A key component of accurate spectroscopic-based cancer diagnostics is the ability to differentiate spectral variations resulting from epithelial tissue dysplasia. Such measurement may be enhanced by discretely probing the optical properties of the epithelial tissue where the morphological and biochemical features vary according to tissue depths. More precisely, layer-specific changes in tissue optical properties correlated to cellular dysplasia can be determined by conventional reflectance spectroscopy when it is coupled with angularly variable fiber geometry. Thus, this study addresses how angularly variable fiber geometry can resolve spatially specific spectral signatures of tissue pathology by interpreting and analyzing the reflectance spectra of increasingly dysplastic epithelial tissue in reflectance-mode Monte Carlo simulation. Specifically, by increasing the obliquity of the collection fibers from 0 to 40 deg in the direction facing toward the illumination fiber, the spectral sensitivity to tissue abnormalities in the epithelial layer is thereby improved, whereas orthogonal fibers are more sensitive to the changes in the stromal layer.
The present study focuses on enhancing the sensitivity and specificity of spectral diagnosis in a stratified architecture that models human cervical epithelia by experimentally demonstrating the efficacy of using angularly variable fiber geometry to achieve the desired layer selection and probing depths. The morphological and biochemical features of epithelial tissue vary in accordance with tissue depths; consequently, the accuracy of spectroscopic diagnosis of epithelial dysplasia may be enhanced by probing the optical properties of this tissue. In the case of cellular dysplasia, layer-specific changes in tissue optical properties may be optimally determined by reflectance spectroscopy when specifically coupled with angularly variable fiber geometry. This study addresses the utility of using such angularly variable fiber geometry for resolving spatially specific spectra of a two-layer epithelial tissue phantom. Spectral sensitivity to the scattering particles embedded in the epithelial phantom layer is shown to significantly improve as the obliquity of the collection fibers increases from 0 to 40 deg. Conversely, the orthogonal fibers are found to be more sensitive to changes in the stromal phantom layer.
Gold nanoshells are positioned to become a scattering-based contrast agent to improve the reflectance signals of nanoshell-targeted tissue. However, our study shows that a greater enhancement of nanoshell-induced reflectance signals can now be achieved when angularly oblique fiber geometries are used in place of the conventional orthogonal fiber geometry. This important finding was confirmed by conducting two experiments. First, diffuse reflectance spectra were collected from nanoshell-infused polystyrene phantoms at 0, 10, 20, 30 and 40 degree collection angles. At the 40 deg. fiber angle, the nanoshell-induced reflectance contrast, with respect to the native polystyrene phantom, is significantly increased. Based on these results, a reflectance study was then conducted for human cervical tissue treated with gold nanoshells at the 0 and 40 degree collection angles. Again, at the 40 deg. fiber angle, the signal level of the nanoshell-induced contrast in tissue is determined as statistically significant. Taken together, these results demonstrate that the use of the angularly oblique fiber geometry does significantly improve reflectance contrast.
The aim of the present study focuses on experimentally demonstrating the efficacy of
using angularly-variable fiber geometry to achieve the desired tissue-layer selection and
probing depths with the further objective of enhancing the sensitivity and specificity of
spectral diagnosis in stratified architectures that resemble human cervical epithelia. The
morphological and biochemical features of epithelial tissue vary in accordance with
tissue depths; consequently, the accuracy of spectroscopic diagnosis of epithelial
dysplasia may be enhanced by probing the optical properties of this tissue. When
correlated to cellular dysplasia, layer-specific changes in tissue optical properties may be
deciphered by reflectance spectroscopy coupled with angularly-variable fiber geometry.
This study addresses the utility of using such angularly-variable fiber geometry for
resolving spatially-specific spectral signatures of tissue pathology. This is accomplished
by interpreting and analyzing the reflectance spectra of increasingly dysplastic epithelial
tissue in two-layer epithelial phantoms. Spectral sensitivity to tissue abnormalities in the
epithelial layer is significantly improved as the obliquity of the collection fibers increases
from 0 to 40 degrees. Conversely, conventionally orthogonal fibers are found to be more
sensitive to changes in stromal tissue properties.
Diffuse reflectance of cervical tissue treated with gold nanoshells is collected at 0 and 40
degrees, measured from the perpendicular to tissue surface. Between the two collection
angles, the infused nanoshells exhibit much stronger scattering signals in contrast to the
ordinary reflectance attributed to the naked tissue when the collection angle of the fiber
probe is obliquely oriented at 40 degrees. At 0 deg. fiber angle, no significant
differentiation is observed between naked and nanoshell-treated tissue samples. This
result indicates a strong potential of combining angularly-variable reflectance
spectroscopy and gold nanoshells in order to achieve synergistically enhanced scattering
contrast in tissue.
KEYWORDS: Reflectivity, Tissue optics, Photons, Tissues, Natural surfaces, Monte Carlo methods, Glasses, Fiber optics, Index matching antireflective coatings, Signal detection
Computer simulation is used to facilitate the design of fiber-probe geometries that enable enhanced detection of optical signals arising from specific tissue depths. Obtaining understanding of the relationship between fiber-probe design and tissue interrogation is critical when developing strategies for optical detection of epithelial precancers that originate at known depths from the tissue surface. The accuracy of spectroscopic diagnostics may be enhanced by discretely probing the optical properties of epithelium and underlying stroma, within which the morphological and biochemical features vary as a function of depth. While previous studies have investigated controlling tissue-probing depth for fluorescence-based modalities, in this study we focus on the detection of reflected light scattered by tissue. We investigate how the depth of optical interrogation may be controlled through combinations of collection angles, source-detector separations, and numerical apertures. We find that increasing the obliquity of collection fibers at a given source-detector separation can effectively enhance the detection of superficially scattered signals. Fiber numerical aperture provides additional depth selectivity; however, the perturbations in sampling depth achieved through this means are modest relative to the changes generated by modifying the angle of collection and source-detection separation.
KEYWORDS: Reflectivity, Tissue optics, Photons, Tissues, Natural surfaces, Monte Carlo methods, Fiber optics, Glasses, Signal detection, Index matching antireflective coatings
Computer simulation was used to facilitate the design of fiber-probe geometries which enable enhanced detection of optical signals arising from specific tissue depths. Obtaining understanding of the relationship between fiber-probe design and tissue interrogation is critical when developing strategies for optical detection of epithelial pre-cancers which originate at known depths from the tissue surface. We investigated how the depth of optical interrogation may be controlled through combinations of collection angles, source-detector separations and numerical apertures. We found that increasing the obliquity of collection fibers at a given source-detector separation can effectively enhance the detection of superficially scattered signals. Fiber numerical aperture provides additional depth selectivity; however, the perturbations in sampling depth achieved through this means are modest relative to the changes generated by modifying the angle of collection and source-detection separation.
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