A portable primary-standard level graphite calorimeter for absolute dosimetry in clinical pencil beam scanning proton beams.

Objective. To report the use of a portable primary standard level graphite calorimeter for direct dose determination in clinical pencil beam scanning proton beams, which forms part of the recommendations of the proposed Institute of Physics and Engineering in Medicine (IPEM) Code of Practice (CoP) for proton therapy dosimetry.Approach. The primary standard proton calorimeter (PSPC) was developed at the National Physical Laboratory (NPL) and measurements were performed at four clinical proton therapy facilities that use pencil beam scanning for beam delivery. Correction factors for the presence of impurities and vacuum gaps were calculated and applied, as well as dose conversion factors to obtain dose to water. Measurements were performed in the middle of 10 × 10 × 10 cm3homogeneous dose volumes, centred at 10.0, 15.0 and 25.0 g·cm-2depth in water. The absorbed dose to water determined with the calorimeter was compared to the dose obtained using PTW Roos-type ionisation chambers calibrated in terms of absorbed dose to water in60Co applying the recommendations in the IAEA TRS-398 CoP.Main results.The relative dose difference between the two protocols varied between 0.4% and 2.1% depending on the facility. The reported overall uncertainty in the determination of absorbed dose to water using the calorimeter is 0.9% (k= 1), which corresponds to a significant reduction of uncertainty in comparison with the TRS-398 CoP (currently with an uncertainty equal or larger than 2.0% (k= 1) for proton beams).Significance. The establishment of a purpose-built primary standard and associated CoP will considerably reduce the uncertainty of the absorbed dose to water determination and ensure improved accuracy and consistency in the dose delivered to patients treated with proton therapy and bring proton reference dosimetry uncertainty in line with megavoltage photon radiotherapy.

Determination of beam quality correction factors for the Roos plane-parallel ionisation chamber exposed to very high energy electron (VHEE) beams using Geant4.

Detailed characterisation of the Roos secondary standard plane-parallel ionisation chamber has been conducted in a novel 200 MeV Very High Energy Electron (VHEE) beam with reference to the standard 12 MeV electron calibration beam used in our experimental work. Stopping-power-ratios and perturbation factors have been determined for both beams and used to calculated the beam quality correction factor using the Geant4 general purpose MC code. These factors have been calculated for a variety of charged particle transport parameters available in Geant4 which were found to pass the Fano cavity test. Stopping-power-ratios for the 12 MeV electron calibration beam quality were found to agree within uncertainties to that quoted by current dosimetry protocols. Perturbation factors were found to vary by up-to 4% for the calibration beam depending on the parameter configuration, compared with only 0.8% for the VHEE beam. Beam quality correction factors were found to describe an approximately 10% lower dose than would be originally calculated if a beam quality correction were not accounted for. Moreover, results presented here largely resolve unphysical chamber measurements, such as collection efficiencies greater than 100%, and assist in the accurate determination of absorbed dose and ion recombination in secondary standard ionisation chambers.

Application of a portable primary standard level graphite calorimeter for absolute dosimetry in a clinical low-energy passively scattered proton beam.

Objective. A calibration service based on a primary standard calorimeter for the direct determination of absorbed dose for proton beams does not exist. A new Code of Practice (CoP) for reference dosimetry of proton beams is being developed by a working party of the UK Institute of Physics and Engineering in Medicine (IPEM), which will recommend that ionisation chambers are calibrated directly in their clinical beams against the proposed Primary Standard Proton Calorimeter (PSPC) developed at the National Physical Laboratory (NPL). The aim of this work is to report on the use of the NPL PSPC to directly calibrate ionisation chambers in a low-energy passively scattered proton beam following recommendations of the upcoming IPEM CoP.Approach. A comparison between the dose derived using the proposed IPEM CoP and the IAEA TRS-398 protocol was performed, andkQvalues were determined experimentally for three types of chambers. In total, 9 plane-parallel and 3 cylindrical chambers were calibrated using the two protocols for two separate visits.Main results. The ratio of absorbed dose to water obtained with the PSPC and with ionisation chambers applying TRS-398 varied between 0.98 and 1.00, depending on the chamber type. The new procedure based on the PSPC provides a significant improvement in uncertainty where absorbed dose to water measured with a user chamber is reported with an uncertainty of 0.9% (1σ), whereas the TRS-398 protocol reports an uncertainty of 2.0% and 2.3% (1σ) for cylindrical and plane-parallel chambers, respectively. ThekQvalues found agree within uncertainties with those from TRS-398 and Monte Carlo calculations.Significance. The establishment of a primary standard calorimeter for the determination of absorbed dose in proton beams combined with the introduction of the associated calibration service following the IPEM recommendations will reduce the uncertainty and improve consistency in the dose delivered to patients.

