WO2001054052A1 - Method and apparatus for internet, intranet, and local viewing of virtual microscope slides - Google Patents

Method and apparatus for internet, intranet, and local viewing of virtual microscope slides Download PDF

Info

Publication number
WO2001054052A1
WO2001054052A1 PCT/US2001/001782 US0101782W WO0154052A1 WO 2001054052 A1 WO2001054052 A1 WO 2001054052A1 US 0101782 W US0101782 W US 0101782W WO 0154052 A1 WO0154052 A1 WO 0154052A1
Authority
WO
WIPO (PCT)
Prior art keywords
image
accordance
digitized
tiles
station
Prior art date
Application number
PCT/US2001/001782
Other languages
French (fr)
Inventor
James W. Bacus
James V. Bacus
Original Assignee
Bacus Research Laboratories, Inc.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=26873422&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=WO2001054052(A1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Bacus Research Laboratories, Inc. filed Critical Bacus Research Laboratories, Inc.
Priority to CA2398736A priority Critical patent/CA2398736C/en
Priority to EP01942762A priority patent/EP1252604A4/en
Priority to AU2001229630A priority patent/AU2001229630A1/en
Publication of WO2001054052A1 publication Critical patent/WO2001054052A1/en
Priority to HK03101687.3A priority patent/HK1049723A1/en

Links

Classifications

    • GPHYSICS
    • G06COMPUTING; CALCULATING OR COUNTING
    • G06TIMAGE DATA PROCESSING OR GENERATION, IN GENERAL
    • G06T7/00Image analysis
    • G06T7/0002Inspection of images, e.g. flaw detection
    • G06T7/0012Biomedical image inspection
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N1/00Sampling; Preparing specimens for investigation
    • G01N1/28Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
    • G01N1/30Staining; Impregnating ; Fixation; Dehydration; Multistep processes for preparing samples of tissue, cell or nucleic acid material and the like for analysis
    • G01N1/31Apparatus therefor
    • G01N1/312Apparatus therefor for samples mounted on planar substrates
    • GPHYSICS
    • G02OPTICS
    • G02BOPTICAL ELEMENTS, SYSTEMS OR APPARATUS
    • G02B21/00Microscopes
    • G02B21/0004Microscopes specially adapted for specific applications
    • GPHYSICS
    • G02OPTICS
    • G02BOPTICAL ELEMENTS, SYSTEMS OR APPARATUS
    • G02B21/00Microscopes
    • G02B21/36Microscopes arranged for photographic purposes or projection purposes or digital imaging or video purposes including associated control and data processing arrangements
    • G02B21/365Control or image processing arrangements for digital or video microscopes
    • G02B21/367Control or image processing arrangements for digital or video microscopes providing an output produced by processing a plurality of individual source images, e.g. image tiling, montage, composite images, depth sectioning, image comparison
    • GPHYSICS
    • G06COMPUTING; CALCULATING OR COUNTING
    • G06TIMAGE DATA PROCESSING OR GENERATION, IN GENERAL
    • G06T3/00Geometric image transformation in the plane of the image
    • G06T3/40Scaling the whole image or part thereof
    • G06T3/4038Scaling the whole image or part thereof for image mosaicing, i.e. plane images composed of plane sub-images
    • GPHYSICS
    • G06COMPUTING; CALCULATING OR COUNTING
    • G06VIMAGE OR VIDEO RECOGNITION OR UNDERSTANDING
    • G06V20/00Scenes; Scene-specific elements
    • G06V20/60Type of objects
    • G06V20/69Microscopic objects, e.g. biological cells or cellular parts
    • GPHYSICS
    • G16INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
    • G16HHEALTHCARE INFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR THE HANDLING OR PROCESSING OF MEDICAL OR HEALTHCARE DATA
    • G16H10/00ICT specially adapted for the handling or processing of patient-related medical or healthcare data
    • G16H10/40ICT specially adapted for the handling or processing of patient-related medical or healthcare data for data related to laboratory analysis, e.g. patient specimen analysis
    • GPHYSICS
    • G16INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
    • G16HHEALTHCARE INFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR THE HANDLING OR PROCESSING OF MEDICAL OR HEALTHCARE DATA
    • G16H40/00ICT specially adapted for the management or administration of healthcare resources or facilities; ICT specially adapted for the management or operation of medical equipment or devices
    • G16H40/60ICT specially adapted for the management or administration of healthcare resources or facilities; ICT specially adapted for the management or operation of medical equipment or devices for the operation of medical equipment or devices
    • G16H40/63ICT specially adapted for the management or administration of healthcare resources or facilities; ICT specially adapted for the management or operation of medical equipment or devices for the operation of medical equipment or devices for local operation
    • GPHYSICS
    • G16INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
    • G16HHEALTHCARE INFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR THE HANDLING OR PROCESSING OF MEDICAL OR HEALTHCARE DATA
    • G16H40/00ICT specially adapted for the management or administration of healthcare resources or facilities; ICT specially adapted for the management or operation of medical equipment or devices
    • G16H40/60ICT specially adapted for the management or administration of healthcare resources or facilities; ICT specially adapted for the management or operation of medical equipment or devices for the operation of medical equipment or devices
    • G16H40/67ICT specially adapted for the management or administration of healthcare resources or facilities; ICT specially adapted for the management or operation of medical equipment or devices for the operation of medical equipment or devices for remote operation
    • GPHYSICS
    • G16INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
    • G16HHEALTHCARE INFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR THE HANDLING OR PROCESSING OF MEDICAL OR HEALTHCARE DATA
    • G16H80/00ICT specially adapted for facilitating communication between medical practitioners or patients, e.g. for collaborative diagnosis, therapy or health monitoring
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N15/00Investigating characteristics of particles; Investigating permeability, pore-volume, or surface-area of porous materials
    • G01N15/10Investigating individual particles
    • G01N15/14Electro-optical investigation, e.g. flow cytometers
    • G01N15/1468Electro-optical investigation, e.g. flow cytometers with spatial resolution of the texture or inner structure of the particle
    • GPHYSICS
    • G16INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
    • G16HHEALTHCARE INFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR THE HANDLING OR PROCESSING OF MEDICAL OR HEALTHCARE DATA
    • G16H30/00ICT specially adapted for the handling or processing of medical images
    • G16H30/20ICT specially adapted for the handling or processing of medical images for handling medical images, e.g. DICOM, HL7 or PACS

Definitions

  • the invention relates to a method of and an apparatus for storing and viewing virtual microscope slides.
  • the method and apparatus are usable over the Internet, an intranet, or on a local computer, and provide an integrated and interlocked combination of a digital image server and multiple virtual microscope client viewers.
  • tissue sections aspirated tissue, and the like, has typically been a localized activity. That is, the tissue is sectioned in a lab. It may be stained and microscopically examined by a light microscope after which a technician and/or a pathologist reaches a conclusion as to the characteristics of the tissue; for instance whether the tissue is benign or malignant and what stage of malignancy the tissue might be in.
  • a number of patents awarded to the instant inventors are directed to that sort of system.
  • Such a system requires a great deal of customization and expense although such systems do include the use of computer-controlled microscopes.
  • microscopes receive commands from a remote location to move to a particular position on a slide so that the television camera may send a television signal out representative of the field of view.
  • This type of system is relatively expensive and clumsy to use do to the necessity for a very expensive robotically-controlled microscope which receives specialized signals over a dedicated link.
  • the invention relates to a method for viewing virtual microscope slides.
  • Virtual microscope slides comprise sets of tiled images.
  • the tiles of the tiled images represent a field of view which may be captured from a microscope having a high-precision controlled stage typically with a stage resolution in the neighborhood of a 1/lOth micron step.
  • the images are captured on a CCD array which generates images in color or black and white and stores them in a frame buffer or on disk in tiled format.
  • Such images are usually very large due to the number of pixels required to reproduce a substantial size tissue specimen at a high magnification, such as 40 power.
  • other sets of tiled images have a lower magnification, for instance at 1.25 power.
  • All of the images are tiled and stored in digital format on a server which may communicate using the hypertext transport protocol used for web-based communications over a packet switching network such as the Internet or an intranet. Because the images have already been captured and coordinated in tiled form, it is unnecessary to provide a robotically-controlled microscope or even the original specimens themselves.
  • One or more clients may communicate with the server containing the image to download a portion or all of the tiled image. The client provides requests to the server indicating the portion which is desired to be viewed and the server supplies the appropriate tiles for that portion of the image. The tiles are received by the client and are assembled into a seamless view which may be scrolled through and scanned in the same manner as a pathologist may move about a microscope slide to find regions of interest.
