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The NHS Breast Screening Programme (NHSBSP) is changing from using film screen to digital mammography. The aim of this research was to determine the optimum display medium for the prior mammograms (from the previous screening round) for the transition period. Three options for the display of the prior mammograms were investigated: film display adjacent to the digital workstation, digitised display on the digital workstation, or not displaying them at all.

This thesis describes the development of a robust and portable calorimeter for use in radiotherapy photon and electron beams. The system consists of the calorimeter itself, means for thermal isolation and temperature control, and a temperature measurement system. The requirement for portability placed restrictions on the design which led to higher heat transfer between components than was desirable and much effort was put into thermodynamic modelling of the system. Effort was also focussed on the development of a temperature control system sensitive enough to allow measurements of temperature rises of the order of 1 mK. The control system maintains the temperature of the calorimeter to within +/- 0.2 mK over several hours in an uncontrolled environment. A full characterisation of the calorimeter was earned out at NPL in 60Co radiation and X-ray and electron beams from the NPL linear accelerator. This showed the system is capable of measuring a dose of 1 Gy at doserates as low as 1.5 Gy min-1 with a measurement uncertainty of +/- 0.3% (1 standard deviation). In comparisons with the present NPL primary standards the calorimeter gave agreement within the overall uncertainties. The robustness and portability of the calorimeter were proven in a number of external tests, firstly in an intercomparison between NPL and the Bureau International des Poids et Mesures in the BIPM's 60Co beam in Paris. In the final test an ion chamber was calibrated in a 6 MV X-ray beam from a clinical linac, yielding a calibration factor 0.68% different from that obtained in the NPL linac beam. This difference is within the measurement uncertainties and indicated that there is no significant error in the transfer of ion chamber calibrations from NPL to the radiotherapy clinic.

Positron Emission Tomography (PET) is considered as the fastest expanding diagnostic imaging system in the world, and has become one of the major tools in diagnosis and staging in oncology. Although all the European countries together do not have yet as many scanners as the USA, they have almost completed Phase One of the PET/Computer Tomography (CT) Services Plan. For example, the number of PET/CT scanners in England has increased by a factor of three during the last three years and the focus is now on the advanced PET/CT system. Combined PET and CT scanning is an advanced imaging modality that offers high patient throughput, but results in increased occupational radiation dose exposure. In addition, mobile PET/CT systems have been used to overcome space and money limitations. However, the working environment in a mobile scanner unit places particular constraints on space, patient handling and workflow. These factors stimulated us to investigate the occupational radiation exposure doses for a number of static and mobile PET and PET/CT services provided by NHS hospitals and private companies. The vital goal of this work was to determine staff doses in both static and mobile PET/CT environments and examine the influence of shielding and design by Monte-Carlo simulation. The PET/CT workflow for staff was divided into six phases that were given operational definitions, and start and end points. Using stopwatches, dose rate meters, electronic personal dosimeters (EPDs) made by Thermo and portable LaBr3 spectrometers and dosimeters made by Canberra, exposure time, dose rate, gamma ray spectrum and dose measurements were performed over a period of time varying between 1 day and 5 weeks by various technologists working in 3 static and 3 mobile PET/CT units. Measurements of exposure rate from more than 1250 patient procedures in total were collected and analysed. Experimental studies concluded that the occupational back ground was quite high (>3 muSv/8hours) in some locations and that injected patients were released with high dose rates exceeding 60 muSv/h in the close contact position (< 40 cm). In addition, in designs where the hot-lab room was located between the reception desk and control room without proper shielding, the exposure dose rate in the air exceeded 15 muSv/h at 120 cm from the wall of the hot-lab. The use of a portable LaBr3 detector was important because it has an excellent energy and timing resolution, superior intrinsic spatial resolution and high detection efficiency. Existing occupational doses recorded previously were analysed and provided information that was used in the experimental design of more detailed measurements. Although these results indicated that occupational background is very high in most units, all staff members currently working in Medical PET and PET/CT units are within the regulatory limits for non-classified occupational exposure (<6 mSv per year). However, many of the staff would exceed the classification level if the occupational background was not subtracted. The average exposure time for staff working in static and mobile environments was around 15 minutes and 25 minutes per patient respectively for all 6 defined workflow phases. The corresponding average exposure dose was 5.0 muSv (static) and 5.7 muSv (mobile) per patient. High exposure times and doses were seen to occur during the injection phase and the scanning phase, where staff members are in prolonged close contact with radioactive patients. In addition, on the mobile PET/CT unit, accompanying the patient to the toilet prior to the scan also incurred a high dose, in particular when patients needed additional assistance. It was found that at least 10% of the total dose was not attributable to any of the defined tasks in the workflow, and instead was attributed to unexpected occupational exposure as well as carelessness. Monte Carlo simulation was used to check the dose map inside the unit and to certify the shielding calculation and design. Also, the simulation was used to compare the staff effective dose per patient. Two types of tallies were used as a cross check and showed excellent agreement. Based on the findings of the experimental and numerical studies, a number of strategies for reducing occupational exposures in all workflow phases are suggested.

