Date of Award
Doctor of Philosophy (PhD)
Physics & Astronomy
Arjun G. Yodh
Diffuse optical spectroscopy/tomography (DOS/DOT) and diffuse correlation spectroscopy (DCS) employ near-infrared light to non-invasively monitor the physiology of deep tissues. These methods are well-suited to investigation of breast cancer due to their sensitivity to physiological parameters, such as hemoglobin concentration, oxygen saturation, and blood flow. This thesis utilizes these techniques to identify and develop diffuse optical biomarkers for the diagnosis and prognosis of breast cancer.
Notably, a novel DOS prognostic marker for predicting pathologic complete response to neoadjuvant chemotherapy using z-score normalization and logistic regression was developed and demonstrated. This investigation found that tumors that were not hypoxic relative to the surrounding tissue were more likely to achieve complete response. Thus, the approach could enable dynamic feedback for the optimization of chemotherapy. Similar logistic regression models based on other optical parameters distinguished tumors from the surrounding normal tissue and diagnosed whether a lesion was malignant or benign. These diagnostic markers improve the ability of DOS/DOT to accurately localize tumors and could serve as a type of optical biopsy to classify suspicious lesions. Another study carried out the first longitudinal DCS blood flow monitoring over a full course of neoadjuvant chemotherapy in humans; this work explored initial correlations between blood flow and response to therapy and showed how DCS and DOS together can more accurately probe tumor physiology than either modality alone. Finally, still other thesis research included the final construction and initial imaging tests of a DOT instrument incorporated into a clinical MRI suite and the optimization of the DOT reconstruction algorithm. In total, these instrumental and algorithmic advances improved DOT image quality, helped to increase contrast between malignant and normal tissue, and eventually could lead to better understanding of tumor microvasculature.
These contributions represent important steps towards the translation of diffuse optics into the clinic, demonstrating significant roles for optics to play in the diagnosis, prognosis, and physiological understanding of breast cancer.
Cochran, Jeffrey Martin, "Diffuse Optical Biomarkers Of Breast Cancer" (2018). Publicly Accessible Penn Dissertations. 2804.