Method and apparatus for testing a progression of neoplasia including cancer chemoprevention testing
First Claim
1. A method of analyzing a tissue sample having a layer of adjacent, connected tissue cells for pre-invasive neoplasia, comprising:
- optically and microscopically scanning the tissue sample having adjacent, connected tissue cells to provide, multiple image fields and electronically recording these image fields to provide spatially adjacent multiple image fields of the tissue sample larger than a single view of the adjacent, connected tissue cells;
forming a reconstituted image of the suspected neoplasia tissue from the multiple, electronically recorded, spatially adjacent image fields larger than a single field of view and having adjacent connected tissue cells in the reconstituted image;
displaying to the viewer the reconstituted tissue image comprised of multiple, spatially adjacent image fields larger than a single field of view;
determining and selecting from the reconstituted, tissue image a region of adjacent connected tissue cells for analysis at a resolution; and
analyzing tissue sample images of the selected region at the resolution for the analysis of pre-invasive neoplasia.
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Accused Products
Abstract
A system is provided for analysis of neoplasia in tissue at a very early stage as well as later stages of its progression and for reporting the progression or regression of the neoplasia. The system performs multi-parametric measurements of the morphological structure and texture of the tissue structure and correlates these measurements on a common morphological grading scale. The system performs certain tissue measurements which are more highly discriminating for one kind of neoplasia and performs other tissue measurement, which are more highly discriminating, for another kind of neoplasia. Diverse tissue measurements may be made on diverse tissue types such as breast, colon, or cervix tissue, etc. from animals or humans which tissue has subjected to different carcinogens or chemopreventive agents. The measurements are made in different units and on different scales; and then these measurements are combined and reported on a valid, objective, common, universal scale. Microscopic images of stained neoplastic tissue sections are optically and microscopically scanned to provide electronic tissue sample images that are electronically recorded. Then, morphometric features of tissue sample images are measured in first unit vales and texture measurements of the tissue samples, such as a Markovian texture measurement. Usually, normal tissue samples and abnormal cancerous tissue samples are analyzed using the same morphometric and texture measurements and their respective results are reported onto a grading common scale so that progression of the cancer can be ascertained relative to the normal tissue.
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Citations
46 Claims
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1. A method of analyzing a tissue sample having a layer of adjacent, connected tissue cells for pre-invasive neoplasia, comprising:
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optically and microscopically scanning the tissue sample having adjacent, connected tissue cells to provide, multiple image fields and electronically recording these image fields to provide spatially adjacent multiple image fields of the tissue sample larger than a single view of the adjacent, connected tissue cells; forming a reconstituted image of the suspected neoplasia tissue from the multiple, electronically recorded, spatially adjacent image fields larger than a single field of view and having adjacent connected tissue cells in the reconstituted image; displaying to the viewer the reconstituted tissue image comprised of multiple, spatially adjacent image fields larger than a single field of view; determining and selecting from the reconstituted, tissue image a region of adjacent connected tissue cells for analysis at a resolution; and analyzing tissue sample images of the selected region at the resolution for the analysis of pre-invasive neoplasia. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14)
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15. A method of analysis of a tissue sample having adjacent, connected tissue cells comprising the steps of:
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optically and mircroscopically scanning the tissue sample to provide multiple tissue sample images having adjacent, connected tissue cells therein, and electronically recording the tissue sample images to provide multiple tissue sample images of the tissue sample; reassembling the recorded tissue sample images to form a reconstituted, tissue sample image comprised of multiple spatially adjacent, microscopic, tissue sample images from the tissue sample; measuring sections of the reconstituted tissue sample image with respect to area; measuring sections of the reconstituted tissue sample image with respect to optical density; measuring the morphological texture of adjacent, connected tissue cells of sections of the reconstituted tissue sample image; analyzing the results of the measured area, optical densities and morphological texture of adjacent, connected tissue cells of the selected sections of the reconstituted tissue sample image of adjacent, connected tissue cells to provide morphological data; and providing the morphological data for an analysis of the reconstituted tissue sample image of adjacent, connected tissue cells. - View Dependent Claims (16, 17, 18, 19, 20, 21)
