Professor Andrew Nisbet

Objective: To evaluate the impact of static magnetic field (SMF) presence on the radiation response of pancreatic cancer cells in polyurethane -based highly macro-porous scaffolds in hypoxic (1% O-2) and normoxic (21% O-2) conditions, towards understanding MR-guided radiotherapy, shedding light on the potential interaction phenomenon between SMF and radiation in a three-dimensional (3D) microenvironment.Methods: Pancreatic cancer cells (PANC- 1, ASPC- 1) were seeded into fibronectin-coated highly porous polyethene scaffolds for biomimicry and cultured for 4 weeks in in vitro normoxia (21% O-2) followed by a 2 -day exposure to either in vitro hypoxia (1% O-2) or maintenance in in vitro normoxia (21% O-2). The samples were then irradi-ated with 6 MV photons in the presence or absence of a 1.5 T field. Thereafter, in situ post-radiation monitoring (1 and 7 days post-irradiation treatment) took place via quantification of (i) live dead and (ii) apoptotic profiles.Results: We report: (i) pancreatic ductal adenocarci-noma hypoxia-associated radioprotection, in line with our previous findings, (ii) an enhanced effect of radia-tion in the presence of SMFin in vitro hypoxia (1% O-2) for both short-(1 day) and long -term (7 days) post -radia-tion analysis and (iii) an enhanced effect of radiation in the presence of SMF in in vitro normoxia (21% O-2) for long -term (7 days) post-radiation analysis within a 3D pancreatic cancer model Conclusion: With limited understanding of the poten-tial interaction phenomenon between SMF and radia-tion, this 3D system allows combination evaluation for a cancer in which the role of radiotherapy is still evolving.Advances in knowledge: This study examined the use of a 3D model to investigate MR-guided radiotherapy in a hypoxic microenvironment, indicating that this could be a useful platform to further understanding of SMF influ-ence on radiation.

The efficiency of radiotherapy treatment regimes varies from tumour to tumour and from patient to patient but it is generally highly influenced by the tumour microenvironment (TME). The TME can be described as a heterogeneous composition of biological, biophysical, biomechanical and biochemical milieus that influence the tumour survival and its' response to treatment. Preclinical research faces challenges in the replication of these milieus for predictable treatment response studies. 2D cell culture is a traditional, simplistic and cost-effective approach to culture cells , however, the nature of the system fails to recapitulate important features of the TME such as structure, cell-cell and cell-matrix interactions. At the same time, the traditional use of animals (Xenografts) in cancer research allows realistic architecture, however foreign physiology, limited heterogeneity and reduced tumour mutation rates impairs relevance to humans. Furthermore, animal research is very time consuming and costly. Tissue engineering is advancing as a promising biomimetic approach, producing 3D models that capture structural, biophysical, biochemical and biomechanical features, therefore, facilitating more realistic treatment response studies for further clinical application. However, currently, the application of 3D models for radiation response studies is an understudied area of research, especially for pancreatic ductal adenocarcinoma (PDAC), a cancer with a notoriously complex microenvironment. At the same time, specific novel and/or more enhanced radiotherapy tumour-targeting techniques such as MRI-guided radiotherapy and proton therapy are emerging to more effectively target pancreatic cancer cells. However, these emerging technologies may have different biological effectiveness as compared to established photon-based radiotherapy. For example, for MRI-guided radiotherapy, the novel use of static magnetic fields (SMF) during radiation delivery is understudied and not fully understood. Thus, reliable biomimetic platforms to test new radiation delivery strategies are required to more accurately predict responses. Here, we aim to collate current 3D models for radiation response studies of PDAC, identifying the state of the art and outlines knowledge gaps. Overall, this review paper highlights the need for further research on the use of 3D models for pre-clinical radiotherapy screening including (i) 3D (re)-modeling of the PDAC hypoxic TME to allow for late effects of ionising radiation (ii) the screening of novel radiotherapy approaches and their combinations as well as (iii) a universally accepted 3D-model image quantification method for evaluating TME components that would facilitate accurate post-treatment(s) quantitative comparisons.

Tissue engineering is evolving to mimic intricate ecosystems of tumour microenvironments (TME) to more readily map realistic in vivo niches of cancerous tissues. Such advanced cancer tissue models enable more accurate preclinical assessment of treatment strategies. Pancreatic cancer is a dangerous disease with high treatment resistance that is directly associated with a highly complex TME. More specifically, the pancreatic cancer TME includes (i) complex structure and complex extracellular matrix (ECM) protein composition; (ii) diverse cell populations (e.g., stellate cells), cancer associated fibroblasts, endothelial cells, which interact with the cancer cells and promote resistance to treatment and metastasis; (iii) accumulation of high amounts of (ECM), which leads to the creation of a fibrotic/desmoplastic reaction around the tumour; and (iv) heterogeneous environmental gradients such as hypoxia, which result from vessel collapse and stiffness increase in the fibrotic/desmoplastic area of the TME. These unique hallmarks are not effectively recapitulated in traditional preclinical research despite radiotherapeutic resistance being largely connected to them. Herein, we investigate, for the first time, the impact of in vitro hypoxia (5% O2) on the radiotherapy treatment response of pancreatic cancer cells (PANC-1) in a novel polymer (polyurethane) based highly macroporous scaffold that was surface modified with proteins (fibronectin) for ECM mimicry. More specifically, PANC-1 cells were seeded in fibronectin coated macroporous scaffolds and were cultured for four weeks in in vitro normoxia (21% O2), followed by a two day exposure to either in vitro hypoxia (5% O2) or maintenance in in vitro normoxia. Thereafter, in situ post-radiation monitoring (one day, three days, seven days post-irradiation) of the 3D cell cultures took place via quantification of (i) live/dead and apoptotic profiles and (ii) ECM (collagen-I) and HIF-1a secretion by the cancer cells. Our results showed increased post-radiation viability, reduced apoptosis, and increased collagen-I and HIF-1a secretion in in vitro hypoxia compared to normoxic cultures, revealing hypoxia-induced radioprotection. Overall, this study employed a low cost, animal free model enabling (i) the possibility of long-term in vitro hypoxic 3D cell culture for pancreatic cancer, and (ii) in vitro hypoxia associated PDAC radio-protection development. Our novel platform for radiation treatment screening can be used for long-term in vitro post-treatment observations as well as for fractionated radiotherapy treatment.

With a very low survival rate, pancreatic ductal adenocarcinoma (PDAC) is a deadly disease. This has been primarily attributed to – (i) its late diagnosis and (ii) its high resistance to current treatment methods. The later, specifically requires the development of robust, realistic in vitro models of PDAC, capable of accurately mimicking the in vivo tumour niche. Advancements in the field of Tissue Engineering (TE) have helped the development of such models for PDAC. Herein, we report for the first time a novel hybrid, poly- urethane (PU) scaffold based, long term, multicellular (tri-culture) model of pancreatic cancer involving cancer cells, endothelial cells and stellate cells. Recognising the importance of ECM proteins for optimal growth of different cell types, the model consists of two different zones/compartments: an inner tumour compartment consisting of cancer cells (fibronectin coated) and a surrounding stromal compartment consisting of stellate and endothelial cells (collagen I coated). Our developed novel hybrid, tri-culture model supports the proliferation of all different cell types for 35 days (5 weeks), which is the longest reported time frame in vitro. Furthermore, the hybrid model showed extensive collagen I production by the cells, mimicking desmoplasia, one of PDAC’s hallmark features. Fibril alignment of the stellate cells was observed, which attested for their activated state. All three cell types expressed various cell specific markers within the scaffolds, throughout the culture period and showed cellular migration between the two zones of the hybrid scaffold. Our novel model has great potential as a low cost tool for in vitro studies of PDAC as well as for treatment screening.

The isolation of chemical compounds from natural origins for medical application has played an important role in modern medicine with a range of novel treatments having emerged from various natural forms over the past decades. Natural compounds have been exploited for their antioxidant, antimicrobial and antitumor capabilities. Specifically, 60% of today’s anticancer drugs originate from natural sources. Moreover, the combination of synthetic and natural treatments has shown applications for (i) reduced side effects, (ii) treatment sensitization and (iii) reduction in treatment resistance. This review aims to collate novel and natural compounds that are being explored for their preclinical anticancer, chemosensitizing and radiosensitizing effects on Pancreatic Ductal Adenocarcinoma (PDAC), which is a lethal disease with current treatments being inefficient and causing serve side effects. Two key points are highlighted by this work: (i) the availability of a range of natural compounds for potentially new therapeutic approaches for PDAC, (ii) potential synergetic impact of natural compounds with advanced chemo- and radio-therapeutic modalities for PDAC.

This report contains the recommendations of the Electron Dosimetry Working Party of the UK Institute of Physics and Engineering in Medicine (IPEM). The recommendations consist of a code of practice for electron dosimetry for radiotherapy beams of initial energy from 4 to 25 MeV. The code is based on the absorbed dose to water calibration service for electron beams provided by the UK standards laboratory, the National Physical Laboratory (NPL). This supplies direct N(D,w) calibration factors, traceable to a calorimetric primary standard, at specified reference depths over a range of electron energies up to approximately 20 MeV. Electron beam quality is specified in terms of R(50,D), the depth in water along the beam central axis at which the dose is 50% of the maximum. The reference depth for any given beam at the NPL for chamber calibration and also for measurements for calibration of clinical beams is 0.6R(50.D) - 0.1 cm in water. Designated chambers are graphite-walled Farmer-type cylindrical chambers and the NACP- and Roos-type parallel-plate chambers. The practical code provides methods to determine the absorbed dose to water under reference conditions and also guidance on methods to transfer this dose to non-reference points and to other irradiation conditions. It also gives procedures and data for extending up to higher energies above the range where direct calibration factors are currently available. The practical procedures are supplemented by comprehensive appendices giving discussion of the background to the formalism and the sources and values of any data required. The electron dosimetry code improves consistency with the similar UK approach to megavoltage photon dosimetry, in use since 1990. It provides reduced uncertainties, approaching 1% standard uncertainty in optimal conditions, and a simpler formalism than previous air kerma calibration based recommendations for electron dosimetry

Purpose/Objective: To investigate the feasibility of using glass beads as a novel thermoluminescence dosimeter (TLD) in clinical proton radiotherapy. The glass beads have several physical characteristics which suggest their suitability for use as TLDs in this area: a spherical physical shape with a hole in the middle that facilitate their use in 2D and 3D arrangements; chemically inert nature; small size of 1.5 mm diameter and 1 mm thickness; inexpensive and readily available; reusable; and importantly their TL light transparency with negligible self-attenuation which is very important for high LET beams. Proton beams have high LET and therefore can deposit dose nonuniformly across a detector. Readout of TL detectors can be influenced if any opacity is present causing self-attenuation of TL light [1], [2]. The transparency of glass beads to TL light means the beads have the potential to avoid such issues.

