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M Partridge

Publications and source records attributed to M Partridge.

At least 19 recordsLinked to original sources
PubMed2006

The application of polymer gel dosimeters to dosimetry for targeted radionuclide therapy.

There is a lack of standardized methodology to perform dose calculations for targeted radionuclide therapy and at present no method exists to objectively evaluate the various approaches employed. The aim of the work described here was to investigate the practicality and accuracy of calibrating polymer gel dosimeters such that dose measurements resulting from complex activity distributions can be verified. Twelve vials of the polymer gel dosimeter, 'MAGIC', were uniformly mixed with varying concentrations of P-32 such that absorbed doses ranged from 0 to 30 Gy after a period of 360 h before being imaged on a magnetic resonance scanner. In addition, nine vials were prepared and irradiated using an external 6 MV x-ray beam. Magnetic resonance transverse relaxation time, T2, maps were obtained using a multi-echo spin echo sequence and converted to R2 maps (where T2 = 1/R2). Absorbed doses for P-32 irradiated gel were calculated according to the medical internal radiation dose schema using EGSnrc Monte Carlo simulations. Here the energy deposited in cylinders representing the irradiated vials was scored. A relationship between dose and R(2) was determined. Effects from oxygen contamination were present in the internally irradiated vials. An increase in O2 sensitivity over those gels irradiated externally was thought to be a result of the longer irradiation period. However, below the region of contamination dose response appeared homogenous. Due do a drop-off of dose at the periphery of the internally irradiated vials, magnetic resonance ringing artefacts were observed. The ringing did not greatly affect the accuracy of calibration, which was comparable for both methods. The largest errors in calculated dose originated from the initial activity measurements, and were approximately 10%. Measured R2 values ranged from 5-35 s(-1) with an average standard deviation of 1%. A clear relationship between R2 and dose was observed, with up to 40% increased sensitivity for internally irradiated gels. Curve fits to the calibration data followed a single exponential function. The correlation coefficients for internally and externally irradiated gels were 0.991 and 0.985, respectively. With the ability to accurately calibrate internally dosed polymer gels, this technology shows promise as a means to evaluate dosimetry methods, particularly in cases of non-uniform uptake of a radionuclide.

Calibration↗
PubMed2006

Comparison of ghosting effects for three commercial a-Si EPIDs.

Many studies have reported dosimetric characteristics of amorphous silicon electronic portal imaging devices (EPIDs). Some studies ascribed a non-linear signal to gain ghosting and image lag. Other reports, however, state the effect is negligible. This study compares the signal-to-monitor unit (MU) ratio for three different brands of EPID systems. The signal was measured for a wide range of monitor units (5-1000), dose-rates, and beam energies. All EPIDs exhibited a relative under-response for beams of few MUs; giving 4 to 10% lower signal-to-MU ratios relative to that of 1000 MUs. This under-response is consistent with ghosting effects due to charge trapping.

Calibration↗
PubMed2006

Advanced imaging applied to radiotherapy planning in head and neck cancer: a clinical review.

Head and neck squamous cell carcinoma represents an ideal model to investigate the application of recent advances in medical imaging to radiotherapy planning. Tumours usually remain localized, and are potentially curable with local radiation. The steep radiation dose-response relationships support the strategies of radiation dose escalation to increase local control. Two-dimensional simulator-based planning and CT planning have significant drawbacks in terms of accurate target volume definition. MRI has enhanced soft tissue delineation, but has to be fused with CT to allow dose calculation. Functional imaging using dynamic contrast enhanced CT or MRI sequences may allow improved knowledge of tumour function. Positron emission tomography (PET) may allow further physiological information to be determined. This review summarizes the current techniques in clinical development in this area.

Carcinoma, Squamous Cell↗
PubMed2005

Association between polymorphisms of the GPX1 gene and second primary tumours after index squamous cell cancer of the head and neck.

