Fiber-optic Raman Probe Coupled with a Ball Lens for Improving Depth-resolved Raman Measurements of Epithelial Tissue: Monte Carlo Simulations

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Raman spectroscopy is a vibrational spectroscopic technique capable of optically probing biomolecular changes of tissue associated with neoplastic transformation, and has shown promise for the noninvasive, in vivo diagnosis and detection of epithelial precancer and cancer in various organs [1-3]. But analyzing Raman spectroscopic information emitted from tissue remains complicated for tissue diagnosis and characterization due to the reasons that the overall Raman signals acquired from the tissue surface usually contain a mixture of Raman information originating from different tissue depths [4, 5], while the changes of tissue morphology or biochemical constituents associated with disease transformation may be depth-dependent in biomedical systems [6]. For instance, the epithelial tissue usually consists of a superficial epithelium and an underlying stroma, the dysplasia-related changes (precancer) may be associated with the thickening of epithelial tissue, which results in the attenuation of the excitation light to penetrate into deeper areas of tissue and also the attenuation of Raman emission from deeper tissue regions (e.g., stroma) [7, 8]. On the other hand, the changes of other optical properties (e.g., absorption coefficient, scattering coefficient, anisotropic factor, refractive index) of tissue are also correlated with tissue physiologic/pathologic status, significantly affecting the overall Raman signal collection from biomedical tissue [9]. Hence, to better understand the origins of Raman signals collected from tissue surface for further improving the diagnosis of epithelial precancer or early cancer, it is highly desirable to develop a depth-resolved Raman spectroscopic technique for facilitating the wide applications of Raman spectroscopy in biomedical diagnosis. A number of fiber-optic probe designs have been reported for depth-resolved optical spectroscopic measurements, but most work are centered on fluorescence and reflectance spectroscopy for tissue diagnosis [10-15]. The depth-resolved fiber probe designs can mainly be classified into two types: (i) single-fiber probe in which the same fiber is used for both light excitation and reflectance/fluorescence/Raman collection, and (ii) multiple-fiber probe