Development of combined Raman spectroscopy - optical coherence tomography for the detection of skin cancer

Abstract

Skin cancer is the most common cancer in the United States, with an incidence rate that continues to rise. Fortunately, it can be highly curable if detected at an early stage. Best clinical practices require physicians to screen large areas of skin, identify suspicious lesions, perform biopsies, and await the results for disease diagnosis. This paradigm is not ideal. Identification of questionable lesions can be subjective, biopsy is invasive and painful, and pathological analysis is time consuming and costly. The potential of a variety of novel optical techniques to perform rapid, non-invasive “optical biopsy” has been widely touted; however these methods suffer unique limitations. Raman spectroscopy (RS) can classify lesions with high accuracy due to its inherent biochemical sensitivity; however it is unable to relate microstructural features of disease. Conversely, optical coherence tomography (OCT) can image tissue microstructure but lacks molecular specificity. The two methods are ideally complimentary and thus well-suited for combination into a single instrument to meet the challenge optical biopsy presents. The primary objective of this dissertation is to develop the novel technique of combined RS-OCT for characterization skin cancers. A pilot study that identifies the capabilities and limitations of RS for skin cancer diagnosis was performed in the first aim, and motivates the development of combined RS-OCT. The second aim demonstrates the feasibility and benefit of combined RS-OCT in a benchtop instrument with integrated RS and OCT sampling optics. The third aim is the development of a second generation instrument which further integrates the systems at the detector level. The final aim reports the implementation of an instrument and probe capable of combined RS-OCT analysis of skin cancers in a clinical setting. The results of this dissertation represent a significant step towards the ultimate goal of optical biopsy.