We investigated the association between genetic polymorphisms in GPX1 gene amongst patients who had index squamous cell carcinoma (SCCHN) and a second primary tumour (SPT) after a primary SCCHN in a case-control study. GPX1 genotypes were determined for 61 patients with SPT and for 259 control subjects by a PCR technique using a fluorescent-labelled primer. Analysis was by an ABI automated fluorescent sequencer. The associations between specific genotypes and the development of SPT were examined by logistic regression. A significant difference was found between the control group and the SPT cases in allele frequencies of GPX1 ALA( *)6 and ALA( *)7 (p(trend)=0.04). These results suggest that polymorphisms in the GPX1 gene may be a marker for SPT development and further studies are indicated.

Adult↗
PubMed2005

Head-and-neck IMRT treatments assessed with a Monte Carlo dose calculation engine.

IMRT is frequently used in the head-and-neck region, which contains materials of widely differing densities (soft tissue, bone, air-cavities). Conventional methods of dose computation for these complex, inhomogeneous IMRT cases involve significant approximations. In the present work, a methodology for the development, commissioning and implementation of a Monte Carlo (MC) dose calculation engine for intensity modulated radiotherapy (MC-IMRT) is proposed which can be used by radiotherapy centres interested in developing MC-IMRT capabilities for research or clinical evaluations. The method proposes three levels for developing, commissioning and maintaining a MC-IMRT dose calculation engine: (a) development of a MC model of the linear accelerator, (b) validation of MC model for IMRT and (c) periodic quality assurance (QA) of the MC-IMRT system. The first step, level (a), in developing an MC-IMRT system is to build a model of the linac that correctly predicts standard open field measurements for percentage depth-dose and off-axis ratios. Validation of MC-IMRT, level (b), can be performed in a rando phantom and in a homogeneous water equivalent phantom. Ultimately, periodic quality assurance of the MC-IMRT system is needed to verify the MC-IMRT dose calculation system, level (c). Once the MC-IMRT dose calculation system is commissioned it can be applied to more complex clinical IMRT treatments. The MC-IMRT system implemented at the Royal Marsden Hospital was used for IMRT calculations for a patient undergoing treatment for primary disease with nodal involvement in the head-and-neck region (primary treated to 65 Gy and nodes to 54 Gy), while sparing the spinal cord, brain stem and parotid glands. Preliminary MC results predict a decrease of approximately 1-2 Gy in the median dose of both the primary tumour and nodal volumes (compared with both pencil beam and collapsed cone). This is possibly due to the large air-cavity (the larynx of the patient) situated in the centre of the primary PTV and the approximations present in the dose calculation.

Algorithms↗
PubMed2004

Measurement of the three-dimensional distribution of radiation dose in grid therapy.

A single large dose of megavoltage x-rays delivered through a grid is currently being utilized by some centres for palliative radiotherapy treatments of large tumours. In this note, we investigate the dosimetry of grid therapy using two-dimensional film dosimetry and three-dimensional gel dosimetry. It is shown that the radiation dose is attenuated more rapidly with depth in a grid field than an open field, and that even shielded regions receive approximately 25% of the dose to the unshielded areas.

Dose Fractionation, Radiation↗
PubMed2004

The use of gel dosimetry for verification of electron and photon treatment plans in carcinoma of the scalp.

In recent years there has been a large amount of research into the potential use of radiation sensitive gels for three-dimensional verification of clinical radiotherapy doses. In this paper we report the use of a MAGIC gel dosimeter (Fong et al 2001 Phys. Med. Biol. 46 3105) for the verification of a specific patient's radiation therapy dose distribution. A 69-year-old male patient presented with a squamous cell carcinoma extending approximately 180 degrees across the top of the scalp (anterior to posterior) and from just over midline to 90 degrees left of the skull. The patient's treatment was commenced using two electron fields. For gel dosimetry, phantoms were produced in which the outer surface spatially corresponded to the outer contours of the patient's anatomy in the region of irradiation. The phantoms were treated with either electrons or intensity modulated radiation therapy (IMRT) with photons. The results identified a hot spot between the matched electron fields and confirmed the more homogeneous dose distribution produced by the IMRT planning system. The IMRT plan was then clinically implemented. The application of a clinical dose to a phantom shaped to a specific patient as well as the ability to select a slice at will during phantom imaging means that gel dosimetry can no longer be considered to simply have potential alone, but is now in fact a useful dosimetric tool.

