The biophysical origins of cervical tissue fluorescence and reflectance spectra : modeling, measurements, and clinical implications
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This dissertation presents research designed to develop a more complete and quantitative understanding of the propagation of light through cervical tissue, in particular investigating the connections between optical spectra and underlying tissue biochemistry, morphology, and architecture. Understanding these relationships is a key factor in optimizing the diagnostic potential of optical spectroscopy. A stepwise approach was used to develop forward models of light propagation, moving from basic experimental and computational investigations of cellular light scattering properties to macroscopic tissue level models of light transport. Six studies are presented. The first two studies used the finite-difference time-domain (FDTD) method to examine light scattering at a cellular level. The studies demonstrated that the scattering patterns of cells are strongly dependent on vii cellular biochemical and morphological structure, including features such as DNA content, nuclear size, and chromatin texture. Next, to examine optical properties at the tissue level, a clinical study was conducted to investigate the autofluorescence of fresh normal and dysplastic cervical tissue sections. At 380 nm excitation, dysplastic tissue exhibited increased epithelial fluorescence and decreased stromal fluorescence relative to paired normal tissue. Using the fluorescence data from this study as model input, a Monte Carlo model was developed in order to quantitatively examine how intrinsic NADH and collagen fluorescence, in combination with tissue scattering and absorption properties, yield measured spectra. Modeled spectra were consistent with clinical measurements, and the results of the study provided a viable explanation of the biophysical origins of differences in normal and dysplastic cervical tissue fluorescence spectra. To facilitate future research, a hybrid FDTD and Monte Carlo model was developed, which incorporates detailed descriptions of the microscopic scattering properties of cells and realistic fiber-optic light delivery and collection geometries. Finally, a preliminary study was completed to assess the potential of acetic acid as a contrast agent for optical imaging. In summary, the work described in this dissertation promotes the development of more sensitive and specific strategies for the detection of epithelial precancers using optical spectroscopy. Furthermore, the completed studies provide valuable insight into the biophysical changes responsible for measured differences in the optical spectra of normal and neoplastic cervix.