Comments on 'Ionization chamber volume determination and quality assurance using micro-CT imaging'.

The authors of a recent paper (McNiven et al 2008 Phys. Med. Biol. 53 5029-43) measured the volume of a particular type of a small ionization chamber using CT images. Using four Exradin A1SL chambers, they find that the volume measured using CT imaging is, on average, 4.3% larger than the value derived from the chamber calibration coefficient. Although they point out that the effective chamber volume is defined by electric field lines between the collector and the chamber body, they do not estimate how the mechanical volume might differ from the effective volume. We have used a commercial software package to calculate the electric field in the cavity and we show that the field lines define a volume that is about 11% smaller than the mechanical volume. We also show that the effective volume is very sensitive to small changes in the chamber geometry near the base of the collector. We conclude that simply determining the mechanical volume without careful consideration of the electric field lines within the cavity is not a useful dosimetric technique.

Comments on 'Cellular response to modulated radiation fields'.

The authors of a recent paper (Claridge Mackonis et al 2007 Phys. Med. Biol. 52 5469-82) measured cell survival in spatially modulated radiation fields. They claim to have identified two new types of radiation-induced bystander effect. We conclude that their claims are not supported by their data.

The effective point of measurement of ionization chambers and the build-up anomaly in MV x-ray beams.

A precision experimental investigation of the effective point of measurement (EPOM) of ion chambers in megavoltage beams has been carried out. A one-dimensional scanning phantom system was developed with an overall accuracy in the positioning of a chamber of better than 0.15 mm. Depth-dose data were acquired for a 25 MV beam from an Elekta Precise linac (field sizes of 10 x 10 cm and 25 x 25 cm) for measurement depths in the range 0.6-6 cm. The results confirmed the Monte Carlo calculations of an earlier theoretical investigation by Kawrakow [Med. Phys. 33, 1829-1839 (2006)] that the standard shift for cylindrical chambers, recommended in dosimetry protocols of -0.6r (where r is the internal radius of the cavity), is incorrect. A wide range of ion chambers were investigated and it was found that errors of up to 1.4 mm could occur for certain chamber designs (although typical errors for common chambers were around 0.5 mm). A comparison between measurements and Monte Carlo simulations showed that once the correct EPOM is used, the details of the linac geometry are correct, and the parameters of the electron beam striking the bremsstrahlung target have been adequately determined, the EGSnrc Monte Carlo package is capable of reproducing the experimental data to 0.2 mm or better. The investigation also confirmed that for the highest accuracy depth-dose curves in megavoltage photon beams one should use a well-guarded parallel-plate ion chamber. Three chamber designs were tested here and found to be satisfactory-the Scanditronix-Wellhöfer NACP-02, PTW Roos and Exradin All.

Measurement of multiple scattering of 13 and 20 MeV electrons by thin foils.

To model the transport of electrons through material requires knowledge of how the electrons lose energy and scatter. Theoretical models are used to describe electron energy loss and scatter and these models are supported by a limited amount of measured data. The purpose of this work was to obtain additional data that can be used to test models of electron scattering. Measurements were carried out using 13 and 20 MeV pencil beams of electrons produced by the National Research Council of Canada research accelerator. The electron fluence was measured at several angular positions from 0 degree to 90 degrees for scattering foils of different thicknesses and with atomic numbers ranging from 4 to 79. The angle, theta 1/e at which the fluence has decreased to 1/e of its value on the central axis was used to characterize the distributions. Measured values of theta 1/e ranged from 1.5 degrees to 8 degrees with a typical uncertainty of about 1%. Distributions calculated using the EGSnrc Monte Carlo code were compared to the measured distributions. In general, the calculated distributions are narrower than the measured ones. Typically, the difference between the measured and calculated values of theta 1/e is about 1.5%, with the maximum difference being 4%. The measured and calculated distributions are related through a simple scaling of the angle, indicating that they have the same shape. No significant trends with atomic number were observed.

Technical Note: An investigation of polarity effects for wide-angle free-air chambers.