Objectives This study tested the hypothesis that shows advanced image analysis can differentiate fit and unfit patients for radical radiotherapy from standard radiotherapy planning imaging, when compared to formal lung function tests (FEV1, Forced Expiratory Volume in 1 second) and TLCO (Transfer Factor of Carbon Monoxide). Methods An apical region of interest (ROI) of lung parenchyma was extracted from a standard radiotherapy planning CT scan. Software using a grey level co-occurrence matrix (GLCM) assigned an entropy score to each voxel, based on its similarity to the voxels around it. Density and entropy scores were compared between a cohort of fit patients (defined as FEV1 and TLCO above 50% predicted value) and unfit patients (FEV1 or TLCO below 50% predicted). Results 29 fit and 32 unfit patients were included. Mean and median density and mean and median entropy were significantly different between fit and unfit patients (p= 0.0021, 0.0019, 0.0357 and 0.0363 respectively, 2 sided t-test). Conclusions Density and entropy assessment can differentiate between fit and unfit patients for radical radiotherapy, using standard CT imaging. Advances in knowledge This study shows that a novel intervention can generate further data from standard CT imaging. This data could be combined with existing studies to form a multi-organ patient fitness assessment from a single CT scan.

This brief work-in-progress outlines two methods that we have attempted for determining the dose at which the linear relation between optical density of a PRESAGE™ dosimeter and the dose deposited breaks down. Both methods were equally successful in mapping the linear relation up to an optical density of approximately 6.25 cm−1 (absorbance 2..5), but no saturation was found in this region.

Previous research on optical computed tomography (CT) microscopy in the context of the synchrotron microbeam has shown the potential of the technique and demonstrated high quality images, but has left two questions unanswered: (i) are the images suitably quantitative for 3D dosimetry? and (ii) what is the impact on the spatial resolution of the system of the limited depth-of-field of the microscope optics? Cuvette and imaging studies are reported here that address these issues. Two sets of cuvettes containing the radiochromic plastic PRESAGE® were irradiated at the ID17 biomedical beamline of the European Synchrotron Radiation facility over the ranges 0-20 and 0-35 Gy and a third set of cuvettes was irradiated over the range 0-20 Gy using a standard medical linac. In parallel, three cylindrical PRESAGE® samples of diameter 9.7 mm were irradiated with test patterns that allowed the quantitative capabilities of the optical CT microscope to be verified, and independent measurements of the imaging modulation transfer function (MTF) to be made via two different methods. Both spectrophotometric analysis and imaging gave a linear dose response, with gradients ranging from 0.036-0.041 cm(-1) Gy(-1) in the three sets of cuvettes and 0.037 (optical CT units) Gy(-1) for the imaging. High-quality, quantitative imaging results were obtained throughout the 3D volume, as illustrated by depth-dose profiles. These profiles are shown to be monoexponential, and the linear attention coefficient of PRESAGE® for the synchrotron-generated x-ray beam is measured to be (0.185 ± 0.02) cm(-1) in excellent agreement with expectations. Low-level (

Dose distribution measurement in clinical high dose rate (HDR) brachytherapy is challenging, because of the high dose gradients, large dose variations, and small scale, but it is essential to verify accurate treatment planning and treatment equipment performance. The authors compare and evaluate three dosimetry systems for potential use in brachytherapy dose distribution measurement: Ge-doped optical fibers, EBT3 Gafchromic film with multichannel analysis, and the radiochromic material PRESAGE(®) with optical-CT readout.

Two thermoluminescent dosimeters (SiO-GeO doped fibres and glass beads (GB)) were used to measure small photon field doses and compared against GAFCHROMIC film, a small ionisation chamber (RK-018) and a p-type silicon diode (SCANDITRONIX, F1356), as well as Monte Carlo simulations with FLUKA and BEAMnrc/DOSXYZnrc. Ge-doped SiO fibres have been shown by this group to offer a viable system for use as dosimeters. The fibres and GB offer good spatial resolution (~120μm and 2mm respectively), large dynamic dose range (with linearity from tens of mGy up to well in excess of many tens of Gy), are non-hygroscopic and are of low cost. Measurements of beam profiles for field sizes of 10mm×10mm, 20mm×20mm, 30mm×30mm, 40mm×40mm, and 100mm×100mm were carried out. Through the use of a customised solid water phantom, doped optical fibres and GBs were placed at defined positions along the x-and y-axes to allow accurate beam profile measurement. The maximum difference between FWHM measurements was 1.8mm. For penumbra measurements (measured between 80% and 20% isodoses), the maximum difference was

Several studies have recently reported on the value of CT texture analysis in predicting survival, although the topic remains controversial, with further validation needed in order to consolidate the evidence base. The aim of this study was to investigate the effect of varying the input parameters in the Kaplan–Meier analysis, to determine whether the resulting P-value can be considered to be a robust indicator of the parameter's prognostic potential. A retrospective analysis of the CT-based normalised entropy of 51 patients with lung cancer was performed and overall survival data for these patients were collected. A normalised entropy cut-off was chosen to split the patient cohort into two groups and log-rank testing was performed to assess the survival difference of the two groups. This was repeated for varying normalised entropy cut-offs and varying follow-up periods. Our findings were also compared with previously published results to assess robustness of this parameter in a multi-centre patient cohort. The P-value was found to be highly sensitive to the choice of cut-off value, with small changes in cut-off producing substantial changes in P. The P-value was also sensitive to follow-up period, with particularly noisy results at short follow-up periods. Using matched conditions to previously published results, a P-value of 0.162 was obtained. Survival analysis results can be highly sensitive to the choice in texture cut-off value in dichotomising patients, which should be taken into account when performing such studies to avoid reporting false positive results. Short follow-up periods also produce unstable results and should therefore be avoided to ensure the results produced are reproducible. Previously published findings that indicated the prognostic value of normalised entropy were not replicated here, but further studies with larger patient numbers would be required to determine the cause of the different outcomes.

X-ray detectors are critical to healthcare diagnostics, cancer therapy and homeland security, with many potential uses limited by system cost and/or detector dimensions. Current X-ray detector sensitivities are limited by the bulk X-ray attenuation of the materials and consequently necessitate thick crystals (~ 1 mm – 1 cm), resulting in rigid structure, high operational voltages and high cost. Here we present a disruptive, flexible, low cost, broad-band, and high sensitivity direct X-ray transduction technology produced by embedding high atomic number bismuth oxide nanoparticles in an organic bulk heterojunction. These hybrid detectors demonstrate sensitivities of 1712 µC mGy-1 cm-3 for “soft” X-rays and ~30 and 58 µC mGy-1 cm-3 under 6 and 15 MV “hard” X-rays generated from a medical linear accelerator; strongly competing with the current solid state detectors, all achieved at low bias voltages (-10 V) and low power, enabling detector operation powered by coin cell batteries.

Recently, a new family of low-cost x-radiation detectors have been developed, based on semiconducting polymer diodes, which are easy to process, mechanically flexible, relatively inexpensive, and able to cover large areas. To test their potential for radiotherapy applications such as beam monitors or dosimeters, as an alternative to the use of solid-state inorganic detectors, we present the direct detection of 6 MV x-rays from a medical linear accelerator using a thick film, semiconducting polymer detector. The diode was subjected to 4 ms pulses of 6 MV x-rays at a rate of 60 Hz, and produces a linear increase in photocurrent with increasing dose rate (from 16.7 to 66.7 mGy s(−1)). The sensitivity of the diode was found to range from 13 to 20 nC mGy(−1) cm(−3), for operating voltages from −50 to −150 V, respectively. The diode response was found to be stable after exposure to doses up to 15 Gy. Testing beyond this dose range was not carried out. Theoretical calculations show that the addition of heavy metallic nanoparticles to polymer films, even at low volume fractions, increases the x-ray sensitivity of the polymer film/nanoparticle composite so that it exceeds that for silicon over a wide range of x-ray energies. The possibility of detecting x-rays with energies relevant to medical oncology applications opens up the potential for these polymer detectors to be used in detection and imaging applications using medical x-ray beams.

The use of rotational therapy as an important method of treatment delivery is expected to increase due in a large part to the development and utilisation of tomotherapy. Rotational therapy minimises the occurrence of hotspots and the irradiation of critical organs, providing more uniform dosing while sparing critical organs. Two important characteristics of rotational radiation are its dynamic nature and dosimetric variability in radiation delivery, both of which present a considerable challenge for clinical physicists seeking appropriate tools to meet the demands of quality assurance.In this paper 15 Delivery Quality Assurance (DQA) plans of head and neck patients were assessed for the Hi-Art tomotherapy system using Kodak X-Omat V film and an A1SL Ref F92722 ion chamber versus MapCheck. Absolute dose measurement showed average differences of 3.42. cGy and 98% Gamma (γ) factor for the Cheese phantom technique. For the MapCheck technique the average difference and Gamma factor were 0.74. cGy and 96%, respectively. Gamma (γ) matrix distribution was used to evaluate the difference between measured and calculated dose distribution. © 2013 Elsevier Ltd.

After a release of radionuclides, accidental or otherwise, there will be an urgent need to identify members of the general public who have received a significant intake of radioactive material, sufficient to require medical treatment or further investigation. A large number of people could be contaminated in such an incident. For gamma-ray emitting radionuclides this screening could be carried out using gamma camera medical imaging systems, such as those that are present in many large UK hospital sites. By making a number of simple reversible changes such as removal of collimators, these cameras could be employed as useful additional screening instruments as well as an aid in contamination control. A study was carried out to investigate which systems were present in sufficient number to offer wide scale coverage of UK population centres. Nine gamma cameras (eight dual head and one single head) were assessed using point source and bottle mannequin (BOMAB) phantom measurements so that a mathematical model could be developed for use with the MCNPX Monte Carlo radiation transport code. The gamma camera models were assessed for practical seated and supine geometries to give calibration factors for a list of target radionuclides that could be released in a radiological incident. The minimum detectable activities (MDAs) that were achieved for a five minute measurement demonstrated that these systems are sufficiently sensitive to be used for screening of the general public and are comparable to other body monitoring facilities. While gamma cameras have on-board software that are designed for imaging and provide for a gamma-ray energy range suitable for radionuclides for diagnostic imaging (such as 99mTc), they are not as versatile as custom-built body monitoring systems.

