An Australian secondary standard dosimetry laboratory participation in IAEA postal dose audits.

For over 30 years, the International Atomic Energy Agency (IAEA) and the World Health Organization (WHO) have jointly monitored activities of secondary standard dosimetry laboratories (SSDLs) through postal dose audits with the aim of achieving consistency in dosimetry throughout the world. The Australian Nuclear Science and Technology Organisation (ANSTO) maintains an SSDL and is a member of the IAEA/WHO SSDL Network. Postal dose audit results at this Australian SSDL from 2001 to 2011 demonstrate the consistency of absorbed dose to water measurements, underpinned by the primary standard maintained at the Australian Radiation Protection and Nuclear Safety Agency (ARPANSA).

Polymer gel dosimetry.

Polymer gel dosimeters are fabricated from radiation sensitive chemicals which, upon irradiation, polymerize as a function of the absorbed radiation dose. These gel dosimeters, with the capacity to uniquely record the radiation dose distribution in three-dimensions (3D), have specific advantages when compared to one-dimensional dosimeters, such as ion chambers, and two-dimensional dosimeters, such as film. These advantages are particularly significant in dosimetry situations where steep dose gradients exist such as in intensity-modulated radiation therapy (IMRT) and stereotactic radiosurgery. Polymer gel dosimeters also have specific advantages for brachytherapy dosimetry. Potential dosimetry applications include those for low-energy x-rays, high-linear energy transfer (LET) and proton therapy, radionuclide and boron capture neutron therapy dosimetries. These 3D dosimeters are radiologically soft-tissue equivalent with properties that may be modified depending on the application. The 3D radiation dose distribution in polymer gel dosimeters may be imaged using magnetic resonance imaging (MRI), optical-computerized tomography (optical-CT), x-ray CT or ultrasound. The fundamental science underpinning polymer gel dosimetry is reviewed along with the various evaluation techniques. Clinical dosimetry applications of polymer gel dosimetry are also presented.

Software tool for portal dosimetry research.

This paper describes a software tool developed for research into the use of an electronic portal imaging device (EPID) to verify dose for intensity modulated radiation therapy (IMRT) beams. A portal dose image prediction (PDIP) model that predicts the EPID response to IMRT beams has been implemented into a commercially available treatment planning system (TPS). The software tool described in this work was developed to modify the TPS PDIP model by incorporating correction factors into the predicted EPID image to account for the difference in EPID response to open beam radiation and multileaf collimator (MLC) transmitted radiation. The processes performed by the software tool include; i) read the MLC file and the PDIP from the TPS, ii) calculate the fraction of beam-on time that each point in the IMRT beam is shielded by MLC leaves, iii) interpolate correction factors from look-up tables, iv) create a corrected PDIP image from the product of the original PDIP and the correction factors and write the corrected image to file, v) display, analyse, and export various image datasets. The software tool was developed using the Microsoft Visual Studio.NET framework with the C# compiler. The operation of the software tool was validated. This software provided useful tools for EPID dosimetry research, and it is being utilised and further developed in ongoing EPID dosimetry and IMRT dosimetry projects.

Radiological properties of the PRESAGE and PAGAT polymer dosimeters.

The radiological properties of the PRESAGE and PAGAT polymer dosimeters have been investigated and their water equivalence determined for use in radiotherapy dosimetry. The radiological water equivalence of each of the polymer dosimeters was determined by comparing the photon and electron interaction cross-sections over the 10 keV-20 MeV energy range and by Monte Carlo modelling the depth dose from a linear accelerator using the BEAMnrc software package. PRESAGE was found to have an effective Z-value and mass density (kgm(-3)) approximately 17% and 10% higher than water, respectively. A maximum difference of 85% was discovered in the photoelectric interaction probability curve of PRESAGE when compared to water over the energy range 10-100 keV, partially due to the Z(3) dependence of the photoelectric effect. The mass radiative stopping power ratios and mass scattering power ratios were both found to have less than 9% difference from water. The depth dose for PRESAGE from a 6MV photon beam had an absolute percentage difference to water of less than 2% and a relative percentage difference of less than 8%. The mass density of PAGAT was found to be 2.6% higher than water due to its high gelatine and monomer concentration. The cross-sectional attenuation and absorption coefficient ratios were found to be within 5% for energies between 10 and 100 keV and within 1% for energies between 100 keV and 20 MeV. The mass collisional stopping power, mass radiative stopping power and mass scattering power ratios were all less than 1% over the energy range studied. The depth dose had an absolute percentage difference to water of less than 1% and a relative percentage difference of less than 2.5%. These results indicate that the PAGAT polymer gel formulation is more radiological water equivalent than the PRESAGE formulation. However, the PRESAGE dosimeter offers some advantages in terms of ease of use and its lack of water equivalence may be overcome with dosimetric correction factors.