PURPOSE: Wide-angle free-air chambers (WAFACs) are used as primary standard measurement devices for establishing the air-kerma strength of low-energy, low-dose rate brachytherapy seeds. The National Research Council of Canada (NRC) is commissioning a primary standard wide-angle free-air chamber (NRC WAFAC) to serve the calibration needs of Canadian clients. The University of Wisconsin has developed a similar variable-aperture free-air chamber (UW VAFAC) to be used as a research tool. As part of the NRC commissioning, measurements were carried out for both polarities of the applied bias voltage and the resulting effects were observed to be very large. Similar effects were identified with the UW VAFAC. The authors describe the measurements carried out to determine the underlying causes of the polarity effect and the approach used to eliminate it. METHODS: The NRC WAFAC is based on the WAFAC design developed at the National Institute of Standards and Technology in the USA. Charge measurements for (125)I and (241)Am sources were carried out for both negative and positive polarities on the NRC WAFAC and UW VAFAC. Two aperture sizes were also investigated with the UW VAFAC. In addition, measurements on the NRC WAFAC were carried out with a small bias between the collecting electrode and the shield foil at the downstream end of the chamber. To mitigate all of the polarity effects, the downstream surface of the collecting electrode was covered with a thin layer of graphite on both the NRC and UW chambers. RESULTS: Both chamber designs showed a difference of more than 30 % between the charge collected with positive and negative bias voltages for the smallest electrode separation. It was shown for the NRC WAFAC that charge could be collected in the small gap downstream of the collecting volume by applying a voltage between the shield foil and the collecting electrode, even though an insulating foil (Mylar or polyimide film) separated the conducting surface from the small gap region. The unwanted additional current was shown to be proportional to the size of the aperture for the UW VAFAC. The extra ionization produced in the small gap region was eliminated for both chambers by covering the insulating side of the collecting electrode with a grounded conducting layer. CONCLUSIONS: The small gap region downstream of the collecting electrode in the NRC WAFAC and UW VAFAC can serve as an unwanted source of ion current. It is concluded that a residual electric field in the small gap region may lead to ion transport and to charge being trapped on the surface of the foil. The foil then acts as a capacitor with an equal charge, but of opposite sign, being attracted to the conducting surface. Covering the back of the collecting electrode surface with a grounded conducting layer eliminated the polarity effect.

Crystals of HIV-1 reverse transcriptase diffracting to 2.2 A resolution.

Reverse transcriptase (RT) from the human immunodeficiency virus type 1 has been crystallized in four closely related forms, the best of which diffract X-rays to 2.2 A resolution. The RT was crystallized as a complex with a non-nucleoside inhibitor, either nevirapine or a nevirapine analogue. Crystals grew from 6% PEG 3400 buffered at pH 5. These were of space group P2(1)2(1)2(1) with unit cell parameters a = 147 A, b = 112 A, c = 79 A (form A), with one RT heterodimer in the asymmetric unit. Changes in unit cell parameters and degree of crystalline order were observed on soaking pregrown crystals in various solutions, giving three further sets of unit cells. These were a = 143 A, b = 112, A, c = 79 A (form B), a = 141 A, b = 111 A, c = 73 A (form C), a = 143 A, b = 117 A, c = 66.5 A (form D). The last two forms diffract X-rays to 2.2 A resolution. Structure determinations of these latter crystal forms of RT should give a detailed atomic model for this therapeutically important drug target.

Rapid purification and characterisation of HIV-1 reverse transcriptase and RNaseH engineered to incorporate a C-terminal tripeptide alpha-tubulin epitope.

The C-termini of p66 and p51 forms of HIV-1 reverse transcriptase have been engineered to contain a Glu-Glu-Phe sequence recognized by a monoclonal antibody to alpha-tubulin, YL1/2. Mutated RTs were purified in a single step using peptide elution from columns of immobilized YL1/2. The known sequence requirements of the YL1/2 epitope are consistent with protein eluting from the column with an intact C-terminus. Kinetic parameters of these mutated RTs are essentially unchanged from wild-type enzyme. The p15 RNaseH domain has been purified using this method and shown to have low enzyme activity compared to the parental p66 subunit.

