Lee, A.C.; (2007) Elastic scattering spectroscopy in the management of breast cancer. Doctoral thesis , University of London.

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Abstract

Elastic scattering spectroscopy (ESS) is an emerging technology capable of detecting malignant changes in tissue using elastic light scattering and light absorption. Pulses of broadband light are delivered to and subsequently collected from tissue to provide a spectrum. Automated spectral analysis using model based analysis (MBA) is under development. Potential clinical applications include ESS guided breast core biopsy, intra-operative assessment of SLN and tumour excision margin. This thesis explores various technical aspects of ESS and factors concerning spectral analysis in relation to the above potential clinical applications. Chapter 5 studied the effects of ambient lighting, tissue handling (i.e. exposure in open laboratory conditions, submersion in saline, chilling in ice) and formaldehyde fixation over time on ESS. The effect of ambient light on the ESS spectra is minimal at intensities below lOOOlux (i.e. in indoor or laboratory), but becomes significant at higher light intensities (i.e. beneath an operating lamp). As for tissue handling and formaldehyde fixation, the changes observed in ESS spectra within the first hour following excision were related to the changes in oxygenation status of haemoglobin. Otherwise, no other changes occurred during this period. However, prolonged formaldehyde fixation (beyond 4 hours) resulted in significant changes. The first part of Chapter 6 investigated the factors influencing the sensitivity and specificity of spectral analysis in differentiating ESS spectra of normal and metastatic axillary lymph nodes. By improving the correlation between ESS spectra and histology, sensitivity and specificity increased to 88-90% and 91-96% respectively from the previously reported sensitivity of 57% and specificity of 85%. The second part of Chapter 6 is a comparative study of ESS and touch imprint cytology (TIC). Based on 89 sentinel lymph nodes, both ESS and TIC identified 6 out of 8 nodes with metastasis giving equal sensitivities of 75%. Specificity was 93% for ESS and 100% for TIC. In Chapter 7, a grid system was used to correlate ESS spectra to the precise histology with the percentage of malignant replacement in breast tissue. Spectral analyses using MBA were performed with different training sets, and showed increasing sensitivity to differentiate normal and malignant breast ESS spectra with increases in the percentage of malignant breast tissue (specificity 0.74): Sensitivity 0.56 0.72 0.60 0.90 0.87 In conclusion, ex-vivo ESS spectra are relatively stable and reproducible within 1 hour of excision irrespective of different tissue handling techniques. Sensitivity and specificity of spectral analysis is dependent on accurate correlation between ESS spectra and histology, and the amount of replacement by malignant tissues.

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