Absolute dosimetry on a dynamically scanned sample for synchrotron radiotherapy using graphite calorimetry and ionization chambers.

The absolute dose delivered to a dynamically scanned sample in the Imaging and Medical Beamline (IMBL) on the Australian Synchrotron was measured with a graphite calorimeter anticipated to be established as a primary standard for synchrotron dosimetry. The calorimetry was compared to measurements using a free-air chamber (FAC), a PTW 31 014 Pinpoint ionization chamber, and a PTW 34 001 Roos ionization chamber. The IMBL beam height is limited to approximately 2 mm. To produce clinically useful beams of a few centimetres the beam must be scanned in the vertical direction. In practice it is the patient/detector that is scanned and the scanning velocity defines the dose that is delivered. The calorimeter, FAC, and Roos chamber measure the dose area product which is then converted to central axis dose with the scanned beam area derived from Monte Carlo (MC) simulations and film measurements. The Pinpoint chamber measures the central axis dose directly and does not require beam area measurements. The calorimeter and FAC measure dose from first principles. The calorimetry requires conversion of the measured absorbed dose to graphite to absorbed dose to water using MC calculations with the EGSnrc code. Air kerma measurements from the free air chamber were converted to absorbed dose to water using the AAPM TG-61 protocol. The two ionization chambers are secondary standards requiring calibration with kilovoltage x-ray tubes. The Roos and Pinpoint chambers were calibrated against the Australian primary standard for air kerma at the Australian Radiation Protection and Nuclear Safety Agency (ARPANSA). Agreement of order 2% or better was obtained between the calorimetry and ionization chambers. The FAC measured a dose 3-5% higher than the calorimetry, within the stated uncertainties.

Structure-activity relationships in a peptidic alpha7 nicotinic acetylcholine receptor antagonist.

alpha-Conotoxins are small disulfide-constrained peptide toxins which act as antagonists at specific subtypes of nicotinic acetylcholine receptors (nACh receptors). In this study, we analyzed the structures and activities of three mutants of alpha-conotoxin ImI, a 12 amino acid peptide active at alpha7 nACh receptors, in order to gain insight into the primary and tertiary structural requirements of neuronal alpha-conotoxin specificity. NMR solution structures were determined for mutants R11E, R7L, and D5N, resulting in representative ensembles of 20 conformers with average pairwise RMSD values of 0.46, 0.52, and 0.62 A from their mean structures, respectively, for the backbone atoms N, C(alpha), and C' of residues 2-11. The R11E mutant was found to have activity near that of wild-type ImI, while R7L and D5N demonstrated activities reduced by at least two orders of magnitude. Comparison of the structures reveals a common two-loop architecture, with variations observed in backbone and side-chain dihedral angles as well as surface electrostatic potentials upon mutation. Correlation of these structures and activities with those from previously published studies emphasizes that existing hypotheses regarding the molecular determinants of alpha-conotoxin specificity are not adequate for explaining peptide activity, and suggests that more subtle features, visualized here at the atomic level, are important for receptor binding. These data, in conjunction with reported characterizations of the acetylcholine binding site, support a model of toxin activity in which a single solvent-accessible toxin side-chain anchors the complex, with supporting weak interactions determining both the efficacy and the subtype specificity of the inhibitory activity.

High spatial resolution dosimetric response maps for radiotherapy ionization chambers measured using kilovoltage synchrotron radiation.

Small circular beams of synchrotron radiation (0.1 mm and 0.4 mm in diameter) were used to irradiate ionization chambers of the types commonly used in radiotherapy. By scanning the chamber through the beam and measuring the ionization current, a spatial map of the dosimetric response of the chamber was recorded. The technique is able to distinguish contributions to the large-field ionization current from the chamber walls, central electrode and chamber stem. Scans were recorded for the NE 2571 Farmer chamber, the PTW 30013, IBA FC65-G Farmer-type chambers, the NE 2611A and IBA CC13 thimble chambers, the PTW 31006 and 31014 pinpoint chambers, the PTW Roos and Advanced Markus plane-parallel chambers, and the PTW 23342 thin-window soft x-ray chamber. In all cases, large contributions to the response arise from areas where the incident beam grazes the cavity surfaces. Quantitative as well as qualitative information about the relative chamber response was extracted from the maps, including the relative contribution of the central electrode. Line scans using monochromatic beams show the effect of the photon energy on the chamber response. For Farmer-type chambers, a simple Monte Carlo model was in good agreement with the measured response.

Comparison of the NMIJ and the ARPANSA standards for absorbed dose to water in high-energy photon beams.