  • the low-magnification image may be displayed in a first window at the client and a higher-magnification image may simultaneously be displayed which retains coherence with the lower- magnification image in order to provide ease of scanning for areas of interest by the pathology, or the like.
  • the client/server relationship may be carried out over multiple clients with one of the clients having control over the image positioning as fed by the server for all other clients via communication between the first client and the server, and then subsequent updating coherent communication between the server and the downstream clients.
  • This does not necessarily require that repeated loading take place of the client images, but only that signals be sent between the server and the secondary clients reflecting the field which the first client is viewing.
  • the overall system can operate similarly to a multiheaded optical microscope of the type used to train physicians in pathology.
  • the system can be used as a multiheaded microscope during a consult so that al persons simultaneously involved in the consult are looking at the same portion of the image and no confusion can arise.
  • a further advantage of the present invention is to provide packet switched chat communications along with the multiheaded virtual microscope feature to allow text to be transferred among the various clients while the images are being viewed.
  • additional lines of communication may be provided among the users of the multiple remote client locations so that they can discuss telephonically or even using a voice-over-Internet protocol-based system to confer in real time on the images that are being seen at each of the client stations.
  • the client in control of the image may relinquish control to a second client; the first client operating on a peer basis with the other clients in a secondary relationship thereafter.
  • a linear measuring or tape measuring feature may be provided in order to determine the distance in microns, or the like, between a pair of points identified by pointing and clicking on portions of the image in order to determine the actual size of particular features shown in the specimen image.
  • the size is computed on the basis of the magnification of the image being shown.
  • FIG. 1 is a block diagram of a system according to the invention for creating and transmitting locally, over an intranet or via the Internet data structures of an image of specimen on a microscope slide;
  • FIG. 1A is representation of a microscope slide which has been arbitrarily assigned to be scanned into eighty tiled images
  • FIG IB is a representation of the detected signals of the individual pixel sensors in a CCD optical array after detecting a selected image area to tile and the referenced data files containing the information describing the detected signals;
  • FIG. 2 is a screen view of a system embodying the present invention showing a low magnification image of a specimen on a microscope slide in one window, a high magnification image of a portion of the low magnification image selected by a region marker and a control window;
  • FIG. 3 is a view of a display screen of the apparatus embodying the present invention showing the control window a low magnification window having a plurality of high magnification micro image regions delineated therein and a high magnification window including one or more of the micro image regions;
  • FIG. 4 is a view of a macro image of an actual breast cancer specimen displayed at 1.25X as seen on a computer monitor;
  • FIG. 5 is a view of the grid portion of FIG. 4 outlining a region of interest selected by a pathologist displayed at 40X magnification;
  • FIG. 6 is a block diagram of the steps in the mapping of the scanned image from the optical sensor array to computer bit map in memory to the display on a user's monitor;
  • FIG. 7A is a file listing such as would be seen under Windows 95 file manager showing the data files included in a data structure for a breast cancer specimen;
  • FIG. 7B is a file listing of a Java applet for controlling a data structure
  • FIG. 8 is file listing such as would be seen under Windows 95 file manager showing the data files included in an alternate data structure for a breast cancer specimen
  • FIGS. 9A and 9B are a block diagram of the apparatus embodying the present invention
  • FIG. 10 is a block diagram of a portion of the apparatus shown in FIG. 9 showing details of a mechanical arrangement of a microscope;
  • FIG. 11 is a flow diagram related to operation of the apparatus
  • FIG. 12 is a flow diagram of details of one of the steps in FIG. 11;
  • FIG. 13 is a display screen showing control parameters to be manipulated thereon;
  • FIG. 14 is a flow chart for a region outlying routine
  • FIG. 15 is a flow chart for a scanning and analyzing routine
  • FIG. 16 is a schematic showing of the limits of travel of the microscope stage with respect to the image tiles
  • FIG. 16A is a perspective view of the microscope stage and stepper motors and encoders providing a closed loop drive for the motors;
  • FIG. 17 is a block diagram of a networked system allowing multiple workstations to obtain access to the microscope and to manipulate the microscope locally at each workstation;
  • FIG. 17A is a view of the system described in connection with FIG. 10;
  • FIG. 18 is a block diagram of a remote networked system for distributing and accessing diagnostic images and data, i.e. virtual microscope slides, through a hypertext transport protocol based server directly or over a packet network;
  • FIG. 19 shows a system having interlinking and an integrated combination of image viewer and server concept using an Internet or intranet connection embodying the present invention;
  • FIG. 20 shows a server comprising a portion of the system shown in FIG. 19 and functioning as a listening socket to respond to GET requests and create event threads in a simultaneous multi-threaded operating environment;
  • FIG. 21 shows logic to determine valid GET requests;
  • FIG. 22A shows an interaction between a thin client browser program and the Internet or intranet server computer with a server program as shown in FIG. 20;
  • FIG. 22B shows an HTML-embedded Java applet viewer window for a client subsystem of the system shown in FIG. 19;
  • FIG. 23 shows an interaction between a Java applet program and Internet or intranet servers executing a server program and embodying the present invention
  • FIG. 24 shows a thin client browser main window upon initial activation of the thin client browser shown in FIG. 22A;
  • FIG. 25 shows a main window with a Slide Tray tab activated, showing available images from a remote server;
  • FIG. 26 shows a selection in the tray holding slide name Prost-zl and showing a thumbnail image of a virtual slide together with associated identification information
  • FIG. 27 shows a main window of the thin client browser showing a tab after selection of a virtual slide for detailed viewing in response to the Slide Tray tab;
  • FIG. 28 shows a Slide View window chosen by selecting a point on the browser main window thumbnail image, a Slide View image shows an overlay set of a tiled region from which one or more higher-magnification Field View images may be chosen;
  • FIG. 29 shows a Field View window chosen by selecting an image tile region of the Slide View window shown in FIG. 28 using a pointer;
  • FIG. 30 is a flow chart of a typical sequence of interactions to view an image
  • FIG. 31 shows a Server tab, showing options for multiple client interaction
  • FIG. 32 shows a right mouse click activated pop-up menu when a pointer is positioned on an x, y location in the image area
  • FIG. 33 shows a pointer position after choosing a "Set the Pointer” option in the menu of FIG. 32;
  • FIG. 34 shows a flow chart for major steps in process of filling in display windows with tiles; and
  • FIG. 35 shows an HTML-embedded Java applet viewer window.
  • FIGS. 36A through 36D are flow charts showing the operation of a server and a plurality of clients connected to the server for performing a virtual multi- headed microscope task.
  • a system 10 for creating, and transmitting over an intranet or via the Internet a virtual microscope slide, i.e. interrelated data structures, which may or may not include display procedures, depicting at multiple resolutions, images of a specimen on a microscope slide.
  • the system includes a microscope with a digital platform for supporting the microscope slide.
  • Digital platform or stage 11 has been specially calibrated to include a large number of increments for locating portions of specimen images with high precision. After calibration and initial registration of stage 11 in the microscope setup, a microscope slide 13 or other substrate with a specimen 13a to be scanned is placed on stage 11.
  • the first step in creating a data structure according to the invention is to establish a macro image of the entire specimen (or that portion of the specimen desired to be stored as the macro image) .
  • the purpose for creating the macro or large area thumbnail image is to enable the viewer to see the entire specimen at once and to use the entire image to choose those significant portions thereon for viewing at greater magnification.
  • the user has selected 1.25X as the magnification to display the entire breast cancer slide.
  • the computer controlled microscope is moved to scan the entire image of specimen 13a.
  • the focusing system is programmed to step through increments which detect/select only the high resolution center area of the field of view in order to avoid storing the blurred areas at the periphery of the field of view.
  • the macro image will be stored in a 10 by 8 array, for a total of 80 contiguous image tiles, as shown in FIG. 1A.
  • a typical microscope slide is about 77mm by 25mm, where the usable area, without including the label, is about 57mm by 25m.
  • Each of the 80 image segments is about 4.8mm by 3.5mm in dimension. This means each of the 80 image segments will be scanned separately and stored as a separate image tile.
  • the precision of the microscope systems is set up so that each step of the motor has a precision of .1 micron (micrometer) .
  • the microscope is set up to move 48,143 steps in the X direction and 35,800 steps in the Y direction at 1.25X magnification for each of the 80 image areas. At higher magnifications, the image areas to be scanned are considerably smaller, so the number of steps is corresponding smaller.
