Investigating the sensitivity of OSLD responses for varying field sizes across matched linear accelerators

When radiation therapy centres are equipped with two or more linear accelerators from the same vendor, they are usually beam-matched. This work tested the sensitivity of optically stimulated luminescence dosimeters (OSLDs) across matched linear accelerators. The responses were compared with an unshielded diode detector for varying field sizes. Clinical studies are currently done with thermoluminescent dosimeters (TLD), which absorb radiation then emit some levels of light determined by the radiation absorption when heated.

An introduction to radiation protection in medicine

"Combining facets of health physics with medicine, An Introduction to Radiation Protection in Medicine covers the background of the subject and the medical situations where radiation is the tool to diagnose or treat human disease. Encouraging newcomers to the field to properly and efficiently function in a versatile and evolving work setting, it familiarizes them with the particular problems faced during the application of ionizing radiation in medicine. The text builds a fundamental knowledge base before providing practical descriptions of radiation safety in medicine. It covers basic issues related to radiation protection, including the physical science behind radiation protection and the radiobiological basis of radiation protection. The text also presents operational and managerial tools for organizing radiation safety in a medical workplace. Subsequent chapters form the core of the book, focusing on the practice of radiation protection in different medical disciplines. They explore a range of individual uses of ionizing radiation in various branches of medicine, including radiology, nuclear medicine, external beam radiotherapy, and brachytherapy. With contributions from experienced practicing physicists, this book provides essential information about dealing with radiation safety in the rapidly shifting and diverse environment of medicine."--publisher website

An experimental approach to air gap optimisation for a correction-less small field diode

Aim A recent Monte Carlo based study has shown that it is possible to design a diode that measures small field output factors equivalent to that in water. This is accomplished by placing an appropriate sized air gap above the silicon chip (1) with experimental results subsequently confirming that a particular Monte Carlo design was accurate (2). The aim of this work was to test if a new correction-less diode could be designed using an entirely experimental methodology. Method: All measurements were performed on a Varian iX at a depth of 5 cm, SSD of 95 cm and field sizes of 5, 6, 8, 10, 20 and 30 mm. Firstly, the experimental transfer of kq,clin,kq,msr from a commonly used diode detector (IBA, stereotactic field diode (SFD)) to another diode detector (Sun Nuclear, unshielded diode, (EDGEe)) was tested. These results were compared to Monte Carlo calculated values of the EDGEe. Secondly, the air gap above the EDGEe silicon chip was optimised empirically. Nine different air gap “tops” were placed above the EDGEe (air depth = 0.3, 0.6, 0.9 mm; air width = 3.06, 4.59, 6.13 mm). The sensitivity of the EDGEe was plotted as a function of air gap thickness for the field sizes measured. Results: The transfer of kq,clin,kq,msr from the SFD to the EDGEe was correct to within the simulation and measurement uncertainties. The EDGEe detector can be made “correction-less” for field sizes of 5 and 6 mm, but was ∼2% from being “correction-less” at field sizes of 8 and 10 mm. Conclusion Different materials will perturb small fields in different ways. A detector is only “correction-less” if all these perturbations happen to cancel out. Designing a “correction-less” diode is a complicated process, thus it is reasonable to expect that Monte Carlo simulations should play an important role.

Evaluation of the spatial distribution of γH2AX following ionizing radiation

An early molecular response to DNA double-strand breaks (DSBs) is phosphorylation of the Ser-139 residue within the terminal SQEY motif of the histone H2AX1,2. This phosphorylation of H2AX is mediated by the phosphatidyl-inosito 3-kinase (PI3K) family of proteins, ataxia telangiectasia mutated (ATM), DNA-protein kinase catalytic subunit and ATM and RAD3-related (ATR)3. The phosphorylated form of H2AX, referred to as γH2AX, spreads to adjacent regions of chromatin from the site of the DSB, forming discrete foci, which are easily visualized by immunofluorecence microscopy3. Analysis and quantitation of γH2AX foci has been widely used to evaluate DSB formation and repair, particularly in response to ionizing radiation and for evaluating the efficacy of various radiation modifying compounds and cytotoxic compounds Given the exquisite specificity and sensitivity of this de novo marker of DSBs, it has provided new insights into the processes of DNA damage and repair in the context of chromatin. For example, in radiation biology the central paradigm is that the nuclear DNA is the critical target with respect to radiation sensitivity. Indeed, the general consensus in the field has largely been to view chromatin as a homogeneous template for DNA damage and repair. However, with the use of γH2AX as molecular marker of DSBs, a disparity in γ-irradiation-induced γH2AX foci formation in euchromatin and heterochromatin has been observed5-7. Recently, we used a panel of antibodies to either mono-, di- or tri- methylated histone H3 at lysine 9 (H3K9me1, H3K9me2, H3K9me3) which are epigenetic imprints of constitutive heterochromatin and transcriptional silencing and lysine 4 (H3K4me1, H3K4me2, H3K4me3), which are tightly correlated actively transcribing euchromatic regions, to investigate the spatial distribution of γH2AX following ionizing radiation8. In accordance with the prevailing ideas regarding chromatin biology, our findings indicated a close correlation between γH2AX formation and active transcription9. Here we demonstrate our immunofluorescence method for detection and quantitation of γH2AX foci in non-adherent cells, with a particular focus on co-localization with other epigenetic markers, image analysis and 3Dmodeling.

