The precise architecture of the vascular system is critical to its many specialised functions. In sharp contrast tumour vascular architecture is highly disorganised and dysfunctional. The reason for this is the grossly abnormal angiogenic signalling prevalent in the tumour microenvironment. Aberrant tumour vasculature is a key determinant of spatial and temporal heterogeneities of blood flows. Additionally, irregularities in the tumour vascular wall, a lack of functional lymphatics and a severely retarded trans-mural hydrostatic pressure gradient also diminish convective transport out of the vessels. Diffusion therefore remains the dominant transport mode in tumours and presents a considerable barrier to macromolecular therapy (e.g. Antibody-directed enzyme prodrug therapy (ADEPT)). A number of recent studies of vascular morphology in both clinical and xenograft tumours have demonstrated the existence of type-specific architectures. Precisely how these type-specific architectures translate to blood flow through the vascular system had not been determined. To address this we have developed a method for studying the 3D architecture of the tumour and simulating flows through it. This technique uses corrosion casts to capture the 3D tumour vascular system. 3D morphometry was determined by stereoimaging and X-ray micro-computed tomography. A computational fluid dynamics model was then used to study the hydrodynamics of the vascular networks. My results show that vessel structure and architecture varies in clinical colon cancers, but these differences were substantially smaller than those of two human colorectal xenografts (LS147T and SW1222) commonly used in pre-clinical studies. The results also provide evidence that LS147T is, in general, a closer model to most clinical colorectal tumours than SW1222. To our knowledge this is the first attempt to utilise X-ray micro-computed tomography to study vascular corrosion casts of tumours, and using this data, produce 3D flow profiles.

Optical Tomography is a medical imaging method for creating three-dimensional images using near infrared light. An instrument, named MONSTIR (Multi-channel Opto-electronic Near-infrared System for Time-resolved Image Reconstruction), has been designed and built to measure the flight times of photons between two positions on the surface of the tissue being imaged. The measurements are used to generate functional images of the newborn infant brain, and to detect and classify breast disease. The aim of my PhD project has been to design a new imaging system, improving on the original design of MONSTIR in order that the images produced from data collected in clinical measurements will lead to improved diagnosis of infant brain trauma and female breast disease, and new functional studies of the neonatal brain. MONSTIR has been used for conducting fundamental investigations into optical tomography, but has been found to be awkward to use in a clinical environment, inefficient, and has components coming to the end of their useful lifetime. New ultrafast timing electronics have been purchased and tested in conjunction with other new instrumentation intended to reduce measurement errors. The new system's capabilities have been quantified, and improved performance tested in a clinical environment. The data accuracy of MONSTIR whilst in the presence of a large magnetic field has also been quantified, as simultaneous acquisition with magnetic resonance imaging (MRI) could provide useful a priori information for reconstruction. The project has focussed on three major instrumentation changes to MONSTIR: new timing electronics, a new laser calibration method, and updated optical attenuators. First, the original timing electronics required a 12 s delay between switching source positions to upload data to the control PC. This dead-time is undesirable during clinical studies as the patient must remain still for 12 minutes, whilst collecting only 6 minutes of data. Second, temporal variations have been found in the laser's power output. A new instrument has been designed and tested, resulting in a reduction in intensity errors between repeated measurements over one hour from 40 % to 1 %. Finally, variable optical attenuators are used to compress the dynamic range of the detected signal and protect the detectors from excessive illumination. The original design, using eight apertures of various sizes, does not provide repeatable attenuation, causing a 3 % variation in intensity measurements. A new design has been implemented using x-ray film that has been variably exposed in ten discrete sections, reducing intensity variations to below 1 %.and increasing the maximum attenuation from 2.2 to 3.7 OD. Implementation of the new instrumentation has improved the system for clinical use. The system is half its original size, takes less than 3 hours to reach thermal stability, and acquires data at 5 s per source containing intensity and meantime uncertainties of 1.9 % and 5.2 ps respectively. The new MONSTIR system requires a delay of 1.5 s between sources, with the result that full 32-channel datasets can be acquired in 3.5 minutes. The increase in acquisition speed allows datasets to be acquired in rapid succession, further reducing data errors in functional imaging. Three dimensional images of breast disease have been produced, and validated using tissue-equivalent phantom studies.