  • the microscope lens will detect only the high resolution center area of the field of view.
  • the optical image from the desired image area is then detected by an optical array sensor 19, which preferably is a CCD sensor array.
  • each of the 80 scanned areas is sensed by the entire array 19, which includes 752 pixels by 480 pixels.
  • the optical array sensor 19 sends electrical signals indicative of the detected image to a microscope- controlled computer 32.
  • the computer 32 stores the scanned images, including the top left X-Y stage coordinates for each of the 80 individual areas of the microscope slide.
  • Each of the 80 scanned image areas' pixel locations are stored in a bit-mapped file (i.e., a file which contains a map of the location of each bit in the area) which corresponds to the layout of the individual images thereon.
  • a bit-mapped file i.e., a file which contains a map of the location of each bit in the area
  • the computer 32 calculates the appropriate portion to be displayed from each image tile depending upon the relative size of the display screen. Since the stored image data is usually greater than the size of the typical monitor, the viewer must scroll through the image on the window to view it entirely. However, an optional compression algorithm can be used to compress the entire image into the viewing window.
  • the X-Y coordinate information is used by the viewing and manipulation program to reconstruct the image tiles into a complete image of the specimen. The resulting image is larger, and with better resolution than would be achieved if optics technology were able to construct a single lens capable of viewing the entire specimen in one field of view.
  • each of the 80 image tiles has digital resolution of 752 x 480 pixels, with corresponding optical resolution of approximate .2 microns at 40X to approximately 6.4 microns at 1.25X.
  • the user then examines the macro image or original specimen for significant details. Typically, the user will highlight with a marking pen the areas to be viewed at higher magnification. The user then changes the magnification of optics system 15 to the desired higher magnification, moves the scanning system to bring the selected region into view.
  • the computer 32 then repeats the scanning and image tile creation process for the selected region, but at higher magnification and with a new grid system to locate the scanned selected regions.
  • the user has selected region B shown on FIG. 1A to perform a second view at a higher magnification. For example the user selects a 40X magnification.
  • the computer 32 calculates the number of tiles needed to fill the selected area at 40X magnification and sets up a second grid.
  • region B crosses over several of the larger tiles in FIG. 1A. Because of the extremely precise 0.1 micron resolution of the instrument, locating such selected regions with high resolution is readily accomplished.
  • Slide image data structure 31 includes all of the bit-mapped image tile files at both magnifications (note that similarly, additional images could be stored at further magnifications, if desired), as well as X-Y coordinate information for the location of the various image tiles.
  • FIG. 7A is a file listing such as would be seen under a Windows 95 file manager showing the data files included in a data structure for a breast cancer specimen. Included in the file listing are FinalScan.ini and SlideScan.ini as well as sixty bit-mapped data files. Slidescan.ini is a listing of all the original bit-mapped (.bmp) files. The bit-mapped files represent the individual image tiles in the scan at, say, 1.25X magnifications. Slidescan.ini is set forth below in
  • Table 1 describes the X-Y coordinates for each image tile file.
  • the program uses the X-Y coordinates to display all the image tiles contiguously.
  • Table 2 is a listing of the file FinalScan.ini, which is a listing the X-Y coordinates of the high magnification image tiles scanned and stored.
  • Computer 32 can also use the scanned image files to create a self-executing data structure.
  • the user can use the data structure as a virtual microscope slide of the original specimen.
  • the dynamic, self-executing program is a Java applet, such as shown on FIG. 7B.
  • Computer 32 can provide the slide image data structure 31 directly or via an intranet browser 33 to local viewer 34, or via an Internet server 38.
  • Slide image data structure 37 is shown as being directly accessible from Internet server 38.
  • a user can download the slide image data structure on his own computer 39, use an internet browser 43 and view the reconstructed images.
  • Another alternative is for computer 32 to store the slide image data structure on a CD-ROM, Jazz drive or other storage medium. To view slide image data structure 31 or 37, the
  • - user who for example, has acquired the data structure via a CD-ROM, first installs the CD-ROM in the CD-ROM drive of his computer. Then the user opens up a browser or other applications program which can read the Java applet installed on the CD-ROM with the image tiles.
  • the CD-ROM may include the complete applications program for viewing, reconstructing and manipulating the image tiles.
  • the user will then select the icon or file listing for the slide image data structure and the control program will display the data files.
  • FIG. 2 is a screen view of a system embodying the present invention showing a low magnification image 24 of a specimen on a microscope slide in one window, a high magnification image 26 of a portion of the low magnification image selected by a region marker 30 and a control window 28.
  • FIG. 3 is a view of a display screen of the apparatus embodying the present invention showing the control window 28, a low magnification window 24 having a plurality of high magnification micro image regions 310 delineated therein and a high magnification window 26 including one or more of the micro image regions 310, 314, 316.
  • FIG. 4 is a view of a macro image of an actual breast cancer specimen displayed at 1.25X as seen on a computer monitor.
  • FIG. 5 is a view of the grid portion of FIG. 4 outlining a region of interest selected by a pathologist displayed at 40X magnification.
  • region A in FIG. 1A was about 4.8mm by 3.5mm.
  • This area creates 752 by 480 pixels of sensed data, or 360,930 pixels of information.
  • Each pixel sends information about its location and the image it sensed to the computer.
  • the computer stores this information in a series of data files (typically .bmp format, but .tif or .gif could also be used) .
  • a series of data files typically .bmp format, but .tif or .gif could also be used.
  • the user To view the entire image, the user must scroll through the ' image tiles. However, scrolling need not be done on a tile, by tile basis. Rather, the user scrolls by pointing to a pixel on the monitor.
  • Figure 6 is a block diagram showing how the control program locates and scrolls through the stored image tiles.
  • a complete data structure has been created.
  • the control program recreates a bit map of the stored data.
  • the bit map of the entire slide is shown in Figure 6.
  • Image tile A is also high-lighted. This bit map enables a user to point to or otherwise reference a location on the slide.
  • the X-Y coordinate information specified in the data structure enables X-Y translation of the specific image tiles and specific pixels within the image tile.
  • the user uses his mouse or pointing device to scroll through the active window to view the entire macro image.
  • the X-Y coordinate information selected by the mouse translates into specific image tiles or portions therein.
  • the computer takes the mouse pointer information and retrieves the image data from the series of stored tile images and displays them on the monitor for viewing the by user.
  • the user may select the high magnification data images. These are outlined by a dark grid, indicating the areas stored.
  • the control program locates the stored X-Y coordinates and retrieves the selected parts of the image, CCD stored pixel by CCD stored pixel.
  • computer 32 can perform a data compression on each of the image tile files.
  • a preferred data compression is JPEG, which is readily transferred and recognized by most Internet browser programs. Also, JPEG allows flexibility in the amount of data to be compressed, from 20 to 80 percent. FIG.
  • file listing such as would be seen under Windows 95 file manager showing the data files included in an alternate data structure, one in which the data files have been compressed or converted to JPEG (-jpg) format for a breast cancer specimen.
  • the file index. html (shown in Table 3) is the listing which contains the X-Y coordinate information for these data files. This is the information that is read by the dynamic, self-executing program for viewing, reconstructing and manipulating the image tiles into the macro and micro views.
  • ⁇ PARAM NAME 'Dal6 X' VALUE - "214532">
  • ⁇ PARAM NAME 'Da64 ⁇ X' VALUE — "179204">
  • ⁇ PARAM NAME 'Da69 ⁇ X' VA.LUE — "171524">
  • the system includes a computer 12 which is a dual Pentium Pro personal computer in combination with a Hitachi HV-C20 video camera 14 associated with a Zeiss Axioplan 2 microscope 16.
  • the computer system 12 is able to receive signals from the camera 14 which captures light from the microscope 16 having a microscope slide 18 positioned on an LUDL encoded motorized stage 20.
  • the encoded motorized stage 20 includes a MAC 2000 stage controller for controlling the stage in response to the computer 12.
  • a microscope slide 18 includes a biological specimen 21 which is to be viewed by the microscope and whose image is to be digitized both at low magnification and at high magnification as selected by a user.
  • the low magnification digitized image is then displayed on a 21 inch liyama video display monitor 22 having resolution of 1600 by 1200 to provide display screens of the type shown in FIGS. 1 through 3 including a low magnification image 24, for instance, at 1.25 power, a high magnification image 26, for instance at 40X power and a control window or image 28.