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22. A method of analyzing a basal layer sample of tissue having adjacent, connected tissue cells evolving from the basal layer for neoplasia, said method comprising the steps of:
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optically and microscopically scanning the adjacent, connected tissue cells along the basal layer over a plurality of tissue sample fields to provide microscopic, multiple spatially adjacent, image fields of the tissue sample; recording these image fields and reassembling these image fields to form a reconstituted, magnified image comprised of multiple image fields of the tissue and having the basal layer thereon; tracing the basal layer for analysis; analyzing the traced basal layer of the reconstituted tissue sample image with respect to area and optical density; analyzing the traced basal layer of the reconstituted tissue sample image with respect to texture by making measurements including the step of an analysis of texture by examining adjacent, neighboring cell images with respect to values above or below a predetermined threshold; and providing the texture analysis of adjacent, connected tissue cells for use in evaluation of neoplasia. - View Dependent Claims (23, 24, 25, 26, 27, 28, 29)
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30. A method of analyzing histological tissue samples of different kinds of tissues having adjacent connected tissue cells having inherent variabilities for pre-invasive cancer comprising the steps of:
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for each of the histological tissue samples, optically scanning the tissue sample at a plurality of non-overlapping tissue sample fields and electronically recording a high resolution tissue sample image representing selected fields for each of the different kinds of tissues; analyzing each of the respective tissue sample images using a combination of morphometric and texture analyses of histological tissue predetermined to be indicative of the progression of cancer development for each of the kinds of tissues; normalizing results of selected analyses performed in the analyzing step for the respective kinds of tissues to a common standard; and deriving values for the respective kinds of tissues so that a comparison can be made indicative of the progression of their respective cancer developments from the normalized results. - View Dependent Claims (31)
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32. A method of analyzing the efficacy of a chemopreventive agent on first and second precancerous tissues of adjacent, connected tissue cells, said method comprising the steps of:
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optically and microscopically scanning the first precancerous tissue to provide image fields and electronically recording the image fields to provide multiple image fields of the first precancerous tissue;
integrating the recorded image fields into a reconstituted, first tissue sample image comprised of multiple image fields representing the first tissue;analyzing tissue regions of the first reconstituted tissue sample image using a first set of morphometric and texture features highly discriminating for the first precancerous tissue; optically and microscopically scanning the second precancerous tissue to provide image fields and electronically recording the image fields to provide multiple image fields of the second precancerous tissue;
integrating the recorded image fields into a reconstituted, second tissue sample image comprised of multiple image fields representing the second tissue;analyzing tissue regions of the second reconstituted tissue sample image using a second set of morphometric and texture features highly discriminating for the second precancerous tissue; combining the morphometric and texture feature measurements of the tissue regions from the first precancerous tissue to a common scale; and combining the morphometric and texture feature measurements of the tissue regions from the second precancerous tissue to the same common scale so that progression of cancer of the first and second tissues can be compared on the same basis. - View Dependent Claims (33, 34, 35, 36, 37, 38, 39)
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40. Apparatus for analyzing a tissue sample having a layer of adjacent, connected tissue cells for pre-invasive neoplasia, comprising:
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a scanning device for optically and microscopically scanning the tissue sample to provide magnified multiple image fields of the tissue sample; a recorder for electronically recording the magnified, multiple image fields; apparatus for forming a reconstituted, low magnification image comprised of the multiple image fields of the suspected neoplasia tissue; a display for displaying to a viewer a reconstituted, low magnification tissue image comprised of multiple image fields; a selector allowing the viewer to select a region from the reconstituted, low magnification image for analyses at a higher resolution; and an analyzer for analyzing the selected tissue sample image fields of the selected region using at least one morphometric and texture measurement for adjacent, connected tissue cells predetermined to be indicative of the progression of pre-invasive neoplasia development in the tissue sample. - View Dependent Claims (41, 42, 43, 44, 45, 46)
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Specification