Generation of bright, extreme-ultraviolet harmonic radiation from a krypton fluoride laser

We present results of experiments studying the efficiency of high harmonic generation from a gas target using the TITANIA krypton fluoride laser at the Rutherford Appleton Laboratory. The variation of harmonic yield for the 7th to 13th harmonics (355-191 Angstrom) is studied as a function of the backing pressure of a solenoid valve gas jet and of the axial position of the laser focus relative to the centre of the gas jet nozzle. Harmonic energies up to 1 mu J were produced in helium and neon targets from laser energies of approximately 200 mJ. This corresponds to absolute conversion efficiencies of up to 5 x 10(-6).

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.

A computational model of cellular response to modulated radiation fields

Purpose:
To develop a model to describe the response of cell populations to spatially modulated radiation exposures of relevance to advanced radiotherapies.

Materials and Methods:
A Monte Carlo model of cellular radiation response was developed. This model incorporated damage from both direct radiation and intercellular communication including bystander signaling. The predictions of this model were compared to previously measured survival curves for a normal human fibroblast line (AGO1522) and prostate tumor cells (DU145) exposed to spatially modulated fields.

Results:
The model was found to be able to accurately reproduce cell survival both in populations which were directly exposed to radiation and those which were outside the primary treatment field. The model predicts that the bystander effect makes a significant contribution to cell killing even in uniformly irradiated cells. The bystander effect contribution varies strongly with dose, falling from a high of 80% at low doses to 25% and 50% at 4 Gy for AGO1522 and DU145 cells, respectively. This was verified using the inducible nitric oxide synthase inhibitor aminoguanidine to inhibit the bystander effect in cells exposed to different doses, which showed significantly larger reductions in cell killing at lower doses.

Conclusions:
The model presented in this work accurately reproduces cell survival following modulated radiation exposures, both in and out of the primary treatment field, by incorporating a bystander component. In addition, the model suggests that the bystander effect is responsible for a significant portion of cell killing in uniformly irradiated cells, 50% and 70% at doses of 2 Gy in AGO1522 and DU145 cells, respectively. This description is a significant departure from accepted radiobiological models and may have a significant impact on optimization of treatment planning approaches if proven to be applicable in vivo.

Bystander responses induced by low LET radiation

Radiation-induced bystander responses are observed when cells respond to their neighbours being irradiated. Considerable evidence is now available regarding the importance of these responses in cell and tissue models. Most studies have utilized two approaches where either a media-transferable factor has been assessed or cells have been exposed to low fluences of charged particles, where only a few percent are exposed. The development of microbeams has allowed nontargeted responses such as bystander effects to be more carefully analysed. As well as charged particle microbeams, X-ray microprobes have been developed, and several groups are also developing electron microbeams. Using the Gray Cancer Institute soft X-ray microprobe, it has been possible to follow the response of individual cells to targeted low doses of carbon-characteristic soft X-rays. Studies in human fibroblasts have shown evidence of a significant radiation quality-dependent bystander effect, measured as chromosomal damage in the form of micronuclei which is radiation quality dependent. Other studies show that even under conditions when only a single cell is targeted with soft X-rays, significant bystander-mediated cell killing is observed. The observation of bystander responses with low LET radiation suggests that these may be important in understanding radiation risk from background levels of radiation, where cells observe only single electron track traversals. Also, the indirect evidence for these responses in vivo indicates that they may have a role to play in current radiotherapy approaches and future novel strategies involving modulating nontargeted responses.