Aged↗
PubMed2003

Investigation into the reasons for preventable drug related admissions to a medical admissions unit: observational study.

OBJECTIVE: To describe the drugs and types of medicine management problems most frequently associated with preventable drug related admissions to an acute medical admissions unit. DESIGN: Observation study. SETTING: Medical admissions unit in a teaching hospital in Nottingham, UK. PARTICIPANTS: 4093 patients seen by pharmacists on the medical admissions unit between 1 January and 30 June 2001. MAIN OUTCOME MEASURES: Proportion of admissions that were drug related and preventable, classification of the underlying causes of preventable drug related admissions, and identification of drugs most commonly associated with preventable drug related admissions. RESULTS: Of the admissions seen by pharmacists, 265 (6.5%) were judged to be drug related and 178 (67%) of these were judged to be preventable. Preventable admissions were mainly due to problems with prescribing (63 cases (35%)), monitoring (46 cases (26%)), and adherence to medication (53 cases (30%)). The drugs most commonly implicated were NSAIDs, antiplatelets, antiepileptics, hypoglycaemics, diuretics, inhaled corticosteroids, cardiac glycosides, and beta-blockers. CONCLUSIONS: Potentially preventable drug related morbidity was associated with 4.3% of admissions to a medical admissions unit. In 91% of cases these admissions were related to problems with either prescribing, monitoring, or adherence.

Adverse Drug Reaction Reporting Systems↗
PubMed2002

Optimization of accelerator target and detector for portal imaging using Monte Carlo simulation and experiment.

Megavoltage portal images suffer from poor quality compared to those produced with kilovoltage x-rays. Several authors have shown that the image quality can be improved by modifying the linear accelerator to generate more low-energy photons. This work addresses the problem of using Monte Carlo simulation and experiment to optimize the beam and detector combination to maximize image quality for a given patient thickness. A simple model of the whole imaging chain was developed for investigation of the effect of the target parameters on the quality of the image. The optimum targets (6 mm thick aluminium and 1.6 mm copper) were installed in an Elekta SL25 accelerator. The first beam will be referred to as A16 and the second as Cu1.6. A tissue-equivalent contrast phantom was imaged with the 6 MV standard photon beam and the experimental beams with standard radiotherapy and mammography film/screen systems. The arrangement with a thin Al target/mammography system improved the contrast from 1.4 cm bone in 5 cm water to 19% compared with 2% for the standard arrangement of a thick, high-Z target/radiotherapy verification system. The linac/phantom/detector system was simulated with the BEAM/EGS4 Monte Carlo code. Contrast calculated from the predicted images was in good agreement with the experiment (to within 2.5%). The use of MC techniques to predict images accurately, taking into account the whole imaging system, is a powerful new method for portal imaging system design optimization.

Bone and Bones↗
PubMed2002

IMRT verification by three-dimensional dose reconstruction from portal beam measurements.

A method of reconstructing three-dimensional, in vivo dose distributions delivered by intensity-modulated radiotherapy (IMRT) is presented. A proof-of-principle experiment is described where an inverse-planned IMRT treatment is delivered to an anthropomorphic phantom. The exact position of the phantom at the time of treatment is measured by acquiring megavoltage CT data with the treatment beam and a research prototype, flat-panel, electronic portal imaging device. Immediately following CT imaging, the planned IMRT beams are delivered using the multiple-static field technique. The delivered fluence is sampled using the same detector as for the CT data. The signal measured by the portal imaging device is converted to primary fluence using an iterative phantom-scatter estimation technique. This primary fluence is back-projected through the previously acquired megavoltage CT model of the phantom, with inverse attenuation correction, to yield an input fluence map. The input fluence maps are used to calculate a "reconstructed" dose distribution using the same convolution/superposition algorithm as for the original planning dose calculation. Both relative and absolute dose reconstructions are shown. For the relative measurements, individual beam weights are taken from measurements but the total dose is normalized at the reference point. The absolute dose reconstructions do not use any dosimetric information from the original plan. Planned and reconstructed dose distributions are compared, with the reconstructed relative dose distribution also being compared to film measurements.

