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Currently several medical imaging techniques are in operation in clinical environments that help the doctors to diagnose diseases before proceeding to treatment. This research investigated and implemented configurations for a medical imaging technique called Optical Coherence Tomography (OCT). The Michelson interferometer has been the principal configuration for OCT systems. For endoscopic OCT applications though such a configuration is susceptible to polarisation induced signal fading due to environmental changes within the sample arm, like fibre bending and temperature fluctuations. The development and testing of a Fizeau interferometer based OCT system demonstrate the elimination of this polarisation induced signal fading as the sample and reference arm of the interferometer experience the same environmental changes. The Fizeau interferometer is formed between the end of the fibre and the sample itself. A secondary processing interferometer is used in this configuration, to compensate the path difference inherent to the Fizeau configuration. Longitudinal resolution is about 19 m in air, and lateral resolution about 23 m. A signal-to-noise ratio of about 80 dB was achieved with this system and several sets of image data were collected from laboratory and biological samples. An OCT system based on a Fizeau interferometer incorporating a coherent fibre imaging bundle was also investigated. Fibres in the bundle are accessed sequentially by a beam focused onto the input face of the bundle, allowing 2D information to be acquired using point detection. Incorporating a fibre optic imaging bundle in Fizeau based interferometer OCT allows mechanical scanning parts to be removed from the sample arm, resulting in a passive probe. Such a configuration can form a compact, robust and “downlead insensitive” OCT system and is a strong candidate for in vivo applications. The performance of leached and wound coherent fibre optic bundles was accessed and an analysis is presented. The longitudinal resolution of the system developed was about 10 m in air, and lateral resolution about 9 m. This thesis demonstrates several sets of image data that were collected from various samples using a Fizeau interferometer based OCT incorporating coherent imaging bundles. 2D image data captured by such a configuration are presented and reported for the first time in this thesis.

The three objectives listed here are the main aim presented in each of the chapters of this thesis. The research work carried out with respect to fulfilling these objectives is one step closer towards extending the possibility of non-invasive imaging modality of OCT and PS-OCT in the field of orthopaedics and tissue engineering. - Non-invasive technique to understand the depth-dependent 3D collagen framework of articular cartilage. - Non-invasive technique to discriminate between different types of connective tissue based on angle-resolved backscattering profiles - Computer based tissue discrimination based on the speckle textural analysis of the OCT images obtained Articular cartilage was imaged using two different schemes of implementation of PS-OCT: time domain PS-OCT and swept source based continuous polarisation modulation PS-OCT system. Detailed analysis is presented for time-domain PS-OCT data obtained from bovine articular cartilage sample over multi-angle measurements and a comparative study of the phase retardance profiles obtained from experimental data is done with those obtained from a layered model of articular cartilage using extended Jones matrix calculus. This includes a noise model chosen for the time domain PS-OCT system to add noise bias to the simulated results. Optimiser algorithms are developed based on this model. This study shows the possibility of using PS-OCT imaging towards non-invasive technique to study the microstructure of articular cartilage. The technique of multi-angle imaging in PS-OCT has also been used in the study of angleresolved backscattering, with the information regarding the reflectivity profiles as obtained from a normal OCT system used for the study. The two connective tissues under study are bovine tendon sample and bovine articular cartilage sample. Articular cartilage is predominantly made of Type II collagen fibrils which are finer and more uniform in nature compared to that in tendon tissue which is predominantly Type I collagen fibrils of larger diameters and coarser packing arrangements. Single scattering model of OCT is used to obtain the angle-resolved backscattering curves and Rayleigh Gans scattering approximation based simulation is carried out to elucidate and understand the results obtained. Speckle texture analysis is carried out to extract sub-resolution based information from OCT towards computer-based classification of different types of OCT images. This has been carried out first on tissue phantoms made of agar-intralipid solutions of different concentrations. Statistical features are extracted and grouped into 3-set features to obtain scatter-plots and receiver operating characteristic curves that determine the correctness of the classification obtained of a particular group of OCT images from the total sample set. With initial success from tissue phantom based speckle textural analysis, this has been extended to study the data classification ability of normal skin from tissue engineered skin with different types of melanoma cell-lines invasion as well as discriminate different types of melanoma invasion of tissue-engineered skin from each other.

