Development and Translation of Light Scatter Imaging and Micro-computed Tomography to Improve the Surgical Resection of Breast Cance

Breast conserving surgery (BCS), when combined with radiation therapy, is a common treatment for localized breast cancer and offers similar outcomes to a mastectomy but with a far less invasive surgical procedure. Unfortunately, 20%-40% of patients who undergo BCS require a second surgery because of an incomplete initial excision, as determined by pathologically positive surgical specimen margins. The fundamental goal of this thesis work is to develop and translate two emerging technologies: light scatter imaging and micro-Computed Tomography (CT), to aid in the surgical resection of breast cancer. A new technique for wide-field sensing and quantification of superficial light scattering was developed, utilizing high spatial frequency structured illumination. This method was validated on solutions of particle suspensions with tunable scattering properties, and subsequently tested on a cohort of n=31 freshly resected breast tissue specimens of various malignant and benign pathologies. This work demonstrated that the quantified light scattering parameters were sensitive to the tissue diagnosis and also predictive of histological features, which in turn could distinguish malignant from benign specimens with 90% sensitivity, 81% specificity, and 84% accuracy. A second generation, multi- spectral structured illumination imaging system was developed and combined with a micro-CT system, allowing for superficial optical scattering to be spatially co-registered to volumetric tumor architecture rendered from the micro-CT, with which a total of n=69 BCS slices have been imaged across 8 malignant tumor subtypes. A reader study was performed to give an initial measurement of the diagnostic potential micro-CT. A cohort of n=32 whole, inked specimens were imaged, and the reader's binary margin diagnosis matched the final pathology for 66% of the specimens with a negative predictive value of 90%. This thesis work experimentally motivates the value for a multi-modal imaging approach for BCS guidance, as the more sensitive light scatter imaging can be guided by the rapid, volumetric micro-CT reading, and will be prospectively evaluated in a future clinical trial.