EPID dosimetry has known drawbacks. The main issue is that a measurable residual signal is observed after the end of irradiation for prolonged periods of time, thus making measurement difficult. We present a detailed analysis of EPID response and suggest a simple, yet accurate approach for calibration that avoids the complexity of incorporating ghosting and image-lag using the maximum integrated signal instead of the total integrated signal. This approach is linear with dose and independent of dose rate. © 2012 Elsevier Ltd.

Review is made of dosimetric studies of Ge-doped SiO telecommunication fibre as a 1-D thermoluminescence (TL) system for therapeutic applications. To-date, the response of these fibres has been investigated for UV sources, superficial X-ray beam therapy facilities, a synchrotron microbeam facility, electron linear accelerators, protons, neutrons and alpha particles, covering the energy range from a few eV to several MeV. Dosimetric characteristics include, reproducibility, fading, dose response, reciprocity between TL yield and dose-rate and energy dependence. The fibres produce a flat response to fixed photon and electron doses to within better than 3% of the mean TL distribution. Irradiated Ge-doped SiO optical fibres show limited signal fading, with an average loss of TL signal of ~0.4% per day. In terms of dose response, Ge-doped SiO optical fibres have been shown to provide linearity to x and electron doses, from a fraction of 1Gy up to 2kGy. The dosimeters have also been used in measuring photoelectron generation from iodinated contrast media; TL yields being some 60% greater in the presence of iodine than in its absence. The review is accompanied by previously unpublished data. © 2012 Elsevier Ltd.

This study provides a review of recent publications on the physics-aspects of dosimetric accuracy in high dose rate (HDR) brachytherapy. The discussion of accuracy is primarily concerned with uncertainties, but methods to improve dose conformation to the prescribed intended dose distribution are also noted. The main aim of the paper is to review current practical techniques and methods employed for HDR brachytherapy dosimetry. This includes work on the determination of dose rate fields around brachytherapy sources, the capability of treatment planning systems, the performance of treatment units and methods to verify dose delivery. This work highlights the determinants of accuracy in HDR dosimetry and treatment delivery and presents a selection of papers, focusing on articles from the last five years, to reflect active areas of research and development. Apart from Monte Carlo modelling of source dosimetry, there is no clear consensus on the optimum techniques to be used to assure dosimetric accuracy through all the processes involved in HDR brachytherapy treatment. With the exception of the ESTRO mailed dosimetry service, there is little dosimetric audit activity reported in the literature, when compared with external beam radiotherapy verification.

Within the field of molecular radiotherapy, there is a significant need for standardisation in dosimetry, in both quantitative imaging and dosimetry calculations. Currently, there are a wide range of techniques used by different clinical centres and as a result there is no means to compare patient doses between centres. To help address this need, a 3 year project was funded by the European Metrology Research Programme, and a number of clinical centres were involved in the project. One of the required outcomes of the project was to develop a calibration protocol for three dimensional quantitative imaging of volumes of interest. Two radionuclides were selected as being of particular interest: iodine-131 (131I, used to treat thyroid disorders) and lutetium-177 (177Lu, used to treat neuroendocrine tumours). A small volume of activity within a scatter medium (water), representing a lesion within a patient body, was chosen as the calibration method. To ensure ease of use in clinical centres, an “off-the-shelf” solution was proposed – to avoid the need for in-house manufacturing. The BIODEX elliptical Jaszczak phantom and 16 ml fillable sphere were selected. The protocol was developed for use on SPECT/CT gamma cameras only, where the CT dataset would be used to correct the imaging data for attenuation of the emitted photons within the phantom. The protocol corrects for scatter of emitted photons using the triple energy window correction technique utilised by most clinical systems. A number of clinical systems were tested in the development of this protocol, covering the major manufacturers of gamma camera generally used in Europe. Initial imaging was performed with 131I and 177Lu at a number of clinical centres, but due to time constraints in the project, some acquisitions were performed with 177Lu only. The protocol is relatively simplistic, and does not account for the effects of dead-time in high activity patients, the presence of background activity surrounding volumes of interest or the partial volume effect of imaging lesions smaller than 16 ml. The development of this simple protocol demonstrates that it is possible to produce a standardised quantitative imaging protocol for molecular radiotherapy dosimetry. However, the protocol needs further development to expand it to incorporate other radionuclides, and to account for the effects that have been disregarded in this initial version

The increase in the number of therapeutic proton and ion beam centres worldwide has prompted renewed interest in measuring and simulating microdosimetric spectra in order to help understand the complexity underlying the Relative Biological Effectiveness (RBE) of these treatment modalities. In this context we have studied the capability of the Geant4 toolkit to simulate microdosimetric spectra measured with a Tissue Equivalent Proportional Counter (TEPC) in a clinical carbon ion beam. The simulated spectra were compared with published experimental data obtained along the depth dose curve of a 194 MeV/u carbon beam at the GSI, Darmstadt (Gerlach et al., 2002). The initial beam energy and energy spread employed in the simulation were tuned to match the calculated and measured depth dose distributions. A good agreement was found at all depths after a shift of 4.025 mm was taken into account with agreement for the microdosimetric derived RBE values to within 0.4% and 11.9% for depths 40 and 66 mm in PMMA (Perspex). This work demonstrates that the Geant4 toolkit can accurately reproduce experimental microdosimetric data and can thus be used for independent calculation of lineal energy spectra from which RBE estimates can be derived using the equation of Pihet et al. (1990). The work highlights the difficulty in using experimental work to benchmark Monte Carlo simulations and the need for detailed descriptions of experimental setups used.

Present interest concerns development of a system to measure photoelectron-enhanced dose close to a tissue interface using analogue gold-coated doped silica-fibre thermoluminescence detectors and an X-ray set operating at 250. kVp. Study is made of the dose enhancement factor for various thicknesses of gold; measurements at a total gold thickness of 160. nm (accounting for incident and exiting photons) produces a mean measured dose enhancement factor of 1.33±0.01 To verify results, simulations of the experimental setup have been performed. © 2013 Elsevier Ltd.

Purpose: The aim of this work was to determine whether a commercial knowledge-based treatment planning (KBP) module can efficiently produce IMRT and VMAT plans in the pelvic region (prostate & cervical cancer), and to assess sensitivity of plan quality to training data and model parameters. Methods: Initial benchmarking of KBP was performed using prostate cancer cases. Structures and dose distributions from 40 patients previously treated using a 5-field IMRT technique were used for model training. Two types of model were created: one excluded statistical outliers (as identified by RapidPlan guidelines) and the other had no exclusions. A separate model for cervix uteri cancer cases was subsequently developed using 37 clinical patients treated for cervical cancer using RapidArcTM VMAT, with no exclusions. The resulting models were then used to generate plans for ten patients from each patient group who had not been included in the modelling process. Comparisons of generated RapidPlans with the corresponding clinical plans were carried out to indicate the required modifications to the models. Model parameters were then iteratively adjusted until plan quality converged with that obtained by experienced planners without KBP. Results: Initial automated model generation settings led to poor conformity, coverage and efficiency compared to clinical plans. Therefore a number of changes to the initial KBP models were required. Before model optimisation, it was found that the PTV coverage was slightly reduced in the superior and inferior directions for RapidPlan compared with clinical plans and therefore PTV parameters were adjusted to improve coverage. OAR doses were similar for both RapidPlan and clinical plans (p > 0.05). Excluding outliers had little effect on plan quality (p 0.05). Manually fixing key optimisation objectives enabled production of clinically acceptable treatment plans without further planner intervention for 9 of 10 prostate test patients and all 10 cervix test patients. Conclusions: The Varian RapidPlanTM system was able to produce IMRT & VMAT treatment plans in the pelvis, in a single optimisation, that had comparable sparing and comparable or better conformity than the original clinically acceptable plans. The system allows for better consistency and efficiency in the treatment planning process and has therefore been adopted clinically within our institute with over 100 patients treated.

This article reviews publications related to the use of CT scans for radiotherapy treatment planning, specifically the impact of scan protocol changes on CT number and treatment planning dosimetry and on CT image quality. A search on PubMed and EMBASE and a subsequent review of references yielded 53 relevant articles. CT scan parameters significantly affect image quality. Some will also affect Hounsfield unit (HU) values, though this is not comprehensively reported on. Changes in tube kilovoltage and, on some scanners, field of view and reconstruction algorithms have been found to produce notable HU changes. The degree of HU change which can be tolerated without changing planning dose by >1% depends on the body region and size, planning algorithms, treatment beam energy and type of plan. A change in soft-tissue HU value has a greater impact than changes in HU for bone and air. The use of anthropomorphic phantoms is recommended when assessing HU changes. There is limited published work on CT scan protocol optimization in radiotherapy. Publications suggest that HU tolerances of ±20 HU for soft tissue and of ±50 HU for the lung and bone would restrict dose changes in the treatment plan to

Quality audits and intercomparisons are important in ensuring control of processes in any system of endeavour. Present interest is in control of dosimetry in teletherapy, there being a need to assess the extent to which there is consistent radiation dose delivery to the patient. In this study we review significant factors that impact upon radiotherapy dosimetry, focusing upon the example situation of radiotherapy delivery in Malaysia, examining existing literature in support of such efforts. A number of recommendations are made to provide for increased quality assurance and control. In addition to this study, the first level of intercomparison audit i.e. measuring beam output under reference conditions at eight selected Malaysian radiotherapy centres is checked; use being made of 9 µm core diameter Ge-doped silica fibres (Ge-9 µm). The results of Malaysian Secondary Standard Dosimetry Laboratory (SSDL) participation in the IAEA/WHO TLD postal dose audit services during the period between 2011 and 2015 will also been discussed. In conclusion, following review of the development of dosimetry audits and the conduct of one such exercise in Malaysia, it is apparent that regular periodic radiotherapy audits and intercomparison programmes should be strongly supported and implemented worldwide. The programmes to-date demonstrate these to be a good indicator of errors and of consistency between centres. A total of ei+ght beams have been checked in eight Malaysian radiotherapy centres. One out of the eight beams checked produced an unacceptable deviation; this was found to be due to unfamiliarity with the irradiation procedures. Prior to a repeat measurement, the mean ratio of measured to quoted dose was found to be 0.99 with standard deviation of 3%. Subsequent to the repeat measurement, the mean distribution was 1.00, and the standard deviation was 1.3%.

