No description available.

No description available.

No description available.

Breast cancer has a significant impact on the well-being of the female population both nationwide and worldwide. This bas motivated the establishment of national breast screening programmes in most western countries, in order to reduce the mortality associated with this disease via early detection. X-ray mammography is considered the current gold standard technique for breast cancer detection in such screening programmes. However, this suffers from performance limitations due to tissue superposition which can either mimic or obscure malignant pathology. Therefore, alternative X-ray modalities, such as digital breast tomosynthesis (DBT), which employs a series of X-ray projections at different (but limited) angles, are being explored in order to improve breast cancer detection rates. In all such X-ray based imaging methods, scattered photons produced deleterious effects on image quality to varying degrees. In order to model such scatter distribution, Monte Carlo (MC) simulations is often chosen as the default approach, and as such is used in this thesis to quantify its effect-s in X-ray mammography and DBT scenarios. Following validation on the use of the GEANT4 MC package for use in mammography, three commercially available full-field digital mammography (FFDM) systems were simulated with their corresponding anti-scatter grids using a CDMAM geometry. It was observed that, for the particular geometry studied, the scattered radiation recorded at the detector was 17% using a linear anti-scatter grid design. However, this figure was reduced by a factor of three when employing a cellular anti-scatter grid geometry. In DBT geometries, scattered radiation is larger than in FFDM and, spatially, may vary more rapidly due to the absence of an anti-scatter grid. The excessively long times needed to run MC simulations (8-10 hours) for such analysis motivates the need for an alternative approach. A non-stationary kernel-based approach has thus been developed. It was found that using kernels based on breast thickness-only, can overestimate scatter radiation by more than 60% (compared to MC simulations) at the breast edge region. Simulation work presented here shows that this overestimation in scatter is largely due to the air gap between the lower curved breast edge and the image receptor. In t his thesis, a more accurate scatter field estimator is proposed for use in DBT which not only considers the breast thickness and primary incidence angle, but also accounts for scatter exiting the breast edge region and traversing an air gap prior to absorption in the image receptor. This proposed approach has reduced such errors to an average error of 10% in scatter, and a maximum of 20% across the projected breast phantom, and has decreased the run-time ten-fold. Such an approach has potential applications in scatter correction methods in DBT, and as an efficient modelling tool in imaging system development and in evaluation of virtual clinical trials.

Professional and public awareness of the hereditary links between family history and breast cancer have resulted in increasing numbers of referrals to regional genetics centres. In a bid to cope with this increasing demand, the appointment of non-medical genetic counsellors with a background in nursing or science, has become commonplace, despite little or no evidence of their effectiveness or acceptability. The aim was to investigate whether genetic nurse counsellors are as effective as current models of service for familial breast cancer counselling, and to explore factors influencing cost-effectiveness. Two randomised controlled trials of equivalence were conducted concurrently in two regional genetics centres. Women who were referred with concerns about a family history of breast cancer were invited to participate and were randomly allocated to genetic counselling delivered by a genetic nurse counsellor (intervention) or a clinical geneticist (control). The primary outcome was patient anxiety, measured using the short form of the STAL the HADS and the mental health and role emotional domains of the SF-36. Acceptability to referring GPs and patients was also assessed. A parallel economic evaluation was conducted. 289 Grampian patients (193 intervention, 96 control) and 297 Wales patients (197 intervention and 100 control) returned a baseline questionnaire and attended. Analysis suggested equivalence in all anxiety scores. No statistically significant differences were detected in other outcomes. The differences in the cost per counselling episode was £10.23 less, 95% (CI-£1.69 to £22.15) for the nurse-based care in the Grampian trial and £10.89 more for nurse-based care in Wales. Care based on nurses was "equivalent" to conventional cancer genetics services across a range of outcomes, and both trial locations. Nurse counselling has the potential to be cost-saving, although the differential costs are sensitive to the grade of doctor (notionally) and the extent of the consultant supervision required by the nurse.

Detecting a target of interest such as a breast tumour is the primary focus of microwave imaging but once detected an additional useful property to have is some measure of the target shape. A combination of a pseudo-random noise (PN) sequence and filter has been employed to pick out the edges of a target that when used to create an image shows the target's shape clearly. A variety of target shapes are investigated with each image giving a good detection and showing the target's shape. Imaging through an outer shell to an inner target and showing both the shell and target on the image is successful with the PN sequence and filter but fails when using a wideband pulse and integrating along its length, picking up only the inner target.