The survival of aerobic and anoxic human glioma and melanoma cells after irradiation at ultrahigh and clinical dose rates.

This in vitro study was undertaken to determine if ultrahigh dose rates could improve the radiation response of human tumors. Two cell lines, human glioma (U-87 MG), which is radioresistant, and human melanoma (HT-144), which is radiosensitive, were irradiated at ultrahigh and high dose rates under aerobic and anoxic conditions to determine if their oxygen enhancement ratios are modified by dose rate. In fact, the survival curves, and hence the oxygen enhancement ratios, were found to be independent of the dose rate. The oxygen enhancement ratio for glioma cells irradiated in plateau phase was 2.8 (+/- 0.3). The oxygen enhancement ratio was 2.7 (+/- 0.4) for melanoma cells in plateau phase and 2.8 (+/- 0.3) in exponential phase. These results indicate that there is no advantage in treating these tumors using ultrahigh dose rates instead of conventional dose rates.

The role of expectations and preferences in health care satisfaction of patients with arthritis.

Studies of patient satisfaction have typically been conducted in general patient populations with little attention to patients suffering from specific illnesses. The purpose of this article is to review literature and raise issues relevant to the satisfaction of patients with chronic arthritis. Individuals suffering from a chronic illness such as arthritis may be different from others who seek medical care in their expectations, what they expect from care, and preferences, what they want from care. These differences may occur because patients with chronic arthritis have greater experience with care seeking and increasing recognition of the potential for poor disease outcomes in spite of adequate care. Literature from marketing research and health care which suggests that both expectations and preferences influence satisfaction with care will be reviewed. Then specific hypotheses about expectations and preferences of patients with chronic arthritis will be proposed. Recommendations for future studies of arthritis patient expectations and preferences will be made.

Evaluation of a psychological treatment package for treating pain in juvenile rheumatoid arthritis.

We examined the utility of psychological treatment procedures for children with high levels of pain associated with juvenile rheumatoid arthritis (JRA). By the use of a multiple baseline across subjects design, four children were assigned to an immediate treatment group, and four children to a delayed treatment group. The six-session treatment included relaxation training, electromyogram, and thermal biofeedback for the child; mothers were trained in the use of behavioral techniques for managing physical therapy and school attendance. Visual inspection of the data indicates small changes on children's self-reported pain diary scores for mean pain and ratings of high (greater than 5 on a 10-point visual analogue scale) pain periods, with 50% to 62% showing at least a 25% reduction in pain immediately after treatment, and 62% to 88% showing a 25% reduction by 6-month follow-up. Maternal reports of changes paralleled those of the children. Comparisons of Mann-Whitney U-tests conducted pre- and posttreatment indicated no differences for children's ratings of mean pain or +5 pain ratings between the immediate and delayed treatment groups; greater improvement for the immediate treatment group was noted on maternal reports of both mean pain (p < 0.05) and +5 pain (p < 0.5) ratings. The reduction of pain reports from pretreatment to follow-up was significant for children's mean pain (p = 0.02), +5 pain ratings (p = 0.02), and mother's reports of mean pain (p = 0.03) and +5 pain periods (p = 0.01). Maternal reports of the number of pain-related behaviors that the child exhibited also declined (p < 0.05). No reduction in physical therapist's ratings of pain during evaluation were noted. No increases in maternal reports of child's psychological adjustment problems were reported following treatment. Results provide modest support for the use of psychological interventions with patients with JRA.

The role of humidity and other correction factors in the AAPM TG-21 dosimetry protocol.

A detailed derivation is presented of the formulas required to determine Ngas and Dmed in the AAPM TG-21 dosimetry protocol. This protocol specifies how to determine the absorbed dose in an electron or photon beam when using exposure or absorbed dose calibrated ion chambers. It is shown that the expression given in TG-21's recent letter of clarification is incorrect. Accounting for humidity correctly increases, by 0.4%, all absorbed dose determinations using an exposure calibrated ion chamber. Taking into account other correction factors in the equation for exposure could also have varying, but significant effects (possibly over 1%). These are the stem scatter correction, the axial nonuniformity correction and the electrode correction for electrodes made of different materials from the wall. Attention is drawn to differences in the definitions of the exposure and absorbed dose calibration factors, Nx and ND, respectively, as supplied by the NBS and the NRCC.