Analysis of dose perturbation factors of a NACP-02 ionization chamber in clinical electron beams.

For well-guarded plane-parallel ionization chambers, international dosimetry protocols recommend a value of unity for electron perturbation factors in water. However, recent data published by various groups have challenged this. Specifically for the NACP-02 chamber, non-unity electron perturbation factors have already been published by Verhaegen et al (2006 Phys. Med. Biol. 51 1221-35) and Buckley and Rogers (2006 Med. Phys. 33 1788-96). Recently it was found that the mass thickness of the front chamber window can be 35% greater than is listed in the IAEA's TRS-398 absorbed dose protocol (Chin et al 2008 Phys. Med. Biol. 53 N119-26). This study therefore recalculated NACP-02 electron perturbation correction factors for energies 4-18 MeV at depths z(ref) and R(50) to determine the effect of the chamber model change. Results showed that perturbation factors at z(ref) are fairly stable for similar chamber models but become highly sensitive to small changes at deeper depths. The results also showed some dependence on using 1 keV versus 10 keV for the transport cut-off. Additional investigations revealed that the wall perturbation factor, p(wall), is strongly influenced by the chamber back wall at z(ref) and at larger depths small changes in the positioning of the effective point of measurement cause large fluctuations in the final value. Finally, the cavity perturbation factor, p(cav), was found to be primarily influenced by electron backscatter.

Survey of patients' experiences after nail surgery.

Nail surgery is performed to aid diagnosis and treatment of nail disease. A survey was conducted to determine whether patients understood the nature and consequences of nail surgery at the time of consent and to ascertain the most important aspects of morbidity after the procedure. The results identified that most patients understood the nature of their surgery and the immediate postoperative limitations they would face. Pain was short-lived, with no patients requiring analgesics after 6 weeks. The most important finding from this survey was that sensory disturbance was recorded by a large proportion (47%; 29/62) of patients. Of these, 35% (22/62) recorded either complete or partial resolution by 6-12 months after surgery, but 11% (7/62) noted no improvement. This is a point that is not made clear in standard surgical texts. The significance of dysaesthesia of a fingertip must be considered when counselling a patient before surgery.

Validation of a Monte Carlo model of a NACP-02 plane-parallel ionization chamber model using electron backscatter experiments.

The accuracy of Monte Carlo (MC) simulation results relies on validating the MC models used in the calculations. In this work, a MC model for the NACP-02 plane-parallel ionization chamber was built and validated against megavoltage electron backscatter experiments using materials of water, graphite, aluminium and copper. Electron energies ranged between 6-18 MeV and the chamber's air cavity was at the depth of maximum dose, z(max). A chamber model based on manufacturer's specifications resulted in systematic discrepancies of several percents between measured and simulated backscatter factors. Tuning of the MC chamber model against backscatter factors to improve agreement increased the chamber's front window mass thickness by 35% over the reported value of 104 mg cm(-2) in the IAEA's TRS-398 absorbed dose protocol. The large increase in chamber window mass thickness was verified by measurements on a disassembled NACP-02 chamber. The new backscatter factor results based on the tuned MC NACP-02 chamber model matched the experimental results within 1-2 standard deviations. We conclude therefore that for MC simulations near z(max), tuning of the NACP-02 chamber model against experimental backscatter measurements is an acceptable method for validating the chamber model.

Evaluation of the water-equivalence of plastic materials in low- and high-energy clinical proton beams.