Polymer gel dosimetry on a multislice computed tomography scanner: effect of changing parameters on CTDI.

Polymer gel dosimetry undertaken on a multislice CT scanner provides an alternative method to conventional dosimetry measurements. Polymer gel dosimeters were used to measure CT radiation doses and compared to TLD and ionization chamber measurements in different diameter phantoms. CTDI was investigated for each of these phantoms for a range of mAs (100-400 mAs), tube voltage (100-135 kV) and nominal slice width (2-32 mm). Linear fits of the CTDI values for mAs show for the smallest phantom diameter an increase in CTDI of 60% for both TLD and polymer gel dosimeters. A similar increase in CTDI of 50% at 100 kVp and 100% for 135 kVp was also noted. It was also shown that slice width variation measured with either polymer gel or TLD was greatest with the smallest slice widths. In summary, it was found that polymer gels can be used as an alternative dosimeter to TLD for the determination of SWDP and subsequent CTDI calculations.

The energy response of a T.P.A. Mk-II ionization chamber using GEANT4 Monte Carlo simulation.

The low energy model of the GEANT4 Monte Carlo toolkit was used to simulate the energy response of a T.P.A. Mk-II ionization chamber under a variety of different conditions. The sample position resulting in the maximum response along the axial direction of the chamber was obtained. The parameters of the simulation were chosen to account for the maximum effect of the particle backscattering and the setting of most suitable values for the production thresholds and the energy cuts in the GEANT4 Monte Carlo code. The chamber response for different compositions of detector elements was also studied. The simulated radioactive source was a glass ampoule containing 3.6 ml of the radionuclide in an aqueous solution. The energy response of the chamber at the maximum response was obtained for simulations for (60)Co, (22)Na and (59)Fe nuclides. Verification of the simulated response was obtained using experimental measurements with radioactive sources. The simulated results were in good agreement with the experimentally measured data to within 0.04-2.0%. In the energy range below 200 keV the response curve was complex due to the increase of photoelectric cross sections of the chamber materials. Effects due to backscattering occur at boundaries between chamber elements and also become significant at sites of lead shielding at photon energies above 700 keV. The chamber response for different compositions of detector elements was also studied. The response of the chamber depended highly on the energies of emitting particles, source position and materials used in electrodes and thimble wall.

Intercomparison of ionisation chamber measurements from (125)I seeds.

The reference air kerma rates of a set of individual (125)I seeds were calculated from current measurements of a calibrated re-entrant ionisation chamber. Single seeds were distributed to seven Australian brachytherapy centres for the same measurement with the user's instrumentation. Results are expressed as the ratio of the reference air kerma rate measured by the Australian Nuclear Science & Technology Organisation (ANSTO) to the reference air kerma rate measured at the centre. The intercomparison ratios of all participants were within +/-5% of unity.

Domains 17-27 of tropoelastin contain key regions of contact for coacervation and contain an unusual turn-containing crosslinking domain.

The central region of tropoelastin including domains 19-25 of human tropoelastin forms a hot-spot for contacts during the inter-molecular association of tropoelastin by coacervation [Wise, S.G., Mithieux, S.M., Raftery, M.J. and Weiss, A.S (2005). "Specificity in the coacervation of tropoelastin: solvent exposed lysines." Journal of Structural Biology 149: 273-81.]. We explored the physical properties of this central region using a sub-fragment bordered by domains 17-27 of human tropoelastin (SHEL 17-27) and identified the intra- and inter-molecular contacts it forms during coacervation. A homobifunctional amine reactive crosslinker (with a maximum reach of 11 A, corresponding to approximately 7 residues in an extended polypeptide chain) was used to capture these contacts and crosslinked regions were identified after protease cleavage and mass spectrometry (MS) with MS/MS verification. An intermolecular crosslink formed between the lysines at positions 353 of each strand of tropoelastin at the lowest of crosslinker concentrations and was observed in all samples tested, suggesting that this residue forms an important initial contact during coacervation. At higher crosslinker concentrations, residues K425 and K437 showed the highest levels of involvement in crosslinks. An intramolecular crosslink between these K425 and K437, separated by 11 residues, indicated that a structural bend must serve to bring these residues into close proximity. These studies were complemented by small angle X-ray scattering studies that confirmed a bend in this important subfragment of the tropoelastin molecule.

The molecular genetics of Marfan syndrome and related disorders.

