Abstract: A method of and apparatus for viewing microscopic images include transmitting tiled microscopic images from a server to a client. The client assembles the tiled images into a seamless virtual slide or specimen image and provides tools for manipulating image magnification and viewpoint. The method and apparatus also provides a virtual multi-headed microscope function which allows scattered viewers to simultaneously view and interact with a coherent magnified microscopic image.

Abstract: A method and apparatus for processing an image of a tissue sample microarray include placing a plurality of tissue samples in an array on a microscope slide. The tissue samples are then simultaneously and uniformly treated, as by staining. Images of the tissue making up the microarray are captured and stored together with identifying information related thereto. The images may be displayed from the digital storage medium using a programmed processor which can select various magnifications for display.

Abstract: A method is disclosed for using a computer controlled microscope system to provide a reconstructed, seamless image from several contiguous fields of view to show the architecture and spatial relationship of biological material in a specimen. The specimen is scanned with a microscope and a digital scanner to provide digitized titles of contiguous, fields of view at a predetermined magnification, optical resolution and pixel resolution. Preferably, an automated X, Y stage with higher positional spatial resolution than the spatial pixel resolution of the digital scanner is used to acquire the contiguous fields of view and the image registration information which is used to reconstruct and to display on a monitor the reconstructed image formed of the contiguous multiple fields of view. Preferably, a macro image of contiguous image titles at a low magnification and optical resolution is obtained and the user navigates within the macro image and selects areas.

Abstract: A method of and apparatus for viewing microscopic images include transmitting tiled microscopic images from a server to a client. The client assembles the tiled images into a seamless virtual slide or specimen image and provides tools for manipulating image magnification and viewpoint. The method and apparatus also provides a virtual multi-headed microscope function which allows scattered viewers to simultaneously view and interact with a coherent magnified microscopic image.

Abstract: An apparatus and method acquires and stores multiple resolution images from a specimen on a support and provides to the user a low magnification, reconstructed macro image of the entire specimen, or a large portion thereof, to aid the person in selecting points of interest to be viewed or analyzed at higher magnifications and resolution. The reconstructed image is formed of a large number of tiled, stored images which are coordinated and assembled to form the macro image of the specimen which is displayed on a monitor. Preferably, the stored, reconstructed image is reduced further in size by a software system before it is displayed to the user. The display may be on a local monitor over a local area network or sent over the Internet to the user who is typically a pathologist. The user selects by a marker such as a cursor the defined area of interest or region and then views higher magnification images or has them analyzed.

Abstract: A method is disclosed for using a computer controlled microscope system to provide a reconstructed, seamless image from several contiguous fields of view to show the architecture and spatial relationship of biological material in a specimen. The specimen is scanned with a microscope and a digital scanner to provide digitized titles of contiguous, fields of view at a predetermined magnification, optical resolution and pixel resolution. Preferably, an automated X, Y stage with higher positional spatial resolution than the spatial pixel resolution of the digital scanner is used to acquire the contiguous fields of view and the image registration information which is used to reconstruct and to display on a monitor the reconstructed image formed of the contiguous multiple fields of view. Preferably, a macro image of contiguous image tiles at a low magnification and optical resolution is obtained and the user navigates within the macro image and selects areas.

Abstract: A method and apparatus are disclosed for constructing a virtual microscope slide comprised of digitally scanned images from a microscope specimen. The digitally scanned images are arranged in a tiled format convenient for viewing without a microscope, and for transferring the tiled images for viewing by another at a remote location. Several original microscope views at a low magnification are digitized and stored as digitized images coherently seamed together to provide an overall virtual, macro image of the specimen at a lower resolution. Several original microscope views at higher magnifications are digitized and stored as digitized images coherently seamed together to provide virtual micro images at higher resolution. A data structure is formed with these virtual macro and micro digitized images along with their mapping coordinates. Preferably, a generic viewing program is also provided in the data structure that allows remote users to manipulate and interpret the tiled images on the user's monitor.

Abstract: A method is disclosed for using a computer controlled microscope system to provide a reconstructed, seamless image from several contiguous fields of view to show the architecture and spatial relationship of biological material in a specimen. The specimen is scanned with a microscope and a digital scanner to provide digitized titles of contiguous, fields of view at a predetermined magnification, optical resolution and pixel resolution. Preferably, an automated X, Y stage with higher positional spatial resolution than the spatial pixel resolution of the digital scanner is used to acquire the contiguous fields of view and the image registration information which is used to reconstruct and to display on a monitor the reconstructed image formed of the contiguous multiple fields of view. Preferably, a macro image of contiguous image tiles at a low magnification and optical resolution is obtained and the user navigates within the macro image and selects areas.

Abstract: An apparatus and method acquires and stores multiple resolution images from a specimen on a support and provides to the user a low magnification, reconstructed macro image of the entire specimen, or a large portion thereof, to aid the person in selecting points of interest to be viewed or analyzed at higher magnifications and resolution. The reconstructed image is formed of a large number of tiled, stored images which are coordinated and assembled to form the macro image of the specimen which is displayed on a monitor. Preferably, the stored, reconstructed image is reduced further in size by a software system before it is displayed to the user. The display may be on a local monitor over a local area network or sent over the Internet to the user who is typically a pathologist. The user selects by a marker such as a cursor the defined area of interest or region and then views higher magnification images or has them analyzed.

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.

