In-vivo dose measurements with MOSFET dosimeters during MV portal imaging

BackgroundThe purpose of this study was to investigate the feasibility of MOSFET dosimeter in measuring eye dose during 2D MV portal imaging for setup verification in radiotherapy.Materials and methodsThe in-vivo dose measurements were performed by placing the dosimeters over the eyes of 30 brain patients during the acquisition of portal images in linear accelerator by delivering 1 MU with the field sizes of 10 × 10 cm² and 15 × 15 cm².ResultsThe mean doses received by the left and right eyes of 10 out of 30 patients when both eyes were completely inside the anterior portal field were found to be 2.56 ± 0.2 cGy and 2.75 ± 0.2, respectively. Similarly, for next 10 patients out of the same 30 patients the mean doses to left and right eyes when both eyes were completely out of the anterior portal fields were found to be 0.13 ± 0.02 cGy and 0.17 ± 0.02 cGy, respectively. The mean doses to ipsilateral and contralateral eye for the last 10 patients when one eye was inside the anterior portal field were found to be 3.28 ± 0.2 cGy and 0.36 ± 0.1 cGy, respectively.ConclusionThe promising results obtained during 2D MV portal imaging using MOSFET have shown that this dosimeter is well suitable for assessing low doses during imaging thereby enabling to optimize the imaging procedure using the dosimetric data obtained. In addition, the documentation of the dose received by the patient during imaging procedure is possible with the help of an in-built software in conjunction with the MOSFET reader module.     

Field output factors for small fields: A large multicentre study

PurposeThe determination of output factors in small field dosimetry is a crucial point, especially when implementing stereotactic radiotherapy (SRT). Herein, a working group of the French medical physicist society (SFPM) was created to collect small field output factors. The objective was to gather and disseminate information on small field output factors based on different detectors for various clinical SRT equipment and measurement configurations.MethodParticipants were surveyed for information about their SRT equipment, including the type of linear particle accelerator (linac), collimator settings, measurement conditions for the output factors and the detectors used. Participants had to report both the ratio of detector readings and the correction factors applied as described in the IAEA TRS-483 code of practice for nominal field sizes smaller or equal to 3 cm. Mean field output factors and their associated standard deviations were calculated when data from at least 3 linacs were available.Results23 centres were enrolled in the project. Standard deviations of the mean field output factors were systematically smaller than 1.5% for field sizes larger or equal to 1 cm and reached 5% for the smallest field size (0.5 cm). Deviations with published data were smaller than 2% except for the 0.5 cm circular fixed aperture collimator of the CyberKnife where it reached 3.5%.ConclusionThese field output factor values obtained via a large multicentre study can be considered as an external cross verification for any radiotherapy centre starting a SRT program and should help minimize systematic errors when determining small field output factors.     

“Edge-on” MOSkin detector for stereotactic beam measurement and verification

Dosimetry in small radiation field is challenging and complicated because of dose volume averaging and beam perturbations in a detector. We evaluated the suitability of the “Edge-on” MOSkin (MOSFET) detector in small radiation field measurement. We also tested the feasibility for dosimetric verification in stereotactic radiosurgery (SRS) and stereotactic radiotherapy (SRT). “Edge-on” MOSkin detector was calibrated and the reproducibility and linearity were determined. Lateral dose profiles and output factors were measured using the “Edge-on” MOSkin detector, ionization chamber, SRS diode and EBT2 film. Dosimetric verification was carried out on two SRS and five SRT plans. In dose profile measurements, the “Edge-on” MOSkin measurements concurred with EBT2 film measurements. It showed full width at half maximum of the dose profile with average difference of 0.11 mm and penumbral width with difference of ±0.2 mm for all SRS cones as compared to EBT2 film measurement. For output factor measurements, a 1.1% difference was observed between the “Edge-on” MOSkin detector and EBT2 film for 4 mm SRS cone. The “Edge-on” MOSkin detector provided reproducible measurements for dose verification in real-time. The measured doses concurred with the calculated dose for SRS (within 1%) and SRT (within 3%). A set of output correction factors for the “Edge-on” MOSkin detector for small radiation fields were derived from EBT2 film measurement and presented. This study showed that the “Edge-on” MOSkin detector is a suitable tool for dose verification in small radiation field.     