Marfan syndrome (MFS), a relatively common autosomal dominant hereditary disorder of connective tissue with prominent manifestations in the skeletal, ocular, and cardiovascular systems, is caused by mutations in the gene for fibrillin-1 (FBN1). The leading cause of premature death in untreated individuals with MFS is acute aortic dissection, which often follows a period of progressive dilatation of the ascending aorta. Recent research on the molecular physiology of fibrillin and the pathophysiology of MFS and related disorders has changed our understanding of this disorder by demonstrating changes in growth factor signalling and in matrix-cell interactions. The purpose of this review is to provide a comprehensive overview of recent advances in the molecular biology of fibrillin and fibrillin-rich microfibrils. Mutations in FBN1 and other genes found in MFS and related disorders will be discussed, and novel concepts concerning the complex and multiple mechanisms of the pathogenesis of MFS will be explained.

Calibration of the Capintec CRC-712M dose calibrator for (18)F.

Primary standardisation was performed on a solution of (18)F using the 4pibeta-gamma coincidence counting efficiency-tracing extrapolation method with (60)Co used as a tracer nuclide. The result was used to calibrate the ANSTO secondary standard ionisation chamber which is used to disseminate Australian activity standards for gamma emitters. Using the secondary activity standard for (18)F, the Capintec CRC-712M dose calibrator at the Australian National Medical Cyclotron (NMC) Positron Emission Tomography (PET) Quality Control (QC) Section was calibrated. The dial setting number recommended by the manufacturer for the measurement of the activity of (18)F is 439. In this work, the dial setting numbers for the activity measurement of the solution of (18)F in Wheaton vials were experimentally determined to be 443+/-12, 446+/-12, 459+/-11, 473+/-15 for 0.1, 1, 4.5 and 9ml solution volumes, respectively. The uncertainties given above are expanded uncertainties (k=2) giving an estimated level of confidence of 95%. The activities determined using the manufacturer recommended setting number 439 are 0.8%, 1.4%, 4.0% and 6.5% higher than the standardised activities, respectively. It is recommended that a single dial setting number of 459 determined for 4.5ml is used for 0.1-9ml solution in Wheaton vials in order to simplify the operation procedure. With this setting the expended uncertainty (k=2) in the activity readout from the Capintec dose calibrator would be less than 6.2%.

A dosimetric evaluation of water equivalent phantoms for kilovoltage x-ray beams.

Solid phantoms are widely used in radiation therapy for both relative and reference dosimetry. Two water equivalent phantoms, RMI-457 Solid Water and Plastic Water, were evaluated for use in kilovoltage x-ray dosimetry in the energy range from 75 to 300 kVp. Relative and reference dosimetry measurements were performed in the solid phantoms and compared with water. The results indicate that RMI-457 Solid Water could be used for output factor determination for all energies tested and the measurement of percentage depth doses for the 300 kVp x-ray beam, with data agreeing to within 1%, compared to the same measurements in water. For the same criteria, Plastic Water could only be used for output factor determination of the 300 kVp x-ray beam. The superior agreement of the calculated mass-energy absorption coefficients for Solid Water and water, as compared to Plastic Water and water was consistent with the experimental results. Reference dosimetry is not recommended with the solid phantoms for the energies studied due to the lack of published correction factors. It is recommended that any solid phantom be tested by comparison with water in the same manner before being used for the dosimetry of kilovoltage x-ray beams.

Investigation of the PAGAT polymer gel dosimeter using magnetic resonance imaging.

Investigation of the normoxic PAGAT polymer gel dosimeter has been undertaken. The concentrations of the chemical components of the gel were varied and its response to ionizing radiation evaluated. Using MRI, the formulation to give the maximum change in the transverse relaxation rate R2 was determined to be 4.5% N, N'-methylene-bis-acrylamide (bis), 4.5% acrylamide (AA), 5% gelatine, 5 mM tetrakis (hydroxymethyl) phosphonium chloride (THPC), 0.01 mM hydroquinone (HQ) and 86% H2O. The optimal post-manufacture irradiation and post-irradiation imaging times were both determined to be 12 h. The R2-dose response was linear up to 7 Gy with R2-dose sensitivities of (0.183 +/- 0.005) s(-1) Gy(-1), (0.182 +/- 0.005) s(-1) Gy(-1) and (0.192 +/- 0.005) s(-1) Gy(-1) when imaged at 12 h, 7 days and 24 days post-irradiation, respectively. The R2-dose sensitivities were within the range of previously published values for the hypoxic PAG formulations. For the imaging parameters used in this study the optimum dose resolution was achieved for low doses. The normalized R2 edge response showed a high degree of spatial stability over a 24 day period. This study has shown that the normoxic PAGAT polymer gel has the properties of a dosimetric tool, which can be used in clinical radiotherapy. The PAGAT polymer gel has been shown to have similar qualities to the PAG polymer gel, while offering the significant advantage of simplification of the manufacturing procedure.