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Pressures on endoscopy units are increasing as a result of the Global Rating Scheme, the 2 and 18 week rules and introduction of bowel cancer screening. Nurse endoscopy has evolved over the last decade with many nurse endoscopists extending practice from flexible sigmoidoscopy to colonoscopy, which may leave service gaps leaving routine flexible sigmoidoscopy at risk. To fill this gap, a pilot study was undertaken to assess the suitability of training unqualified individuals to undertake flexible sigmoidoscopy. An Inter-professional, flexible entry training programme was developed - BSc (Gastroenterology). Nine individuals were enrolled onto the programme, with achievements of the students being closely followed over two years. Academic components of the training included FS theory and practice, professional practice, anatomy and physiology and coloproctology. Practical hands-on endoscopy training was regularly provided at an endoscopy training centre in conjunction with the students base Trust. Summative assessment was undertaken for practical skill and theoretical knowledge and understanding. At the end of year 2, 5 students( 56%) had progressed to full procedures under direct supervision within 15 months of commencing the programme. 3 of the students moved onto undertaking procedures under proximal supervision by month 16. Of the remaining 4, 2 commenced proximally supervised procedures at 22 months. In respect of academic achievement, the rate of successful completion at first attempt was 93%. At the end of year 2, all 9 students progressed onto the optional third and final year of the BSc programme. The results included within this thesis illustrate the suitability of the curriculum to develop endoscopic practitioners who are safe, competent and effective within flexible sigmoidoscopy. The curriculum provides a realistic opportunity to develop alternative individuals to undertake flexible sigmoidoscopy, providing a realistic option to contribute to service provision and delivery within endoscopy and gastroenterology without undermining nursing and medical staffing.

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Emission Optical Projection Tomography (eO PT) is a relatively new imag- ing modality that bridges a gap between micro Magnetic Resonance Imag- ing and Confocal Laser Scanning Microscopy. eO PT can be used to image the anatomy and gene expression of intact biological specimens at high resolution and thus provides an alternative to time consuming methods such as serial sectioning. Tomographic image reconstruction for eOPT is currently performed using the Filtered Back Projection algorithm which, while being fast, does not account for the physics of image formation and thus can result in reconstructions of reduced resolution and questionable quantitative consistency. This thesis describes work that was done on eOPT in three areas, including image formation, tomographic reconstruction, and memory savings, the latter of which were required to bring implementation of 3D iterative reconstruction algorithms within reach for the relatively high-resolution eO PT imaging modality. In the area of image formation, measurements were taken to reveal the effects of optical blurring, diffraction and charge-coupled device (CCD) camera noise. Accurate models of each of these phenomena were developed and compared against the measurements. The subject of image reconstruction was first addressed with a modi- fication to the FBP algorithm designed to correct for the quantitative inaccuracies suspected of being introduced by the FBP algorithm when reconstructing specimens consisting of very fine detail. This was done by incorporating the quantitative aspects of the model of image formation into the FBP algorithm. The full model of image formation was incorpo- rated into the iterative Maximum Likelihood Expectation Maximisation (MLEM) algorithm. The third strand of this thesis focuses on various memory saving meth- ods developed to enable the implementation and testing of a variation of MLEM known as the Ordered Subsets Expectation Maximisation (OSEM). , Without such memory saving methods, the implementation of an iterative 3D reconstruction algorithm such as MLEM or OSEM using a full model of image formation would have remained beyond the capacity of modern computers for the foreseeable future, requiring several Terabytes of RAM. Comparisons were made between the quality of and the time required to produce FBP and OSEM reconstructions of the same data sets given the availability of limited computing resources. The feasibility of adopting OSEM reconstructions as an alternative to FBP reconstructions was dis- cussed, based on the use of currently available cutting edge computing hardware.