Dosimetric characterization of a small-scale (Zn,Cd)S:Ag inorganic scintillating detector to be used in radiotherapy

PurposeIn modern radiotherapy techniques, to ensure an accurate beam modeling process, dosimeters with high accuracy and spatial resolution are required. Therefore, this work aims to propose a simple, robust, and a small-scale fiber-integrated X-ray inorganic detector and investigate the dosimetric characteristics used in radiotherapy.MethodsThe detector is based on red-emitting silver-activated zinc-cadmium sulfide (Zn,Cd)S:Ag nanoclusters and the proposed system has been tested under 6 MV photons with standard dose rate used in the patient treatment protocol. The article presents the performances of the detector in terms of dose linearity, repeatability, reproducibility, percentage depth dose distribution, and field output factor. A comparative study is shown using a microdiamond dosimeter and considering data from recent literature.ResultsWe accurately measured a small field beam profile of 0.5 × 0.5 cm² at a spatial resolution of 100 µm using a LINAC system. The dose linearity at 400 MU/min has shown less than 0.53% and 1.10% deviations from perfect linearity for the regular and smallest field. Percentage depth dose measurement agrees with microdiamond measurements within 1.30% and 2.94%, respectively for regular to small field beams. Besides, the stem effect analysis shows a negligible contribution in the measurements for fields smaller than 3x3 cm². This study highlights the drastic decrease of the convolution effect using a point-like detector, especially in small dimension beam characterization. Field output factor has shown a good agreement while comparing it with the microdiamond dosimeter.ConclusionAll the results presented here anticipated that the developed detector can accurately measure delivered dose to the region of interest, claim accurate depth dose distribution hence it can be a suitable candidate for beam characterization and quality assurance of LINAC system.     

A novel high-resolution 2D silicon array detector for small field dosimetry with FFF photon beams

PurposeFlattening filter free (FFF) beams are increasingly being considered for stereotactic radiotherapy (SRT). For the first time, the performance of a monolithic silicon array detector under 6 and 10 MV FFF beams was evaluated. The dosimeter, named “Octa” and designed by the Centre for Medical Radiation Physics (CMRP), was tested also under flattened beams for comparison.MethodsOutput factors (OFs), percentage depth-dose (PDD), dose profiles (DPs) and dose per pulse (DPP) dependence were investigated. Results were benchmarked against commercially available detectors for small field dosimetry.ResultsThe dosimeter was shown to be a ‘correction-free’ silicon array detector for OFs and PDD measurements for all the beam qualities investigated. Measured OFs were accurate within 3% and PDD values within 2% compared against the benchmarks. Cross-plane, in-plane and diagonal DPs were measured simultaneously with high spatial resolution (0.3 mm) and real time read-out. A DPP dependence (24% at 0.021 mGy/pulse relative to 0.278 mGy/pulse) was found and could be easily corrected for in the case of machine specific quality assurance applications.ConclusionsResults were consistent with those for monolithic silicon array detectors designed by the CMRP and previously characterized under flattened beams only, supporting the robustness of this technology for relative dosimetry for a wide range of beam qualities and dose per pulses. In contrast to its predecessors, the design of the Octa offers an exhaustive high-resolution 2D dose map characterization, making it a unique real-time radiation detector for small field dosimetry for field sizes up to 3 cm side.     

