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Title: Applications of Raman spectroscopy and fluorescence spectrometry in glioma surgery and neuropathology
Author: Livermore, Laurent James
ISNI:       0000 0004 8503 5578
Awarding Body: University of Oxford
Current Institution: University of Oxford
Date of Award: 2019
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The diagnosis and management of patients with diffuse gliomas presents a significant challenge due to the aggressive nature of these tumours. Currently, there is no cure, and therefore the aim of treatment is to prolong survival and maintain quality of life for as long as possible. Surgical resection is an important part of the treatment, with evidence that increasing the extent of tumour resection results in prolonged survival, but the intraoperative identification of tumour boundaries is difficult. Techniques such as fluorescence-guided surgery have been shown to increase the extent of resection. The molecular genetic classification of gliomas, particularly identification of isocitrate dehydrogenase mutation and 1p/19q-codeletion, has also been shown to be critical for clinical and surgical decision-making. Raman spectroscopy probes the unique molecular vibrations of a sample in order to accurately characterise its molecular composition. No sample processing is required, allowing for rapid analysis of tissue. The first aim of this project was to apply Raman spectroscopy to intraoperative and neuropathology analysis of gliomas both in terms of genetic subtyping and identification of the tumour/normal tissue boundary. Ex vivo Raman analysis of fresh tissue samples, from 62 patients collected straight from surgery, demonstrated 79%-94% sensitivity and 90-100% specificity for predicting the three most common glioma genetic subtypes. Raman spectroscopy was also compared with intraoperative visual fluorescence and was found to be significantly better at identifying tumour at the tumour boundary compared to the gold standard of visual fluorescence. The second aim of the project was to develop a fluorescence spectrometry laboratory setup to allow for testing of enhanced fluorescence visualisation methods. Here, a laboratory-based fluorescence setup was correlated with the intraoperative light sources. A stable fluorescence standard was proposed and developed, using a laser dye, and was correlated with the intraoperative fluorescence. This experimental setup was used to prove the hypothesis that the operative endoscope is more sensitive at detecting visual fluorescence than the operative microscope.
Supervisor: Vallance, Claire ; Ansorge, Olaf ; Plaha, Puneet Sponsor: Cancer Research UK
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available