Optical coherence tomography for "optical biopsy" of axillary lymph nodes involved in breast cancer metastasis

[Truncated abstract] One of the pathways for the spread of metastatic breast cancer throughout the body is the lymphatic system. Accurate determination of the presence and extent of metastatic deposits in lymph nodes of the axilla (staging) is critical to the management of the disease. Currently, lymph nodes are assessed by microscopic examination after surgical excision. However, this can mean removal of healthy lymph nodes without metastatic disease, and may result in unnecessary lymphoedema; that is, swelling due to accumulation of tissue fluid as a result of disruption to normal lymphatic pathway function. This thesis presents an investigation into a possible optical method of lymph node assessment based on optical coherence tomography (OCT) that has the potential to provide in situ "optical biopsy" of lymph node involvement. In situ biopsy could reduce the rate of unnecessary lymphoedema and improve efficiency of node assessment. In this thesis, an investigation of the baseline appearance of the morphology of human axillary lymph nodes imaged using OCT is first presented. We assess OCT images of excised human axillary lymph nodes; both healthy nodes and nodes involved in metastatic spread of breast cancer are imaged using a benchtop OCT system. We compare OCT images with the structural and cellular composition identified using the gold standard technique of histopathology. The results identify a higher OCT signal from metastatic deposits and show that OCT can successfully image the micro-architecture in lymph nodes. It was evident from this study, however, that the diagnostic capability of OCT requires improvement. The native contrast of intensity-based OCT is not, in itself, sufficient to differentiate metastatic deposits in involved lymph nodes, primarily because interpretation of such contrast is ambiguous and subject to artefacts. One of the most problematic artefacts occurs as a result of the variable attenuation of light in tissue. In this thesis, we therefore present a method for processing the OCT data to overcome these ambiguities. The method exploits the attenuation of light in tissue to provide a quantitative measure of contrast. It utilises a single-scattering model to describe the OCT reflectance from tissue and extract optical attenuation coefficients. The attenuation coefficient is an optical property of tissue that is determined by its unique cellular and structural composition and is, therefore, expected to vary between healthy and malignant tissue...