Optical spectroscopy for the evaluation of surgical margin status following breast cancer resection

Abstract

The presence of tumor within 1-2 millimeters of the surgical margin following partial mastectomies is strongly correlated with the risk of local breast tumor recurrence; thus, there is a need to develop a non-invasive, real-time, accurate margin evaluation tool to assure complete tumor removal. We previously showed that both Raman spectroscopy and combined autofluorescence and diffuse reflectance spectroscopy can accurately discriminate normal from malignant breast tissues. In this work, the successful use of fluorescence and reflectance-based spectroscopy and spectral imaging for superficial margin evaluation was demonstrated. To achieve greater depth sampling, spatially offset Raman spectroscopy (SORS) was implemented. The feasibility of SORS for breast surgical margin analysis was established by detecting breast tumor signatures through a maximum of 2 mm of normal human breast tissue. A SORS Monte Carlo simulation model was then developed to investigate the effects of varying both normal and tumor layer thicknesses over a wide range of values. The experimental and theoretical SORS results were then used to design a multi-separation SORS probe capable of detecting tumor signatures from below a maximum of 2 mm of normal breast tissue. This probe was used to acquire Raman spectra from frozen-thawed normal breast and breast tumor samples in the laboratory, and a probabilistic classification scheme was developed to determine whether any tumor signature was present in the first 2 mm of tissue under the probe site. Measurements were then made on a small set of freshly excised breast specimens in the clinic to ensure the feasibility of translating this technique to the operating room.