Methylproamine protects against ionizing radiation by preventing DNA double-strand breaks

Purpose The majority of cancer patients will receive radiotherapy (RT), therefore, investigations into advances of this modality are important. Conventional RT dose intensities are limited by adverse responses in normal tissues and a primary goal is to ameliorate adverse normal tissue effects. The aim of these experiments is to further our understanding regarding the mechanism of radioprotection by the DNA minor groove binder, methylproamine, in a cellular context at the DNA level. Materials and methods We used immunocytochemical methods to measure the accumulation of phosphorylated H2AX (γH2AX) foci following ionizing radiation (IR) in patient-derived lymphoblastoid cells exposed to methylproamine. Furthermore, we performed pulsed field gel electrophoresis DNA damage and repair assays to directly interrogate the action of methylproamine on DNA in irradiated cells. Results We found that methylproamine-treated cells had fewer γH2AX foci after IR compared to untreated cells. Also, the presence of methylproamine decreased the amount of lower molecular weight DNA entering the gel as shown by the pulsed field gel electrophoresis assay. Conclusions These results suggest that methylproamine acts by preventing the formation of DNA double-strand breaks (dsbs) and support the hypothesis that radioprotection by methylproamine is mediated, at least in part, by decreasing initial DNA damage.

γ-radiation-induced γH2AX formation occurs preferentially in actively transcribing euchromatic loci

The central dogma in radiation biology is that nuclear DNA is the critical target with respect to radiosensitivity. In accordance with the theoretical expectations, and in the absence of a conclusive model, the general consensus in the field has been to view chromatin as a homogeneous template for DNA damage and repair. This paradigm has been called into question by recent findings indicating a disparity in γ-irradiation-induced γH2AX foci formation in euchromatin and heterochromatin. Here, we have extended those studies and provide evidence that γH2AX foci form preferentially in actively transcribing euchromatin following γ-irradiation.

An external field prior for the hidden Potts model with application to cone-beam computed tomography

In images with low contrast-to-noise ratio (CNR), the information gain from the observed pixel values can be insufficient to distinguish foreground objects. A Bayesian approach to this problem is to incorporate prior information about the objects into a statistical model. A method for representing spatial prior information as an external field in a hidden Potts model is introduced. This prior distribution over the latent pixel labels is a mixture of Gaussian fields, centred on the positions of the objects at a previous point in time. It is particularly applicable in longitudinal imaging studies, where the manual segmentation of one image can be used as a prior for automatic segmentation of subsequent images. The method is demonstrated by application to cone-beam computed tomography (CT), an imaging modality that exhibits distortions in pixel values due to X-ray scatter. The external field prior results in a substantial improvement in segmentation accuracy, reducing the mean pixel misclassification rate for an electron density phantom from 87% to 6%. The method is also applied to radiotherapy patient data, demonstrating how to derive the external field prior in a clinical context.

Field size consistency of nominally matched linacs

Given that there is increasing recognition of the effect that submillimetre changes in collimator position can have on radiotherapy beam dosimetry, this study aimed to evaluate the potential variability in small field collimation that may exist between otherwise matched linacs. Field sizes and field output factors were measured using radiochromic film and an electron diode, for jaw- and MLC-collimated fields produced by eight dosimetrically matched Varian iX linacs (Varian Medical Systems, Palo Alto, USA). This study used nominal sizes from 0.6×0.6 to 10×10 cm215 , for jaw-collimated fields,and from 1×1 to 10×10 cm216 , for MLC-collimated fields, delivered from a zero (head up, beam directed vertically downward) gantry angle. Differences between the field sizes measured for the eight linacs exceeded the uncertainty of the film measurements and the repositioning uncertainty of the jaws and MLCs on one linac. The dimensions of fields defined by MLC leaves were more consistent between linacs, while also differing more from their nominal values than fields defined by orthogonal jaws. The field output factors measured for the different linacs generally increased with increasing measured field size for the nominal 0.6×0.6 and 1×1 cm2 fields, and became consistent between linacs for nominal field sizes of 2×2 cm2 25 and larger. The inclusion in radiotherapy treatment planning system beam data of small field output factors acquired in fields collimated by jaws (rather than the more-reproducible MLCs), associated with either the nominal or the measured field sizes, should be viewed with caution. The size and reproducibility of the fields (especially the small fields) used to acquire treatment planning data should be investigated thoroughly as part of the linac or planning system commissioning process. Further investigation of these issues, using different linac models, collimation systems and beam orientations, is recommended.

Comparison of Radiation Doses for Catheter Ablation Procedures for Atrial Fibrillation with Percutaneous Coronary Intervention Cases

Background: Catheter ablation procedures for atrial fibrillation (AF) may frequently require long fluoroscopic times. We sought to undertake a review of radiation safety practice in our Cardiac Electrophysiology Laboratory and implement changes to minimize fluoroscopic doses. We also sought to compare the results with radiation doses for percutaneous coronary intervention (PCI) cases performed in our hospital. Methods: Fluoroscopic times and doses for AF ablation procedures performed by a single operator on a Philips Integris H3000 image-intensifier were analysed for 11-month period. Results were compared with all PCI procedures performed over a similar period by multiple operators on a Philips Integris Allura FD system. Comprehensive review of radiation practice in the Electrophysiology laboratory identified the potential to reduce pulse frame rates and doses, and to narrow the field of interest without impacting the performance of the procedure. These changes were implemented and results analysed after a further 11 months. Results: In the pre-intervention period 50 AF catheter ablations had a mean fluoroscopic time of 86.4 min and mean fluoroscopic dose 68.4 Gy/cm2. Post-intervention 75 procedures had a mean fluorosocopic time of 68.9 min (p < 0.0001) and mean dose of 14.3 Gy/cm2 (p < 0.0001) 128 PCI procedures had a mean combined fluoroscopic and image acquisition time of 10.0 min and mean total dose 38.8 Gy/cm2. Conclusions: Catheter ablation procedures for AF may require lengthy use of fluoroscopy but simple modifications to radiation practice can result in marked reductions in radiation dose that compare favourably with PCI case doses