Spatially-resolved reflectance spectroscopy with variable fiber geometry
Drezek, Rebekah A.
Doctor of Philosophy
Optical techniques based on spectroscopic analysis have the potential for in vivo detection of early malignancies in tissue. Many optical modalities, including reflectance spectroscopy, use fiber optics as the means of light delivery and detection. However, the influence of fiber geometry on sampled optical spectra is not well understood. Since various configurations of fiber-optic probes may produce disparate optical spectra that are unique to individual optical systems, direct comparison among spectroscopic measurements using different optical systems may be difficult. Despite the various configurations of fiber-optic probes and optical modalities, light undergoes an identical sequence in all optical diagnostic techniques, including photon delivery, light-tissue interaction, and photon detection. Therefore, design and optimization of fiber-optic geometry must be combined with a strong understanding of tissue-photon interaction. To meet this requirement, computational models have been constructed and experiments conducted to investigate the influence of fiber geometry on the reflectance spectra. Monte Carlo simulations of photon propagation in stratified tissue models show that the spatial distribution of reflected photons varies as a function of the angles with respect to the tissue surface. More specifically, the spatial distribution of the reflectance favors superficially scattered photons when the exit trajectories of the reflected light become increasingly oblique. Therefore, it is possible to vary the collection angles of fiber probes to achieve spatially-selective reflectance from the epithelial layers, which is particularly pertinent to the diagnosis of early dysplastic transformation occurring at superficial depths. By testing angularly-variable fiber geometry on layered tissue phantoms, we confirm the theoretical predictions of the computational models. Furthermore, the angled fiber geometry may be coupled with gold nanoshells to provide significantly enhanced scattering contrast when nanoshells are selectively conjugated with dysplastic epithelial tissue. An equal magnitude of scattering contrast can be induced with markedly less gold nanoshell dosage when the angled fiber geometry is used in place of the conventional orthogonal fiber geometry. Combining reflectance-based diagnostic modalities with enhanced scattering contrast offers greater diagnostic sensitivity for clinical practitioners and greater safety for patients.