Order-based analyses of cell and tissue structure

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382133, G01N 3348, G01N 33483, G06F 17159

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active

057197849

DESCRIPTION:

BRIEF SUMMARY
FIELD OF THE INVENTION

This invention relates generally to the analysis of cell and tissue structure and, more particularly, to the use of such analyses in the diagnosis of conditions associated with variations in such structure.


BACKGROUND OF THE INVENTION

The evaluation of cell and tissue structure (hereinafter referred to as "microstructure") is of considerable importance to a variety of disciplines in the medical field. For example, the degeneration of microstructure may be associated with pathological conditions, traumatic events, and aging. While the effective treatment of these conditions often depends upon the early detection of the degenerative microstructure, conventional approaches to the identification of, for example, pathologically significant spatial fluctuations in cell density, have met with limited success.
One potentially useful application for the evaluation of microstructure is in the development of methods for diagnosis of cataracts. In a healthy eye, light from an object being viewed is sequentially focused upon the retina by the cornea and lens. The cornea is a fixed component responsible for the most of the refraction experienced by the light. The lens, on the other hand, is an adjustable component that is controlled by surrounding muscle fibers to ensure proper focusing of the image on the retina, regardless of the distance to the object being viewed.
Obviously, both the cornea and the lens must be transparent or vision will be impaired. While the microstructure of a healthy cornea or lens is organized for virtually complete transparency, this microstructure commonly degenerates, causing significant scattering of light and cornea or lens opacity. In lens tissue, this apparently irregular structural degeneration is known as cataracts and, in advanced stages, results in complete loss of sight.
FIGS. 1-5 illustrate the degeneration of the microstructure of a lens associated with cataracts. In that regard, FIG. 1 is an electron micrograph of a substantially transparent (i.e., cataract free) region of a lens, produced by an electron microscope at a magnification of 10k. As shown, the lens is composed of various cells C, having cell membranes M that enclose cytoplasm. Visual observation of FIGS. 1 and 2 indicates that the cell microstructure is organized in an apparently random fashion. The ability of the lens to transmit light without scattering, and, hence, the transparency of the lens, is dependent upon this structure.
FIGS. 3-5 are electron micrographs illustrating the spatial variations in microstructure and, hence, refractive index, associated with progressively more opaque regions of a lens. Visual observations suggests that the cell microstructure is organized in an apparently random fashion.
Given the limitations of visual evaluation, more advanced analytical techniques have been investigated. For example, signal processing techniques have been used to interpret the data collected by the electron microscope. In that regard, a digitized electron micrograph is an image formed from a 256-by-256 array of pixels, spatially representative of the region of the tissue section being imaged. Each pixel is assigned an intensity, or gray-scale value, ranging from zero to 255. This gray-scale value is representative of the density of the image associated with the corresponding tissue section and, hence, the cellular density at that section. The gray-scale data associated with one row of this array represents the variation in cellular density across one line scan of the biopsy. An illustrative line scan is plotted in FIG. 6.
Discussing now several types of signal processing techniques applied to the analysis of such line scans, Fourier transform methods have been used to detect the differences between line scans associated with normal, transparent microstructures and pathological, opaque microstructures. Details regarding the use of one-dimensional Fourier processing techniques are included in Vaezy et al, "A Quantitative Analysis of Transparency in the Human Sclera and Cornea Using Four

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