The aim of this work was to evaluate the water-equivalence of new trial plastics designed specifically for light-ion beam dosimetry as well as commercially available plastics in clinical proton beams. The water-equivalence of materials was tested by computing a plastic-to-water conversion factor, [Formula: see text]. Trial materials were characterized experimentally in 60 MeV and 226 MeV un-modulated proton beams and the results were compared with Monte Carlo simulations using the FLUKA code. For the high-energy beam, a comparison between the trial plastics and various commercial plastics was also performed using FLUKA and Geant4 Monte Carlo codes. Experimental information was obtained from laterally integrated depth-dose ionization chamber measurements in water, with and without plastic slabs with variable thicknesses in front of the water phantom. Fluence correction factors, [Formula: see text], between water and various materials were also derived using the Monte Carlo method. For the 60 MeV proton beam, [Formula: see text] and [Formula: see text] factors were within 1% from unity for all trial plastics. For the 226 MeV proton beam, experimental [Formula: see text] values deviated from unity by a maximum of about 1% for the three trial plastics and experimental results showed no advantage regarding which of the plastics was the most equivalent to water. Different magnitudes of corrections were found between Geant4 and FLUKA for the various materials due mainly to the use of different nonelastic nuclear data. Nevertheless, for the 226 MeV proton beam, [Formula: see text] correction factors were within 2% from unity for all the materials. Considering the results from the two Monte Carlo codes, PMMA and trial plastic #3 had the smallest [Formula: see text] values, where maximum deviations from unity were 1%, however, PMMA range differed by 16% from that of water. Overall, [Formula: see text] factors were deviating more from unity than [Formula: see text] factors and could amount to a few percent for some materials.

Perturbation correction factors for the NACP-02 plane-parallel ionization chamber in water in high-energy electron beams.

Recent dosimetry protocols for clinical high-energy electron beams recommend measurements of absorbed dose-to-water with a plane-parallel or cylindrical ionization chamber. For well-guarded plane-parallel ionization chambers, the ionization chamber perturbation factor in water, p(Q), has a recommended value of unity in all protocols. This assumption was investigated in detail in this study for one of the recommended ionization chambers in the protocols: the Scanditronix NACP-02 plane-parallel ionization chamber. Monte Carlo (MC) simulations of the NACP-02 ionization chamber with the EGSnrc code were validated against backscatter experiments. MC simulations were then used to calculate p(wall), p(cav) and p(Q) perturbation factors and water-to-air Spencer-Attix stopping powers in 4-19 MeV electron beams of a calibration laboratory (NPL), and in 6-22 MeV clinical electron beams from a Varian CL2300 accelerator. Differences between calculated and the currently recommended (Burns et al 1996 Med. Phys. 23 383-8) stopping powers, water-to-air, were found to be limited to 0.9% at depths between the reference depth z(ref) and the depth where the dose has decreased to 50% of the maximum dose, R50. p(wall) was found to exceed unity by 2.3% in the 4 MeV NPL calibration beam at z(ref). For higher energy electron beams p(wall) decreased to a value of about 1%. Combined with a p(cav) about 1% below unity for all energies at z(ref), this was found to cause p(Q) to exceed unity significantly for all energies. In clinical electron beams all three perturbation factors were found to increase with depth. Our findings indicate that the perturbation factors have to be taken into account in calibration procedures and for clinical depth dose measurements with the NACP-02 ionization chamber.

Roos and NACP-02 ion chamber perturbations and water-air stopping-power ratios for clinical electron beams for energies from 4 to 22 MeV.

Empirical fits are developed for depth-compensated wall- and cavity-replacement perturbations in the PTW Roos 34001 and IBA / Scanditronix NACP-02 parallel-plate ionisation chambers, for electron beam qualities from 4 to 22 MeV for depths up to approximately 1.1 × R50,D. These are based on calculations using the Monte Carlo radiation transport code EGSnrc and its user codes with a full simulation of the linac treatment head modelled using BEAMnrc. These fits are used with calculated restricted stopping-power ratios between air and water to match measured depth-dose distributions in water from an Elekta Synergy clinical linear accelerator at the UK National Physical Laboratory. Results compare well with those from recent publications and from the IPEM 2003 electron beam radiotherapy Code of Practice.