  • the low magnification image may have identified therein a region 30 which is reproduced at high magnification in high magnification screen or window 26 so that a pathologist or other operator of the system can review architectural regions of interest in low magnification image 24 and simultaneously view them in high magnification in the high magnification screen or window 26 to determine whether the cells forming a portion of the architectural feature need be examined further for cancer or the like or not.
  • the computer 10 is constructed around a PCI system bus 40 and has a first Pentium Pro microprocessor 42 and a second pentium pro microprocessor 44 connected thereto.
  • the system bus 40 has connected to it a PCI bus 50 and an ISA bus 52.
  • the PCI bus 50 has a SCSI controller 60 connected thereto to send and receive information from a hard disk 62.
  • the hard disk 62 also is coupled in daisy chain SCSI fashion to a high capacity removal disk and to a CD Rom drive 66.
  • the hard disks 62 contains the programs for operating the system for controlling the microscope 16 and for processing the images as well as for doing a quantitative analysis of the selected portions of the histological specimens being viewed on the slide 18.
  • the system bus 40 also has connected to it a random access memory 70 within which portions of the program being executed are stored as well as a read only memory 72 for holding a bootstrap loader as well as portions of the basic input/output operating system.
  • a floppy disk controller 74 is coupled to the system bus 40 and has connected to it a floppy disk drive 76 for reading and writing information to a floppy disk as appropriate.
  • a mouse controller 60 is coupled to the system bus and has a mouse 82 which operates as a pointing device for controlling manipulations on the screen 22 and within the windows 24, 26 and 28.
  • a keyboard controller 90 is connected to the system bus and has a keyboard 92 connected thereto. The keyboard 92 may be used to send and receive alpha numeric signals to other portions of the computer.
  • An audio controller 100 has a plurality of speakers 102 and a microphone 104 connected thereto for audio input and output and is coupled to the system bus 40.
  • a network interface such as a network interface card 104, is connected to the system bus and can provide signals via a channel 106 to other portions of a network or internet to which the system may be connected. Likewise, signals can be sent out of the system through a modem 110 connected to the ISA bus 52 and may be sent via a channel 112, for instance, to the internet.
  • a printer 116 is connected via a parallel I/O controller 118 to the system bus in order to provide printouts as appropriate of screens and other information as it is generated.
  • a serial I/O controller 122 is connected to the system bus and has connected to it a camera controller 124 which is coupled to CCD sensors 126 in the cameras. The CCD sensors 126 supply pixel or image signals representative of what is found on the slide 18 to an Epix pixci image acquisition controller 130 coupled to the PCI bus 50.
  • the microscope 16 includes a base 140 having a stage 20 positioned thereon as well as an objective turret 142 having a plurality of objectives 144, 146 and 148 thereon.
  • the objective 144 may be of 1.25x objective.
  • the objective 146 may be a 20X objective.
  • the objective 148 may be a 40X objective. Signals from the camera sensors and controller are supplied over a bus 128 to the image acquisition system where they are digitized and supplied to the PCI bus for storage in RAM or for backing storage on the hard disk 62.
  • stage 20 When a specimen is on the slide 18 the stage 20 may be manipulated under the control of the computer through a stage controller 160 coupled to the serial I/O controller 122.
  • a microscope controller 162 controls aspects of the microscope such as the illumination, the color temperature or spectral output of a lamp 16 ⁇ and the like.
  • the processors 42 or 44 send a command through the system bus to cause the serial I/O controller 122 to signal the microscope controller to change magnification to 1.25X in a step 202. This is done by rotating the objective turret of the Axioplan 2 microscope to select the objective 144.
  • the controller sets the color temperature of the lamp 168, sets a pair of neutral density filter wheels 170 and 172 and sets a field diaphragm 174 for the correct illumination.
  • a condenser diaphragm 176 is also controlled and a color filter wheel 180 may also be controlled to apply the appropriate filter color to the CCD censors 126 in the camera.
  • the entire slide is then scanned in a step 204.
  • the images are tiled and melded together into the overall image 24 supplied on the screen 22 to provide the operator in the step 206 with a visually inspectable macro image of relevant regions of the slide of interest.
  • the mouse may be moved to identify a marker segment or region which, for instance, may be a rectangular region which will cause the microscope to change magnification as at step 208 to 4x, 20x, 40x, etc., by rotating the turret to bring the appropriate objective lens system into viewing position.
  • a test is made to determine whether the user has commanded continued inspection. If the user has, a test is made in a step 209c to determine if the magnification is to be changed by changing the selected objective. In the event the magnification is to be changed control is transferred to the step 208. If the magnification is to remain unchanged control is transferred to the step 209a. In the event inspection is not to continue the region selected is outlined for higher magnification scan in a step 209d. In a step 209e, a . command may be received to scan or acquire the higher magnification image for display in screen 26. The image may then be archived for later analysis, displayed or analyzed immediately.
  • the overall illumination and control of the microscope will be controlled so that in a step 210 the objective turret 142 will be rotated to place the higher power objective above the slide 16.
  • voltage to the lamp will be changed to adjust the lamp 168 to provide the proper illumination and color temperature as predetermined for the selected objective.
  • the condenser diaphragm 176 will have its opening selected as appropriate to provide the proper illumination for that objective.
  • the filter turret 180 will select the proper light wavelength filter to be supplied to the camera sensors. For instance, a red, blue or green filter, as appropriate, particularly if the specimen has been stained.
  • a step 218 the field diaphragm 174 will have its opening changed.
  • the neutral density filter wheel 170 will select a neutral density filter and in a step 222 the neutral density filter wheel 172 will also select a neutral density filter.
  • the X, Y and Z offsets will be used for reconstruction of the recorded image at the magnification and in a step 226 the current position will be read from encoders in the stage which are accurate to .10 micron.
  • the mouse In order to identify the selected region the mouse is moved to that area of the region in a pointing operation in a step 240 as shown in FIG. 14.
  • the mouse may be moved to draw a box around the region selected.
  • the X and Y screen points are computed for the edges of the regions selected and the computed image or pixel points are translated to stage coordinate points in order to control the stage of the microscope.
  • a list of all of the X fields for positioning the stage for the objective is stored in random access memory and may be backed up on the hard disk. The information from the X offsets for the objective and the stage offsets is used as well as the size of the field to position the slide properly under the objective to capture the micro image.
  • stage is positioned for each of the X and Y coordinate values in stage coordinate values and the digitized image is captured by the cameras and stored in RAM and backed up on the hard disk.
  • the image may be then analyzed quantitatively in various manners such as those set forth in the previously-identified United States application.
  • the image may be stored for archival purposes in a step 254.
  • FIG. 13 is a view of the settings of the microscope objective properties of the Axioplan 2, computer- controlled microscope.
  • the X and Y positioning is specifically carried out as shown in FIG. 16 where the slide 18 is shown with a slide boundary 270, 272, 274 and 276.
  • Stage boundary for limits of the stage travel for purposes of the stage the stage can be moved all the way from an upper left hand corner of travel 276 to a lower right hand corner of travel 280.
  • At the upper left hand bounded corner of travel 276 limits which a signal that the end of travel has been reached and the stage is then translated a short distance 262 in the extra action and a short distance 284 in the Y direction to define the first tile 288 in terms of a reference point 290 at its upper left hand corner. Since the size of the macro image tile 288 is known, the next macro image tile 292 may be placed contiguous with it by moving the stage appropriately and by measuring the location of the stage from the stage in counters without the necessity of performing any image manipulation.
  • the image tiles 288 and 292 may be abutted without any substantial overlap or they may be overlapped slightly, such as a one pixel with overlap, which is negligible insofar as blurring of any adjacent edges of abutted image tiles.
  • the upper left hand corner 300 of the tile 292 defines the rest of 292 and other tiles can be so defined.
  • Micro image tiles can likewise be defined so that they are contiguous but not substantially overlapping, as would interfere with the composite image. This avoids the problems encountered with having to perform extended computations on digital images in a frame storer or multiple frame storage in order to match or bring the images into contiguity without blurriness at the edges of contiguous image tiles.
  • the low power image 24 has a plurality of micro images defined therein which are tiled and which are shown in higher magnification as individual tiles
  • the region 310 when magnified as shown in the window 26 may exceed the bounds of the window and thus the window may include scroll bars or other means for allowing the image 310 which is larger than the window 26 to be examined from within the window 26.
  • the stage 200 is best seen in FIG. 16A and includes the X 'and Y stepper motors 279 and 281 with their respective encoders, which provide a closed loop system to give the .1 micron accuracy versus the usual 5 or 6 micron accuracy of most microscope stages without a closed loop system.