The authors report the results of an indirect comparison of the standards of absorbed dose to water in high-energy photon beams from a clinical linac and (60)Co radiation beam performed between the National Metrology Institute of Japan (NMIJ) and the Australian Radiation Protection and Nuclear Safety Agency (ARPANSA). Three ionisation chambers were calibrated by the NMIJ in April and June 2013 and by the ARPANSA in May 2013. The average ratios of the calibration coefficients for the three ionisation chambers obtained by the NMIJ to those obtained by the ARPANSA were 0.9994, 1.0040 and 1.0045 for 6-, 10- and 15-MV (18 MV at the ARPANSA) high-energy photon beams, respectively. The relative standard uncertainty of the value was 7.2 × 10(-3). The ratio for (60)Co radiation was 0.9986(66), which is consistent with the results published in the key comparison of BIPM.RI(I)-K4.

Direct megavoltage photon calibration service in Australia.

The Australian Radiation Protection and Nuclear Safety Agency (ARPANSA) maintains the Australian primary standard of absorbed dose. Until recently, the standard was used to calibrate ionisation chambers only in (60)Co gamma rays. These chambers are then used by radiotherapy clinics to determine linac output, using a correction factor (k Q) to take into account the different spectra of (60)Co and the linac. Over the period 2010-2013, ARPANSA adapted the primary standard to work in megavoltage linac beams, and has developed a calibration service at three photon beams (6, 10 and 18 MV) from an Elekta Synergy linac. We describe the details of the new calibration service, the method validation and the use of the new calibration factors with the International Atomic Energy Agency's TRS-398 dosimetry Code of Practice. The expected changes in absorbed dose measurements in the clinic when shifting from (60)Co to the direct calibration are determined. For a Farmer chamber (model 2571), the measured chamber calibration coefficient is expected to be reduced by 0.4, 1.0 and 1.1 % respectively for these three beams when compared to the factor derived from (60)Co. These results are in overall agreement with international absorbed dose standards and calculations by Muir and Rogers in 2010 of k Q factors using Monte Carlo techniques. The reasons for and against moving to the new service are discussed in the light of the requirements of clinical dosimetry.

Absolute x-ray dosimetry on a synchrotron medical beam line with a graphite calorimeter.

PURPOSE: The absolute dose rate of the Imaging and Medical Beamline (IMBL) on the Australian Synchrotron was measured with a graphite calorimeter. The calorimetry results were compared to measurements from the existing free-air chamber, to provide a robust determination of the absolute dose in the synchrotron beam and provide confidence in the first implementation of a graphite calorimeter on a synchrotron medical beam line. METHODS: The graphite calorimeter has a core which rises in temperature when irradiated by the beam. A collimated x-ray beam from the synchrotron with well-defined edges was used to partially irradiate the core. Two filtration sets were used, one corresponding to an average beam energy of about 80 keV, with dose rate about 50 Gy/s, and the second filtration set corresponding to average beam energy of 90 keV, with dose rate about 20 Gy/s. The temperature rise from this beam was measured by a calibrated thermistor embedded in the core which was then converted to absorbed dose to graphite by multiplying the rise in temperature by the specific heat capacity for graphite and the ratio of cross-sectional areas of the core and beam. Conversion of the measured absorbed dose to graphite to absorbed dose to water was achieved using Monte Carlo calculations with the EGSnrc code. The air kerma measurements from the free-air chamber were converted to absorbed dose to water using the AAPM TG-61 protocol. RESULTS: Absolute measurements of the IMBL dose rate were made using the graphite calorimeter and compared to measurements with the free-air chamber. The measurements were at three different depths in graphite and two different filtrations. The calorimetry measurements at depths in graphite show agreement within 1% with free-air chamber measurements, when converted to absorbed dose to water. The calorimetry at the surface and free-air chamber results show agreement of order 3% when converted to absorbed dose to water. The combined standard uncertainty is 3.9%. CONCLUSIONS: The good agreement of the graphite calorimeter and free-air chamber results indicates that both devices are performing as expected. Further investigations at higher dose rates than 50 Gy/s are planned. At higher dose rates, recombination effects for the free-air chamber are much higher and expected to lead to much larger uncertainties. Since the graphite calorimeter does not have problems associated with dose rate, it is an appropriate primary standard detector for the synchrotron IMBL x rays and is the more accurate dosimeter for the higher dose rates expected in radiotherapy applications.

Direct MC conversion of absorbed dose to graphite to absorbed dose to water for 60Co radiation.

The ARPANSA calibration service for (60)Co gamma rays is based on a primary standard graphite calorimeter that measures absorbed dose to graphite. Measurements with the calorimeter are converted to the absorbed dose to water using the calculation of the ratio of the absorbed dose in the calorimeter to the absorbed dose in a water phantom. ARPANSA has recently changed the basis of this calculation from a photon fluence scaling method to a direct Monte Carlo (MC) calculation. The MC conversion uses an EGSnrc model of the cobalt source that has been validated against water tank and graphite phantom measurements, a step that is required to quantify uncertainties in the underlying interaction coefficients in the MC code. A comparison with the Bureau International des Poids et Mesures (BIPM) as part of the key comparison BIPM.RI(I)-K4 showed an agreement of 0.9973 (53).