Source geometry factors for HDR ¹9²Ir brachytherapy secondary standard well-type ionization chamber calibrations.

Well-type ionization chambers are used for measuring the source strength of radioactive brachytherapy sources before clinical use. Initially, the well chambers are calibrated against a suitable national standard. For high dose rate (HDR) (192)Ir, this calibration is usually a two-step process. Firstly, the calibration source is traceably calibrated against an air kerma primary standard in terms of either reference air kerma rate or air kerma strength. The calibrated (192)Ir source is then used to calibrate the secondary standard well-type ionization chamber. Calibration laboratories are usually only equipped with one type of HDR (192)Ir source. If the clinical source type is different from that used for the calibration of the well chamber at the standards laboratory, a source geometry factor, k(sg), is required to correct the calibration coefficient for any change of the well chamber response due to geometric differences between the sources. In this work we present source geometry factors for six different HDR (192)Ir brachytherapy sources which have been determined using Monte Carlo techniques for a specific ionization chamber, the Standard Imaging HDR 1000 Plus well chamber with a type 70010 HDR iridium source holder. The calculated correction factors were normalized to the old and new type of calibration source used at the National Physical Laboratory. With the old Nucletron microSelectron-v1 (classic) HDR (192)Ir calibration source, ksg was found to be in the range 0.983 to 0.999 and with the new Isodose Control HDR (192)Ir Flexisource k(sg) was found to be in the range 0.987 to 1.004 with a relative uncertainty of 0.4% (k = 2). Source geometry factors for different combinations of calibration sources, clinical sources, well chambers and associated source holders, can be calculated with the formalism discussed in this paper.

The haemoglobin-like protein (HMP) of Escherichia coli has ferrisiderophore reductase activity and its C-terminal domain shares homology with ferredoxin NADP+ reductases.

Three soluble ferrisiderophore reductases (FsrA, FsrB and FsrC) were detected in Escherichia coli. FsrB was purified and identified as the haemoglobin-like protein (HMP) by size and N-terminal sequence analyses. HMP was previously isolated as a dihydropteridine reductase and is now shown to have ferrisiderophore reductase activity. Database searches revealed that the C-terminal region of HMP (FsrB) is homologous to members of a family of flavoprotein oxidoreductases which includes ferredoxin NADP+ reductase (FNR). The combination of FNR-like and haemoglobin-like regions in HMP (FsrB) represents a novel pairing of functionally and structurally distinct domains. Structure-function properties of other FNR-like proteins, including LuxG and VanB, are also discussed.

Drug-induced urticaria. Recognition and treatment.

Urticaria is the second most common cutaneous manifestation of drug allergy. Drug-induced urticaria is seen in 0.16% of medical inpatients and accounts for 9% of chronic urticaria or angioedema seen in dermatology outpatient departments. Occurring within 24 hours of drug ingestion, it is most commonly caused by penicillins, sulfonamides and nonsteroidal anti-inflammatory drugs. Drug-induced urticaria is seen in association with anaphylaxis, angioedema, and serum sickness. Diagnosis requires a detailed history, knowledge of the most likely agents sometimes supplemented with in vitro and skin testing. For mild reactions, avoidance of the causative drug and treatment with antihistamines will suffice. For anaphylactic shock, treatment with epinephrine (adrenaline), corticosteroids and antihistamines is required. Patients should be educated to inform medical staff about previous drug reactions, and to avoid these and cross-reacting drugs if possible. Medical staff need to routinely enquire about allergy and avoid unnecessary prescriptions.

Comparison of conversion factors for x-ray beams from a Philips SL15 and the NPL linear accelerator.