The investigations reported herein concern the bone and overlying cartilage in thin sections of articular joints. The focus is on essential and trace elemental distribution and the structural organization of the component collagen fibres. Use is made of several nuclear analytical techniques (NATs), including micro-proton induced x-ray emission (mu-PIXE), Rutherford back scattering technique (RBS), micro proton-induced gamma emission (mu-PIGE), synchrotron radiation micro x-ray fluorescence (SR-muXRF) and synchrotron radiation small angle x-ray scattering (SR-SAXS). Sections of healthy and diseased human femoral heads were examined by a combination of mu-PIXE, RBS and PIGE to investigate the accumulation of some essential and trace elements such as zinc (Zn), calcium (Ca), phosphorus (P), sulfur (S), sodium (Na) and potassium (K) and their concentrations in these sections. Enhanced accumulations of these elements were noted at the bone-cartilage interface in both normal and diseased sections, and suggest an increased activity of bone/cartilage formation and degrading enzymes whose function rely on the presence of Zn, Ca, K and P as co-enzymes. Their high concentrations in the calcified zone of cartilage affected by OA may reflect an enhanced metabolic activity of chondrocytes that are associated with their reparative response to osteoarthritis and also as an indicator of bone growth. SR-muXRF has also been employed in mapping the distribution of Ca, P, K, S, Na and Cl in equine metacarpophalengeal joint, the samples comprising healthy and diseased tissues at the bone-cartilage interface. Of interest was that the mu-SXRF technique showed for the first time the change in shape of the tidemark and cement line in accord with the expectation of an abraded cartilage surface. To investigate the molecular and structural features of bone and cartilage on the nanometre scale, a Pilatus 2M detector was used for the first time in investigation of collagen fibres arrangements in diseased calcified human femoral head sections. Well defined intensity and orientation maps were obtained The findings of this study have shown that the use of these physical techniques in qualitative analysis and quantification of the elemental content and collagen orientation in bone and cartilage tissues offer the ability to make an assessment of the initiation and progress of OA at the micro and nanometre scale.

Solid state radiation dosimetry systems depending upon the thermal release of stored radiation energy may be based on observation of thermoluminescence (TL), thermally stimulated exo-electron emission (TSEE) or thermally stimulated currents (TSC). The thesis begins with a brief review of the physics of solid state integrating dosimeters, and each of these three systems is then described and assessed. Following this an account is given of problems associated with the introduction of a routine TLD personnel monitoring service in a group of Scottish hospitals. Research into the design of suitable readout systems for TSEE and TSC dosimetry, and into the extent to which such systems are likely to be of practical value in the near future, is then described. The next section shows how observations of all three phenomena can contribute to an understanding of the physical processes which lead to the supralinear response of some dosimetry phosphors. Finally,investigations into a series of small problems arising in routine work in the National Health Service which have been solved by use of TL or TSEE dosimeters are reported. Throughout the thesis particular attention is paid to the associated instrumental problems, and detailed accounts are given of the TL, TSEE and TSC dosimeter readers designed for the various studies reported.

Some new methods have been developed using an electron microprobe analyser to study gallstones. These methods have been used to show the distribution of major and trace elements, and to investigate the chemical bonding of sulphur present in small highly pigmented regions, from which chemical information would have been difficult to extract using other methods. Supporting methods of X-ray diffraction and infrared spectroscopy have been used to identify the crystalline and amorphous constituents of the regions of interest located by microprobe analysis. The observed patterns of materials distribution have been interpreted in terms of some possible formative events. Particular significance has been attached to the distribution of iron and other trace metals, and to the precise arrangement of the different layers of calcium salts and cholesterol. It has been inferred from the arrangement of the materials present that the calcium salts and cholesterol may not have precipiated independently during stone formation. Calcium salt precipitation appeared to precede that of cholesterol in all the stones examined, and evidence has been presented to show that the cholesterol may have precipitated as a consequence of damage to the gallbladder wall, caused by the calcium salts.