  • This closed loop system and this very high accuracy allow the abutting of the tile images for both high magnification and low magnification images without the substantial overlap and the time-consuming and expensive software currently used to eliminate the overlap and blurriness at the overlapping edges of adjacent image tiles.
  • the tiles may be positioned precisely in a horizontal row and precisely in vertical rows to reconstruct the macro image and the micro image. This reconstruction is done without the use, as in the prior art, of extensive software manipulation to eliminate overlapping image tiles, horizontally or vertically or the haphazard orientation of image tiles.
  • the present invention also includes the facility for allowing remote observation to occur by being able to couple the system either over a network communication facility to an intranet, for instance via the network interface, or via a modem or other suitable connection, to an internet so that once the image has been scanned and stored in memory on hard disks or other storage, remote users may be able to access the low magnification image as well as the high magnification image and move around within both images to make determinations as to the histological characteristics of the samples.
  • An additional feature of the system includes a plurality of networked workstations coupled to a first computer console 12 having a display screen 22 connected to the microscope 14. Satellite work stations 350 and 352 are substantially identical to the work station 12 including respective computers 354 and 356 coupled to displays 358 and 360. The devices can be manipulated through input devices 360 and 362 which may include a keyboard, mouse and the like. Also a third device can be connected including a work station 370, having a display 372, a computer 374 and an input device 376. Each of the devices is connected over respective network lines 380,
  • Each of the different operators at the physically separate viewing stations can locate regions from the view of entire tissue cross sections via a macro view and label the regions for subsequent scanning and/or quantitative analysis.
  • a single operator at the instrument station 12 can locate regions to view the entire tissue cross section. Those regions can be labeled for subsequent scanning and/or quantitative analysis with subsequent review and physically remote viewing stations, for instance, in an operating room or in individual pathologists ' signout areas in order to review analysis results while still maintaining and reviewing the entire macro view of the tissue and/or the individual stored images from which the quantitative results were obtained.
  • the viewing stations 350, 352 and 370 can comprise desk top computers, laptops, etc. There is no need for a microscope at the network stations 350, 352 and 370.
  • remote workstations 400, 402, 404, 406 and 408 may be connected through a server 410 which may be supplied via a packet switched network.
  • the server 410 and may be a hypertext transport protocol based server of the type used for the World Wide Web or may be a telnet type server as used previously in internet remote operation applications.
  • the server 410 communicates via a communications channel 414 with a local computer 416 having a display 418 associated therewith, the local computer 416 being connected to the microscope 420.
  • Each of the remote work stations 400, 402, 404, 406 and 408 may perform the same operations as the stations 350, 352 and 370 although they do it from nearby buildings or even from around the world, thus providing additional flexibility for others to make use of the specimen obtained and being viewed under the microscope 420.
  • stored images may be disseminated through the server 410 to the remote servers 400 through 408 for further analysis and review.
  • the server was designed to interact with either a thin client browser or with a Java applet viewer, operating through an HTML browser such as Netscape or the Microsoft Internet Explorer.
  • the server runs on a standard PC under a Windows operating system. It uses HTTP Internet communication protocols.
  • the computer has stored on its storage media already collected data files having the data structure disclosed above.
  • This data structure consists of "tiled” sets of digital images, with x, y information organized to aid the viewer program to "reconstruct” and spatially align physically-contiguous images, at multiple resolutions.
  • the server responds to HTTP "Get” requests from multiple thin client browsers or other browsers with embedded Java applet viewers. As such, it uses a “listening socket” and a number of short-lived “threads” which handle “Get” requests independently and simultaneously, as shown in FIG. 28.
  • the server After initial logic, as shown in FIG. 29, to determine whether the HTTP request is valid and, if so, whether it is a Java request for a thin client request, the server generates a response thread, depending upon the request as detailed in Table 1, to send back the requested information to the client. Large numbers of these requests can be handled at one time.
  • the server 12 was designed to interact with a client having either a thin client browser or with a Java applet viewer, operating through an HTML browser such as Netscape Navigator or Microsoft Internet Explorer.
  • the server 12 runs on a standard PC under a Windows operating system. It uses the HTTP communication protocol.
  • the computer 12 has stored on its storage media already collected data files of with the data structure disclosed in U.S. application no. 09/032,514, filed February 27, 1998, which is incorporated herein by reference.
  • This data structure consists of "tiled” sets of digital images, with x, y information organized to aid the viewer program to "reconstruct” and spatially align physically-contiguous images, at multiple resolutions.
  • the server responds to HTTP "GET" requests from multiple thin client browsers or other browsers with embedded Java applet viewers. As such, it uses a “listening socket” and a number of short-lived “threads” which handle "GET” requests independently and simultaneously, as shown in FIG. 19.
  • the server After initial logic, as shown in FIG. 20, to determine whether the HTTP request is valid and, if so, whether it is a Java request or a thin client request, the server generates a response thread, depending upon the request as detailed in Table 4, to send back the requested information to the client. Large numbers of these requests can be handled at one time.
  • Each image has a PreviewSlide.jpg image contained m its data structure. This is a "thumbnail” image reconstructed from all of the tiles from the low magnification, 1.25x slide view image tiles. The reconstructed composite image has been digitally reduced to an image size of 454 x 240.
  • FIGS. 21A, 21B and 22 illustrate two different virtual microscope slide viewing implementations. These suit two different needs.
  • the thin client browser has three screens and many more functions. As described in more detail below, there is a main screen that displays the thumbnail Preview Slide image, and uses a tabbed interface to implement different functionalities to the browser.
  • a SlideTray tab which allows for the selection of any of the stored images hosted on the server computer
  • a server tab which allows coordination of views and chats with multiple other clients all logged-in at the same time
  • an Applet Creation tab to select specific region views for HTML applets viewed by the Java Applet viewer.
  • the other two windows, Slide View and Field View allow viewing of low-magnification tiled images and high-magnification tiled images with scrolling and coordination between the two views.
  • the thin client browser is more suited to secondary opinion expert pathology consultations, and sophisticated professional pathology users m departmental pathology practice, for review of cases and as archival backup virtual slide records. In operation, the browser program is loaded separately, once on a client computer.
  • the HTML applet viewer is simpler than the thin client browser, and may be used in medical student, dental student, veterinary and undergraduate biology teaching situations. Advantage is taken of the fact that most students are familiar with an HTML browser. Instructors can easily add course "content" text to provide different descriptions of the virtual microscope slide images. Since the virtual microscope slides will often be used for longer periods, and since there is no premium on speed of scanning, entire specimens can be scanned offline at high magnification which takes a longer time. In this viewer simply acts as a "portal,” or a small window, in a fixed position on a specific HTML page.
  • each applet instance relates to a specific image on a specific server computer.
  • the upper part of the portal is a display of the Preview Slide image.
  • the bottom part of the portal initially shows a selected view from that image at one of four magnifications.
  • a plurality of radio button choices loaded on a bar between the views allows for additional magnification choices in the bottom view.
  • the bottom view is also scrollable, and can be changed by pointing the mouse to a region on the Preview Slide image. It will be appreciated that this viewer is simpler to learn initially and to operate than the thin client browser. It has the disadvantage of being slower and of only addressing one image at a time. It has an advantage of being simple, having various types of explanatory text right next to the image, and of being cross platform with regard to operating system, computer type and HTML browser type. These are all helpful in the educational market .
  • the Slide Tray concept is used in the server and the browser programs and is central to providing an organizational construct to collections of images. It is set forth in Table 6 below.
  • the image data structure includes two modifiable text string byte arrays which are used to hold the file name and the folder name that identifies an individual image.
  • server program searches all of its available storage (indicated in a setup file) , finds any images present, reads the folder names and the file names of all of the images and creates URL path extensions for each one.
  • FIG. 24 When the image browser initially starts its Main Window looks like FIG. 24. This is before a Login request has been initiated.
  • the browser first sends a client Login Request using a specific server Internet address, such as shown in the address line of FIG. 20, and as indicated in Table 4.
  • the browser After the Login Request has been acknowledged, the browser then sends a Slide Tray Request.
  • the server response to this is to send the list of image names and header text, their associated file folders, and the URL path extensions depending upon various image data structure storage locations on the server.
  • the browser then constructs and displays m the Slide Tray tab of its main window a file folder tree structure display such as shown in FIG. 25. This is a dynamic display, such that a mouse click on the file folder opens up the file and displays its contained images.
  • the browser responses are set forth m Tale 7 below.
  • tSlideYRef + ' & ' ; tResponse tResponse + FrmMain Client . 3 ] .