The National Physical Laboratory provides a megavoltage photon calibration service for secondary standard dosemeter systems in terms of absorbed dose to water using a graphite calorimeter. It is therefore necessary to evaluate factors to convert absorbed dose calibrations from graphite to water for all energies provided by the calibration service. A portable graphite calorimeter is currently being developed at the NPL for measuring absorbed dose in the radiotherapy clinic (McEwen and Duane 2000 Phys. Med. Biol. 45 3675-91) and so factors are now required to be able to convert absorbed dose calibrations from graphite to water in the clinical beam. The factors used to convert absorbed dose calibrations from graphite to water which are currently in use at the NPL were determined in previous work by Burns and Dale (1990 NPL Report RSA (EXT) 7) for all photon energies provided by the high-energy x-ray calibration service. Nutbrown et al (2000 NPL Report CIRM 37) have since re-evaluated these conversion factors using two methods. In this paper the factors to convert absorbed dose calibrations from graphite to water for two clinical beams from a Philips SL15 LINAC (6 and 10 MV) that were determined using both methods are presented and compared with values for the NPL heavily filtered beams. The results from the measurements made on the clinical machines using both methods agree within 1sigma uncertainty. The weighted average of these results agrees to within 1sigma uncertainty with results given by Burns and Dale and Nutbrown et al. The uncertainty in the determination of the graphite to water conversion factors at the 1sigma level is estimated to be 0.4%.

Evaluation of factors to convert absorbed dose calibrations from graphite to water for the NPL high-energy photon calibration service.

The National Physical Laboratory (NPL) provides a high-energy photon calibration service using 4-19 MV x-rays and 60Co gamma-radiation for secondary standard dosemeters in terms of absorbed dose to water. The primary standard used for this service is a graphite calorimeter and so absorbed dose calibrations must be converted from graphite to water. The conversion factors currently in use were determined prior to the launch of this service in 1988. Since then, it has been found that the differences in inherent filtration between the NPL LINAC and typical clinical machines are large enough to affect absorbed dose calibrations and, since 1992, calibrations have been performed in heavily filtered qualities. The conversion factors for heavily filtered qualities were determined by interpolation and extrapolation of lightly filtered results as a function of tissue phantom ratio 20,10 (TPR20,10). This paper aims to evaluate these factors for all mega-voltage photon energies provided by the NPL LINAC for both lightly and heavily filtered qualities and for 60Co y-radiation in two ways. The first method involves the use of the photon fluence-scaling theorem. This states that if two blocks of different material are irradiated by the same photon beam, and if all dimensions are scaled in the inverse ratio of the electron densities of the two media, then, assuming that all photon interactions occur by Compton scatter the photon attenuation and scatter factors at corresponding scaled points of measurement in the phantom will be identical. The second method involves making in-phantom measurements of chamber response at a constant target-chamber distance. Monte Carlo techniques are then used to determine the corresponding dose to the medium in order to determine the chamber calibration factor directly. Values of the ratio of absorbed dose calibration factors in water and in graphite determined in these two ways agree with each other to within 0.2% (1sigma uncertainty). The best fit to both sets of results agrees with values determined in previous work to within 0.3% (1sigma uncertainty). It is found that the conversion factor is not sensitive to beam filtration.

Clinical evaluation and care of the insensitive foot.

Until fairly recently, foot deformity was accepted as part of the natural course of a disease with associated sensory loss such as Hansen's disease or diabetes. Now we recognize that most of this deformity is caused by physical forces and that, with proper care, deformity can be prevented. The therapist must perform accurate methods of assessment such as inspecting and palpating the skin, testing for sensory loss, recording footprints, and measuring foot volume and must provide knowledgeable treatment techniques. The patient must be taught how to care for his feet and how to prevent continued trauma with subsequent infection and bony absorption, which ultimately result in deformity that could have been prevented. These evaluation, treatment, and education techniques are discussed in detail.

Reference dosimetry for light-ion beams based on graphite calorimetry.

Developments in hadron therapy require efforts to improve the accuracy of the dose delivered to a target volume. Here, the determination of the absorbed dose under reference conditions was analysed. Based on the International Atomic Energy Agency TRS-398 code of practice, for hadron beams, the combined standard uncertainty on absorbed dose to water under reference conditions, derived from ionisation chambers, is too large. This uncertainty is dominated by the beam quality correction factors, [Formula: see text], mainly due to the mean energy to produce one ion pair in air, wair. A method to reduce this uncertainty is to carry out primary dosimetry, using calorimetry. A [Formula: see text]-value can be derived from a direct comparison between calorimetry and ionometry. Here, this comparison is performed using a graphite calorimeter in an 80-MeV A(-1) carbon ion beam. Assuming recommended TRS-398 values of water-to-graphite stopping power ratio and the perturbation factor for an ionisation chamber, preliminary results indicate a wair-value of 35.5 ± 0.9 J C(-1).

