at megavoltage energies where gold's relative energy absorption is lowest. This work investigates whether GNPs create dose inhomogeneities on a sub-cellular scale which combine with non-linear dose dependence of cell survival to be the source of radiosensitisation at megavoltage energies.

Dependence of spatial coherence of 23.2-23.6-nm radiation on the geometry of a multielement germanium x-ray laser target

The spatial coherence of a nanosecond pulsed germanium collisionally excited x-ray laser is measured experimentally for three target configurations. The diagnostic is based on Young's slit interference fringes with a dispersing element to resolve the 23.2- and 23.6-nm spectral lines. Target configurations include a double-slab target, known as the injector, and geometries in which the injector image is image relayed to seed either an additional single-slab target or a second double-slab target. A special feature of this study is the observation of the change in the apparent source size with angle of refraction across the diverging laser beam. Source sizes derived with a Gaussian source model decrease from 44 mu m for the injector target by a variable factor of as much as 2, according to target configuration, for beams leaving the additional amplifiers after strong refraction in the plasma. (C) 1998 Optical Society of America [S0740-3224(98)00810-8].

Time dependence of the spatial coherence of the 23.6- and 23.2-nm radiation from the germanium soft-x-ray laser

The time dependence of the spatial coherence of the combined spectral lines at 23.2 and 23.6 nm from the Ge XXIII collisionally pumped soft-x-ray laser with a double-slab target is examined within a single nanosecond pulse by use of Young's interference fringes and a streak camera. High source intensity is linked with low spatial coherence and vice verse. Calculations of the source intensity, size, and position have also been made; these calculations refer to a single-slab source. Comparison between the observed and calculated intensities, and of the source sizes both calculated and derived from the Young's fringes by interpretation with a Gaussian model of source emission, show good agreement in general trends. (C) 1998 Optical Society of America [S0740-3224(98)01905-5].

Imaging of high harmonic radiation emitted during the interaction of a 20 TW laser with a solid target

We present images of the source of extreme ultraviolet (XUV) harmonic emission at a wavelength of 220 Angstrom from the interaction of a 20 TW, 1.053 mu m Nd:glass laser beam focused to intensities up to 4x10(18) W cm(-2) onto a solid target. From these measurements we determine an upper limit to the source size and brightness of the harmonic emission to show its efficacy as a novel source of short-pulse, coherent XUV radiation. We also demonstrate the empirical scaling of the harmonic generation efficiency with irradiance up to 10(19) W mu m(2) cm(-2), and extrapolate to estimate the possible source brightness at higher irradiances. These source brightnesses are compared to those available from an x-ray laser system. (C) 1997 American Institute of Physics.

Calcium fluxes modulate the radiation-induced bystander responses in targeted glioma and fibroblast cells

Bystander responses have been reported to be a major determinant of the response of cells to radiation exposure at low doses, including those of relevance to therapy. This study investigated the role of changes in calcium levels in bystander responses leading to chromosomal damage in nonirradiated T98G glioma cells and AG01522 fibroblasts that had been either exposed to conditioned medium from irradiated cells or co-cultured with a population where a fraction of cells were individually targeted through the nucleus or cytoplasm with a precise number of microbeam helium-3 particles. After the recipient cells were treated with conditioned medium from T98G or AG01522 cells that had been irradiated through either nucleus or cytoplasm, rapid calcium fluxes were monitored in the nonirradiated recipient cells. Their characteristics were dependent on the source of the conditioned medium but had no dependence on radiation dose. When recipient cells were co-cultured with an irradiated population of either T98G or AG01522 cells, micronuclei were induced in the nonirradiated cells, but this response was eliminated by treating the cells with calcicludine (CaC), a potent blocker of Ca2+ channels. Moreover, both the calcium fluxes and the bystander effect were inhibited when the irradiated T98G cells were treated with aminoguanidine, an inhibitor of nitric oxide synthase (NOS), and when the irradiated AG01522 cells were treated with DMSO, a scavenger of reactive oxygen species (ROS), which indicates that NO and ROS were involved in the bystander responses generated from irradiated T98G and AG01522 cells, respectively. Our findings indicate that calcium signaling may be an early response in radiation-induced bystander effects leading to chromosome damage. (c) 2006 by Radiation Research Society.