  • tFmalZoomLevel + ' & ' ; tResponse tResponse + FrmMain Client ' . 3 ] .
  • tXRe f + ' & ' ; tResponse tResponse + FrmMain Client :D ] .
  • tYRef ' & '
  • tResponse tResponse + FrmMain Client :DI .tSlideScanMode + ' & '
  • tResponse tResponse + FrmMain Client . 3 ] . tPomterX + ' & '
  • tResponse tResponse + FrmMain Client [ 3 ] . tPointerY + ' & '
  • tResponse tResponse + FrmMain Client [ 3 ] . tPointerY + ' & '
  • a mouse click on a specific image file name activates a client Image Request to the server, and the server sends back the requested thumbnail image which is displayed m the tab image area, as shown m FIG. 25.
  • the client browser sends a Select Slide Request.
  • the server then sends the larger Preview Slide image along with the x, y coordinate list of all image tiles associated with that virtual slide. The tab changes from the Slide Tray to the image tab and the Preview Slide image is displayed in the image display area, as shown in FIG. 26.
  • This virtual slide tray organizational design is that the folder names are carried as part of the image data set structure. This is different from a standard file structure where the file name is created and files are moved into the created folder. In a virtual microscope slide environment, collections of slides may come from different sources, e.g., on CD-ROMs or other storage media. This method carries the file folder information with the slide. The server can then automatically organize, on startup, all of the file folders depending upon the media in place at that time. For read/write media, the folder names can be edited to put specific images into different folders. This method also allows for automatic folder generation during the image creation process, which reduces the possibility of mixup for collections of slides that go together.
  • the image data set is created initially by scanning the microscope slide at two different magnifications.
  • the initial scan which is referred to as the Slide View scan
  • the second, higher-magnification scan is referred to as the Field View scan, and can occupy variable regions. These regions are mapped to the Slide View regions, and can be shown as overlaid areas.
  • FIG. 22 there are a number of overlays in the image tab of the main image browser window that can be used as aids in navigating the images. Two of these are shown there. They indicate potential regions that could have been scanned and those that were actually scanned on the specimen.
  • the browser By clicking in the region of one of these tiles, the browser is instructed to bring up its third window, the Field View window, shown overlain on top of the other two windows in FIG. 28. It uses the same procedure, e.g., the size of the Field View window to determine which high-magnification image tiles to request.
  • the size of the Field View and Slide View windows can be changed to suit the user, for example, to fill the available viewing screen, and the browser program will request and fill in the necessary tiles to fill the viewing area.
  • a number of other viewing options are available, including changing the digital image magnification, i.e., lowering from 40x to 5x . In this case, more tiles are requested to fill in the available viewing area.
  • the combination of the ability to change the various windows position and size, and the digital magnification (zoom) allows for full inspection of the virtual microscope specimen at high and low magnifications throughout the entire specimen. As additional image tiles are requested, they are cached locally so that additional inspection becomes quicker.
  • FIG. 29 is a flow chart of typical usage to further illustrate the above. This flow chart is shown as a sequence of related steps since some should occur before others and this is a typical sequence. However, it should be appreciated that the browser is multithreaded as well as event driven. Most of the time, for example, the Update Request process is running on its own thread concurrently with client user event-driven processes, a shown in FIG. 29.
  • Update Requests are generated by each user logged in the client browser at one-second intervals. Through the use of these Update Requests, the server is essentially functioning as a total system
  • the server can pass information regarding all of the other logged-in users, with regard to which slide they are viewing, where on that slide they are looking, the status of any pointer locations, etc. This all happens at one-second intervals for all logged-in clients.
  • the browser then can use this information if desired to view the same images seen by other clients. This essentially means that the network of client viewers operates as a virtual multi-headed microscope, letting each other simultaneously view the same virtual slide. Additional features of the browser, as shown in
  • FIG. 30, enhance this capability.
  • the server tab in the main browser window, shown in FIG. 30, is used to activate a multi-headed virtual microscope function.
  • a browser logged onto a server initially displays only the current user's information in the server tab.
  • Update Requests are serviced, if additional clients log onto the same server that information is also displayed in the Server tab, using additional login lines.
  • FIG. 30 shows two users logged into the same server. Also shown are buttons “Display another's view” and “Sync with another's view.” After point and click highlighting of one of the logged-in user lines, the current user can then, for example, click on the button "Display another's view” and the browser will use the last update information on that user to send a Select Slide Request, and whatever Image Tile requests are necessary to display the same image view that the user is looking at. In a similar manner, if the user clicked on "Sync with another's view,” then the browser would continue to use the update requests to change fields, zoom levels, etc. In the meantime, the various clients involved could communicate through the chat screen about the specimen under consideration.
  • a pointer may be drawn at any x, y location on an image screen view.
  • a right click mouse event on an image where the pointer is desired activates program code which creates a pop-up menu, as shown in FIG. 31.
  • the position of the pointer is computed in x, y stage coordinate units and those position values are put in the main window Pointer tab and kept in memory to pass along to the server on the next update.
  • a pointer is placed on the image, as shown in FIG. 32. when another client, logged on at the same time, activates "Display another's view” (as shown in FIG.
  • Tiled images can be captured at a matching pixel and optical resolution, and displayed seamlessly by the present invention, to achieve true virtual images.
  • the same method automatically overcomes the limited "field of view” issue to preserve high resolution over large areas in the original high- magnification image plane of the microscope specimen.
  • the method of retrieving and displaying these tiles as a coherent connected image is depicted in the flow diagram of FIG. 33.
  • This flow diagram is relevant for choosing by a point and click, an image point in the Preview Slide image of the main browser window to open and display the Slide View window (or to choose another region to display in an already open Slide View window) , or to open and display at a higher magnification the Field View window from a point in the Slide View window, or to display image areas not already pre-loaded in the Java applet portal window in an HTML browser page.
  • An important factor in accomplishing seamless tiled image display according to the methods of this invention is to maintain an image x, y pixel reference to the original mechanical stage x, y coordinate reference.
  • the x, y stage resolution is .1 micrometers per step.
  • Each image tile is a known number of pixels, in this instance 752 x 480 pixels. Through calibration setup procedures during instrument construction, the number of stage coordinate steps per pixel is determined. This varies slightly from system to system and is different for each microscope objective. It is therefore recorded as part of each image data set. Table 8 shows some typical examples of one system.
  • the initial step is to translate the starting display image size in pixels into the virtual stage coordinates. For example, if the image is the 452 x 240 Preview Slide image then each x pixel increments by 1,148 x virtual stage coordinates and each y pixel increments by 1,104 virtual stage coordinates. A given mouse click resulting in an x, y pixel location can then be easily translated into a known virtual image x, y location.
  • the new display image window in this case the Slide View image, -is opened, and some of the possible 8 x 10 1.25x image tiles may be displayed. This window will either have a present initial size or will have been set by a previous call.
  • the size of the window in pixels can be determined from the associated windows properties parameter ' s, accessible to the program. The size and placement of this window can then be calculated in the virtual coordinate space. The program assumes that the pixel point chosen in the previous window is associated with the center of the new window to do this.
  • the image stage coordinate list was previously transferred to find all candidate tiles which should be displayed according to size of the window.
  • the tiles can be two types; they may already have been viewed and are there, and are therefore cached and available locally, or they exist on the server. If they are on the server, a Send Image Request is initiated and the server sends back the requested tile. Otherwise, they are read from the cache. It should be appreciated again in the case of the program's execution, shown in the flow chart of FIG. 33, that the program is event driven and multi-threaded. The final operation is to fill in the display window with the chosen tile.
  • the additional approach of this invention is to make available to the applet, the entire virtual slide. This is accomplished using the techniques already described for the browser.
  • the upper panel Preview Slide Image can be used by a mouse point and click, to locate an x, y position. This is translated into x, y virtual stage coordinates, and the needed tiles are requested through an Image Request to the server. If the magnification choices are used the operation of this application is handled by the same methods of zoom and calling for images as in the browser, all relating to the size of the window and which image tiles are needed from what virtual x, y location to fill in the window.
  • the lower portion of the portal window is also enabled for scrolling. So the virtual slide advantage of scrolling and zooming in and out are available but in a limited size window. They are accessible, however, from an HTML document that has embedded content.
  • the controlling HTML web-page code may be calling the content for the page from a computer other than the image computer.
  • the advantage of this is that it decouples the text content from the image collections. In a teaching environment this enables many different users to create their own course content, using standard HTML methods, and simply provides a call to the server at appropriate places in the HTML code.
