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Biomedical subjects

C Baldock

Publications and source records attributed to C Baldock.

At least 19 recordsLinked to original sources
PubMed2006

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.

Amino Acid Sequence↗
PubMed2006

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.

Activin Receptors, Type I↗
PubMed2005

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%.

Calibration↗
PubMed2005

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.

Calibration↗
PubMed2005

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.

Acrylamide↗
PubMed2005

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.

Australia↗
PubMed2005

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.

Dose-Response Relationship, Radiation↗
PubMed2005

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.

Gelatin↗
PubMed2005

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.

Ascorbic Acid↗
PubMed2005

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.

Ascorbic Acid↗
PubMed2004

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.

Acrylic Resins↗
PubMed2004

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.

Acrylamides↗
PubMed2003

The effect of water molecular self-diffusion on quantitative high-resolution MRI polymer gel dosimetry.

In polymer gel dosimetry, magnetic resonance imaging (MRI) is used to determine the spin-spin relaxation rate (R2) which in turn can be correlated with absorbed dose to provide a map of the spatial distribution of the absorbed dose in the irradiated dosimeter. High accuracy, precision and reproducibility of these dose maps are essential. Moreover, for dose verification around brachytherapy sources used for intravascular brachytherapy, a high spatial resolution is required (typically 0.01-0.1 mm). To achieve these microscopic resolutions, strong imaging gradients are applied. The Brownian motion of water molecules in the presence of these strong magnetic field gradients causes an attenuation of the MR signal. When using a multiple spin-echo sequence, this may result in a significant deviation in the measured R2. The diffusion-related change in R2 at high resolutions was investigated experimentally and correlated with predictions that were obtained numerically and algebraically. Diffusion weighting is determined by the self-diffusion coefficient D, and imaging parameters, quantified by the b-factor. The b-factor was calculated for a multiple spin-echo sequence for different gradient strengths and gradient pulse durations. The variations in R2 that were observed when changing the matrix size and slice thickness are explained. It is shown that a linear correlation between the matrix size and the variation in R2 is based on the diffusion weighting caused by the read-out gradients and slice selective gradients. In conclusion, the essence of taking into account molecular self-diffusion to quantify variations in the measured dose-R2 response when using high-resolution MRI in polymer gel dosimetry is emphasized.

Algorithms↗
PubMed2003

Effect of saccharide additives on response of ferrous-agarose-xylenol orange radiotherapy gel dosimeters.

Glucose, sucrose, starch, and locust bean gum have been used as additives to the ferrous-agarose-xylenol orange (FAX) gel dosimeter. The saccharide enhanced dosimeters were found to have a higher dose sensitivity over a standard FAX gel as measured by both optical density change and magnetic resonance imaging (MRI). With optical density measurement, OD-dose sensitivity increases were up to 55% for glucose, 122% for sucrose and 43% for starch, while locust bean gum did not give a consistent response. With MRI, R1-dose sensitivity increases were up to 178% with sucrose addition. The FAX gel with sucrose was studied in greatest detail. The OD-dose sensitivity dependence on cooling rate was reduced for the sucrose FAX gel over the standard FAX gel, which has significant implications for uniform dose sensitivity in large gel phantoms. The thermal oxidation rate in the sucrose FAX gel was up to 2.3 times higher than in the standard gel. The OD-dose sensitivity of oxygenated sucrose FAX gels was 4.3 times greater than standard FAX gels, while continued enhancement in OD-dose sensitivity with increased sucrose concentrations beyond 2.0 g/l was found only for the oxygenated sucrose FAX gels. Both the molar absorption coefficient of the ferric ion-xylenol orange complex at 543 nm and gel pH were not affected by the presence of sucrose, with the implication that the higher OD-dose sensitivity of gels with saccharides is due to increased chain reaction production of ferric ions.

Carbohydrates↗
PubMed2003

Radiation dose distribution in polymer gels by Raman spectroscopy.

The Raman spectroscopy of polymer gel dosimeters has been investigated with a view to developing a novel dosimetry technique that is capable of determining radiation dose within a micrometer of spatial resolution. The polymer gel dosimeter, known as the PAG dosimeter, is typically made up of acrylamide, N,N'-methylene-bis--acrylamide, gelatin, and water. A polyacrylamide network within the gelatin matrix forms in response to an absorbed dose. The loss of monomers may be monitored by corresponding changes to the Raman spectrum. Principal component analysis offers a simple method of quantifying the absorbed radiation dose from the Raman spectrum of the polymer gel. The background luminescence in the spectrum increased significantly with dose and is shown to originate in the glass of the sample vial. The competing effects of elastic scatter, which increases with dose due to the formation of polymer, and sample absorption were quantified and found to introduce errors of up to 5% under certain conditions. Raman spectra as a function of distance from the air-surface interface have been measured for samples that were subjected to doses delivered by a clinical linear accelerator. The depth dose profile thus obtained compared favorably with "gold standard" ion-chamber measurements.

Acrylic Resins↗