Field carcinogenesis is the initial stage of cancer progression. Understanding field carcinogenesis is valuable for both cancer biology and clinical medicine. Here, we used inverse spectroscopic optical coherence tomography to study colorectal cancer (CRC) and pancreatic cancer (PC) field carcinogenesis. Depth-resolved optical and ultrastructural properties of the mucosa were quantified from histologically normal rectal biopsies from patients with and without colon adenomas (n=85) as well as from histologically normal peri-ampullary duodenal biopsies from patients with and without PC (n=22). Changes in the epithelium and stroma in CRC field carcinogenesis were separately quantified. In both compartments, optical and ultra-structural alterations were consistent. Optical alterations included lower backscattering (μb) and reduced scattering (μs') coefficients and higher anisotropy factor g. Ultrastructurally pronounced alterations were observed at length scales up to ∼450  nm, with the shape of the mass density correlation function having a higher shape factor D, thus implying a shift to larger length scales. Similar alterations were found in the PC field carcinogenesis despite the difference in genetic pathways and etiologies. We further verified that the chromatin clumping in epithelial cells and collagen cross-linking caused D to increase in vitro and could be among the mechanisms responsible for the observed changes in epithelium and stroma, respectively.

Low-coherence enhanced backscattering (LEBS) is a technique that has recently shown promise for tissue characterization and the detection of early pre-cancer. Although several Monte Carlo models of LEBS have been described, these models have not been accurate enough to predict all of the experimentally observed LEBS features. We present an appropriate Monte Carlo model to simulate LEBS peak properties from polystyrene microsphere suspensions in water. Results show that the choice of the phase function greatly impacts the accuracy of the simulation when the transport mean free path (ls*) is much greater than the spatial coherence length (L SC ). When ls* < L SC , a diffusion approximation based model of LEBS is sufficiently accurate. We also use the Monte Carlo model to validate that LEBS can be used to measure the radial scattering probability distribution (radial point spread function), p(r), at small length scales and demonstrate LEBS measurements of p(r) from biological tissue. In particular, we show that pre-cancerous and benign mucosal tissues have different small length scale light transport properties.

Since the early 1980’s, the enhanced backscattering (EBS) phenomenon has been well-studied in a large variety of non-biological materials. Yet, until recently the use of conventional EBS for the characterization of biological tissue has been fairly limited. In this work we detail the unique ability of EBS to provide spectroscopic, polarimetric, and depth-resolved characterization of biological tissue using a simple backscattering instrument. We first explain the experimental and numerical procedures used to accurately measure and model the full azimuthal EBS peak shape in biological tissue. Next we explore the peak shape and height dependencies for different polarization channels and spatial coherence of illumination. We then illustrate the extraordinary sensitivity of EBS to the shape of the scattering phase function using suspensions of latex microspheres. Finally, we apply EBS to biological tissue samples in order to measure optical properties and observe the spatial length-scales at which backscattering is altered in early colon carcinogenesis.

Abstract. Optical characterization of biological tissue in field carcinogenesis offers a method with which to study the mechanisms behind early cancer development and the potential to perform clinical diagnosis. Previously, lowcoherence enhanced backscattering spectroscopy (LEBS) has demonstrated the ability to discriminate between normal and diseased organs based on measurements of histologically normal-appearing tissue in the field of colorectal (CRC) and pancreatic (PC) cancers. Here, we implement the more comprehensive enhanced backscattering (EBS) spectroscopy to better understand the structural and optical changes which lead to the previous findings. EBS provides high-resolution measurement of the spatial reflectance profile Pðr s Þ between 30 microns and 2.7 mm, where information about nanoscale mass density fluctuations in the mucosa can be quantified. A demonstration of the length-scales at which Pðr s Þ is optimally altered in CRC and PC field carcinogenesis is given and subsequently these changes are related to the tissue's structural composition. Three main conclusions are made. First, the most significant changes in Pðr s Þ occur at short length-scales corresponding to the superficial mucosal layer. Second, these changes are predominantly attributable to a reduction in the presence of subdiffractional structures. Third, similar trends are seen for both cancer types, suggesting a common progression of structural alterations in each. © The Authors.Published by SPIE under a Creative Commons Attribution 3.0 Unported License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI.

Abstract. Low-coherence enhanced backscattering (LEBS) is a depth selective technique that allows noninvasive characterization of turbid media such as biological tissue. LEBS provides a spectral measurement of the tissue reflectance distribution as a function of distance between incident and reflected ray pairs through the use of partial spatial coherence broadband illumination. We present LEBS as a new depth-selective technique to measure optical properties of tissue in situ. Because LEBS enables measurements of reflectance due to initial scattering events, LEBS is sensitive to the shape of the phase function in addition to the reduced scattering coefficient (μ * s ). We introduce a simulation of LEBS that implements a two parameter phase function based on the Whittle-Matérn refractive index correlation function model. We show that the LEBS enhancement factor (E) primarily depends on μ * s , the normalized spectral dependence of E (S n ) depends on one of the two parameters of the phase function that also defines the functional type of the refractive index correlation function (m), and the LEBS peak width depends on both the anisotropy factor (g) and m. Three inverse models for calculating these optical properties are described and the calculations are validated with an experimental measurement from a tissue phantom. C 2011 Society of Photo-Optical Instrumentation Engineers (SPIE).