Development of a Fourier Domain Low Coherence Interferometry Optical System for Applications in Early Cancer Detection

Abstract

Cancer is a disease that affects millions of people each year. While methods for the prevention and treatment of the disease continue to advance, the early detection of precancerous development remains a key factor in reducing mortality and morbidity among patients. The current gold standard for cancer detection is the systematic biopsy. While this method has been used for decades, it is not without limitations. Fortunately, optical detection of cancer techniques are particularly well suited to overcome these limitations. This dissertation chronicles the development of one such technique called Fourier domain low coherence interferometry (fLCI). The presented work first describes a detailed analysis of temporal and spatial coherence. The study shows that temporal coherence information in time frequency distributions contains valuable structural information about experimental samples. Additionally, the study of spatial coherence demonstrates the necessity of spatial resolution in white light interferometry systems. The coherence analysis also leads to the development of a new data processing technique that generates depth resolved spectroscopic information with simultaneously high depth and spectral resolution. The development of two new fLCI optical systems is also presented. These systems are used to complete a series of controlled experiments validating the theoretical basis and functionality of the fLCI system and processing methods. First, the imaging capabilities of the fLCI system are validated through scattering standard experiments and animal tissue imaging. Next, the new processing method is validated by a series of absorption phantom experiments. Additionally, the nuclear sizing capabilities of the fLCI technique are validated by a study measuring the nuclear morphology of in vitro cell monolayers.The validation experiments set the stage for two animal studies: an initial, pilot study and a complete animal trial. The results of these animal studies show that fLCI can distinguish between normal and dyplastic epithelial tissue with high sensitivity and specificity. The results of the work presented in this dissertation show that fLCI has great potential to develop into an effective method for early cancer detection.