Browsing by Author "Kuncic, Z"

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    Dose enhancement effects to the nucleus and mitochondria from gold nanoparticles in the cytosol
    (IOP Publishing, 2016-07-20) McNamara, AL; Kam, WWY; Scales, N; McMahon, SJ; Bennett, JW; Byrne, HL; Schuemann, J; Paganetti, H; Banati, RB; Kuncic, Z
    Gold nanoparticles (GNPs) have shown potential as dose enhancers for radiation therapy. Since damage to the genome affects the viability of a cell, it is generally assumed that GNPs have to localise within the cell nucleus. In practice, however, GNPs tend to localise in the cytoplasm yet still appear to have a dose enhancing effect on the cell. Whether this effect can be attributed to stress-induced biological mechanisms or to physical damage to extra-nuclear cellular targets is still unclear. There is however growing evidence to suggest that the cellular response to radiation can also be influenced by indirect processes induced when the nucleus is not directly targeted by radiation. The mitochondrion in particular may be an effective extra-nuclear radiation target given its many important functional roles in the cell. To more accurately predict the physical effect of radiation within different cell organelles, we measured the full chemical composition of a whole human lymphocytic JURKAT cell as well as two separate organelles; the cell nucleus and the mitochondrion. The experimental measurements found that all three biological materials had similar ionisation energies  ~70 eV, substantially lower than that of liquid water  ~78 eV. Monte Carlo simulations for 10–50 keV incident photons showed higher energy deposition and ionisation numbers in the cell and organelle materials compared to liquid water. Adding a 1% mass fraction of gold to each material increased the energy deposition by a factor of  ~1.8 when averaged over all incident photon energies. Simulations of a realistic compartmentalised cell show that the presence of gold in the cytosol increases the energy deposition in the mitochondrial volume more than within the nuclear volume. We find this is due to sub-micron delocalisation of energy by photoelectrons, making the mitochondria a potentially viable indirect radiation target for GNPs that localise to the cytosol. © 2016 Institute of Physics and Engineering in Medicine
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    Positron emission tomography coincidence detection with photon polarization correlation
    (SPIE, 2013-02-09) McNamara, AL; Wu, KW; Boardman, DA; Reinhard, MI; Kuncic, Z
    Two-photon annihilation quanta are emitted in a pure quantum state and when detected in coincidence, the photon pairs possess orthogonal polarizations. We propose that this polarization correlation can be exploited in Positron Emission Tomography (PET), which relies crucially on accurate coincidence detection of photon pairs. In this proof of concept study, we investigate how photon polarization information can be exploited in PET imaging by developing a method to discern true coincidences using the polarization correlation of annihilation pairs. We demonstrate that the unique identification of true photon pairs with their polarization correlation can dramatically enhance overall PET image quality, especially for high emission rates, when conventional, energy- based coincidence detection methods become increasingly unreliable. Our results suggest that polarization-based coincidence detection offers new prospects for in vivo molecular imaging with next-generation PET systems. © 2013 Society of Photo-Optical Instrumentation Engineers (SPIE).
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    Predicted ionisation in mitochondria and observed acute changes in the mitochondrial transcriptome after gamma irradiation: a Monte Carlo simulation and quantitative PCR study
    (Elsevier B.V., 2013-11-01) Kam, WWY; McNamara, AL; Lake, V; Banos, C; Davies, JB; Kuncic, Z; Banati, RB
    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 1 g/cm3), nucleus (diameter 8.5 μm; 40% of cell volume) as well as cylindrical mitochondria (diameter 1 μm; volume 0.5 μm3) of three different densities (1, 2 and 10 g/cm3) 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 cell's 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. © 2013 Elsevier B.V.
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    Radiological characterization and water equivalency of genipin gel for x-ray and electron beam dosimetry
    (IOP Publishing, 2011-08-07) Gorjiara, T; Hill, R; Kuncic, Z; Bosi, SG; Davies, JB; Baldock, C
    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 fromwater by less than 1%. The mass energy absorption coefficient is approximately 3%higher thanwater for energies<60 keVdue 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 ofwater, 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. © 2011 IOP Publishing LTD.