J.B. Davies

Initial investigation of a novel light-scattering gel phantom for evaluation of optical CT scanners for radiotherapy gel dosimetry

There is a need for stable gel materials for phantoms used to validate optical computerized tomography (CT) scanners used in conjunction with radiation-induced polymerizing gel dosimeters. Phantoms based on addition of light-absorbing dyes to gelatine to simulate gel dosimeters have been employed. However, to more accurately simulate polymerizing gels one requires phantoms that employ light-scattering colloidal suspensions added to the gel. In this paper, we present the initial results of using an optical CT scanner to evaluate a novel phantom in which radiation-exposed polymer gels are simulated by the addition of colloidal suspensions of varying turbidity. The phantom may be useful as a calibration transfer standard for polymer gel dosimeters. The tests reveal some phenomena peculiar to light-scattering gels that need to be taken into account when calibrating polymer gel dosimeters.

Radiological characterization and water equivalency of genipin gel for x-ray and electron beam dosimetry.

The genipin radiochromic gel offers enormous potential as a three-dimensional dosimeter in advanced radiotherapy techniques. We have used several methods (including Monte Carlo simulation), to investigate the water equivalency of genipin gel by characterizing its radiological properties, including mass and electron densities, photon interaction cross sections, mass energy absorption coefficient, effective atomic number, collisional, radiative and total mass stopping powers and electron mass scattering power. Depth doses were also calculated for clinical kilovoltage and megavoltage x-ray beams as well as megavoltage electron beams. The mass density, electron density and effective atomic number of genipin were found to differ from water by less than 2%. For energies below 150 keV, photoelectric absorption cross sections are more than 3% higher than water due to the strong dependence on atomic number. Compton scattering and pair production interaction cross sections for genipin gel differ from water by less than 1%. The mass energy absorption coefficient is approximately 3% higher than water for energies <60 keV due to the dominance of photoelectric absorption in this energy range. The electron mass stopping power and mass scattering power differ from water by approximately 0.3%. X-ray depth dose curves for genipin gel agree to within 1% with those for water. Our results demonstrate that genipin gel can be considered water equivalent for kilovoltage and megavoltage x-ray beam dosimetry. For megavoltage electron beam dosimetry, however, our results suggest that a correction factor may be needed to convert measured dose in genipin gel to that of water, since differences in some radiological properties of up to 3% compared to water are observed. Our results indicate that genipin gel exhibits greater water equivalency than polymer gels and PRESAGE formulations.

Predicted ionisation in mitochondria and observed acute changes in the mitochondrial transcriptome after gamma irradiation: a Monte Carlo simulation and quantitative PCR study.

It is a widely accepted that the cell nucleus is the primary site of radiation damage while extra-nuclear radiation effects are not yet systematically included into models of radiation damage. We performed Monte Carlo simulations assuming a spherical cell (diameter 11.5 μm) modelled after JURKAT cells with the inclusion of realistic elemental composition data based on published literature. The cell model consists of cytoplasm (density 1g/cm(3)), nucleus (diameter 8.5 μm; 40% of cell volume) as well as cylindrical mitochondria (diameter 1 μm; volume 0.5 μm(3)) of three different densities (1, 2 and 10 g/cm(3)) and total mitochondrial volume relative to the cell volume (10, 20, 30%). Our simulation predicts that if mitochondria take up more than 20% of a cells volume, ionisation events will be the preferentially located in mitochondria rather than in the cell nucleus. Using quantitative polymerase chain reaction, we substantiate in JURKAT cells that human mitochondria respond to gamma radiation with early (within 30 min) differential changes in the expression levels of 18 mitochondrially encoded genes, whereby the number of regulated genes varies in a dose-dependent but non-linear pattern (10 Gy: 1 gene; 50 Gy: 5 genes; 100 Gy: 12 genes). The simulation data as well as the experimental observations suggest that current models of acute radiation effects, which largely focus on nuclear effects, might benefit from more systematic considerations of the early mitochondrial responses and how these may subsequently determine cell response to ionising radiation.

The characterisation of a genipin-gelatin gel dosimeter

Genipin cross links gelatin to slowly form a blue colour that bleaches upon irradiation. Spectrophotometric measurements of the absorbance change following irradiation to doses up to 100 Gy gives a linear dose response for certain concentrations of the gel ingredients; genipin, gelatin and sulphuric acid. Dose sensitivity increases with increasing concentrations of sulphuric acid and genipin and is also strongly dependent on the time allowed for the genipin-gelatin cross linking reaction (referred to here as blending) to take place. The optimum formulation of this gel was found for genipin concentration between 0.3 – 0.5 mM and blending time of at least 4 h.

Apparent polyploidization after gamma irradiation: pitfalls in the use of quantitative polymerase chain reaction (qPCR) for the estimation of mitochondrial and nuclear DNA gene copy numbers.

Quantitative polymerase chain reaction (qPCR) has been widely used to quantify changes in gene copy numbers after radiation exposure. Here, we show that gamma irradiation ranging from 10 to 100 Gy of cells and cell-free DNA samples significantly affects the measured qPCR yield, due to radiation-induced fragmentation of the DNA template and, therefore, introduces errors into the estimation of gene copy numbers. The radiation-induced DNA fragmentation and, thus, measured qPCR yield varies with temperature not only in living cells, but also in isolated DNA irradiated under cell-free conditions. In summary, the variability in measured qPCR yield from irradiated samples introduces a significant error into the estimation of both mitochondrial and nuclear gene copy numbers and may give spurious evidence for polyploidization.

Photometric calibration of a radiochromic gel dosimeter

Measurement traceability of dosimetry systems to standards of measurement underpins reliable radiation treatments. A method to determine the product of the molar linear absorption coefficient and the radiation chemical yield is presented, which provides a means of photometric calibration of chemical dosimetry systems in order that the absorbed dose be determined directly from photometric measurements.

Verification of a non-diffusing gel dosimeter

An evaluation of the diffusion coefficient of a genipin-gelatin gel dosimeter was carried out by fitting an inverse square root function to image profile data. A comparison was made with a Fricke-gelatin-xylenol orange (FGX) gel dosimeter, in which the ions are known to diffuse. The diffusion coefficient for this FGX gel, consisting of 0.5 mM ferrous ammonium sulphate, 50 mM sulphuric acid, 0.15 mM xylenol orange and 3 % by weight gelatin was 0.70 ± 0.05 mm2 h−1 at 5 Gy. The genipin-gelatin gel consisted of 50 μM genipin, 4 % by weight gelatin and 100 mM sulphuric acid. The fitted parameter that is proportional to the diffusion coefficient did not significantly change over time, demonstrating that this genipin-gelatin gel is a non-diffusing dosimeter.