Investigation of vacuum pumping on the dose response of the MAGAS normoxic polymer gel dosimeter.

The effect of vacuum pumping on the dose response of the MAGAS polymer gel dosimeter has been investigated. A delay of several days post-manufacture before irradiation was previously necessary due to the slow oxygen scavenging of ascorbic acid. The MAGAS polymer gel dosimeter was vacuum pumped before gelation to remove dissolved oxygen. The MAGAS polymer gel dosimeter was poured into glass screw-top vials, which were irradiated at various times, post-manufacture to a range of doses. Magnetic resonance imaging techniques were used to determine the R2-dose response and R2-dose sensitivity of the MAGAS polymer gel. The results were compared with a control batch of MAGAS polymer gel that was not vacuum pumped. It was shown that vacuum pumping on the MAGAS polymer gel solution immediately prior to sealing in glass screw-top vials initially increases the R2-dose response and R2-dose sensitivity of the dosimeter. An increase in the R2-dose response and R2-dose sensitivity was observed with increasing time between manufacture and irradiation. Over the range of post-manufacture irradiation times investigated, the greatest R2-dose response and R2-dose sensitivity occurred at 96 hours.

A study of a normoxic polymer gel dosimeter comprising methacrylic acid, gelatin and tetrakis (hydroxymethyl) phosphonium chloride (MAGAT).

In this study, the response to ionsing radiation of the normoxic polymer gel dosimeter comprising tetrakis (hydroxymethyl) phosphonium chloride (THPC) with methacrylic acid (MAA) and gelatin, named MAGAT, has been investigated. Using magnetic resonance imaging (MRI), the R2-dose response or change in R2 (DeltaR2) is evaluated for different concentrations of the component chemicals: THPC, MAA, gelatin and hydroquinone (HQ). The formulation for which the MAGAT polymer gel dosimeter had a maximum response was determined, and the spatial and temporal stability for this formulation analyzed. It was found that the formulation that provided the greatest change in R2 was 10 mM THPC, 0-0.05 mM HQ, 6-7% gelatin and 4-6% MAA (evaluated one day post-irradiation). MAGAT polymer gel dosimeters comprising 10mM THPC, 0.05 mM HQ, 6-9% MAA and 4-6% gelatin have shown potential for use in radiation therapy dosimetry.

The dose response of normoxic polymer gel dosimeters measured using X-ray CT.

X-ray CT was used to determine the dose response of normoxic polymer gel dosimeters. Normoxic polymer gel dosimeters were manufactured and irradiated up to 150 Gy. Up to 50 CT images were acquired on a Toshiba Aquilion Multislice CT scanner using protocols for 80 kV and 135 kV to determine dose response. HU-dose sensitivity, the linear regression of data for the HU versus dose for the linear part of the curve up to 60 Gy was 0.38+/-0.07 HU Gy(-1) for 135 kV and 0.37+/-0.01 HU Gy(-1) for 80 kV. Dose resolution was found to be < 1.3 Gy for an absorbed dose range up to 70 Gy for 135 kV, similar to that measured previously for polyacrylamide gel (PAG). Although the HU-dose sensitivity was lower than that previously measured for PAG gel dosimeters it had a greater range of absorbed dose indicating that normoxic polymer gel dosimeters have potential in CT gel dosimetry.

Development of activity standard for 90 Y microspheres.

(90)Y microspheres are important therapeutic radiopharmaceuticals used in the treatment of liver cancer through a process known as selective internal radiation therapy. SIR-spheres is a radiopharmaceutical product that is comprised of (90)Y microspheres suspended in sterile, pyrogen-free water for injection into patients. It is necessary to establish for the SIR-spheres production the capability of accurately measuring the activity of this product to a traceable national measurement standard. An activity standard for SIR-spheres was developed from a standard for (90)Y solution, employing a highly quantifiable chemical digestion process. Calibration factors for the manufacturer's ionisation chambers were determined for 1 and 5 ml of the SIR-spheres product placed in Wheaton vials, for both 34% and 44% of (90)Y microsphere concentration.

Radiological properties of normoxic polymer gel dosimeters.