In this thesis a method for Electrical lmpedance lmaging (EIT) during epileptic activity is developed. The first chapter provides an introduction to the impedance properties of the tissues of the head, to epilepsy and related conditions and how bioimpedance changes with these. In the second chapter a method for simultaneous recording of EIT and EEG is developed, as the latter may be corrupted by the current injected by the former, to permit clinical reporting and correlation between the two methods. The work in the third chapter analyzes fully a pilot clinical study with EIT during seizures, to see if any significant changes could be measured. In the event, this analysis proved negative, so the fourth and fifth chapters re-examine the engineering aspects of the problem and specify an improved system. In particular their aim was to examine the feasibility of undertaking EIT during seizured with scalp electrodes: a detailed finite element model of the head was used in order to estimate the likely amplitude of scalp potentials, and these were considered in relation to the baseline noise of three available EIT systems. The purpose of this was to determine if EIT appeared feasible, suggest optimal recording conditions (such as optimal applied frequency) and choose the best available system for a clinical study. In the sixth and seventh chapter new measuring protocols were devised and a study was undertaken in saline filled tanks to determine if indeed the performance of the two best systems appeared sufficient for a clinical study. I then summarize the finding of the work in this thesis, discuss their overall significance and propose future work required for EIT in epilepsy.

The theoretical advantage of perfusion data over wall motion data for diagnosing coronary artery stenosis relates to the temporal sequence of these phenomena in the ischaemic cascade. Myocardial perfusion evaluation could thus provide earlier information than wall motion assessment, with important clinical consequences. This thesis examines myocardial perfusion assessment using ultrasound and micro-bubble contrast in stable coronary artery stenosis. The first set of experiments were undertaken to establish both a means of infusing Optison (GE Healthcare, UK), and of displaying static frame contrast signal using Power Contrast Imaging (Acuson Sequoia, Siemens Medical Solutions, Mountain View, CA, USA.). Three Optison concentrations, five infusion rates, and five trigger intervals were evaluated. This revealed an appropriate concentration and infusion rate for Optison and identified an ideal trigger interval of one in four cardiac cycles. The second part of this study evaluated Power Contrast Imaging with Optison infusion in stable single or double vessel coronary artery stenosis. Perfusion assessment during Adenosine vasodilator stress was compared with standard wall motion assessment during Dobutamine stress, coronary angiography being the diagnostic standard. Among twenty-eight subjects and eighty-four coronary territories, Power Contrast Imaging had low sensitivity but equivalent specificity compared to wall motion assessment. The third component of this research evaluated micro-bubble preserving real time Coherent Contrast Imaging (Acuson Sequoia , Siemens Medical Solutions) alongside Optison infusion in stable single or double vessel coronary stenosis. Thirty-eight subjects and one hundred and fourteen coronary arteries were evaluated. Each subject underwent Dobutamine stress, during which standard wall motion, contrast wall motion, and contrast perfusion imaging were all assessed, the diagnostic standard being coronary angiography. This demonstrated that contrast wall motion evaluation is accurate and that combined contrast wall motion and perfusion imaging is at least equivalent to standard wall motion imaging alone for detecting underlying coronary stenosis.

The principle objectives of this study were to investigate deposition around test objects of a more complex geometry than bodies of revolution, using ultrasound, whilst over coming some of the problems previously encountered with ultrasonic imaging. Development of a new deaeration system reduced the number of bubbles (which attenuate ultrasound) in the milk flow to a satisfactory level, subsequently improving the quality of the ultrasound images. Further changes included the selection of a new rennet due to the unavailability of the original rennet used in the milk studies. Several rennets were investigated basing the final selection upon the similarity in behaviour, of the new and the original rennets, in response to agitation. A new test chamber was designed which allowed ultrasonic observation of the progressive development of clot structures and rate of deposition around various test objects, namely monoleaflet mechanical heart valves and monoleaflet valve models, during steady flow. Deposition resulting from pulsatile flow was too thin to be detected by ultrasound. It was seen from ultrasonic and visual observation that deposition thickness in regions of highest shear was thinner than in lower shear regions. Several mechanisms of deposition structure development were observed ultrasonically during steady flow, including a previously unreported mechanism.