Use of PTW-microDiamond for relative dosimetry of unflattened photon beams

PurposeThe increasing interest in SBRT treatments encourages the use of flattening filter free (FFF) beams. Aim of this work was to evaluate the performance of the PTW60019 microDiamond detector under 6 MV and 10MVFFF beams delivered with the EDGE accelerator (Varian Medical System, Palo Alto, USA). A flattened 6 MV beam was also considered for comparison.MethodsShort term stability, dose linearity and dose rate dependence were evaluated. Dose per pulse dependence was investigated in the range 0.2–2.2 mGy/pulse. MicroDiamond profiles and output factors (OFs) were compared to those obtained with other detectors for field sizes ranging from 40 × 40 cm² to 0.6 × 0.6 cm². In small fields, volume averaging effects were evaluated and the relevant correction factors were applied for each detector.ResultsMicroDiamond short term stability, dose linearity and dependence on monitor unit rate were less than 0.8% for all energies. Response variations with dose per pulse were found within 1.8%. MicroDiamond output factors (OF) values differed from those measured with the reference ion-chamber for less than 1% up to 40 × 40 cm² fields where silicon diodes overestimate the dose of ≈3%. For small fields (<3 × 3 cm²) microDiamond and the unshielded silicon diode were in good agreement.ConclusionsMicroDiamond showed optimal characteristics for relative dosimetry even under high dose rate beams. The effects due to dose per pulse dependence up to 2.2 mGy/pulse are negligible. Compared to other detectors, microDiamond provides accurate OF measurements in the whole range of field sizes. For fields <1 cm correction factors accounting for fluence perturbation and volume averaging could be required.     

An optimized differential heat conduction solution microcalorimeter for thermal kinetic measurements

Heat conduction calorimeters are widely used in biological sciences, but baseline instability, low resolution, electrical noise and motion artifacts have limited their utility. Two main sources of noise, baseline fluctuation or drift and a motion artifact, were traced to amplifier drift, a small (0.015°C) gradient within the constant temperature cylinder, and the method of installing the thermopiles. The addition of heaters to the top and bottom of the cylinder reduced the gradient to approximately 0.003°C and greatly reduced the slow component of the motion artifact. The drift error was reduced by proper mounting of the amplifier and its external components and the enclosure of the calorimeter in a temperature-controlled box.An R-C model of the heat flow in the calorimeter was developed which was employed to discover several means of increasing sensitivity without increasing the rise-time of the calorimeter. Analysis, also based on the model, showed that variations in the air gap between the cell holder can be a major source of error when the calorimeter is used to investigate the kinetics of a chemical reaction. This analysis also showed that the time for the heat to flow through the solution through the solution in the cell can be the dominant factor in determining the rise-time of the instrument.The heat conduction calorimeter described here has improved characterics: a baseline stability of 200 nJ · s^?1 (peak-to-peak) over a 48 h period; a resolution of 200 nJ · s^?1; a sensitivity of 6.504 ± 0.045 J · V^?1 · s^?1 referred to the sensor output; and a rise-time of 122 s for the 10–90% response.     

An optimized method for mycelial compatibility testing in Sclerotinia sclerotiorum

Classification of isolates into mycelial compatibility groups (MCGs) is used routinely in many laboratories as a quick marker for genotyping Sclerotinia sclerotiorum within populations. Scoring each new sample requires optimization of standardized conditions to support adequate growth of all paired isolates. Appropriate conditions for growth are especially important because diverse compatibility reactions are difficult to categorize and score (e.g., in samples from populations with high genetic diversity, such as those that receive immigration from genetically diverse sources or those that deviate from strict clonality). The current standard medium for MCG testing can be inhibitory to isolates from some samples, confounding scoring of compatibility. We identified two foci for optimization: (i) choice of medium, in this experiment, Patterson's medium amended with red food coloring (termed modified Patterson's medium, MPM, the current standard medium) versus potato dextrose agar (PDA) and (ii) amount of McCormick's red food coloring amended to the growth medium. The red food coloring often yields a red reaction line in incompatible interactions; alternative incompatible reactions are a line of thick or thin hyphae. Based on results to date, self-self pairings of S. sclerotiorum are compatible and are a reliable standard for scoring compatible self-nonself mycelial interactions. PDA amended with 75 microl/L of McCormick's red food coloring was identified as optimal for isolates inhibited by MPM from a highly diverse, recombining population sample. This precisely amended PDA was also suitable for isolates from highly clonal populations that were not inhibited by MPM or by higher concentrations of red food coloring. Under the optimized, standardized conditions all paired isolates grew together and produced interactions that could be scored in repeatedly identifiable categories, compatible or incompatible. Workers are advised to optimize conditions before screening a new population sample.     