Feasibility Studies↗
PubMed2002

Assessing patients' preferences for characteristics associated with homeopathic and conventional treatment of asthma: a conjoint analysis study.

BACKGROUND: A study was undertaken to investigate the preferences of patients with asthma for attributes or characteristics associated with treatment for their asthma and to investigate the extent to which such preferences may differ between patient subgroups. METHODS: The economic technique of conjoint analysis (CA) was used to investigate patients' strength of preference for several key attributes associated with services for the treatment of asthma. A CA questionnaire was administered to two groups of asthma outpatients aged 18 years or older, 150 receiving conventional treatment at Whipps Cross Hospital (WC) and 150 receiving homeopathic treatment at the Royal London Homoeopathic Hospital (RL). RESULTS: An overall response rate of 47% (n=142) was achieved. Statistically significant attributes in influencing preferences for both the WC and RL respondents were (1) the extent to which the doctor gave sufficient time to listen to what the patient has to say, (2) the extent to which the treatment seemed to relieve symptoms, and (3) the travel costs of attending for an asthma consultation. The extent to which the doctor treated the patient as a whole person was also a statistically significant attribute for the RL respondents. CONCLUSIONS: This study has shown that aspects associated with the process of delivery of asthma services are important to patients in addition to treatment outcomes. The homeopathic respondents expressed stronger preferences for the doctor to treat them as a whole person than the patients receiving conventional treatment. Overall, the preferences for the attributes included in the study were similar for both groups.

Adult↗
PubMed2001

Differences in the expression of human class I MHC alleles and their associated peptides in the presence of proteasome inhibitors.

We have studied the contributions of proteasome inhibitor-sensitive and -insensitive proteases to the generation of class I MHC-associated peptides. The cell surface expression of 13 different human class I MHC alleles was inhibited by as much as 90% or as little as 40% when cells were incubated with saturating concentrations of three different proteasome inhibitors. Inhibitor-resistant class I MHC expression was not due to TAP-independent expression or preexisting internal stores of peptides. Furthermore, it did not correlate with the amount or specificity of residual proteasome activity as determined in in vitro proteolysis assays and was not augmented by simultaneous incubation with multiple inhibitors. Mass spectrometry was used to directly characterize the peptides expressed in the presence and absence of proteasome inhibitors. The number of peptide species detected correlated with the levels of class I detected by flow cytometry. Thus, for many alleles, a significant proportion of associated peptide species continue to be generated in the presence of saturating levels of proteasome inhibitors. Comparison of the peptide-binding motifs of inhibitor-sensitive and -resistant class I alleles further suggested that inhibitor-resistant proteolytic activities display a wide diversity of cleavage specificities, including a trypsin-like activity. Sequence analysis demonstrated that inhibitor-resistant peptides contain diverse carboxyl termini and are derived from protein substrates dispersed throughout the cell. The possible contributions of inhibitor-resistant proteasome activities and nonproteasomal proteases residing in the cytosol to the peptide profiles associated with many class I MHC alleles are discussed.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2001

The pattern of expression of the 5T4 oncofoetal antigen on normal, dysplastic and malignant oral mucosa.

The human 5T4 oncofoetal antigen is expressed by all types of trophoblast in pregnancy but is not detected on most adult tissues, although low levels are found on some epithelia. However, this antigen is strongly expressed by many cancers and tumour-associated labelling correlates with metastatic spread and poor clinical outcome for patients with gastric and colon cancer. Over-expression of the gene influences cell adhesion, shape and motility, which may be related to changes in the cellular localisation of the 5T4 oncofoetal antigen as malignancy develops. To establish whether the 5T4 oncofoetal antigen can serve as a tumour-specific marker for oral cancer and precancer, we have evaluated the pattern of expression on biopsies of normal, inflamed and dysplastic oral mucosa using immunohistochemistry. Oral mucosa, taken from different sites in the mouth, expressed the 5T4 oncofoetal antigen with varying intensity and pattern. The majority of the immunoreactivity was detected in the basal and suprabasal layers, with expression extending into the spinous cells at fully keratinised sites and when inflammation was present. This antigen was also detected in the underlying connective tissue. Oral squamous cell carcinoma showed a variety of patterns and intensity of staining corresponding to those found for normal mucosa. However, 21 of 41 cases showed no stromal labelling, a finding also observed for dysplastic lesions. The alterations in the pattern and intensity of 5T4 oncofoetal antigen expression were not related to clinicopathological features of the tumours examined. These data show that the 5T4 oncofoetal antigen is expressed on normal oral mucosa, such that this target cannot be used for detection of neoplastic or preneoplastic cells, although altered expression may contribute to the pathogenesis of these lesions.