The radiological properties of the normoxic polymer gel dosimeters MAGIC, MAGAS, and MAGAT [methacrylic and ascorbic acid in gelatin initiated by copper; methacrylic acid gelatine gel with ascorbic acid; and methacrylic acid gelatine and tetrakis (hydroxymethyl) phosphonium chloride, respectively] have been investigated. The radiological water equivalence was determined by comparing the polymer gel macroscopic photon and electron interaction cross sections over the energy range from 10 keV to 20 MeV and by Monte Carlo modeling of depth doses. Normoxic polymer gel dosimeters have a high gelatine and monomer concentration and therefore mass density (kg m(-3)) up to 3.8% higher than water. This results in differences between the cross-section ratios of the normoxic polymer gels and water of up to 3% for the attenuation, energy absorption, and collision stopping power coefficient ratios through the Compton dominant energy range. The mass cross-section ratios were within 2% of water except for the mass attenuation and energy absorption coefficients ratios, which showed differences with water of up to 6% for energies less than 100 keV. Monte Carlo modeling was undertaken for the polymer gel dosimeters to model the electron and photon transport resulting from a 6 MV photon beam. The absolute percentage differences between gel and water were within 1% and the relative percentage differences were within 3.5%. The results show that the MAGAT gel formulation is the most radiological water equivalent of the normoxic polymer gel dosimeters investigated due to its lower mass density measurement compared with MAGAS and MAGIC gels.

Experimental study of attenuation properties of normoxic polymer gel dosimeters.

The change in linear attenuation coefficient with absorbed dose has been investigated for aqueous polyacrylamide, gelatine and tetrakis (PAGAT) and aqueous methacrylic acid, gelatine and tetrakis (MAGAT) normoxic polymer gel dosimeters using tetrakis (hydroxy methyl) phosphonium chloride as the antioxidant. The measured linear attenuation coefficient increased linearly with absorbed dose up to 15 Gy for PAGAT gels and 10 Gy for MAGAT gels. Computerized tomography (CT) numbers or Hounsfield units (H) were calculated from the linear attenuation coefficients and compared with values obtained using a CT scanner. Both calculated and measured CT numbers followed a similar pattern when fitted with a biexponential curve. The CT numbers obtained from linear attenuation measurements were found to be greater than that obtained with the CT scanner for both PAGAT and MAGAT polymer gels. The H-dose sensitivities of the MAGAT and PAGAT polymer gel dosimeters measured on a CT scanner were calculated to be (0.85 +/- 0.08) H Gy(-1) and (0.31 +/- 0.03) H Gy(-1), respectively. The H-dose sensitivities of the MAGAT and PAGAT polymer gel dosimeters from attenuation measurements were found to be (1.10 +/- 0.66) H Gy(-1) and (0.34 +/- 0.01) H Gy(-1), respectively.

Dose resolution in gel dosimetry: effect of uncertainty in the calibration function.

Dose resolution, DdeltaP, is becoming a common method for characterizing the performance of a gel dosimeter. In this note we examine how the goodness of fit of the calibration function affects DdeltaP and show that its inclusion in the calculation of DdeltaP is essential to avoid overestimating the performance of the gel.

Development and optimization of a 2-hydroxyethylacrylate MRI polymer gel dosimeter.

In this study, radiation induced changes in a polymer gel dosimeter manufactured using 2-hydroxyethylacrylate (HEA) and N,N'-methylene-bisacrylamide (BIS) were investigated using magnetic resonance imaging (MRI) and FT-Raman spectroscopy. The variation in magnetic resonance relaxation time (T2) with absorbed dose was modelled assuming fast exchange of magnetization. Overall good agreement between the model and experimental data was obtained. However, comparison with FT-Raman data suggests that not all the protons attached to the polymer contribute to the relaxation process. Furthermore, for certain compositions improved agreement with experimental data was achieved when a lower fraction of polymer protons available for exchange with water was assumed in the low dose region. This indicates that the T2 value is influenced by the composition and topology of the formed polymer, which may vary with absorbed dose. The concept of percentage dose resolution (Dp delta, %) was introduced to enable optimization of gel compositions for use in relative dosimetry applications. This concept was applied to demonstrate the effects of varying the gelatine concentration, the total fraction of monomer/crosslinker (%T) and the relative fraction of crosslinker (%C) on gel performance in HEA gels as well as compare the performance of HEA and a standard polyacrylamide gel (PAG). The percentage dose resolution was improved for all HEA gels compared to the PAG dosimeter containing 3% acrylamide and 3% BIS. Increasing the total concentration of monomer was shown to have the largest single effect. In the range of doses of interest for clinical radiation therapy, Dp delta, % for the optimal HEA gel (4% HEA, 4% BIS) was lower than 2.3%, compared to 3.8% for the PAG dosimeter.