  • the server also interacts with a second type of viewer, an HTML embedded applet, in this case written in the Java programming language, as set forth in Table 9 below.
  • This viewer is simpler, and used for different purposes than the browser, but uses many of the same techniques of transferring image tiles.
  • FIG. 34 illustrates the layout and features of the HTM] portal window created by this applet.
  • This viewer consists of two views; a low-magnification view (which is the Preview Slide image discussed above) shown as an upper portion in FIG. 34, and a higher-magnification view shown in the lower portion.
  • the two views are separated by a menu bar with four magnification choices.
  • HTML applet creation process which is another browser tab portion. This enables the creation of both the HTML code to generate a Java applet request and additional pre-configured images for the applet to use when it runs.
  • the applet creation process enables the location of a specific view on a given image, i.e., it specifies a center x, y position for the region and specifies a final view window size, of the same size as the lower portion of the portal window, and assembles from the tiled data structure four zoom level views corresponding to the menu bar magnification options.
  • the zoom levels start with the highest Field View magnification level, usually 40x or 20x, and the viewer creates a lower-magnification image of each tile by using every other pixel at each lower zoom magnification.
  • Additional tiles are brought in and assembled from the image data structure as needed to fill in the fixed field size of the lower HTML portal window.
  • These four assembled images are referred to as Preview images, are given specific names in the creation process and are stored in a file accessible to the server program, on the same computer that the related image is located.
  • the first thing the Java applet does then after it is loaded is to send a Login and Virtual Slide Request as indicated in Table 1. If the slide name and server identity is correct, the server response is to send the Preview Slide image for the upper panel, the four Preview images that will be used for the lower panel, and the x, y list of all image tiles m the associated data structure.
  • the HTML applet generation process specified which of the magnification choices would be loaded first. The other are available to the applet through the radio button event generated from the menu bar.
  • the virtual slide link is set forth m Table 10 below.
  • a plurality of clients are logged on, which might include a client A and a client B .
  • client B elects to consult with logged on client A and highlights client A' s name in logged on l ist in a step 800 , as shown in FIG . 35A .
  • the client B selects a synchroni zation and user function by cl icking on the sync on user button and a thin cl ient browser enters a synchroni zation state keyed on signal s from client A in a step 802 .
  • client B monitors cl ient A' s update state variables , as set forth in the l isting in Table 6 , and uses the variables necessary to display the same location and magni f ication of the slide data set that cl ient A is currently viewing .
  • a plurality of the state variables include state variable values that indicate whether those variables are disabled, for instance 999999999 . Otherwise , the variable state is considered to contain active data and, during the one-second interval update, decisions are made by the state variables by client B, as set forth in step 804 . Control is then transferred to a step 806 to determine whether the chat messenger index on the server is greater than the current state variable index .
  • control is transferred to a step 808 to request each missing chat message from the server and displayed in the chat window at the client until the chat message index on the server is equal to the state variable index following which the routine returns in a step 810 to a test in a step 812 to determine whether the state variables have been placed in sync mode. If they have not, control is transferred back to the step 806, as shown in FIG. 35D.
  • a test is made in a step 814, as shown in FIG. 35A, to determine whether the virtual slide image selected from the slide tray data collection is the same as the one that is currently displayed. If it is not, the position in the slide tray is updated in a step 816. If it is, control is transferred either from step 814 or 816 to a step 818 where a test -is made to determine whether the low-magnification x, y position location state variables are in the disabled state. If they are, control is transferred back to step 814. If they are not, the slide view window is displayed and updated for the low-magnification view to t-he lower-magnification position previously selected by client A using client A's current magnification state variable in step 820 in order to synchronize the views.
  • a test is then made in a step 822 similar to the step 818 to determine whether the high-magnification x, y location state variables are in the disabled state in a step 822. If they are disabled, control is transferred back to step 814. If they are not, control is transferred to a step 824 which displays the field view window on the client and/or updates the high-magnification view to synchronize with client A's x, y high-magnification selected position also using client A's current magnification state variables.
  • the slide scan mode state variable indicates whether what is being displayed is the low-magnification or high-magnification data and each of the data's associated coordinate systems in field of view. Control is then transferred to a step 830, as shown in FIG.
  • step 35C where a test is made to determine the mouse pointer or display pointer x, y position state variables in the disabled state or not. If they are not disabled, the pointer is displayed at the location selected by client A and control is transferred to step 814. If the state variables are disabled, control is transferred directly to step 814.
  • the updating function from the client A variables may take place not just with one client, client B, but over multiple clients in order to provide image coherency from the client, in this example client A, which in effect controls the command token for the virtual multiheaded microscope remote emulation.

Abstract

A method of and apparatus for viewing microscopic images include transmitting tiled microscopic images from a server to a client (112). The client assembles the tiled images into a seamless virtual slide or specimen image and provides tools for manipulating image magnification and viewpoint (24). 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 (146).

Description

METHOD AND APPARATUS FOR INTERNET, INTRANET, AND LOCAL VIEWING OF VIRTUAL MICROSCOPE SLIDES
CROSS REFERENCE TO RELATED APPLICATIONS
Priority is claimed from U.S. provisional application number 60/177,550, filed January 21, 2000,, the content of which is hereby incorporated by reference.
BACKGROUND OF THE INVENTION
The invention relates to a method of and an apparatus for storing and viewing virtual microscope slides. The method and apparatus are usable over the Internet, an intranet, or on a local computer, and provide an integrated and interlocked combination of a digital image server and multiple virtual microscope client viewers.
Examination of tissue sections, aspirated tissue, and the like, has typically been a localized activity. That is, the tissue is sectioned in a lab. It may be stained and microscopically examined by a light microscope after which a technician and/or a pathologist reaches a conclusion as to the characteristics of the tissue; for instance whether the tissue is benign or malignant and what stage of malignancy the tissue might be in. A number of patents awarded to the instant inventors are directed to that sort of system.
In some cases, however, it may be desirable where results are indefinite or where particular sophistication is needed for the human analysis of the images to be able to supply the slides to an offsite expert who might be across the country or on the other side of the world. In the past, the approach which has been taken to solve this problem has involved the transfer of the slides themselves by air express or post, often involving significant time delays which it would be desirable to avoid if a patient is suspected of being severely ill. In the alternative, telepathology systems have been made available involving the use of television transmissions requiring a 6 MHz bandwidth, either through a satellite link or possibly through a coaxial cable, both of which must, in effect, be dedicated lines and previously set up. Such a system, however, requires a great deal of customization and expense although such systems do include the use of computer-controlled microscopes. Such microscopes receive commands from a remote location to move to a particular position on a slide so that the television camera may send a television signal out representative of the field of view. This type of system is relatively expensive and clumsy to use do to the necessity for a very expensive robotically-controlled microscope which receives specialized signals over a dedicated link.
What is needed then is a system and apparatus which can allow a remote consult to take place related to tissue specimens, and the like, which may be done quickly, conveniently, and easily. SUMMARY OF THE INVENTION
The invention relates to a method for viewing virtual microscope slides. Virtual microscope slides comprise sets of tiled images. The tiles of the tiled images represent a field of view which may be captured from a microscope having a high-precision controlled stage typically with a stage resolution in the neighborhood of a 1/lOth micron step. The images are captured on a CCD array which generates images in color or black and white and stores them in a frame buffer or on disk in tiled format. Such images are usually very large due to the number of pixels required to reproduce a substantial size tissue specimen at a high magnification, such as 40 power. In addition, in order to provide ease of use, particularly on a remote basis, other sets of tiled images have a lower magnification, for instance at 1.25 power. All of the images are tiled and stored in digital format on a server which may communicate using the hypertext transport protocol used for web-based communications over a packet switching network such as the Internet or an intranet. Because the images have already been captured and coordinated in tiled form, it is unnecessary to provide a robotically-controlled microscope or even the original specimens themselves. One or more clients may communicate with the server containing the image to download a portion or all of the tiled image. The client provides requests to the server indicating the portion which is desired to be viewed and the server supplies the appropriate tiles for that portion of the image. The tiles are received by the client and are assembled into a seamless view which may be scrolled through and scanned in the same manner as a pathologist may move about a microscope slide to find regions of interest. In addition, the low-magnification image may be displayed in a first window at the client and a higher-magnification image may simultaneously be displayed which retains coherence with the lower- magnification image in order to provide ease of scanning for areas of interest by the pathology, or the like.