The effect of various dissolved gases on the heat defect of water.

Recent measurements of the absorbed dose to air-saturated water, made using water calorimetry and assuming a zero heat defect for irradiated water, gave results 2%-5% higher than those determined by more conventional means. According to the current radiation chemical model for air-saturated water, the dose measured by water calorimetry assuming a zero heat defect should actually be 2% too low because of the endothermicity of the radiolysis processes in water. In order to examine possible sources for this discrepancy, we have constructed a small calorimeter (holding 100 ml of water) with which to measure the temperature rise in irradiated water saturated with various gases. The gases used were air, oxygen, argon, nitrogen, and hydrogen/oxygen mixtures. Irradiations were carried out with 20-MV x rays at a dose rate of 0.41 Gy/s. Our results are consistent with model calculations, except for some differences for accumulated doses of less than 100 Gy. The discrepancies we find at low doses and the discrepancies observed by others using water calorimeters may arise from impurities in the water.

Angular distribution of bremsstrahlung from 15-MeV electrons incident on thick targets of Be, Al, and Pb.

Bremsstrahlung spectra from thick cylindrical targets of Be, Al, and Pb have been measured at angles of 0 degrees, 1 degree, 2 degrees, 4 degrees, 10 degrees, 30 degrees, 60 degrees, and 90 degrees relative to the beam axis for electrons of 15-MeV incident energy. The spectra are absolute (photons per incident electron) and have a 145-keV lower-energy cutoff. The target thickness were nominally 110% of the electron CSDA range. A thin transmission detector, calibrated against a toroidal current monitor, was placed upstream of the target to measure the beam current. The spectrometer was a 20-cm-diam by 25-cm-long cylindrical NaI detector. Measured spectra were corrected for pile-up, background, detector response, detector efficiency, attenuation in materials between the target and detector and collimator effects. Spectra were also calculated using the EGS4 Monte Carlo system for simulating the radiation transport. There was excellent agreement between the measured and calculated spectral shapes. The measured yield of photons per incident electron was 9% and 7% greater than the calculated yield for Be and Al, respectively, and 2% less for Pb, all with an uncertainty of +/- 5%. There was no significant angular variation in the ratio of the measured and calculated yields. The angular distributions of bremsstrahlung calculated using available analytical theories dropped off more quickly with angle than the measured distributions. The predictions of the theories would be improved by including target-scattered photons.

Forward-directed bremsstrahlung of 10- to 30-MeV electrons incident on thick targets of Al and Pb.

Bremsstrahlung spectra from thick targets of Al and Pb have been measured absolutely (photons per incident electron) along the beam axis for electrons of 10-, 15-, 20-, 25-, and 30-MeV incident energy. The spectra have a 220-keV low-energy cutoff. The targets were cylinders with nominal thicknesses of 110% of the electron CSDA range. A thin transmission detector, calibrated against a toroidal current monitor, was placed upstream of the target to measure the beam current. The spectrometer was a 20-cm diameter by 25-cm-long cylindrical NaI detector. Measured spectra were corrected for pile-up, background, detector response, detector efficiency, attenuation in materials between the target and detector and the collimator effect. Spectra were calculated using the EGS4 Monte Carlo system for simulating the radiation transport. The simulation model included the small amount of material upstream of the target. This material contributed about 40% of the spectrum, but its presence or absence had little effect on the calculated bremsstrahlung yield. The shapes of the measured and calculated spectra were in excellent agreement. The ratio of the total number of photons in each measured spectrum to those in the corresponding calculated spectrum varied from 0.97 +/- 0.06 to 1.12 +/- 0.06, depending largely on the atomic number of the target. Absolute spectral measurements in the literature agreed with our calculations of spectral shape but showed a range of +/- 30% in the number of photons per incident electron relative to the calculated values, which is contrary to our result.

Absorbed-dose beam quality conversion factors for cylindrical chambers in high energy photon beams.