Recent developments in advanced radiotherapy techniques using small field photon beams, require small detectors to determine the delivered dose in steep dose gradient fields. Commercially available glass jewellery beads exhibit thermoluminescent properties and have the potential to be used as dosimeters in radiotherapy due to their small size (

Purpose: Investigating the feasibility of using low-cost commercially available silica beads as novel thermo-luminescence dosimeters (TLD) for postal dosimetry audit. Methods: A mail-based dosimetry audit was designed to assess the positional and dosimetric accuracy of SABR-lung treatment delivery using alanine and EBT3-film, placed in a CIRS-anthropomorphic thorax phantom. In conjunction, the silica beads were dosimetrically characterised as TLDs and cross-calibrated against the alanine. A CT-scan of the phantom with pre-delineated volumes was sent to 20 RT centres and used to create a SABR plan using local current protocols and techniques. The silica beads were held in an insert, designed to match that of the alanine holder and ionisation chamber to give the same measurement length. The doses determined by the silica beads were compared to those measured by alanine, the local ionisation chamber, film and the TPS calculation. Results: The mean percentage difference between the doses measured by the silica beads and the calculated doses by the TPS was found to be 0.7% and differed by 0.6%, 0.7%, and 1.3% from the alanine, film and local ionisation chamber measurements respectively. Conclusions: Results obtained with the silica beads agree well with those obtained from conventional detectors including alanine, film and ionisation chambers. This together with the waterproof and inert characteristics and minimal dose fading associated with silica bead TLDs confirm their potential as a postal dosimetry audit tool in both water and plastic phantoms which could withstand challenges of temperature and humidity variation, as well as postal service delays.

We investigate the ability of high spatial resolution (∼120μm) Ge-doped SiO(2) TL dosimeters to measure photoelectron dose enhancement resulting from the use of a moderate to high-Z target (an iodinated contrast media) irradiated by 90kVp X-rays. We imagine its application in a novel radiation synovectomy technique, modelled by a phantom containing a reservoir of I(2) molecules at the interface of which the doped silica dosimeters are located. Measurements outside of the iodine photoelectron range are provided for using a stepped-design that allows insertion of the fibres within the phantom. Monte Carlo simulation (MCNPX) is used for verification. At the phantom medium I(2)-interface additional photoelectron generation is observed, ∼60% above that in the absence of the I(2), simulations providing agreement to within 3%. Percentage depth doses measured away from the iodine contrast medium reservoir are bounded by published PDDs at 80kVp and 100kVp.

The steep dose gradients close to brachytherapy sources limit the ability to obtain accurate measurements of dose. Here we use a novel high spatial resolution dosimeter to measure dose around a I source and compare against simulations. Ge-doped optical fibres, used as thermoluminescent dosimeters, offer sub-mm spatial resolution, linear response from 10cGy to >1kGy and dose-rate independence. For a I brachytherapy seed in a PMMA phantom, doses were obtained for source-dosimeter separations from 0.1cm up to several cm, supported by EGSnrc/DOSRZznrc Monte Carlo simulations and treatment planning system data. The measurements agree with simulations to within 2.3%±0.3% along the transverse and perpendicular axes and within 3.0%±0.5% for measurements investigating anisotropy in angular dose distribution. Measured and Veriseed™ brachytherapy treatment planning system (TPS) values agreed to within 2.7%±0.5%.Ge-doped optical fibre dosimeters allow detailed dose mapping around brachytherapy sources, not least in situations of high dose gradient. © 2013 Elsevier Ltd.

While commercial jewellery glass beads offer the basis of novel radiotherapy TL dosimetry (Jafari et al. 2014a,b,c, 2015a,b), detailed study of TL variation is required for the products from various manufacturers. Investigation is made for glass beads from four manufacturers from four countries: China (Rocaille), Japan (Mill Hill), Indonesia (TOHO™) and Czech Republic (Czech). Sample composition was determined using an energy-dispersive X-ray unit coupled to a scanning electron microscope. Values of mass attenuation coefficient, μ/ρ, as a function of photon energy were then calculated for photons of energy 1 keV to 10 MeV, using the National Institute of Standards and Technology XCOM program. Radiation and energy response were determined using X-rays generated at accelerating potentials from 80 kVp to 6 MV (TPR20/10¼0.670). All bead types showed TL to be linear with dose (R240.999). Glow curve dosimetric peaks reached a maximum value at 300 °C for the Toho and 290 °C for the Czech and Mill Hill products but was between 200–250 °C for the Rocaille product. Radiation sensitivity following mass normalisation varied within an order of magnitude; Toho samples showed the greatest and Rocaille the least sensitivity. For the Toho, Czech, Rocaille and Mill Hill samples the energy responses at 80 kVp were 5.0, 4.0, 3.6 and 3.3 times that obtained at 6 MV. All four glass bead types offer potential use as TL dosimeters over doses commonly applied in radiotherapy. Energy response variation was o1% at 6 MV but significant variation was found for photon beam energies covering the kV range; careful characterisation is required if use at this range is intended.

Purpose To develop a methodology for the use of a commercial detector array in dosimetry audits of rotational radiotherapy. Materials and methods The methodology was developed as part of the development of a national audit of rotational radiotherapy. Ten cancer centres were asked to create a rotational radiotherapy treatment plan for a three-dimensional treatment-planning-system (3DTPS) test and audited. Phantom measurements using a commercial 2D ionisation chamber (IC) array were compared with measurements using 0.125 cm IC, Gafchromic film and alanine pellets in the same plane. Relative and absolute gamma index (γ) comparisons were made for Gafchromic film and 2D-Array planes, respectively. Results Comparisons between individual detectors within the 2D-Array against the corresponding IC and alanine measurement showed a statistically significant concordance correlation coefficient (both ρ > 0.998, p < 0.001) with mean difference of -1.1 ± 1.1% and -0.8 ± 1.1%, respectively, in a high dose PTV. In the γ comparison between the 2D-Array and film it was that the 2D-Array was more likely to fail planes where there was a dose discrepancy due to the absolute analysis performed. Conclusions It has been found that using a commercial detector array for a dosimetry audit of rotational radiotherapy is suitable in place of standard systems of dosimetry. © 2013 Elsevier Ireland Ltd. All rights reserved.

Ge-doped optical fibres offer promising thermoluminescence (TL) properties together with small physical size and modest cost. Their use as dosimeters for postal radiotherapy dose audits of megavoltage photon beams has been investigated. Key dosimetric characteristics including reproducibility, linearity, dose rate, temperature and angular dependence have been established. A methodology of measuring absorbed dose under reference conditions was developed. The Ge-doped optical fibres offer linearity between TL yield and dose, with a reproducibility of better than 5%, following repeated measurements (n=5) for doses from 5cGy to 1000cGy. The fibres also offer dose rate, angular and temperature independence, while an energy-dependent response of 7% was found over the energy range 6MV to 15MV (TPR of 0.660, 0.723 and 0.774 for 6, 10 and 15MV respectively). The audit methodology has been developed with an expanded uncertainty of 4.22% at 95% confidence interval for the photon beams studied. © 2013 Elsevier Ltd.

A survey of quality control (QC) currently undertaken in UK radiotherapy centres for high dose rate (HDR) and pulsed dose rate (PDR) brachytherapy has been conducted. The purpose was to benchmark current accepted practice of tests, frequencies and tolerances to assure acceptable HDR/PDR equipment performance. It is 20 years since a similar survey was conducted in the UK and the current review is timed to coincide with a revision of the IPEM Report 81 guidelines for quality control in radiotherapy.

Glass beads are a novel TL dosimeter in radiotherapy. An important characteristic of TL dosimeters is their energy response, especially when intended for use in radiotherapy applications over a wide range of energies (typically from X-rays generated at 80 kVp up to 25 MV photon and MeV electron beams). In this paper, the energy response of glass beads (Mill Hill, Japan) is investigated for their TL response to kV X-rays from an orthovoltage radiotherapy unit and also for MV photon and MeV electron beams from a medical linear accelerator. The experimental findings show that for photon and electron beams, the TL response of this particular glass bead, normalised to unity for 6 MV X-rays (TPR20/10¼0.670), decreases to 0.9670.02 for 15 MV X-rays (TPR20/10¼0.761) and to 0.9570.01 for 20 MeV electron beams (R50,D¼8.35 cm). This compares favourably with other TLD materials such as LiF and also alanine dosimeters that are readout with an EPR system. For kV X-rays, the response increases to 4.5270.05 for 80 kV X-rays (HVL¼2.4 mm Al) which approaches 3 times that of LiF TLDs and 5 times that of alanine. In conclusion, the particular glass beads, when used as a dosimeter material, show a relatively small energy dependence over the megavoltage range of clinically relevant radiation qualities, being clearly advantageous for accurate dosimetry. Conversely, the energy response is significant for photon beam energies covering the kV range. In both circumstances, in dosimetric evaluations the energy response needs to be taken into account.

CT scans are an integral component of modern radiotherapy treatments, enabling the accurate localisation of the treatment target and organs-at-risk, and providing the tissue density information required for dose calculations in the treatment planning system. For these reasons, it is important to ensure exposures are optimised to give the required clinical image quality with doses that are as low as reasonably achievable. However, there is little guidance on dose levels in radiotherapy CT imaging either within the UK or internationally. This IPEM topical report presents the results of the first UK wide survey of dose indices in radiotherapy CT planning scans. Patient dose indices were collected for prostate, gynaecological, breast, 3D-lung, 4D-lung, brain and head/neck scans. Median values per scanner and examination type were calculated and national dose reference levels and 'achievable levels' of CT dose index (CTDIvol), dose-length-product (DLP) and scan length are proposed based on the third quartile and median values of these distributions, respectively. A total of 68 radiotherapy CT scanners were included in this audit. The proposed dose reference levels for CTDIvol and DLP are; prostate 16 mGy and 570 mGy.cm, gynaecological 16 mGy and 610 mGy.cm, breast 10 mGy and 390 mGy.cm, 3D-lung 14 mGy and 550 mGy.cm, 4D-lung 63 mGy and 1750 mGy.cm, brain 50 mGy and 1500 mGy.cm and head/neck 49 mGy and 2150 mGy.cm. Significant variations in dose indices were noted, with head/neck and 4D-lung yielding a factor of eighteen difference between the lowest and highest dose scanners. There was also evidence of some clustering in the data by scanner manufacturer, which may be indicative of a lack of local optimisation of individual systems to the clinical task. It is anticipated that providing this data to the UK and wider radiotherapy community will aid the optimisation of treatment planning CT scan protocols.