Conversion from dose-to-graphite to dose-to-water in an 80 MeV/A carbon ion beam.

Based on experiments and numerical simulations, a study is carried out pertaining to the conversion of dose-to-graphite to dose-to-water in a carbon ion beam. This conversion is needed to establish graphite calorimeters as primary standards of absorbed dose in these beams. It is governed by the water-to-graphite mass collision stopping power ratio and fluence correction factors, which depend on the particle fluence distributions in each of the two media. The paper focuses on the experimental and numerical determination of this fluence correction factor for an 80 MeV/A carbon ion beam. Measurements have been performed in the nuclear physics laboratory INFN-LNS in Catania (Sicily, Italy). The numerical simulations have been made with a Geant4 Monte Carlo code through the GATE simulation platform. The experimental data are in good agreement with the simulated results for the fluence correction factors and are found to be close to unity. The experimental values increase with depth reaching 1.010 before the Bragg peak region. They have been determined with an uncertainty of 0.25%. Different numerical results are obtained depending on the level of approximation made in calculating the fluence correction factors. When considering carbon ions only, the difference between measured and calculated values is maximal just before the Bragg peak, but its value is less than 1.005. The numerical value is close to unity at the surface and increases to 1.005 near the Bragg peak. When the fluence of all charged particles is considered, the fluence correction factors are lower than unity at the surface and increase with depth up to 1.025 before the Bragg peak. Besides carbon ions, secondary particles created due to nuclear interactions have to be included in the analysis: boron ions ((10)B and (11)B), beryllium ions ((7)Be), alpha particles and protons. At the conclusion of this work, we have the conversion of dose-to-graphite to dose-to-water to apply to the response of a graphite calorimeter in an 80 MeV/A carbon ion beam. This conversion consists of the product of two contributions: the water-to-graphite electronic mass collision stopping power ratio, which is equal to 1.115, and the fluence correction factor which varies linearly with depth, as k(fl, all) = 0.9995 + 0.0048(zw-eq). The latter has been determined on the basis of experiments and numerical simulations.

Fluence correction factors for graphite calorimetry in a low-energy clinical proton beam: I. Analytical and Monte Carlo simulations.

The conversion of absorbed dose-to-graphite in a graphite phantom to absorbed dose-to-water in a water phantom is performed by water to graphite stopping power ratios. If, however, the charged particle fluence is not equal at equivalent depths in graphite and water, a fluence correction factor, kfl, is required as well. This is particularly relevant to the derivation of absorbed dose-to-water, the quantity of interest in radiotherapy, from a measurement of absorbed dose-to-graphite obtained with a graphite calorimeter. In this work, fluence correction factors for the conversion from dose-to-graphite in a graphite phantom to dose-to-water in a water phantom for 60 MeV mono-energetic protons were calculated using an analytical model and five different Monte Carlo codes (Geant4, FLUKA, MCNPX, SHIELD-HIT and McPTRAN.MEDIA). In general the fluence correction factors are found to be close to unity and the analytical and Monte Carlo codes give consistent values when considering the differences in secondary particle transport. When considering only protons the fluence correction factors are unity at the surface and increase with depth by 0.5% to 1.5% depending on the code. When the fluence of all charged particles is considered, the fluence correction factor is about 0.5% lower than unity at shallow depths predominantly due to the contributions from alpha particles and increases to values above unity near the Bragg peak. Fluence correction factors directly derived from the fluence distributions differential in energy at equivalent depths in water and graphite can be described by kfl = 0.9964 + 0.0024·zw-eq with a relative standard uncertainty of 0.2%. Fluence correction factors derived from a ratio of calculated doses at equivalent depths in water and graphite can be described by kfl = 0.9947 + 0.0024·zw-eq with a relative standard uncertainty of 0.3%. These results are of direct relevance to graphite calorimetry in low-energy protons but given that the fluence correction factor is almost solely influenced by non-elastic nuclear interactions the results are also relevant for plastic phantoms that consist of carbon, oxygen and hydrogen atoms as well as for soft tissues.