Thymidylate synthase (1YMS) catalyses the conversion of dUMP to TMP and is the target of 5-fluorouracil (5FU). Expression of 1YMS modulates sensitivity to 5FU and polymorphisms in the TYMS gene have been associated with expression and response to 5FU. Methylenetetrahydrofolate reductase (MTHFR) catalyses the reductive methylation of 5,10-methylenetetrahydrofolate, a critical component of the complex formed when 5FU binds and inhibits 1YMS. A polymorphism of MTHFR leads to a thermolabile enzyme with reduced activity, and may alter sensitivity to 5FU. The majority of studies examining the relationship between TYMS and MTHFR and response to 5FU have been carried out in Gl cancers with conflicting results. The aim of this study was to examine the relationship between TYMS and MTHFR polymorph isms, and 1YMS protein expression and outcome, in women with early breast cancer who received adjuvant cyclophosphamide, methotrexate and 5FU (CMF). DNA was extracted from archival tumour tissue blocks, using laser capture microdissection where appropriate, from eighty-six women who received CMF, and from blood samples from 190 women who received doxorubicin and cyclophosphamide (AC). TYMS polymorphisms were analysed using PCR and restriction fragment length polymorphism techniques. PCR products were analysed by high performance capillary polyacrylamide gel electrophoresis with fluorescence detection. The MTHFR polymorphism was analysed by pyrosequencing. 1YMS protein expression was measured in a subset of CMF patients using immunohistochemistry. For patients receiving CMF, carrying a TYMS 3R allele was associated with a significantly increased risk of relapse and death (DFS HR=5.1 [95% er 1.2-21.9], p=D.O'l ; OS HR=4.3 [95% Cl 1.0-18.5], p=0.03). The TSdel6 polymorphism appeared to have some association with DFS and OS, with the 6 bp insertion (+6) homozygotes having the best outcome (p=0.08 and p=0.07, respectively). Patients who were homozygous for both the 2R and +6 alleles had significantly longer DFS (HR=30.1 [95% Cl 0.4-2400], p=O.Ol) and OS (HR=30 [95% er 0.2-3600], p=0.02) compared to all others, and none relapsed or died during the follow up period. These findings were not observed in the AC patients, indicating the differences seen in the CMF patients were treatment related. 1YMS protein expression was not associated with outcome after CMF, nor did it correlate with TS VNTR genotype, suggesting that expression was not the mechanism underlying the association between genotype and outcome. No association was observed between MTHFR C677T genotype and outcome in either the CMF or AC treated patients. The TS VNTR and TSdel6 polymorph isms yielded a significant association with outcome, and the 2R2R-+6+6 diplotype selected a group of patients who had not relapsed or died during the follow up period. The TS VNTR-deI6 diplotype may select breast cancer patients who would benefit from adjuvant CMF chemotherapy.

The purpose of the research is to investigate the feasibility of a 1-0 imaging method utilizing Ultrasonic Vibration Potential (UVP). In this study, ultrasound is used as an external energy to vibrate charged particles or ions in colloids, producing electric dipole moments and generating electrical signals which are in relation to their properties. It is also expected that UVP can also be generated from biological colloids although very few studies involve the area of biological features were reported. The study was proposed with interest of revealing new feature of breast cancer in its earlier stages with the UVP technique, which is the ultimate goal of the research in a long term scope. As the initiation of the research, the main challenges and objectives of this study are to understand the theoretical foundation, establish the experimental methodology and conduct experimental verification for the potential of the technique to characterise particle, in terms of concentration and particle size, which would be the fundamental step of the investigation. This work begins with a critical review of the existing methods and equipment used for UVP measurement and the theoretical models. The O'Brien's local UVP theory with a slab model and an electric dipole model are verified and successfully applied to express the mechanism of UVP in the study. An experimental phantom with a specimen chamber and two types of signal sensors was designed. Effects of two types of sensors, in terms of the sensor in direct or indirect contact with the colloidal sample were investigated. Electrical signals were carefully verified on their sourcing locations. The intensity of measured UVP signals is in a range from 0.04 to 3.35 ~ in respect to silica suspensions with concentrations of 0.5-5%wt and various particle sizes. Trial tests on tumour cell lines were also conducted, which revealed the challenges in measuring biological cells. Ionic solutions were also tested with different concentrations of 2 mol/L and 3 mol/L respectively. Overall, this work demonstrates the feasibility and possibility of the technique in characterising concentration and particle size effects in particular to ionic solutions and colloids. Results are reported and existing challenges are addressed.

No description available.

Breast cancer is the most frequently diagnosed form of cancer and leading cause of cancer death in females. Current screening techniques, such as mammography, are inadequate. Screening reduces the number of deaths caused by breast cancer but also results in a large number of women with non-life threatening forms of the disease being treated unnecessarily. Initial screening can produce a false positive result, which causes much anxiety. Clearly there is a need for a more reliable approach; nuclear magnetic resonance (NMR)-based metabolomics has been used to this end. Plasma and urine from female patients with breast cancer or abnormal but non-cancerous breast state and extracts from tumour and adjacent normal tissue obtained from those afflicted with the disease have been analysed in an attempt to elucidate a biomarker of disease presence or tumour grade. Aqueous extracts of tumour tissue compared to healthy adjacent (normal) tissue revealed increased levels of lactate, alanine, creatine, glutamate, glutamine, glycerophosphocholine (GPC), glycerophospholipids, phosphocholine (PCho), taurine, uridine-5'-diphosphate-N-acetylgalactosamine, (UDP-GaINAc) and uridine-5'-diphosphate-N-acetylglucosamine (UDP-GlcNAc) and decreased levels of glucose. Increased lactate and decreased glucose is in agreement with the Warburg effect whereby cancer cells predominantly produce energy by a high rate of glycolysis. Analysis of lipophilic extracts did not reveal a difference between tumour and normal samples. Metabolite levels did not indicate the tumour grade using either type of extracts. Singly, plasma and urine data did not identify changing metabolite levels with breast cancer or tumour grade but correlations between the two biofluids were established using statistical heterospectroscopy (SHY). Through an unidentified species it was implied that a negative correlation existed between glycerol and certain lipids for patients with breast cancer. These studies have provided useful insights into tumour metabolism and correlations of metabolites in different biofluids.