This paper studies the sensitivity of a range of image texture parameters used in radiomics to: i) the number of intensity levels, ii) the method of quantisation to select the intensity levels and iii) the use of an intensity threshold. 43 commonly used texture features were studied for the gross target volume outlined on the CT component of PET/CT scans of 50 patients with non-small cell lung carcinoma (NSCLC). All cases were quantised for all values between 4 and 128 intensity levels using four commonly used quantisation methods. All results were analysed with and without a threshold range of -200 HU to 300 HU. Cases were ranked for each texture feature and for all quantisation methods with the Spearman's rank correlation coefficient determined to evaluate stability. Results showed large fluctuations in ranking, particularly for low numbers of levels, differences between quantisation methods and with the use of a threshold, with values Spearman's Rank Correlation for many parameters below 0.2. Our results demonstrated the sensitivity of radiomics features to the parameters used during analysis and highlight the risk of low reproducibility comparing studies with slightly different parameters. In terms of the lung cancer CT datasets, this study supports the use of 128 intensity levels, the same uniform quantiser applied to all scans and thresholding of the data. It also supports several of the features recommended in the literature for such studies such as skewness and kurtosis. A recommended framework is presented for curation of the data analysis process to ensure stability of results.

Stereotactic radiosurgery (SRS), a non-invasive therapeutic technique, seeks delivery of elevated doses of ionizing radiation to precisely defined targets while at the same time preserving surrounding tissue viability. SRS was developed for treatment of various functional abnormalities, extending also to benign and malignant lesions (the latter sometimes referred to as stereotactic body radiation therapy, SBRT). Local tumour control for single and multiple brain metastases at low complication rates is one such outcome. Notable commercial SRS platforms include Gamma Knife and the linac-based systems, Novalis and Cyberknife. Such systems use imaging techniques that include computed tomography (CT) and magnetic resonance imaging (MRI) in localizing SRS targets, down to a small fraction of one mm. With a wide range of platforms for delivery of SRS, greater investigation and standardization is called for. Present work concerns a multi-centre dosimetric audit (20 centres in all), investigating the range of SRS machines and techniques for a single brain metastasis using a series of small dimension detectors (1.55 mm and less) and an anthropomorphic head phantom. With the lens as one of the more radiosensitive tissues, the aim has been to determine the scattered radiation lens dose received during an SRS treatment, as well as the imaging dose received during planning-stage CT-scanning. Custom-designed holders were fabricated to carry three types of thermoluminescence dosimeters: Ge-doped silica fibres, silica glass beads and TLD-100, the latter as a reference dosimeter (being also of larger dimension than the silica-based dosimeters). For reproducible placement of the TLD holders, a bespoke 3D-printed goggle insert was produced for the head phantom. International guidance is to seek reduction in lens dose down to 0.5 Gy. Present results show lens dose values below 0.5 Gy, albeit sometimes to modest degree, there being need to continue to exercise associated due care in SRS planning and delivery.

To estimate target and cardiac doses from breast cancer radiotherapy in Denmark and in the Stockholm and Umeå areas of Sweden during 1977-2001.

This work addresses purpose-made thermoluminescence dosimeters (TLD) based on doped silica fibres and sol–gel nanoparticles, produced via Modified Chemical Vapour Deposition (MCVD) and wet chemistry techniques respectively. These seek to improve upon the versatility offered by conventional phosphor-based TLD forms such as that of doped LiF. Fabrication and irradiation-dependent factors are seen to produce defects of differing origin, influencing the luminescence of the media. In coming to a close, we illustrate the utility of Ge-doped silica media for ionizing radiation dosimetry, first showing results from gamma-irradiated Ag-decorated nanoparticles, in the particular instance pointing to an extended dynamic range of dose. For the fibres, at radiotherapy dose levels, we show high spatial resolution (0.1 mm) depth-dose results for proton irradiations. For novel microstructured fibres (photonic crystal fibres, PCFs) we show first results from a study of undisturbed and technologically modified naturally occurring radioactivity environments, measuring doses of some 10 s of μGy over a period of several months.

A number of codes of practice (CoP) for electron and photon radiotherapy beam dosimetry are currently in use. Comparison is made of the more widely used of these, specifically those of the International Atomic Energy Agency (IAEA TRS-398), the American Association of Physicists in Medicine (AAPM TG-51) and the Institute of Physics and Engineering in Medicine (IPEM 2003). All are based on calibration of ionization chambers in terms of absorbed dose to water, each seeking to reduce uncertainty in delivered dose, providing an even stronger system of primary standards than previous air-kerma based approaches. They also provide a firm, traceable and straight-forward formalism (Radiology, 1996). Included in making dose assessments for the three CoP are calibration coefficients for a range of beam quality indices. Measurements have been performed using clinical photon and electron beams, the absorbed dose to water being obtained following the recommendations given by each code. Electron beam comparisons have been carried out using measurements for electron beams of nominal energies 6, 9, 12, 16 and 20 MeV. Comparisons were also carried out for photon beams of nominal energies 6 and 18 MV. For photon beams use was made of NE2571 cylindrical graphite walled ionization chambers, cross-calibrated against an NE2611 Secondary Standard; for electron beams, PTW Markus and NACP-02 plane-parallel chambers were used. Irradiations were made using Varian 600C/2100C linacs, supported by water tanks and Virtual Water™ phantoms. The absorbed doses for photon and electron beams obtained following these CoP are all in good agreement, with deviations of less than 2%. A number of studies have been carried out by different groups in different countries to examine the consistency of dosimetry codes of practice or protocols. The aim of these studies is to confirm that the goal of those codes is met, namely uniformity in establishment of dosimetry of all radiation beam types used in cancer therapy in the world, and this is one of the studies.

Objectives: To adapt and validate an anthropomorphic head phantom for use in a cranial radiosurgery audit. Methods: Two bespoke inserts were produced for the phantom: one for providing the target and organ at risk for delineation, and one for performing dose measurements. The inserts were tested to assess their positional accuracy. A basic treatment plan dose verification with an ionisation chamber was performed to establish a baseline accuracy for the phantom and beam model. The phantom and inserts were then used to perform dose verification measurements of a radiosurgery plan. The dose was measured with alanine pellets, EBT-XD film and a plastic scintillation detector (PSD). Results: Both inserts showed reproducible positioning (±0.5 mm) and good positional agreement between them (±0.6 mm). The basic treatment plan measurements showed agreement to the Treatment Planning System (TPS) within 0.5%. Repeated film measurements showed consistent gamma passing rates with good agreement to the TPS. For 2%-2mm global gamma, the mean passing rate was 96.7% and the variation in passing rates did not exceed 2.1%. The alanine pellets and PSD showed good agreement with the TPS (-0.1 and 0.3% dose difference in the target) and good agreement with each other (within 1%). Conclusions: The adaptations to the phantom showed acceptable accuracies. The presence of alanine and PSD do not affect film measurements significantly, enabling simultaneous measurements by all three detectors. Advancements in knowledge: A novel method for thorough end-to-end test of radiosurgery, with capability to incorporate all steps of the clinical pathway in a time-efficient and reproducible manner, suitable for a national audit.

We describe investigation of a novel undoped flat fibre fabricated for medical radiation dosimetry. Using high energy X-ray beams generated at a potential of 6MV, comparison has been made of the TL yield of silica flat fibres, TLD-100 chips and Ge-doped silica fibres. The flat fibres provide competitive TL yield to that of TLD-100 chips, being some 100 times that of the Ge-doped fibres. Pt-coated flat fibres have then been used to increase photoelectron production and hence local dose deposition, obtaining significant increase in dose sensitivity over that of undoped flat fibres. Using 250kVp X-ray beams, the TL yield reveals a progressive linear increase in dose for Pt thicknesses from 20nm up to 80nm. The dose enhancement factor (DEF) of (0.0150±0.0003)nm Pt is comparable to that obtained using gold, agreeing at the 1% level with the value expected on the basis of photoelectron generation. Finally, X-ray photoelectron spectroscopy (XPS) has been employed to characterize the surface oxidation state of the fibre medium. The charge state of Si2p was found to lie on 103.86eV of binding energy and the atomic percentage obtained from the XPS analysis is 22.41%. © 2014 Elsevier Ltd.

© 2014 IEEE.NanoSQUIDs made from Nb thin films have been produced with nanometre loop sizes down to 200 nm, using weak-link junctions with dimensions less than 60 nm. These composite (W/Nb) single layer thin film devices, patterned by FIB milling, show extremely good low-noise performance ~170 nΦ0 at temperatures between 5 and 8.5 K and can operate in rather high magnetic fields (at least up to 1 T). The devices produced so far have a limited operating temperature range, typically only 1-2 K. We have the goal of achieving operation at 4.2 K, to be compatible with the best SQUID series array (SSA) preamplifier available. Using the SSA to readout the nanoSQUIDs provides us with a means of investigating the intrinsic noise of the former. In this paper we report improved white noise levels of these nanoSQUIDs, enabling potential detection of a single electronic spin flip in a 1-Hz bandwidth. At low frequencies the noise performance is already limited by SSA preamplifier noise.

Fluorine-18-fluorodeoxyglucose-positron emission tomography ((18)F-FDG-PET)-guided focal dose escalation in oropharyngeal cancer may potentially improve local control. We evaluated the feasibility of this approach using volumetric-modulated arc therapy (RapidArc) and compared these plans with fixed-field intensity-modulated radiotherapy (IMRT) focal dose escalation plans. Materials and methods: An initial study of 20 patients compared RapidArc with fixed-field IMRT using standard dose prescriptions. From this cohort, 10 were included in a dose escalation planning study. Dose escalation was applied to (18)F-FDG-PET-positive regions in the primary tumor at dose levels of 5% (DL1), 10% (DL2), and 15% (DL3) above standard radical dose (65 Gy in 30 fractions). Fixed-field IMRT and double-arc RapidArc plans were generated for each dataset. Dose-volume histograms were used for plan evaluation and comparison. The Paddick conformity index (CI(Paddick)) and monitor units (MU) for each plan were recorded and compared. Both IMRT and RapidArc produced clinically acceptable plans and achieved planning objectives for target volumes. Dose conformity was significantly better in the RapidArc plans, with lower CI(Paddick) scores in both primary (PTV1) and elective (PTV2) planning target volumes (largest difference in PTV1 at DL3; 0.81 ± 0.03 [RapidArc] vs. 0.77 ± 0.07 [IMRT], p = 0.04). Maximum dose constraints for spinal cord and brainstem were not exceeded in both RapidArc and IMRT plans, but mean doses were higher with RapidArc (by 2.7 ± 1 Gy for spinal cord and 1.9 ± 1 Gy for brainstem). Contralateral parotid mean dose was lower with RapidArc, which was statistically significant at DL1 (29.0 vs. 29.9 Gy, p = 0.01) and DL2 (29.3 vs. 30.3 Gy, p = 0.03). MU were reduced by 39.8-49.2% with RapidArc (largest difference at DL3, 641 ± 94 vs. 1261 ± 118, p < 0.01). (18)F-FDG-PET-guided focal dose escalation in oropharyngeal cancer is feasible with RapidArc. Compared with conventional fixed-field IMRT, RapidArc can achieve better dose conformity, improve contralateral parotid sparing, and uses fewer MU.