The research detailed in this thesis investigates the performance of several advanced signal processing techniques when analysis heart sound, and investigates the feasibility of such a method for monitoring the condition of bioprosthetic heart valves. A data-acquisition system was designed which records and digitises heart sounds in a wide variety of cases ranging from sounds produced by native heart valves to mechanical prosthetic heart values. Heart sounds were recorded from more than 150 patients including subjects with normal and abnormal native, bioprosthetic, and mechanical prosthetic heart values. The acquired sounds were pre-processed in order to extract the signal of interest. Various spectral estimation techniques were investigated with a view to assessing the performance and suitability of these methods when analysing the first and second heart sounds. The performance of the following methods is analysed: the classical Fourier transform, autoregressive modelling based on two different approaches, autoregressive-moving average modelling, and Prony's spectral method. In general, it was also found that all parametric methods based on the singular value decomposition technique produce a more accurate spectral representation than the conventional methods (i.e. Fourier transform and autoregressive modelling) in terms of spectral resolution. Among these, the Prony's method is the best. In addition a modified forward-backward overdetermined Prony's algorithm is proposed for analysing heart sounds which produces an improvement of more than 10% over previous methods in terms of normalised mean-square error. Furthermore, a new method for estimating the model order is proposed for the case of heart sounds based on the distribution of the eigenvalues of the data matrix.

Coronary heart disease is the most common cause of death in the UK affecting more than one in five men and one in six women. The cause is generally a constriction of the coronary arteries which supply the heart muscle, or myocardium with blood. In around 95% of cases, the constriction is caused by the process of arteriosclerosis which results in the development of a plaque on the vessel wall. Even though these plaques tend to develop quite slowly, they are sometimes liable to sudden rupture, which causes clotting of the blood in the vessel and hence a sudden reduction in the supply of blood to the myocardium. This thesis is concerned with the signal processing techniques which are used in the form of Doppler Tissue Imaging (DTI) and real-time B-Mode imaging to study the motion of cardiac structures. Although these techniques are well suited to this task, improvements in B-mode contrast resolution and DTI velocity resolution are required if image quality and quantitative measurements are to reach a more acceptable level. Results are presented which demonstrate that the accuracy of the velocity estimations made using DTI can be improved with the use of model based signal processing techniques. The use of the fractional Fourier transform is explored in the context of coded excitation, which is a technique to allow improvements in imaging depth and axial resolution and results are shown which show that this technique is able to offer improvements similar to matched filtering. The combined techniques of empirical mode decomposition and the Hilbert spectrum are used to demonstrate a new interpretation of the physical process underlying non-linear acoustic wave propagation and the existing technique of tissue harmonic imaging.

As a result of the inevitable patient risk associated with the Carpentier-Edwards bioprosthesis, reliable, periodic, post-operative evaluation of the integrity of the implanted valve is essential. The research detailed in this thesis proposes a method whereby diagnostic information concerning the functionality of the valve is extracted from the acoustic output produced by the operation of the prosthesis. This is achieved by analysing the spectral characteristics of the principal heart sound components contained within this acoustic signal. Results show that normally functioning, leaky and stiffening prostheses each exhibit unique spectral characteristics. Normally functioning aortic prostheses are characterised by four to five dominant frequency peaks, with the major concentration of spectral energy occurring in the region between 25Hz and 125Hz. Normally functioning mitral prostheses are characterised by two to three dominant peaks with the major concentration of spectral energy occurring in the region between d.c. and 100Hz. For leaky regurgitant bioprostheses and prostheses diagnosed as having stiffening calcified cusps, a shift was observed in spectral energy. For leaky mitral and aortic prostheses, the major distribution of spectral energy now occurs in the region between d.c. and 75Hz, whereas for stiffening aortic prostheses, the major concentration of spectral energy now occurs in the region between 50Hz and 200Hz. It was observed that the highest frequency which occurs at a level of -10dB below the maximum spectral response (0dB), may be used to discriminate between normally functioning, leaky and stiffening aortic prostheses, where mean frequencies for these conditions at the -10dB level were observed to be 113.6Hz, 53.7Hz and 238.1Hz respectively. A single discriminating parameter was not observed from the analysis of mitral sounds.