An optimized enumeration method for sorbitol-fermenting Bifidobacteria in water samples

With increased focus on watershed protection under the Surface Water Treatment Rule, indicators that discriminate among sources of microbial inputs (microbial source tracking) are needed to supplement the quantitative information provided by total and fecal coliform measurements for drinking water monitoring. Bifidobacteria are found in the digestive tract and feces of humans and other animals, and also in sewage. Sorbitol is a food additive used exclusively in food intended for human consumption. Therefore, the presence of sorbitol-fermenting Bifidobacteria in environmental waters can be indicative of sources of human fecal contamination. A series of media were evaluated using ATCC cultures of B. breve and B. adolescentis, feces from different animals, and domestic wastewater samples. The media evaluated were Human Bifid Sorbitol agar (HBSA), modified Human Bifid Sorbitol agar, Beerens Medium, modified Beerens Medium, Reinforced Clostridial agar, BIM-25 Medium, and modified BIM-25 Medium. Variables such as sample preservation, incubation time, different pH indicators, plating technique, and discontinuous exposure to sorbitol were also evaluated. A series of biochemical tests were used to confirm positive colonies enumerated on the various media. Membrane filtration and enumeration of sodium sulfite preserved samples on HBSA containing bromocresol purple using loose lidded plates for 48 h provided the best recoveries for presumptive positive colonies. A number of sorbitol-fermenters that were not Bifidobacteria were able to grow on all media tested, resulting in false-positives. Therefore, plating on HBSA should be followed by a confirmation step when monitoring for sorbitol-fermenting Bifidobacteria in environmental waters. A year-long sampling survey of a managed reservoir in Massachusetts provided field validation of the proposed methodology for sorbitol-fermenting Bifidobacteria as a human-related source tracking indicator tool.     

An optimized method for suicide vector-based allelic exchange in Klebsiella pneumoniae

Klebsiella pneumoniae is an important and versatile bacterium that can be found in diverse environments and is also a frequent cause of human infections. Limited data exists on the mechanisms of interaction between K. pneumoniae and the human host and of adaptations to other environments. Coupled with the high genetic diversity of this species, these factors highlight the necessity for substantial further K. pneumoniae-focused molecular genetics studies.In this report we describe a simple and efficient experimental protocol for suicide vector-based allelic exchange in K. pneumoniae. The protocol has been validated by mutating multiple loci in four distinct K. pneumoniae strains, including highly capsulated and/or multi-antibiotic resistant clinical isolates. Three key enhancements are reported:(1) Use of pDS132-derived conjugative plasmids carrying improved cloning sites, (2) Performance of sacB counterselection at 25 °C as opposed to higher temperatures, and (3) Exploitation of Flp-recombinase-mediated deletion of FRT (Flp recombinase target) flanked resistance cassettes to allow for reiterative manipulations with a single selectable marker. This study also highlights a problem that may be encountered when the aacC1 gentamicin resistance marker is used in K. pneumoniae and suggests alternative markers.The protocol developed in this study will help investigate the plethora of uncharacterized genes present in the K. pneumoniae pan-genome and shed further light upon clinically and industrially important phenotypes observed in this ubiquitous species.     

An optimized guanidination method for large‐scale proteomic studies

As an ε–amine specific derivatization method, guanidination is widely used in proteomic studies for mainly two reasons: the significant improvement in ionization efficiency and the selective protection of ε–amine. Herein, we employed a systematic comparison of two widely used guanidination approaches and revealed the advantages and disadvantages of each method. The sodium buffer based approach resulted in an unexpected side modification, +57 Da, which is reported for the first time; whereas the ammonium buffer based approach resulted in relatively lower yield. We carried out an optimization study by testing different buffer compositions, pH, temperatures and reaction times, and consequently discovered the optimized guanidination condition. Furthermore, we decoded the +57 Da side product as the addition of C₂H₃NO and proposed a possible mechanism of the side reaction. Importantly, our study demonstrated that mass spectrometry is a powerful tool in discovering minor side reactions which are often impossible by other techniques, and hence suggested that chemical derivatization methods should be investigated more carefully prior to extensive applications in proteomics field.     