Purpose: To define a method and investigate how the adjustment of scan parameters affected the image quality and Hounsfield units (HUs) on a CT scanner used for radiotherapy treatment planning. A lack of similar investigations in the literature may be a contributing factor in the apparent reluctance to optimise radiotherapy CT protocols. Method: A Catphan phantom was used to assess how image quality on a Toshiba Aquilion LB scanner changed with scan parameters. Acquisition and reconstruction field-of-view (FOV), collimation, image slice thickness, effective mAs per rotation and reconstruction algorithm were varied. Changes were assessed for HUs of different materials, high contrast spatial resolution (HCSR), contrast-noise ratio (CNR), HU uniformity, scan direction low contrast and CT dose-index. Results: CNR and HCSR varied most with reconstruction algorithm, reconstruction FOV and effective mAs. Collimation, but not image slice width, had a significant effect on CT dose-index with narrower collimation giving higher doses. Dose increased with effective mAs. Highest HU differences were seen when changing reconstruction algorithm: 56 HU for densities close to water and 117 HU for bone-like materials. Acquisition FOV affected the HUs but reconstruction FOV and effective mAs did not. Conclusions: All the scan parameters investigated affected the image quality metrics. Reconstruction algorithm, reconstruction FOV, collimation and effective mAs were most important. Reconstruction algorithm and acquisition FOV had significant effect on HU. The methodology is applicable to radiotherapy CT scanners when investigating image quality optimisation, prior to assessing the impact of scan protocol changes on clinical CT images and treatment plans.

The Ionizing Radiation (Medical Exposure) Regulations 2000, IR(ME)R, apply to the safety of the patient referred for a medical exposure to ionizing radiation. In Scotland, the Scottish Executive (Department of Health) is responsible for carrying out inspections of compliance with these regulations. IR(ME)R specifically addresses issues concerned with Employer's duties, responsibilities of the Practitioner, Operator and Referrer, justification of individual medical exposures for diagnosis and treatment, optimization of all procedures, clinical audit and adequate training of all duty holders. A proactive IR(ME)R inspection of the Clinical Oncology Department, Raigmore Hospital, Inverness, was carried out in November 2001 by inspectors based at the Department of Health, London, and seconded by the Scottish Executive, Department of Health. The aim of the inspection was to assess the degree of compliance with the regulations. In this case study the experiences of a proactive inspection are described in detail and some of the important elements of implementing IR(ME)R in a department that operates an ISO 9000-2000 Quality Management System addressed. The identification of IR(ME)R Duty Holders' responsibilities is one important aspect which may be inadequately described by the existing Quality Management System documentation. Other key elements of the inspection include the methods of authorizing the justification, the importance of the treatment prescription sheets in the demonstration of compliance with IR(ME)R, patient identification and pregnancy questions and dose recording procedures. The integration of the standard operating procedures as described in Schedule 1 of the regulations is also important. Where the existing Quality Management System documentation is written to include the IR(ME)R requirements of duty holder's responsibilities and the allocation of all the important tasks, then there is no need to re-badge these documents for IR(ME)R purposes. IR(ME)R encourages departments to focus on the safety of the patient and to document good practice. In order to comply, departments will have to show evidence of optimization of their procedures and must address the clinical governance issues associated with delivery of treatment.

Scintillation detectors are considered highly suitable for dosimetric measurement of small fields in radiotherapy due to their near-tissue equivalence and their small size. A commercially available scintillation detector, the Exradin W1 (Standard Imaging, Middleton, USA), has been previously characterised by two independent studies (Beierholm et al., 2014; Carrasco et al., 2015a ; Carrasco et al., 2015b) but the results from these publications differed in some aspects (e.g. energy dependence, long term stability). The respective authors highlighted the need for more studies to be published (Beierholm et al., 2015; Carrasco et al., 2015a ; Carrasco et al., 2015b). In this work, the Exradin W1 was characterised in terms of dose response, dependence on dose rate, energy, temperature and angle of irradiation, and long-term stability. The observed dose linearity, short-term repeatability and temperature dependence were in good agreement with previously published data. Appropriate corrections should therefore be applied, where possible, in order to achieve measurements with low-uncertainty. The angular dependence was characterised along both the symmetrical and polar axis of the detector for the first time in this work and a dose variation of up to 1% was observed. The response of the detector was observed to decrease at a rate of approximately 1.6% kGy−1 for the first 5 kGy delivered, and then stabilised to 0.2% kGy−1 in the subsequent 20 kGy. The main goal of this work was to assess the suitability of the Exradin W1 for use in dose verification measurements for stereotactic radiosurgery. The results obtained confirm that the detector is suitable for use in such situations. The detector is now utilised in a multi-centre stereotactic radiosurgery dosimetric audit, with the application of appropriate correction factors.

Preclinical investigations of thick microbeams show these to be feasible for use in radiotherapeutic dose delivery. To create the beams we access a radiotherapy x-ray tube that is familiarly used within a conventional clinical environment, coupling this with beam-defining grids. Beam characterisation, both single and in the form of arrays, has been by use of both MCNP simulation and direct Gafchromic EBT film dosimetry. As a first step in defining optimal exit-beam profiles over a range of beam energies, simulation has been made of the x-ray tube and numbers of beam-defining parallel geometry grids, the latter being made to vary in thickness, slit separation and material composition. For a grid positioned after the treatment applicator, and of similar design to those used in the first part of the study, MCNP simulation and Gafchromic EBT film were then applied in examining the resultant radiation profiles. MCNP simulations and direct dosimetry both show useful thick microbeams to be produced from the x-ray tube, with peak-to-valley dose ratios (PVDRs) in the approximate range 8.8–13.9. Although the potential to create thick microbeams using radiotherapy x-ray tubes and a grid has been demonstrated, Microbeam Radiation Therapy (MRT) would still need to be approved outside of the preclinical setting, a viable treatment technique of clinical interest needing to benefit for instance from substantially improved x-ray tube dose rates.

Quality assurance (QA) for intensity- and volumetric-modulated radiotherapy (IMRT and VMAT) has evolved substantially. In recent years, various commercial 2D and 3D ionization chamber or diode detector arrays have become available, allowing for absolute verification with near real time results, allowing for streamlined QA. However, detector arrays are limited by their resolution, giving rise to concerns about their sensitivity to errors. Understanding the limitations of these devices is therefore critical. In this study, the sensitivity and resolution of the PTW 2D-ARRAY seven29 and OCTAVIUS II phantom combination was comprehensively characterized for use in dynamic sliding window IMRT and RapidArc verification. Measurement comparisons were made between single acquisition and a multiple merged acquisition techniques to improve the effective resolution of the 2D-ARRAY, as well as comparisons against GAFCHROMIC EBT2 film and electronic portal imaging dosimetry (EPID). The sensitivity and resolution of the 2D-ARRAY was tested using two gantry angle 0° modulated test fields. Deliberate multileaf collimator (MLC) errors of 1, 2, and 5 mm and collimator rotation errors were inserted into IMRT and RapidArc plans for pelvis and head & neck sites, to test sensitivity to errors. The radiobiological impact of these errors was assessed to determine the gamma index passing criteria to be used with the 2D-ARRAY to detect clinically relevant errors. For gamma index distributions, it was found that the 2D-ARRAY in single acquisition mode was comparable to multiple acquisition modes, as well as film and EPID. It was found that the commonly used gamma index criteria of 3% dose difference or 3 mm distance to agreement may potentially mask clinically relevant errors. Gamma index criteria of 3%/2 mm with a passing threshold of 98%, or 2%/2 mm with a passing threshold of 95%, were found to be more sensitive. We suggest that the gamma index passing thresholds may be used for guidance, but also should be combined with a visual inspection of the gamma index distribution and calculation of the dose difference to assess whether there may be a clinical impact in failed regions.

This study aims to establish the sensitive, ~120μm high spatial resolution, high dynamic range Ge-doped optical fibres as thermoluminescence (TL) dosimeters for brachytherapy dose distribution. This requires investigation to accommodate sensitivity of detection, both for the possibility of short range dose deposition from beta components as well as gamma/x-mediated dose. In-air measurements are made at distances close to radionuclide sources, evaluating the fall off in dose along the transverse axis of Ba and Co radioactive sources, at distances from 2mm up to 20mm from their midpoints. Measurements have been compared with Monte Carlo code DOSRZnrc simulations for photon-mediated dose only, agreement being obtained to within 3% and 1% for the Ba and Co sources, respectively. As such, in both cases it is determined that as intended, beta dose has been filtered out by source encapsulation. © 2012 Elsevier Ltd.

The high uncertainty in the Relative Biological Effectiveness (RBE) values of particle therapy beam, which are used in combination with the quantity absorbed dose in radiotherapy, together with the increase in the number of particle therapy centres worldwide necessitate a better understating of the biological effect of such modalities. The present novel study is part of performance testing and development of a micro-calorimeter based on Superconducting QUantum Interference Devices (SQUIDs). Unlike other microdosimetric detectors that are used for investigating the energy distribution, this detector provides a direct measurement of energy deposition at the micrometre scale, that can be used to improve our understanding of biological effects in particle therapy application, radiation protection and environmental dosimetry. Temperature rises of less than 1μK are detectable and when combined with the low specific heat capacity of the absorber at cryogenic temperature, extremely high energy deposition sensitivity of approximately 0.4 eV can be achieved. The detector consists of 3 layers: tissue equivalent (TE) absorber, superconducting (SC) absorber and silicon substrate. Ideally all energy would be absorbed in the TE absorber and heat rise in the superconducting layer would arise due to heat conduction from the TE layer. However, in practice direct particle absorption occurs in all 3 layers and must be corrected for. To investigate the thermal behaviour within the detector, and quantify any possible correction, particle tracks were simulated employing Geant4 (v9.6) Monte Carlo simulations. The track information was then passed to the COMSOL Multiphysics (Finite Element Method) software. The 3D heat transfer within each layer was then evaluated in a time-dependent model. For a statistically reliable outcome, the simulations had to be repeated for a large number of particles. An automated system has been developed that couples Geant4 Monte Carlo output to COMSOL for determining the expected distribution of proton tracks and their thermal contribution within the detector. The correction factor for a 3.8 MeV proton pencil beam was determined and applied to the expected spectra. The corrected microdosimetric spectra was shown to have a good agreement with the ideal spectra.