Abstract: An apparatus and method for measuring the thickness of a tissue section with an automated image analysis system, preferably using polyploid nuclear DNA content, for subsequent use in analyzing cell objects of a specimen cell sample for the diagnosis and treatment of actual or suspected cancer or monitoring any variation in the nominal thickness in a microtome setting. An image of a measurement material, such as a rat liver tissue section, having known cell object attributes is first digitized and the morphological attributes, including area and DNA mass of the cell objects, are automatically measured from the digitized image. The measured attributes are compared to ranges of attribute values which are preestablished to select particular cell objects. After the selection of the cell objects, the operator may review the automatically selected cell objects and accept or change the measured cell object attribute values.

Abstract: A method and apparatus are provided for selecting and analyzing a subpopulation of cells or cell objects for a certain parameter such as DNA using image analysis means. The cells are first stained with an alkaline phosphatase technique including a monoclonal antibody specific to a protein in at least one of the cell's cytoplasm or on a cell membrane, thereby marking any cells including the protein as to type. A second staining of the DNA in the nucleus is accomplished by a Feulgen technique that destroys the cell cytoplasm. After the staining and marking, the cells may then be gated using the image analysis means on the visual parameter such as colored DNA or colored antigen into a subpopulation that is to be measured. The selected cells may then be examined by digital image processing and measured for a parameter such as a true actual measurement of DNA in picograms. A quantitation of the measured parameter may be generated and provided.

Abstract: An apparatus and method for analyzing the cell objects of a cell sample for the diagnosis and treatment of actual or suspected cancer is disclosed. An image of the cell sample is first digitized and morphological attributes, including area and DNA mass of the cell objects are automatically measured from the digitized image. The measured attributes are compared to ranges of attribute values which are preestablished to select particular cell objects having value in cancer analysis. After the selection of cell objects, the image is displayed to an operator and indicia of selection is displayed with each selected cell object. The operator then reviews the automatically selected cell objects, with the benefit of the measured cell object attribute values and accepts or changes the automatic selection of cell objects.

Abstract: A kit for the quantitation of components in cell nuclei is described wherein the kit includes a stain and microscopic slides. Each slide has reference cell objects and a specimen cell area for receipt of specimen cells which are stained simultaneously with the reference cell objects.

Abstract: An apparatus and method for automated assay of biological specimens positioned on microscope slides. The apparatus comprises an interactive optical subsystem for viewing the biological specimen on the slide and for producing an interactive video signal corresponding to the viewed image. An automated optical subsystem includes a single high power microscope objective for scanning a rack of slides, portions of which having been previously identified for assay in the interactive optical subsystem. The system also includes a processor for processing the interactive and automatic video signals from the two optical subsystems. The processor receives the automatic video signal and performs biological assay functions upon it.

Abstract: An apparatus and method for automated assay of biological specimens positioned on microscope slides. The apparatus comprises an interactive optical subsystem for viewing the biological specimen on the slide and for producing an interactive video signal corresponding to the viewed image. An automated optical subsystem includes a single high power microscope objective for scanning a rack of slides, portions of which having been previously identified for assay in the interactive optical means. The system also includes a processor for processing the interactive and automatic video signals for the two optical subsystems. The processor receives the automatic video signal and performs biological assay functions upon it. A method and apparatus are also disclosed for marking points for later analysis on the microscope slides and for associating an analysis function with each marked point.

Abstract: A method and apparatus are provided for selecting and analyzing a subpopulation of cells or cell objects for a certain parameter such as DNA using image analysis means. The cells are first stained with an alkaline phosphatase technique including a monoclonal antibody specific to a protein in at least one of the cell's cytoplasm or on a cell membrane, thereby marking any cells including the protein as to type. A second staining of the DNA in the nucleus is accomplished by a Feulgen technique that destroys the cell cytoplasm. After the staining and marking, the cells may then be gated using the image analysis means on the visual parameter such as colored DNA or colored antigen into a subpopulation that is to be measured. The selected cells may then be examined by digital image processing and measured for a parameter such as a true actual measurement of DNA in picograms. A quantitation of the measured parameter may be generated and provided.

Abstract: An apparatus and method for determining an amount of oncogene protein product copies in a cell includes an optical conversion module for measuring an amount of optically enhanced DNA in a cell sample. A subsystem for measuring an amount of an optically enhanced oncogene protein product protein product is coupled to the DNA measuring means. A subsystem for comparing the measured DNA amount and measured oncogene protein product protein product amount produces a oncogene protein product copy measurement which is fed to an output device for producing an output indicative of the amounts of the oncogene protein product in the cells of the cell sample.

Abstract: An apparatus and method for analyzing the cell objects of a cell sample for the diagnosis and treatment of actual or suspected cancer is disclosed. An image of the cell sample is first digitized and morphological attributes, including area and DNA mass of the cell objects are automatically measured from the digitized image. The measured attributes are compared to ranges of attribute values which are preestablished to select particular cell objects having value in cancer analysis. After the selection of cell objects, the image is displayed to an operator and indicia of selection is displayed with each selected cell object. The operator then reviews the automatically selected cell objects, with the benefit of the measured cell object attribute values and accepts or changes the automatic selection of cell objects.

Abstract: An image analysis system is used for the quantitation of nuclear proteins in cell populations. Particularly, the hormonal receptor content of fine needle aspirates of human breast carcinomas are evaluated. Estrogen or progesterone receptors are amplified and visualized in the specimen by a staining technique of the immunoperoxidase type. Monoclonal antibodies specific against the receptor are attached to the receptor sites and are then amplified by a bridging antibody which attaches to the monoclonal antibody and a peroxidase-antiperoxidase complex. A chromagen, diaminobenzidine is combined with the complex and treated with hydrogen peroxide to react with the peroxidase forming an insoluble brown precipitate which marks the receptor sites for optical identification. The specimen is then counterstained with another chromagen, methyl green which is specific to the nucleus of each cell.