Competence to practise and the acquisition of key clinical skills in therapeutic radiography is an important issue in the NHS (Department of Health, 2000c) and the undergraduates of today are expected to be fit for purpose as therapeutic radiographers of tomorrow. New ways of working will require a greater understanding of how competence in clinical practice can be achieved and developed across all staff groups in the NHS. Patients' place a great trust in NHS professionals and this trust should act as a motivator for all professionals to develop the highest standards in practice. The issue for educators of these professionals, centres on how to develop training programmes, which reflect the current needs of the service for the benefit of the patients. There is no evidence-base generated through research, which looks at the achievement of clinical competence in therapeutic radiography, nor has there been a curriculum review which, attempts to match learning in clinical practice to achievement of competence. Therapeutic radiography undergraduate programmes have traditionally followed curriculum models based on content or learning outcome derived systems which do not necessarily encourage a more proactive approach to skill acquisition and learning. The enquiry employs action research as one of the key methods in order to identify the skills associated with competence to practise. A focus group interview with one cohort of final year therapeutic radiography undergraduates identifies aspects of learning which students consider necessary in order to achieve clinical competence. The interview is followed up using two of the original cohort (post qualification) to verify further, skill acquisition for competence. A national competence survey, for one cohort of newly qualified therapeutic radiographers, suggests that the level of competence achieved by this cohort is at a level considered acceptable for clinical practice. Some of the more able staff is able to demonstrate higher level skills, which are considered necessary for higher level practice. There were only a small number of newly qualified therapeutic radiographers in the survey who had not yet achieved a satisfactory level ofThis enquiry identifies the skills and learner characteristics associated with achievement of competence such as reflection, adaptability, the need to see learning wholes rather than individual parts and the importance of self- confidence. Models of learning and issues surrounding competence to practise were reviewed and considered in the light of the findings from the action research. It is suggested that undergraduate learners achieve competence through progressive achievement of higher level skills indicative of what might be termed, a `competence continuum model' of learning. There is evidence to suggest that in current undergraduate education for therapeutic radiographers, more consideration should be given to the process of learning as part of curriculum design based on a competence continuum model. In terms of current levels of competence in newly qualified therapeutic radiographers, the findings of this research suggest that extant undergraduate programmes in therapeutic radiography are meeting the needs of the service in the modem NHS. There are opportunities, however, to develop the curriculum for clinical education, which focuses more directly on process. For example the task-based learning approach for the continuing development of clinical competence is shown to be a suitable model for curriculum design for undergraduate learners in therapeutic radiography. Examples of how task-based learning can enhance the current programme are provided in the final chapter of this thesis

A new reflectance fibre optic photoplethysmographic (PPG) sensor, comprising of red (660 nm) and infrared (850 nm) emitters, a photodiode and 600 ?m fibre optic cables, was developed to allow for the intraoperative assessment of PPG signals and the preliminary estimation of SpO2 from splanchnic organs. An identical peripheral sensor was also developed to allow for the qualitative and quantitative comparison between PPG signals obtained from splanchnic organs and those from the traditional peripheral site (finger or toe). A three channel instrumentation system (splanchnic PPG, peripheral PPG, and ECG) and software algorithms implemented in LabVIEW allowed for the continuous acquisition of PPG and ECG signals and the estimation of SpO2. The feasibility of the fibre optic sensors to allow for sufficient illumination of the tissue and to adequately detect PPG signals was explored and validated in the laboratory. A detailed investigation to determine the optimal transmitting-receiving fibre separation distance, found that the optimum separation distance was between 3 mm and 4 mm. An in vivo evaluation of the fibre optic splanchnic PPG sensor on 20 patients under-going open laparotomy demonstrated that good quality PPG signals can be obtained from the surface of the small bowel, large bowel, liver and stomach. Due to underlying differences in vasculature, the splanchnic ac and dc PPG signals were found to be of larger amplitudes than those obtained from the periphery, and statistical analysis showed that there is a statistical significant difference between splanchnic and peripheral PPG signals. Also, preliminary estimation of SpO2 from the uncalibrated fibre optic splanchnic sensor showed good agreement between the SpO2 estimated at the periphery. The results from the clinical measurements have confirmed that fibre optic pulse oximetry might be the way forward in monitoring splanchnic perfusion.