Background and Purpose Audit is imperative in delivering consistent and safe radiotherapy and the UK has a strong history of radiotherapy audit. The National Physical Laboratory (NPL) has undertaken audit measurements since 1994 and this work examines results from these audits. Materials and Methods This paper reviews audit results from 209 separate beams from 82 on-site visits to National Health Service (NHS) radiotherapy departments conducted between June 1994 and February 2015. Measurements were undertaken following the relevant UK code of practice. The accuracy of the implementation of absorbed dose calibration across the UK is quantified for MV photon, MeV electron and kV x-ray radiotherapy beams. Results Over the measurement period the standard deviation of MV photon beam output has reduced from 0.8 % to 0.4 %. The switch from air kerma- to absorbed dose-based electron code of practice contributed to a reduction in the difference of electron beam output of 0.6 % (p < 0.01). The mean difference in NPL to local measurement for radiation output calibration was less than 0.25 % for all beam modalities. Conclusions The introduction of the 2003 electron code of practice based on absorbed dose to water decreased the difference between absolute dose measurements by the centre and NPL. The use of a single photon code of practice over the period of measurements has contributed to a reduction in measurement variation. Within the clinical setting, on-site audit visits have been shown to identify areas of improvement for determining and implementing absolute dose calibrations.

The Ge dopant in commercially available silica optical fibres gives rise to appreciable thermoluminscence (TL), weight-for-weight offering sensitivity to MV X-rays several times that of the LiF dosimeter TLD100. The response of these fibres to UV radiation, X-rays, electrons, protons, neutrons and alpha particles, with doses from a fraction of 1Gy up to 10kGy, have stimulated further investigation of the magnitude of the TL signal for intrinsic and doped SiO fibres. We represent a consortium effort between Malaysian partners and the University of Surrey, aimed at production of silica fibres with specific TL dosimetry applications, utilizing modified chemical vapour deposition (MCVD) doped silica-glass production and fibre-pulling facilities. The work is informed by defect and dopant concentration and various production dependences including pulling parameters such as temperature, speed and tension; the fibres also provide for spatial resolutions down to

Objective: To investigate the effect of 6 and 15 MV photon energies on intensity-modulated radiation therapy (IMRT) prostate cancer treatment plan outcome and to compare the theoretical risks of secondary induced malignancies. Methods: Separate prostate cancer IMRT plans were prepared for 6 and 15 MV beams. Organ equivalent doses were obtained through thermoluminescent dosimeter (TLD) measurements in a Rando phantom. The neutron dose contribution at 15 MV was measured using polyallyl-diglycol-carbonate (PADC) neutron track etch detectors. Risk coefficients from ICRP Report 103 were used to compare the risk of fatal secondary induced malignancies in out-of-field organs and tissues for 6 and 15 MV. For the bladder and the rectum, a comparative evaluation of the risk using three separate models was carried out. Dose-volume parameters for the rectum, bladder and prostate planning-target-volume were evaluated, as well as normal tissue complication probability (NTCP) and tumour control probability (TCP) calculations. Results: There is a small increased theoretical risk of developing a fatal cancer from 6 MV compared with 15 MV, taking into account all the organs. Dose-volume parameters for the rectum and bladder show that 15 MV results in better volume sparing in the regions below 70 Gy, but the volume exposed increases slightly beyond this in comparison to 6 MV, resulting in a higher NTCP for the rectum of 3.6% versus 3.0% (p = 0.166). Conclusion: The choice to treat using IMRT at 15 MV should not be excluded, but should be based on risk versus benefit, considering the age and life expectancy of the patient together with the relative risk of radiation-induced cancer and NTCPs.

To investigate the variability of the global gamma index (γ) analysis in various commercial IMRT/VMAT QA systems and to assess the impact of measurement with low resolution detector arrays on γ.

Purpose This inter-comparison exercise was performed to demonstrate the variability of quantitative SPECT/CT imaging for lutetium-177 (177Lu) in current clinical practice. Our aim was to assess the feasibility of using international inter-comparison exercises as a means to ensure consistency between clinical sites whilst enabling the sites to use their own choice of quantitative imaging protocols, specific to their systems. Methods Dual-compartment concentric spherical sources of accurately known activity concentrations were prepared and sent to seven European clinical sites. The site staff were not aware of the true volumes or activity within the sources - they performed SPECT/CT imaging of the source, positioned within a water-filled phantom, using their own choice of parameters and reported their estimate of the activities within the source. Results The volumes reported by the participants for the inner section of the source were all within 29% of the true value, and within 60% of the true value for the outer section. The activities reported by the participants for the inner section of the source were all within 20% of the true value, whilst those reported for the outer section were up to 83% different to the true value. Conclusions A variety of calibration and segmentation methods were used by the participants for this exercise which demonstrated the variability of quantitative imaging across clinical sites. . This paper presents a method to assess consistency between sites using different calibration and segmentation methods.

Glioblastoma (GBM), a Grade IV brain tumour, is a well-known radioresistant cancer. To investigate one of the causes of radioresistance, we studied the capacity for potential lethal damage repair (PLDR) of three altered strains of GBM: T98G, U87 and LN18, irradiated with various ions and various levels of linear energy transfer (LET). The GBM cells were exposed to 12C and 28Si ion beams with LETs of 55, 100 and 200 keV/μm, and with X-ray beams of 1.7 keV/μm. Mono-energetic 12C ions and 28Si ions were generated by the Heavy Ion Medical Accelerator at the National Institute of Radiological Science, Chiba, Japan. Clonogenic assays were used to determine cell inactivation. The ability of the cells to repair potential lethal damage was demonstrated by allowing one identical set of irradiated cells to repair for 24 h before subplating. The results show there is definite PLDR with X-rays, some evidence of PLDR at 55 keV/μm, and minimal PLDR at 100 keV/μm. There is no observable PLDR at 200 keV/μm. This is the first study, to the authors’ knowledge, demonstrating the capability of GBM cells to repair potential lethal damage following charged ion irradiations. It is concluded that a GBM’s PLDR is dependent on LET, dose and GBM strain; and the more radioresistant the cell strain, the greater the PLDR.

Radiotherapy treatment planning of complex radiotherapy techniques, such as Intensity Modulated Radiotherapy (IMRT) and Volumetric Modulated Arc Therapy (VMAT), is a resource-intensive process requiring a high level of treatment planner intervention to ensure high plan quality. This can lead to variability in the quality of treatment plans and the efficiency in which plans are produced, depending on the skills and experience of the operator and available planning time. Within the last few years, there has been significant progress in the research and development of IMRT treatment planning approaches with automation support, with most commercial manufacturers now offering some form of solution. There is a rapidly growing number of research articles published in the scientific literature on the topic. This paper critically reviews the body of publications up to April 2018. The review describes the different types of automation algorithms, including the advantages and current limitations. Also included is a discussion on the potential issues with routine clinical implementation of such software, and highlights areas for future research.

Background and Purpose Motor failure in multi-leaf collimators (MLC) is a common reason for unscheduled accelerator maintenance, disrupting the workflow of a radiotherapy treatment centre. Predicting MLC replacement needs ahead of time would allow for proactive maintenance scheduling, reducing the impact MLC replacement has on treatment workflow. We propose a multivariate approach to analysis of trajectory log data, which can be used to predict upcoming MLC replacement needs. Materials and Methods Trajectory log files from two accelerators, spanning six and seven months respectively, have been collected and analysed. The average error in each of the parameters for each log file was calculated and used for further analysis. A performance index (PI) was generated by applying moving window principal component analysis to the prepared data. Drops in the PI were thought to indicate an upcoming MLC replacement requirement; therefore, PI was tracked with exponentially weighted moving average (EWMA) control charts complete with a lower control limit. Results The best compromise of fault detection and minimising false alarm rate was achieved using a weighting parameter (λ) of 0.05 and a control limit based on three standard deviations and an 80 data point window. The approach identified eight out of thirteen logged MLC replacements, one to three working days in advance whilst, on average, raising a false alarm, on average, 1.1 times a month. Conclusions This approach to analysing trajectory log data has been shown to enable prediction of certain upcoming MLC failures, albeit at a cost of false alarms.

Volumetric modulated arc therapy (VMAT) is a novel radiation technique, which can achieve highly conformal dose distributions with improved target volume coverage and sparing of normal tissues compared with conventional radiotherapy techniques. VMAT also has the potential to offer additional advantages, such as reduced treatment delivery time compared with conventional static field intensity modulated radiotherapy (IMRT). The clinical worldwide use of VMAT is increasing significantly. Currently the majority of published data on VMAT are limited to planning and feasibility studies, although there is emerging clinical outcome data in several tumour sites. This article aims to discuss the current use of VMAT techniques in practice and review the available data from planning and clinical outcome studies in various tumour sites including prostate, pelvis (lower gastrointestinal, gynaecological), head and neck, thoracic, central nervous system, breast and other tumour sites.

Lung cancer is the leading cause of cancer mortality worldwide. Treatment pathways include regular cross-sectional imaging, generating large data sets which present intriguing possibilities for exploitation beyond standard visual interpretation. This additional data mining has been termed ‘radiomics’ and includes semantic and agnostic approaches. Texture Analysis (TA) is an example of the latter, and uses a range of mathematically derived features to describe an image or region of an image. Often TA is used to describe a suspected or known tumour. TA is an attractive tool as large existing image sets can be submitted to diverse techniques for data processing, presentation, interpretation and hypothesis testing with annotated clinical outcomes. There is a growing anthology of published data using different TA techniques to differentiate between benign and malignant lung nodules, differentiate tissue sub-types of lung cancer, prognosticate and predict outcome and treatment response, as well as predict treatment side effects and potentially aid radiotherapy planning. The aim of this systematic review is to summarise the current published data and understand the potential future role of TA in managing lung cancer.

The clinical introduction of magnetic resonance imaging guided radiotherapy has prompted consideration of the potential impact of the static magnetic field on biological responses to radiation. This review provides an introduction to the mechanisms of biological interaction of radiation and magnetic fields individually, in addition to a description of the magnetic field effects on megavoltage photon beams at the macroscale, microscale and nanoscale arising from the Lorentz force on secondary charged particles. A relatively small number of scientific studies have measured the impact of combined static magnetic fields and ionising radiation on biological endpoints of relevance to radiotherapy. Approximately half of these investigations found that static magnetic fields in combination with ionising radiation produced a significantly different outcome compared with ionising radiation alone. MRI strength static magnetic fields appear to modestly influence the radiation response via a mechanism distinct from modification to the dose distribution. This review intends to serve as a reference for future biological studies, such that understanding of static magnetic field plus ionising radiation synergism may be improved, and if necessary, accounted for in magnetic resonance imaging guided radiotherapy treatment planning.