Recent working groups of the AAPM [Almond et al., Med. Phys. 26, 1847 (1999)] and the IAEA (Andreo et al., Draft V.7 of "An International Code of Practice for Dosimetry based on Standards of Absorbed Dose to Water," IAEA, 2000) have described guidelines to base reference dosimetry of high energy photon beams on absorbed dose to water standards. In these protocols use is made of the absorbed-dose beam quality conversion factor, kQ which scales an absorbed-dose calibration factor at the reference quality 60Co to a quality Q, and which is calculated based on state-of-the-art ion chamber theory and data. In this paper we present the measurement and analysis of beam quality conversion factors kQ for cylindrical chambers in high-energy photon beams. At least three chambers of six different types were calibrated against the Canadian primary standard for absorbed dose based on a sealed water calorimeter at 60Co [TPR10(20)=0.572, %dd(10)x=58.4], 10 MV [TPR10(20)=0.682, %dd(10)x=69.6), 20 MV (TPR10(20)=0.758, %dd(10)x= 80.5] and 30 MV [TPR10(20) = 0.794, %dd(10)x= 88.4]. The uncertainty on the calorimetric determination of kQ for a single chamber is typically 0.36% and the overall 1sigma uncertainty on a set of chambers of the same type is typically 0.45%. The maximum deviation between a measured kQ and the TG-51 protocol value is 0.8%. The overall rms deviation between measurement and the TG-51 values, based on 20 chambers at the three energies, is 0.41%. When the effect of a 1 mm PMMA waterproofing sleeve is taken into account in the calculations, the maximum deviation is 1.1% and the overall rms deviation between measurement and calculation 0.48%. When the beam is specified using TPR10(20), and measurements are compared with kQ values calculated using the version of TG-21 with corrected formalism and data, differences are up to 1.6% when no sleeve corrections are taken into account. For the NE2571 and the NE2611A chamber types, for which the most literature data are available, using %dd(10)x, all published data show a spread of 0.4% and 0.6%, respectively, over the entire measurement range, compared to spreads of up to 1.1% for both chambers when the kQ values are expressed as a function of TPR10(20). For the PR06-C chamber no clear preference of beam quality specifier could be identified. When comparing the differences of our kQ measurements and calculations with an analysis in terms of air-kerma protocols with the same underlying calculations but expressed in terms of a compound conversion factor CQ, we observe that a system making use of absorbed-dose calibrations and calculated kQ values, is more accurate than a system based on air-kerma calibrations in combination with calculated CQ (rms deviation of 0.48% versus 0.67%, respectively).

Comparison of measured and Monte Carlo calculated dose distributions from the NRC linac.

We have benchmarked photon beam simulations with the EGS4 user code BEAM [Rogers et al., Med. Phys. 22, 503-524 (1995)] by comparing calculated and measured relative ionization distributions in water from the 10 and 20 MV photon beams of the NRC linac. Unlike previous calculations, the incident electron energy is known independently to 1%, the entire extra-focal radiation is simulated, and electron contamination is accounted for. The full Monte Carlo simulation of the linac includes the electron exit window, target, flattening filter, monitor chambers, collimators, as well as the PMMA walls of the water phantom. Dose distributions are calculated using a modified version of the EGS4 user code DOSXYZ which additionally allows scoring of average energy and energy fluence in the phantom. Dose is converted to ionization by accounting for the (L/rho)water(air) variation in the phantom, calculated in an identical geometry for the realistic beams using a new EGS4 user code, SPRXYZ. The variation of (L/rho)water(air) with depth is a 1.25% correction at 10 MV and a 2% correction at 20 MV. At both energies, the calculated and the measured values of ionization on the central axis in the buildup region agree within 1% of maximum ionization relative to the ionization at 10 cm depth. The agreement is well within statistics elsewhere. The electron contamination contributes 0.35(+/- 0.02) to 1.37(+/- 0.03)% of the maximum dose in the buildup region at 10 MV and 0.26(+/- 0.03) to 3.14(+/- 0.07)% of the maximum dose at 20 MV. The penumbrae at 3 depths in each beam (in g/cm2), 1.99 (dmax, 10 MV only), 3.29 (dmax, 20 MV only), 9.79 and 19.79, agree with ionization chamber measurements to better than 1 mm. Possible causes for the discrepancy between calculations and measurements are analyzed and discussed in detail.