MALDI Imaging has gained huge interest in the past few years with an ever increasing population of specialists choosing to investigate samples using MALDI imaging, including growing interest and financial backing from pharma and contract research organisations. Presented within this thesis is the development and application of MALDI imaging techniques for a variety of analytical problems. The use of various software packages have been employed in the interpretation of the data acquired from MALDI experiments including, the use of statistical analysis for the identification of ion of interest from 6 distinct brain regions and also for the identification of ions of interest associated with small molecule tumour markers. The advantages of MALDI-IMS-MSI as a further separation stage within MALDI-MSI have been shown. Demonstrated is a method for MALDI-IMS-MS imaging of endogenous lipids in healthy tissue and tumours, also demonstrated is the application of MALDI-IMS-MS to xenobiotic distribution studies, it has been clearly shown that ion mobility separation within MALDI-MSI experiments can improve the analysis of xenobiotics by removing any interfering ions. With instrumentation development for MALDI a high repetition rate Nd:YVO4 laser has been assessed as a possible method for decreasing acquisition time.

The purpose of the work described in this thesis was to develop and apply efficient methodologies based on MALDI-MSI for the direct analysis and targeting of protein tumour biomarkers within both frozen and formalin fixed paraffin embedded (FFPE) cancerous tissue sections. Method development for protein analysis directly in tumour tissue sections were performed using tumour xenograft models. This involved improvements in sample preparation, such as tissue washing protocols, and the development of data pre-processing methods prior to statistical analysis using a freely available software package, which referred to as Spec Align. The use of MALDI-MSI for studying proteome patterns directly from tumour tissue sections with no requirement for known targets is demonstrated. In addition, in situ identification of proteins within tumour tissue sections was achieved and correlated with their localisation. The method demonstrated here involved the use of octyl glucoside, a non-ionic detergent, which aims to improve the solubilisation and detection of low abundance and membrane-associated proteins within tumour tissue section after on-tissue digestion. The coupling of MALDI-MSI with ion mobility separation (IMS) has been found to improve the specificity and selectivity of the method. Combining these two methodological approaches allowed the targeting and identification of known tumour biomarkers and potential protein markers in various tumour tissue samples including frozen AQ4N dosed colon tumour xenografts and FFPE human adenocarcinoma tissue sections. The localisation and identification of proteins correlated to tumour growth and aggressiveness were studied using IMS-Tag MALDI-MSI, a novel concept developed in this work. In order to demonstrate its use as a potential biomarker discovery tool, MALDI-MSI was used for high throughput analysis of proteins within tissue micro arrays. Combining MALDI-MSI with statistical analysis allowed the design of a novel tumour classification model based on proteomic imaging information after on-tissue digestion. Another challenge for the MALDI-MSI technology is to achieve more targeted quantitative approaches for in situ analysis of proteins. A proof-of-concept based on multiple reaction monitoring (MRM) analysis with MALDI-MSI is described using a high repetition rate solid state laser. This aimed to improve the sensitivity and specificity of the methodology for the investigation of peptides/proteins directly within tumour tissue sections.

Since Body Section Radiography, now generally known as Tomography, was introduced, a fairly large amount of literature ha grown around this special method of radiography. ?onographs have been written on this subject by EacDougall and Weinbren,who give a general account of its applications, but do not attempt an historical or technical survey. i,part from these two authors and Twining, the great majority of publications have been from foreign sources. This is hardly surprising, since all the initial develotments were carried out on the Continent and in America. In my radiological practice Tomography is employed to a considerable extent as a method of investigation. about two years ago I heard that a 'new' method for obtaining horizontal body sections by radiography was being carried out in Italy. I knew that an apparatus for this purpose had been constructed in England in 1939, and following trials in several hospitals had produced disappointing results. Suspecting that the latter may have been due to to the lack of facilities in overworked x -ray departments early in the war, I determined to carry out experiments in our department. The Medical Supply Association, Ltd., kindly placed their apparatus at my disposal, and having worked out the principles, this never having been properly done before, I was able to produce radiographs of horizontal sections of the thorax of good diagnostic quality and far surpassing the results previously obtained. It is the purpose of the first part of this Thesis to consider briefly the history of Tomography together with the principles involved and its role as a diagnostic procedure. The second part deals with the history of its development in the horizontal plane. The apparatus which I am using is described in detail and the technique of its employment is given. Finally, after describing the anatomical features shown in the normal thorax by this method, a number of cases of interesting intrathoracic lesions are demonstrated.