Background and Purpose Radiotherapy requires tight control of the delivered dose. This should include the variation in beam output as this may directly affect treatment outcomes. This work provides results from a multi-centre analysis of routine beam output measurements. Materials and Methods A request for 6MV beam output data was submitted to all radiotherapy centres in the UK, covering the period January 2015 – July 2015. An analysis of the received data was performed, grouping the data by manufacturer, machine age, and recording method to quantify any observed differences. Trends in beam output drift over time were assessed as well as inter-centre variability. Annual trends were calculated by linear extrapolation of the fitted data. Results Data was received from 204 treatment machines across 52 centres. Results were normally distributed with mean of 0.0% (percentage deviation from initial calibration) and a 0.8% standard deviation, with 98.1% of results within ±2%. There were eight centres relying solely on paper records. Annual trends varied greatly between machines with a mean drift of +0.9%/year with 95th percentiles of +5.1%/year and -2.2%/year. For the machines of known age 25% were over ten years old, however there was no significant differences observed with machine age. Conclusions Machine beam output measurements were largely within ±2% of 1.00cGy/MU. Clear trends in measured output over time were seen, with some machines having large drifts which would result in additional burden to maintain within acceptable tolerances. This work may act as a baseline for future comparison of beam output measurements.

The gamma index (c) is one of the most commonly used metrics for the verification of complex modulated radiotherapy. The mathematical definition of the c is computationally expensive and various techniques have been reported to speed up the calculation either by mathematically refining the c or employing various computational techniques. These techniques can cause variation in output with different software implementations. The c has traditionally been used to compare a 2D measured plane against a 2D or 3D dose distribution. Recently, software algorithm and hardware improvements have led to the possibility of using measured 2D data from commercial detector arrays to reconstruct a 3D-dose distribution and perform a volumetric comparison against the treatment planning system (TPS). A limitation in this approach is that commercial detector arrays have so far been limited by their spatial resolution which may affect the accuracy of the reconstructed 3D volume and subsequently the c calculation. Additionally, 3D versus 3D c comparison adds a layer of complication in the calculation of the c given the increase in the number of calculation points and the result cannot be as easily interpreted in the same way as 2D comparison. This review summarises and highlights the computational challenges of the c calculation and sheds light on some of these issues by means of a bespoke MATLAB software to demonstrate the impact of interpolation, c search distance, resolution and 2D and 3D calculations. Finally, a recommendation is made on the minimum information that should be reported when publishing c results.

Space radiation exposures to the heavier particles found in galactic cosmic rays (GCR) present a risk in manned space travel, particularly to the central nervous system (CNS). GCR are made up of a mixture of multiple charged particles such as protons, 4He, and 56Fe heavy ions. The most harmful to the CNS are the more highly charged and energetic (HZE) particles, including 56Fe because of their significant biological effect contribution to GCR dose and high linear energy transfer. These HZE particles can result in altered cognitive function, reduced motor function and behavioural changes and long term chronic brain disease. There is currently a lack of data on the biological response to 56Fe ions. In this regard, ground based experiments could be used to infer the effects of the cosmic environment on cell survival. A mono-energetic beam of 56Fe ions was generated by the Heavy Ion Medical Accelerator Chiba, National Institute of Radiological Sciences, Chiba, Japan. Three different types of glioblastoma multiforme (GBM) cell lines were studied. Using GBM cell lines which arise from the glia cells could aid in the understanding of the effects of space radiation to the brain. Clonogenic assay was used to determine the efficacy of the radiations. Certain strains of GBM are low-dose hypersensitive and hence, the very low doses used to study space radiation here are relevant. Results show that 0.2 Gy 56Fe (500 MeV/- 200 keV/μm) ions were able to inactivate approximately 8% of T98G, 15% LN18 and 27% of U87 cells. These results may infer and demonstrate the deleterious effects of 56Fe ions on human CNS, since a significant percentage of GBM cells were killed at very low doses. The data presented may therefore be employed in assessing risk related to high LET radiation exposure, simulating the effects in space radiation. •Space radiation exposures are a risk to the central nervous system.•There is a lack of data on the biological response to 56Fe ions.•Even low dose of 0.2 Gy of 56Fe ions has deleterious effects on glioblastoma cells.•Data presented could be used to assess risk related to high LET space radiation exposure.

Purpose/Objective: To examine whether the impact of respiratory motion on the delivered dose distributions for a range of tumour sizes in SABR, differs between 3DCRT,sliding window IMRT and RapidArc. Materials and Methods: Three patient data sets with different lung tumour sizes were selected: T1=6cc, T2=31cc and T3=60cc. Each was planned in Eclipse for SABR using 3DCRT, sliding window IMRT and VMAT, creating 9 treatment plans which were then delivered to a dynamic thorax phantom. The phantom was programmed to move at a typical patient breathing amplitude of 15mm with a period of 5 seconds and Varian linacs were used for the delivery. EBT3 Gafchromic film was used in coronal and sagittal planes for measuring dose distributions. Static phantom measurements were compared with the TPS calculated plans to establish agreement between expected and measured dose distributions without motion, using the software OmniPro I'mRT. Comparisons of static and dynamic phantom measurements followed. Global gamma analysis was used to carry out a relative comparison between the three delivery techniques. Five regions of the gamma index map (Middle, Proximal Left, Proximal Right, Distal Left, Distal Right) were analysed to quantify the differences along the axis of motion. The criteria used for the gamma analysis were 3%/3mm, with a threshold of 20%. Results: The setup and delivery accuracy was confirmed by the agreement between planned and static delivered dose distributions. The average percentage of pixels passing was 100% (T1),100% (T2) and 98.46% (T3). The comparison of films with and without motion gave lower percentages of pixels passing, ranging between 33.68 - 59.94% (T1), 47.86 - 61.77% (T2) and 43.44 - 64.32% (T3). Comparison of the delivery technique, showed passing rates of 33.63 - 52.25% (3DCRT), 43.44 - 64.52% (IMRT) and 46.58- 56.08% (VMAT). Analysis of the five regions for all delivery techniques gave averages of 93.76% (Middle), 58.7% (Proximal) and 12.8% (Distal). For 3DCRT results were 87.08% (Middle), 46.52% (Proximal) and 12.54% (Distal), for IMRT were 96.45%, 69.20%, 14.14% and for VMAT 97.75%, 60.39% and 11.71%, respectively. Conclusions: The results are indicative of the intra-fractional respiratory motion-induced dosimetric inaccuracies caused in three SABR delivery techniques.On average, the impact is greatest in the distal regions, significant in the proximal regions, whereas the middle region is less susceptible to these effects. No noticeable difference was observedbetween coronal and sagittal planes. The results also suggest that the effect of motion is greater in the proximal regions for 3DCRT in relation to the other techniques, particularly with smaller tumour sizes.

An important requirement across a range of sensitive detectors is to determine accurately the energy deposited by the impact of a particle in a small volume. The particle may be anything from a visible photon through to an X-ray or massive charged particle. We have been developing nanobridge Josephson junctions based SQUIDs and nanoSQUID devices covering the entire range of particle detection energies from 1eV to MeV. In this paper we discuss some developments in nanobridge Josephson junctions fabrication using focussed ion beam (FIB) and how these developments impact future applications. We focus on tuning of the transition temperature of a superconducting thin-film absorber, with the aim to match the absorber Tc to the working temperature range of the SQUID and also on using a new Xe FIB to improve Josephson junction and superconducting film quality.

Small field (≤ 4 × 4 cm) photon radiotherapy treatments include intensity-modulated radiation therapy (IMRT)and stereotactic body radiation therapy (SBRT). These require small, high spatial resolution dosimeters of adequate dynamic range. In this study, field sizes of 1 cm × 1 cm, 2 cm × 2 cm, 3 cm × 3 cm, 4 cm × 4 cm, and 10 cm × 10 cm have been investigated using commercially available silica-based fibres and glass beads (GB) as TL dosimeters and a Varian linear accelerator operating at 6, 10 and 15 MV. Ge-doped SiO2 fibres have previously been shown by this group to offer a viable system for use as dosimeters. The fibres and GB, offer good spatial resolution (∼120 μm and 2 mm respectively), large dynamic dose range (with linearity from tens of mGy up to well in excess of many tens of Gy), a non-hygroscopic nature and low cost. The main aim of this present work is to investigate the use of Ge-doped optical fibres and GBs as thermoluminescence dosimeters in small photon fields for different photon beam energies, comparing the measurements against Gafchromic films, hospital commissioning data obtained from small ionisation chambers and photon diodes and Monte Carlo simulations with FLUKA and BEAMnrc.

This work considers a previously overlooked uncertainty present in film dosimetry which results from moderate curvature of films during the scanning process. Small film samples are particularly susceptible to film curling which may be undetected or deemed insignificant. In this study, we consider test cases with controlled induced curvature of film and with film raised horizontally above the scanner plate. We also evaluate the difference in scans of a film irradiated with a typical brachytherapy dose distribution with the film naturally curved and with the film held flat on the scanner. Typical naturally occurring curvature of film at scanning, giving rise to a maximum height 1 to 2 mm above the scan plane, may introduce dose errors of 1% to 4%, and considerably reduce gamma evaluation passing rates when comparing film-measured doses with treatment planning system-calculated dose distributions, a common application of film dosimetry in radiotherapy. The use of a triple-channel dosimetry algorithm appeared to mitigate the error due to film curvature compared to conventional single-channel film dosimetry. The change in pixel value and calibrated reported dose with film curling or height above the scanner plate may be due to variations in illumination characteristics, optical disturbances, or a Callier-type effect. There is a clear requirement for physically flat films at scanning to avoid the introduction of a substantial error source in film dosimetry. Particularly for small film samples, a compression glass plate above the film is recommended to ensure flat-film scanning. This effect has been overlooked to date in the literature.

This series of practical handbooks are aimed at physicians both training and practising in radiotherapy, as well as medical physicists, dosimetrists, radiographers and senior nurses.

Examinations have been made of a low cost commercially available material which is potentially useful as a dosimeter in radiotherapy. An investigation of the thermoluminescent (TL) yield and electron paramagnetic resonance (EPR) signal was performed by irradiating acid-washed glass jewellery beads to MV photons using a medical linear-accelerator and 60Co gamma rays. For comparison, irradiation exposures were also carried out on 5 mm length of Ge-doped optical fibres that have been widely investigated for their TL properties [1]. The dose response was linear for the investigated dose range of 1 to 2500 cGy, with an R2 correlation coefficient of > 0.999 and reproducibility of 1.7%. The results suggest the potential for use of glass beads as TL dosimeters in radiotherapy.