PhD, EngD and MSc by research theses (Cranfield Health)

Permanent URI for this collection

https://dspace.lib.cranfield.ac.uk/handle/1826/2004

Browse

Browsing PhD, EngD and MSc by research theses (Cranfield Health) by Author "Barr, H."

Now showing 1 - 4 of 4
  • Thumbnail Image
    ItemOpen Access
    Advancing the clinical application of Raman spectroscopic diagnosis of oesophageal pre-malignancies
    (Cranfield University, 2009-01) Hutchings, J.; Stone, Nicholas; Kendall, Catherine; Barr, H.
    Raman spectroscopy is a technique that utilises inelastic scattering processes to provide a biochemical fingerprint that has been shown to successfully discriminate oesophageal pathologies. The aim of this study was to develop Raman spectroscopy as a clinical tool; both in vivo for ‘targeted biopsy’, and in ex vivo for ‘automated histopathology’. Two different Raman probes were evaluated and compared and tissue classification models generated ex vivo. A preliminary classification model of a novel single collection fibre probe demonstrated potential for the probe design. Both probes were shown to discriminate three different oesophageal pathology groups. A cross-validated tissue classification model (88 samples) discriminated normal, Barrett’s and neoplasia with an overall accuracy of 86.5% with a sensitivity of 83.3-89.5% and specificity of 89.2-97.1%. A novel rapid Raman mapping technique was evaluated. It was shown that sufficient biochemical information for pathology diagnosis could be extracted from low signal to noise ratio data using multivariate analysis providing the dataset was sufficiently large, thus demonstrating the feasibility of automated histopathology in a clinically realistic time frame. Furthermore, it was demonstrated that high spatial resolution imaging was not necessarily required for automated histopathology using novel interpretation of multivariate techniques. A tissue classification model generated from two rapid Raman maps containing separated substrate, normal, HGD, luminescence and fibrous connective tissue with an overall training performance of 97.5% Problems limiting clinical implementation of Raman techniques were investigated and methods of overcoming devised.
  • Thumbnail Image
    ItemOpen Access
    The hydraulic lung
    (2004-10) Prime, David; Turner, Anthony P. F.; Barr, H.
    A Hydraulic Lung has been designed and constructed. The Hydraulic Lung can inhale through a Dry Powder Inhaler (DPI) with a pre-determined level of inspiratory effort, and the characteristics of the inhalation profile generated, such as the peak pressure drop, peak flow rate and the flow acceleration are determined by the resistivity of the inhaler. The Hydraulic Lung has been used to explore the relationship between the level of inspiratory effort, the DPI resistivity and the resultant profile characteristics. A simple empirical equation has been found to describe the peak pressure drop achieved for any given level of inspiratory effort and device resistivity. This equation can be adapted to provide the equivalent peak inspiratory flow rate. A second simple empirical equation was found to describe the flow acceleration rate achieved under defined conditions of inspiratory effort and device resistivity. A clinical study has been performed to generate equivalent human inhalation data. A comparison between the relationships derived from the Hydraulic Lung data and the human inhalation data has demonstrated the validity of the key equation for pressure drop as a tool for predicHng human inhalation characteristics. The equation for flow acceleration rate was found to underestimate the flow accelerations achieved by human volunteers, but with slight modification could be used for this purpose. Correlations were established between the findings from this study and the work of earlier researchers in this area, which was based on clinical data alone. The Hydraulic Lung was also used as a practical tool for the evaluation of DPI performance in-vitro, including the behaviour of devices with variable resistivity which cannot easily be assessed using either standard pumps or sophisticated apparatus such as the Electronic Lung.
  • Thumbnail Image
    ItemOpen Access
    The study of molecular markers for the progression of Barrett's Oesophagus to adenocarcinoma to identify markers that can be used as diagnostic tools.
    (Cranfield University, 2002-05) Cadd, Verity Anne; Warner, P.; Barr, H.; Shepherd, N. A.
    Barrett's oesophagus is a complication of gastro-oesophageal reflux disease and is the single most important predisposing factor for the development of adenocarcinoma of the oesophagus. New molecular markers are needed for early diagnosis and to monitor disease progression. Telomerase is a ribonuclear protein with reverse transcriptase activity, which uses its own RNA component as a template for the addition of telomeric repeats to the end of chromosomes. Telomerase activity has been studied during the neoplastic progression of Barrett's oesophagus using a TRAP based ELISA technique, which found telomerase to be reactivated early during . disease progression. A non-isotopic method of in situ hybridisation for the detection of the RNA component of telomerase has also been successfully developed. Plasminogen activation is an inducible extracellular proteolytic system involved in the regulation of cellular interactions and invasion. The components of the urokinase-type Plasminogen Activator system have been fully investigated during the progression of Barrett's oesophagus to adenocarcinoma utilising immunohistochemistry and ELISA techniques. Changes in the expression of this invasive phenotype were found to occur late during disease progression in malignant tissues. Two-oesophageal cell-lines have been characterised using molecular biological techniques to detect a range of molecular markers to produce ex vivo models of oesophageal adenocarcinoma and oesophageal squamous cell carcinoma. In order to assess the effects of bile salts and acidity on oesophageal tissues these celllines were then utilised as ex vivo models. Exposure to acidic conditions both alone and with bile salts altered the morphological appearance of the cells and disrupted adhesion molecules in the cellular membrane. Investigations into both telomerase reactivation and the plasminogen activator system have provided new information concerning the nature and timing of molecular changes during the Barrett's metaplasia/dysplasia/ adenocarcinoma sequence.
  • Thumbnail Image
    ItemOpen Access
    Towards objective endoscopic diagnosis of Barrett's associated early neoplasia using fibre-optic Raman Spectroscopy
    (Cranfield University, 2012-08) Almond, Laurence Maximilian; Kendall, Catherine; Hutchings, J.; Morgan, Sarah; Barr, H.
    This translational research evaluates a novel, custom-built Raman probe for potential application as an in vivo diagnostic tool in the oesophagus. Raman spectroscopy (RS) is a well established analytical technique which is capable of probing the biochemical changes associated with neoplastic progression in oesophageal tissue. RS relies on measurement of subtle inelastic scattering signals following monochromatic laser excitation. Clinical utilisation of RS within hollow organs requires accurate collection and transmission of signal through fibre-optic cables. This research aims to evaluate the ability of a custom built fibre-optic Raman probe, in conjunction with multivariate classification models, to differentiate between benign and neoplastic oesophageal pathologies ex vivo. The need for spectral stability and reproducibility are addressed, as are difficulties associated with multisystem reliability. In addition, the biochemical basis of spectral classification is evaluated and discussed. Cont/d.