A simple magnetic spectrometer for radiotherapy electron beams.

A small, lightweight, single-focusing magnetic spectrometer was designed, assembled, and tested for analysis of electron beams from radiotherapy electron linacs. The objective was to develop a low cost, simple device that could be easily replicated in other medical centers, and to demonstrate the practicality of individual electron counting for precise analysis of electron spectra. Two methods of spectroscopy have been developed. One method consists of counting electrons individually as a function of magnetic field setting. Electrons are deflected through 90 degrees in the magnetic spectrometer, through an exit slit, and into a scintillation detector. A second method consists of recording the complete spectrum of electron energies from the accelerator on a strip of film at a single magnetic field setting. A critical design element is the 10-cm long collimator for electrons entering the magnet gap, with defining apertures and scraper slits. The spectrometer's cleanliness of transmission, energy calibration, and resolution were all tested at 10 and 16 MeV using the nearly monoenergetic electron beam of the accelerator at the National Research Council of Canada (NRCC). These accelerator tests, and also Monte Carlo trajectory simulations, both show that contamination of the transmitted spectrum due to scattered or knock-on electrons is negligible. Low-energy characteristics were tested using a 90Sr + 90Y beta-particle source. The energy calibration of the 90 degree spectrometer mode was based on mapping the magnetic field and also electron trajectory computer simulations. That calibration agrees with the NRCC's own calibrated scale to 0.8% for the single-particle counting method and to 1.3% for the film method. The energy resolution was measured to be 2% at 10 MeV, which is adequate for radiotherapy linac measurements. The acceptance half angle is 0.5 degrees or less, depending on the aperture size, which is adequate for electron angular distribution measurements within the forward cone of the electron beam. Used with film, the spectrometer is a simple, accurate, and highly transportable device for measuring radiotherapy electron energy spectra.

Wall-correction and absorbed-dose conversion factors for Fricke dosimetry: Monte Carlo calculations and measurements.

For megavoltage radiotherapy photon beams, EGS4 Monte Carlo calculations show, and experimental measurements confirm with an accuracy of 0.2%, that glass or quartz-walled vials used in Fricke dosimetry increase the dose in the Fricke solution. This is mainly caused by increased electron scattering from the glass which increases the dose to the Fricke solution. The dose perturbation is shown to vary from nothing in a 60Co beam up to 2% in a 24-MV beam. For plastic vials of similar shapes, calculations demonstrate that the effect is in the opposite direction and even at high energies it is much less (0.2% to 0.5%).

Two-stage cell shrinkage and the OER for radiation-induced apoptosis of rat thymocytes.

Suspensions of rat thymocytes were given 0.09-100 Gy using 60Co gamma-rays. The radiation-induced changes in the thymocytes were examined from minutes to hours post-irradiation using electron microscopy, agarose gel electrophoresis, staining and Coulter Counter sizing. Sizing by Coulter Counter showed, for the first time, that thymocytes which undergo apoptosis shrink in two distinct stages, first by a sudden decrease from an original volume of 99 microns 3 to a volume of 76 microns 3, followed by a gradual decrease to 57 microns 3 over the space of a few hours. The oxygen enhancement ratio for apoptosis was measured to be about 3.5, similar to the value for reproductive death for many mammalian cells.

Water calorimetry for radiation dosimetry.

Calorimetry has a long history as a technique for establishing the absorbed dose, and graphite calorimetry has often been used to establish absorbed dose standards for use in radiation therapy. However, a conversion process is necessary to convert from dose to graphite to dose to water, which is the quantity of clinical interest. In order to more directly measure the dose to water, considerable effort has been devoted in the last fifteen years to the development of water calorimetry. This article reviews these developments and summarizes the present status of water calorimetry. Absorbed dose standards based on water calorimetry and with a relative standard uncertainty of 0.5-1% now seem achievable.