Dose, dose-rate and field size effects on cell survival following exposure to non-uniform radiation fields

For the delivery of intensity-modulated radiation therapy (IMRT), highly modulated fields are used to achieve dose conformity across a target tumour volume. Recent in vitro evidence has demonstrated significant alterations in cell survival occurring out-of-field which cannot be accounted for on the basis of scattered dose. The radiobiological effect of area, dose and dose-rate on out-of-field cell survival responses following exposure to intensity-modulated radiation fields is presented in this study. Cell survival was determined by clonogenic assay in human prostate cancer (DU-145) and primary fibroblast (AG0-1522) cells following exposure to different modulated field configurations delivered using a X-Rad 225 kVp x-ray source. Uniform survival responses were compared to in- and out-of-field responses in which 25-99% of the cell population was shielded. Dose delivered to the out-of-field region was varied from 1.6-37.2% of that delivered to the in-field region using different levels of brass shielding. Dose rate effects were determined for 0.2-4 Gy min⁻¹ for uniform and modulated exposures with no effect seen in- or out-of-field. Survival responses showed little dependence on dose rate and area in- and out-of-field with a trend towards increased survival with decreased in-field area. Out-of-field survival responses were shown to scale in proportion to dose delivered to the in-field region and also local dose delivered out-of-field. Mathematical modelling of these findings has shown survival response to be highly dependent on dose delivered in- and out-of-field but not on area or dose rate. These data provide further insight into the radiobiological parameters impacting on cell survival following exposure to modulated irradiation fields highlighting the need for refinement of existing radiobiological models to incorporate non-targeted effects and modulated dose distributions.

Application of laser radiation for the treatment of waste materials using a photocatalyst

One effective approach is to destroy industrial waste and pollution is the use of a semiconductor photocatalysis system. To date such, photocatalysis systems have employed conventional linear light sources. Initial results from a study of a photocatalysis system incorporating a tripled Nd:YAG laser are reported. The laser light not only played a roll as a light source for activating the photocatalyst(TiO₂), but also destroyed the organic species directly via a photochemical process. The reaction intermediates and changes in their concentrations are monitored using HPLC. The relationship between the power of laser and kinetics of photoreaction are discussed.

(223)Ra and other bone-targeting radiopharmaceuticals-the translation of radiation biology into clinical practice

Osseous metastases are a source of significant morbidity for patients with a variety of cancers. Radiotherapy is well established as an effective means of palliating symptoms associated with such metastases. The role of external beam radiotherapy is limited where sites of metastases are numerous and widespread. Low linear energy transfer (LET) radionuclides have been utilized to allow targeted delivery of radiotherapy to disparate sites of disease, with evidence of palliative benefit. More recently, the bone targeting, high LET radionuclide (223)Ra has been shown to not only have a palliative effect but also a survival prolonging effect in metastatic, castration-resistant prostate cancer with bone metastases. This article reviews the different radionuclide-based approaches for targeting bone metastases, with an emphasis on (223)Ra, and key elements of the underlying radiobiology of these that will impact their clinical effectiveness. Consideration is given to the remaining unknowns of both the basic radiobiological and applied clinical effects of (223)Ra as targets for future research.

Impact of fractionation on out-of-field survival and DNA damage responses following exposure to intensity modulated radiation fields

To limit toxicity to normal tissues adjacent to the target tumour volume, radiotherapy is delivered using fractionated regimes whereby the total prescribed dose is given as a series of sequential smaller doses separated by specific time intervals. The impact of fractionation on out-of-field survival and DNA damage responses was determined in AGO-1522 primary human fibroblasts and MCF-7 breast tumour cells using uniform and modulated exposures delivered using a 225 kVp x-ray source. Responses to fractionated schedules (two equal fractions delivered with time intervals from 4 h to 48 h) were compared to those following acute exposures. Cell survival and DNA damage repair measurements indicate that cellular responses to fractionated non-uniform exposures differ from those seen in uniform exposures for the investigated cell lines. Specifically, there is a consistent lack of repair observed in the out-of-field populations during intervals between fractions, confirming the importance of cell signalling to out-of-field responses in a fractionated radiation schedule, and this needs to be confirmed for a wider range of cell lines and conditions.