ELF in vitro exposure systems for inducing uniform electric and magnetic fields in cell culture media.

Many in vitro experiments on the biological effects of extremely low frequency (ELF) electromagnetic fields utilize a uniform external magnetic flux density (B) to expose biological materials. A significant number of researchers do not measure or estimate the resulting electric field strength (E) or current density (J) in the sample medium. The magnitude and spatial distribution of the induced E field are highly dependent on the sample geometry and its relative orientation with respect to the magnetic field. We have studied the E fields induced in several of the most frequently used laboratory culture dishes and flasks under various exposure conditions. Measurements and calculations of the E field distributions in the aqueous sample volume in the containers were performed, and a set of simple, quantitative tables was developed. These tables allow a biological researcher to determine, in a straightforward fashion, the magnitudes and distributions of the electric fields that are induced in the aqueous sample when it is subjected to a uniform, sinusoidal magnetic field of known strength and frequency. In addition, we present a novel exposure technique based on a standard organ culture dish containing two circular, concentric annular rings. Exposure of the organ culture dish to a uniform magnetic field induces different average electric fields in the liquid medium in the inner and outer rings. Results of experiments with this system, which were reported in a separate paper, have shown the dominant role of the magnetically induced E field in producing specific biological effects on cells, in vitro. These results emphasize the need to report data about the induced E field in ELF in-vitro studies, involving magnetic field exposures. Our data tables on E and J in standard containers provide simple means to enable determination of these parameters.     

An analytical model for the calculation of the change in transmembrane potential produced by an ultrawideband electromagnetic pulse

The electric field pulse shape and change in transmembrane potential produced at various points within a sphere by an intense, ultrawideband pulse are calculated in a four stage, analytical procedure. Spheres of two sizes are used to represent the head of a human and the head of a rat. In the first stage, the pulse is decomposed into its Fourier components. In the second stage, Mie scattering analysis (MSA) is performed for a particular point in the sphere on each of the Fourier components, and the resulting electric field pulse shape is obtained for that point. In the third stage, the long wavelength approximation (LWA) is used to obtain the change in transmembrane potential in a cell at that point. In the final stage, an energy analysis is performed. These calculations are performed at 45 points within each sphere. Large electric fields and transmembrane potential changes on the order of a millivolt are produced within the brain, but on a time scale on the order of nanoseconds. The pulse shape within the brain differs considerably from that of the incident pulse. Comparison of the results for spheres of different sizes indicates that scaling of such pulses across species is complicated.     

Optimized method for in vivo dosimetry with small films in pelvic IOERT for rectal cancer

PurposeIntra-Operative Electron Radiation Therapy (IOERT) is used to treat rectal cancer at our institution, and in vivo measurements with Gafchromic EBT3® films were introduced as quality assurance. The purpose of this work was to quantify the uncertainties associated with digitization of very small EBT3 films irradiated simultaneously, in order to optimize in vivo dosimetry for IOERT.MethodsFilm samples of different sizes - M1 (5×5cm²), M2 (1.5×1.5 cm²), M3 (1.0×1.5 cm²) and M4 (0.75×1.5 cm²) – were used to quantify typical variations (uncertainties) due to scanner fluctuations, misalignment, film inhomogeneity, long-term effect of film cutting, small rotations, film curling, edge effects and the influence of opaque templates. Fitting functions and temporal validity of sensitometric curves were also assessed.ResultsFilm curling, intra-film variability and scanner fluctuations are important effects that need to be minimized or considered in the uncertainty budget. Small rotations, misalignments and film cutting have little or no influence on the readings. Most fitting functions perform well, but the quantity used for dose quantification determines over- or under-valuation of dose in the long term. Edge effects and the influence of opaque templates need to be well understood, to allow optimization of methodology to the intended purpose.ConclusionThe proposed method allows practical and simultaneous digitization of up to ten small irradiated film samples, with an experimental uncertainty of 1%.