Assessment of leakage doses around the treatment heads of different linear accelerators.

Out-of-field doses to untargeted organs may have long-term detrimental health effects for patients treated with radiotherapy. It has been observed that equivalent treatments delivered to patients with different accelerators may result in significant differences in the out-of-field dose. In this work, the points of leakage dose are identified about the gantry of several treatment units. The origin of the observed higher doses is investigated. LiF:Mg,Cu,P thermoluminescent dosimetry has been employed to quantify the dose at a several points around the linac head of various linear accelerators (linacs): a Varian 600C, Varian 21-iX, Siemens Primus and Elekta Synergy-II. Comparisons are also made between different energy modes, collimator rotations and field sizes. Significant differences in leaked photon doses were identified when comparing the various linac models. The isocentric-waveguide 600C generally exhibits the lowest leakage directed towards the patient. The Siemens and Elekta models generally produce a greater leakage than the Varian models. The leakage 'hotspots' are evident on the gantry section housing the waveguide on the 21-iX. For all machines, there are significant differences in the x and y directions. Larger field sizes result in a greater leakage at the interface plate. There is a greater leakage around the waveguide when operating in a low-energy mode, but a greater leakage for the high-energy mode at the linac face. Of the vendors investigated, the Varian 600C showed the lowest average leakage dose. The Varian 21-iX showed double the dose of the 600C. The Elekta Synergy-II had on average four times the dose leakage than the 600C, and the Siemens Primus showed an average of five times that of the 600C. All vendors show strong differences in the x and y directions. The results offer the potential for patient-positioning strategies, linac choice and shielding strategies to reduce the leakage dose to patients.

Activated polymorphonuclear cells promote injury and excitability of dorsal root ganglia neurons.

Therapies aimed at depleting or blocking the migration of polymorphonuclear leukocytes (PMN or neutrophils) are partially successful in the treatment of neuroinflammatory conditions and in attenuating pain following peripheral nerve injury or subcutaneous inflammation. However, the functional effects of PMN on peripheral sensory neurons such as dorsal root ganglia (DRG) neurons are largely unknown. We hypothesized that PMN are detrimental to neuronal viability in culture and increase neuronal activity and excitability. We demonstrate that isolated peripheral PMN are initially in a relatively resting state but undergo internal oxidative burst and activation by an unknown mechanism within 10 min of co-culture with dissociated DRG cells. Co-culture for 24 h decreases neuronal count at a threshold<0.4:1 PMN:DRG cell ratio and increases the number of injured and apoptotic neurons. Within 3 min of PMN addition, fluorometric calcium imaging reveals intracellular calcium transients in small size (<25 microm diam) and large size (>25 microm diam) neurons, as well as in capsaicin-sensitive neurons. Furthermore, small size isolectin B4-labeled neurons undergo hyperexcitability manifested as decreased current threshold and increased firing frequency. Although co-culture of PMN and DRG cells does not perfectly model neuroinflammatory conditions in vivo, these findings suggest that activated PMN can potentially aggravate neuronal injury and cause functional changes to peripheral sensory neurons. Distinguishing the beneficial from the detrimental effects of PMN on neurons may aid in the development of more effective drug therapies for neurological disorders involving neuroinflammation, including painful neuropathies.

Femoral artery compression device for outpatient angiography.

To avoid late bleeding from the femoral artery puncture site after outpatient femoral angiography, a compression device was designed to exert continuous pressure over the groin, even when the patient is upright. It has been successfully used in more than 2,000 arterial catheter procedures. The device can also help prevent bleeding in patients who are at increased risk because of hypertension or anticoagulant therapy.

Preparation and properties of fluorescent polysaccharides.

A new method for preparing fluorescein derivatives of polysaccharides is described. These derivatives are prepared by activation of the polysaccharide with cyanogen bromide and subsequent reaction with fluoresceinamine. The optimum conditions for coupling have been established in this report. Using this procedure, we have prepared fluorescein derivatives of a wide variety of polysaccharides. Degrees of substitution in the range of 3.0 X 10(-3) to 2.4 X 10(-2) mol of fluorescein per mole of monosaccharide equivalent were obtained. The fluorescent derivatives are stable: no free fluorescein was detected after incubation at 22 degrees C for 48 h or at -10 degrees C for 4 months. The fluorescein-derivatized polysaccharides were found to have the same potency in inhibiting lectin-mediated hemagglutination as the underivatized polysaccharide. In addition, these fluorescent polysaccharides can be radioiodinated to specific activities exceeding 10(6) dpm/micrograms due to incorporation of 125I into fluorescein. The cell binding properties of 125I-fucoidin and 125I-heparin are indistinguishable from the corresponding underivatized polysaccharides. This general approach for preparing fluorescent polysaccharides should produce useful reagents for localizing and quantifying cell surface carbohydrate-binding proteins (lectins).