Laser-driven x-ray and neutron source development for industrial applications of plasma accelerators

Pulsed beams of energetic x-rays and neutrons from intense laser interactions with solid foils are promising for applications where bright, small emission area sources, capable of multi-modal delivery are ideal. Possible end users of laser-driven multi-modal sources are those requiring advanced non-destructive inspection techniques in industry sectors of high value commerce such as aerospace, nuclear and advanced manufacturing. We report on experimental work that demonstrates multi-modal operation of high power laser-solid interactions for neutron and x-ray beam generation. Measurements and Monte Carlo radiation transport simulations show that neutron yield is increased by a factor ∼2 when a 1 mm copper foil is placed behind a 2 mm lithium foil, compared to using a 2 cm block of lithium only. We explore x-ray generation with a 10 picosecond drive pulse in order to tailor the spectral content for radiography with medium density alloy metals. The impact of using >1 ps pulse duration on laser-accelerated electron beam generation and transport is discussed alongside the optimisation of subsequent bremsstrahlung emission in thin, high atomic number target foils. X-ray spectra are deconvolved from spectrometer measurements and simulation data generated using the GEANT4 Monte Carlo code. We also demonstrate the unique capability of laser-driven x-rays in being able to deliver single pulse high spatial resolution projection imaging of thick metallic objects. Active detector radiographic imaging of industrially relevant sample objects with a 10 ps drive pulse is presented for the first time, demonstrating that features of 200 μm size are resolved when projected at high magnification.

A high-energy, high-flux source of gamma-rays from all-optical nonlinear Thomson scattering

γ-Ray sources are among the most fundamental experimental tools currently available to modern physics. As well as the obvious benefits to fundamental research, an ultra-bright source of γ-rays could form the foundation of scanning of shipping containers for special nuclear materials and provide the bases for new types of cancer therapy.

However, for these applications to prove viable, γ-ray sources must become compact and relatively cheap to manufacture. In recent years, advances in laser technology have formed the cornerstone of optical sources of high energy electrons which already have been used to generate synchrotron radiation on a compact scale. Exploiting the scattering induced by a second laser, one can further enhance the energy and number of photons produced provided the problems of synchronisation and compact γ-ray detection are solved.

Here, we report on the work that has been done in developing an all-optical and hence, compact non-linear Thomson scattering source, including the new methods of synchronisation and compact γ-ray detection. We present evidence of the generation of multi-MeV (maximum 16–18 MeV) and ultra-high brilliance (exceeding 10²⁰ photons s⁻¹mm⁻²mrad⁻² 0.1% BW at 15 MeV) γ-ray beams. These characteristics are appealing for the paramount practical applications mentioned above.

MPGDs based radiation imaging devices and applications

Este trabalho descreve o desenvolvimento e aplicação de sistemas baseados em detetores gasosos microestruturados, para imagiologia de fluorescência de raios-X por dispersão em energia (EDXRF). A técnica de imagiologia por fluorescência de raios-X assume-se como uma técnica poderosa, não-destrutiva, em análises da distribuição espacial de elementos em materiais. Os sistemas para imagiologia de EDXRF desenvolvidos são constituídos por: um tubo de raios-X, usado para excitar os elementos da amostra; um detetor gasoso microestruturado; e uma lente pinhole que foca a radiação de fluorescência no plano do detetor formando assim a imagem e permitindo a sua ampliação. Por outro lado é estudada a influência do diâmetro da abertura do pinhole bem como do fator de ampliação obtido para a imagem, na resolução em posição do sistema. Foram usados dois conceitos diferentes de detetores gasosos microestruturados. O primeiro, baseado na microestrutura designada por 2D-Micro-Hole & Strip Plate (2D-MHSP) com uma área ativa de 3 3 cm2, enquanto que o segundo, baseado na estrutura 2D-Thick-COBRA (2D-THCOBRA) apresenta uma área ativa de deteção de 10 10 cm2. Estes detetores de raios-X de baixo custo têm a particularidade de funcionar em regime de fotão único permitindo a determinação da energia e posição de interação de cada fotão que chega ao detetor. Deste modo permitem detetar a energia dos fotões X de fluorescência, bem como obter imagens 2D da distribuição desses fotões X para o intervalo de energias desejado. São por isso adequados a aplicações de imagiologia de EDXRF. Os detetores desenvolvidos mostraram resoluções em energia de 17% e 22% para fotões incidentes com uma energia de 5.9 keV, respectivamente para o detetor 2D-MHSP e 2D-THCOBRA e resoluções em posição adequadas para um vasto número de aplicações. Ao longo deste trabalho é detalhado o desenvolvimento, o estudo das características e do desempenho de cada um dos detetores, e sua influência na performance final de cada sistema proposto. Numa fase mais avançada apresentam-se os resultados correspondentes à aplicação dos dois sistemas a diversas amostras, incluindo algumas do nosso património cultural e também uma amostra biológica.

Contribution to fundamental aspects of biophysics, radiobiology, and modeling of cellular response to low radiation doses

Tese de doutoramento, Engenharia Biomédica e Biofísica, Universidade de Lisboa, Faculdade de Ciências, 2014