Adult↗
PubMed2001

An intercomparison of IMRT delivery techniques: a case study for breast treatment.

Intensity-modulated radiotherapy beams can be delivered using a multileaf collimator by one of two methods: either by superposition of a series of multiple-static fields, or by moving the collimators while the beam is on to produce 'dynamically' modulated beams. The leaf trajectories in this dynamic mode are given by a series of linear steps between control points defining each collimator position at known intervals throughout an exposure. The complexity of the resulting modulation is limited in the first case by the number of fields superposed and in the second case by the number of control points defined. Results are presented for an experimental study that investigates the effect of changing both the number of fields for the multiple-static technique, and the number of control points for a dynamic 'close-in' technique. All deliveries studied are clinical intensity-modulated breast fields. The effect of using a universal wedge in conjunction with the multileaf collimator is also studied, together with a comparison of the relative efficiency, time taken and the absolute dosimetric accuracy of the various delivery options. It is shown that all delivery techniques produce equivalent dose distributions when using 15 control points, with 10 control points being sufficient to produce an adequate breast compensator distribution. Except for the case of a four-control-point dynamic delivery, the universal wedge makes no significant difference to the dose distribution. However, it makes the delivery less efficient. The close-in interpreter consistently produces deliveries that are more efficient than the more conventional sliding-window technique and faster than the multiple-static-field technique. Finally the close-in technique is compared to the more 'standard' leaf-sweep technique and shown to be equivalent.

Breast Neoplasms↗
PubMed2001

An iterative algorithm for reconstructing incident beam distributions from transmission measurements using electronic portal imaging.

The problem of reconstructing incident radiotherapy beam profiles from electronic portal images recorded behind a phantom is addressed. To this end an iterative algorithm is presented, which is able to extract the input beam profile from a portal image by compensating for the attenuation of the beam and subtracting the amount of scatter emitted by the phantom. The algorithm requires only a thickness map of the phantom. Scatter is estimated using a superposition method based on precalculated Monte Carlo scatter kernels. The method is tested for a homogeneous water-equivalent slab phantom for simple rectangular and complex multileaf collimated fields. It is shown that the method produces a stable result within four iterations yielding an accuracy for the incident beam distribution of better than 3%.

Algorithms↗
PubMed2001

Sampling considerations for intensity modulated radiotherapy verification using electronic portal imaging.

A model has been developed to describe the sampling process that occurs when intensity modulated radiotherapy treatments (delivered with a multileaf collimator) are imaged with an electronic portal imaging device that acquires a set of frames with a finite dead-time between them. The effects of the imaging duty cycle and frame rate on the accuracy of dosimetric verification have been studied. A frame interval of 1 s with 25%, 50% and 75% duty cycle, and a 50% duty cycle with frame intervals of 1, 2, 4, 8, and 16 s have been studied for a smoothly varying hemispherical intensity profile, and a 50% duty cycle with frame intervals of 1, 2, 4, and 8 s for a pixellated distribution. In addition an intensity modulated beam for breast radiotherapy has been modeled and imaged for 0.33 s frame time and 1, 2, and 3 s frame separation. The results show that under sparse temporal sampling conditions, errors of the order of 10% may ensue and occur with an oscillatory pattern. For the beams studied, imaging with a 1 or 2 s frame interval resulted in small errors at the 1%-2% level, for all duty cycles shown.

Breast↗