Using Raman Spectroscopy for Intraoperative Margin Analysis in Breast Conserving Surgery

Abstract

Breast Conserving Surgery (BCS) in the treatment of breast cancer aims to provide optimal oncological results, with minimal tissue excision to optimise cosmetic outcome. Positive margins due to an inadequate resection occurs in 17% of UK patients undergoing BCS and prompts recommendation for further tissue re-excision to reduce recurrence risk. A second operation causes patient anxiety and significant healthcare costs. This issue could be resolved with accurate intra-operative margin analysis (IMA) to enable excision of all cancerous tissue at the index procedure. High wavenumber Raman Spectroscopy (HWN RS) is a vibrational spectroscopy highly sensitive to changes in protein/lipid environment and water content –biochemical differences found between tumour and normal breast tissue. We proposed that HWN RS could be used to differentiate between tumour and non-tumour breast tissue with a view to future IMA. This thesis presents the development of a Raman system to measure the HWN region capable of accurately detecting changes in protein, lipid and water content, in the presence of highly fluorescent surgical pigments such as blue dye that are present in surgically excised specimens. We investigate the relationship between changes in the HWN spectra with changes in water content in constructed breast phantoms to mimic protein and lipid rich environments and biological tissue. Human breast tissue of paired tumour and non-tumour samples were then measured and analysed. We found that breast tumour tissue is a protein rich, high water, low fat environment and that non-tumour is a low protein, fat rich environment with a low water content, and this can be used to identify breast cancer using HWN RS with excellent accuracy of over 90%. This thesis demonstrates a HWN RS Raman system capable of differentiating between tumour and non-tumour tissue in human breast tissue, and this has the potential to provide IMA in BCS.