In vivo measurement of the shape of the tissue-refractive-index correlation function and its applicationto detection of colorectal field carcinogenesis

Abstract

Abstract. Polarization-gated spectroscopy is an established method to depth-selectively interrogate the structural properties of biological tissue. We employ this method in vivo in the azoxymethane (AOM)-treated rat model to monitor the morphological changes that occur in the field of a tumor during early carcinogenesis. The results demonstrate a statistically significant change in the shape of the refractive-index correlation function for AOMtreated rats versus saline-treated controls. Since refractive index is linearly proportional to mass density, these refractive-index changes can be directly linked to alterations in the spatial distribution patterns of macromolecular density. Furthermore, we found that alterations in the shape of the refractive-index correlation function shape were an indicator of both present and future risk of tumor development. These results suggest that noninvasive measurement of the shape of the refractive-index correlation function could be a promising marker of early cancer development.

Open source software for electric field Monte Carlo simulation of coherent backscattering in biological media containing birefringence

“…In this paper, we implement two spherically symmetrical models for the composition of the scattering material: first, discrete spheres and second, statistically homogeneous continuous random media with refractive index distributions specified by the Whittle-Matérn family of correlation functions. 1,17,24,36,37 …”

“…1 Typically, models of diffuse reflectance neglect the presence of birefringent materials due to the assumption that their contribution to the measured signal should be small. Yet, biological tissue contains a large number of structures which exhibit either linear birefringence due to structural alignment (e.g., lipid bilayers, collagen fibers, and muscle fibers) or circular birefringence, also known as optical activity, due to the presence of chiral molecules (e.g., glucose and certain amino acids).…”

Subdiffusion reflectance spectroscopy to measure tissue ultrastructure and microvasculature: model and inverse algorithm

“…Most biological tissues are composed of a variety of arbitrarily shaped structures ranging in size from tens of nanometers (e.g., chromatin fibers or ribosomes) to microns (e.g., collagen fibers) to tens of microns (e.g., cells). Because of this continuous distribution of sizes and widely varying shapes, most biological tissues are best modeled as a continuous random media, 4,14,21,31,32 such as the examples shown in Fig. 1.…”

“…[1][2][3][4][5][6] Along with this increased sensitivity comes the need for improved models of light scattering that are both versatile and contribute improved insights into tissue characterization. However, despite the direct link between scattering and fundamental tissue ultrastructure, many models of light scattering focus on the role of wavelength-dependent empirical parameters, which determine the shape of PðθÞ, rather than the more insightful physical properties.…”

“…Furthermore, a number of recent publications demonstrate the suitability of using the Whittle-Matérn model for characterizing tissue mucosa. 4,[22][23][24] In this paper, we present a unified model to quantify six physical tissue properties (three ultrastructural and three microvascular) from a single spectral measurement of the spatial reflectance profile pðr; λÞ at subdiffusion lengthscales. Toward this end, there are four primary goals of the current work: (1) to present a unified model (using two previously developed models) that relates light propagation in biological media to the underlying tissue ultrastructure and microvasculature; (2) to provide a new empirical Monte Carlo-based model that enables rapid generation of pðr; λÞ, specifically at subdiffusion lengthscales; (3) to demonstrate the application of a newly developed inverse algorithm to extract physical properties from a measurement of pðr; λÞ; and (4) to announce MATLAB codes posted online 25 for use by other researchers, who wish to carry out the methods and analysis presented in this work.…”