Furthermore, the client/server relationship may be carried out over multiple clients with one of the clients having control over the image positioning as fed by the server for all other clients via communication between the first client and the server, and then subsequent updating coherent communication between the server and the downstream clients. This does not necessarily require that repeated loading take place of the client images, but only that signals be sent between the server and the secondary clients reflecting the field which the first client is viewing. In this way, the overall system can operate similarly to a multiheaded optical microscope of the type used to train physicians in pathology.
Furthermore, the system can be used as a multiheaded microscope during a consult so that al persons simultaneously involved in the consult are looking at the same portion of the image and no confusion can arise. A further advantage of the present invention is to provide packet switched chat communications along with the multiheaded virtual microscope feature to allow text to be transferred among the various clients while the images are being viewed. Finally, additional lines of communication may be provided among the users of the multiple remote client locations so that they can discuss telephonically or even using a voice-over-Internet protocol-based system to confer in real time on the images that are being seen at each of the client stations.
Furthermore, the client in control of the image may relinquish control to a second client; the first client operating on a peer basis with the other clients in a secondary relationship thereafter.
In order to provide further analysis features, a linear measuring or tape measuring feature may be provided in order to determine the distance in microns, or the like, between a pair of points identified by pointing and clicking on portions of the image in order to determine the actual size of particular features shown in the specimen image. The size, of course, is computed on the basis of the magnification of the image being shown.
Other objects and advantages of the present invention will become obvious to one of ordinary skill in the art upon a perusal of the following specification and claims in light of the accompanying drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a block diagram of a system according to the invention for creating and transmitting locally, over an intranet or via the Internet data structures of an image of specimen on a microscope slide;
FIG. 1A is representation of a microscope slide which has been arbitrarily assigned to be scanned into eighty tiled images; FIG IB is a representation of the detected signals of the individual pixel sensors in a CCD optical array after detecting a selected image area to tile and the referenced data files containing the information describing the detected signals;
FIG. 2 is a screen view of a system embodying the present invention showing a low magnification image of a specimen on a microscope slide in one window, a high magnification image of a portion of the low magnification image selected by a region marker and a control window;
FIG. 3 is a view of a display screen of the apparatus embodying the present invention showing the control window a low magnification window having a plurality of high magnification micro image regions delineated therein and a high magnification window including one or more of the micro image regions;
FIG. 4 is a view of a macro image of an actual breast cancer specimen displayed at 1.25X as seen on a computer monitor;
FIG. 5 is a view of the grid portion of FIG. 4 outlining a region of interest selected by a pathologist displayed at 40X magnification; FIG. 6 is a block diagram of the steps in the mapping of the scanned image from the optical sensor array to computer bit map in memory to the display on a user's monitor;
FIG. 7A is a file listing such as would be seen under Windows 95 file manager showing the data files included in a data structure for a breast cancer specimen;
FIG. 7B is a file listing of a Java applet for controlling a data structure; FIG. 8 is file listing such as would be seen under Windows 95 file manager showing the data files included in an alternate data structure for a breast cancer specimen; FIGS. 9A and 9B are a block diagram of the apparatus embodying the present invention;
FIG. 10 is a block diagram of a portion of the apparatus shown in FIG. 9 showing details of a mechanical arrangement of a microscope;
FIG. 11 is a flow diagram related to operation of the apparatus;
FIG. 12 is a flow diagram of details of one of the steps in FIG. 11; FIG. 13 is a display screen showing control parameters to be manipulated thereon;
FIG. 14 is a flow chart for a region outlying routine;
FIG. 15 is a flow chart for a scanning and analyzing routine;
FIG. 16 is a schematic showing of the limits of travel of the microscope stage with respect to the image tiles;
FIG. 16A is a perspective view of the microscope stage and stepper motors and encoders providing a closed loop drive for the motors;
FIG. 17 is a block diagram of a networked system allowing multiple workstations to obtain access to the microscope and to manipulate the microscope locally at each workstation;
FIG. 17A is a view of the system described in connection with FIG. 10;
FIG. 18 is a block diagram of a remote networked system for distributing and accessing diagnostic images and data, i.e. virtual microscope slides, through a hypertext transport protocol based server directly or over a packet network; FIG. 19 shows a system having interlinking and an integrated combination of image viewer and server concept using an Internet or intranet connection embodying the present invention; FIG. 20 shows a server comprising a portion of the system shown in FIG. 19 and functioning as a listening socket to respond to GET requests and create event threads in a simultaneous multi-threaded operating environment; FIG. 21 shows logic to determine valid GET requests;
FIG. 22A shows an interaction between a thin client browser program and the Internet or intranet server computer with a server program as shown in FIG. 20;
FIG. 22B shows an HTML-embedded Java applet viewer window for a client subsystem of the system shown in FIG. 19;
FIG. 23 shows an interaction between a Java applet program and Internet or intranet servers executing a server program and embodying the present invention;
FIG. 24 shows a thin client browser main window upon initial activation of the thin client browser shown in FIG. 22A; FIG. 25 shows a main window with a Slide Tray tab activated, showing available images from a remote server;
FIG. 26 shows a selection in the tray holding slide name Prost-zl and showing a thumbnail image of a virtual slide together with associated identification information;
FIG. 27 shows a main window of the thin client browser showing a tab after selection of a virtual slide for detailed viewing in response to the Slide Tray tab; FIG. 28 shows a Slide View window chosen by selecting a point on the browser main window thumbnail image, a Slide View image shows an overlay set of a tiled region from which one or more higher-magnification Field View images may be chosen;
FIG. 29 shows a Field View window chosen by selecting an image tile region of the Slide View window shown in FIG. 28 using a pointer;
FIG. 30 is a flow chart of a typical sequence of interactions to view an image;
FIG. 31 shows a Server tab, showing options for multiple client interaction;
FIG. 32 shows a right mouse click activated pop-up menu when a pointer is positioned on an x, y location in the image area;
FIG. 33 shows a pointer position after choosing a "Set the Pointer" option in the menu of FIG. 32;
FIG. 34 shows a flow chart for major steps in process of filling in display windows with tiles; and FIG. 35 shows an HTML-embedded Java applet viewer window.
FIGS. 36A through 36D are flow charts showing the operation of a server and a plurality of clients connected to the server for performing a virtual multi- headed microscope task.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
Referring now to the drawings and especially to FIG. 1, a system 10 according to the invention is shown therein for creating, and transmitting over an intranet or via the Internet a virtual microscope slide, i.e. interrelated data structures, which may or may not include display procedures, depicting at multiple resolutions, images of a specimen on a microscope slide. The system includes a microscope with a digital platform for supporting the microscope slide. Digital platform or stage 11 has been specially calibrated to include a large number of increments for locating portions of specimen images with high precision. After calibration and initial registration of stage 11 in the microscope setup, a microscope slide 13 or other substrate with a specimen 13a to be scanned is placed on stage 11.
For exemplary purposes, the creation of virtual microscope slide specimen according to the invention will be described with respect to a breast cancer specimen. The first step in creating a data structure according to the invention is to establish a macro image of the entire specimen (or that portion of the specimen desired to be stored as the macro image) . The purpose for creating the macro or large area thumbnail image is to enable the viewer to see the entire specimen at once and to use the entire image to choose those significant portions thereon for viewing at greater magnification. In this example, the user has selected 1.25X as the magnification to display the entire breast cancer slide. Once specimen •13a has been placed on stage 11, rotating optical assembly 15 are rotated to select lens 17 which corresponds to the 1.25X magnification.
In accordance with the teachings of the prior patent application, the computer controlled microscope is moved to scan the entire image of specimen 13a. The focusing system is programmed to step through increments which detect/select only the high resolution center area of the field of view in order to avoid storing the blurred areas at the periphery of the field of view. In this example, the macro image will be stored in a 10 by 8 array, for a total of 80 contiguous image tiles, as shown in FIG. 1A.
A typical microscope slide is about 77mm by 25mm, where the usable area, without including the label, is about 57mm by 25m. Each of the 80 image segments is about 4.8mm by 3.5mm in dimension. This means each of the 80 image segments will be scanned separately and stored as a separate image tile. The precision of the microscope systems is set up so that each step of the motor has a precision of .1 micron (micrometer) . In this example, the microscope is set up to move 48,143 steps in the X direction and 35,800 steps in the Y direction at 1.25X magnification for each of the 80 image areas. At higher magnifications, the image areas to be scanned are considerably smaller, so the number of steps is corresponding smaller. For each of the 80 image areas, the microscope lens will detect only the high resolution center area of the field of view.
The optical image from the desired image area is then detected by an optical array sensor 19, which preferably is a CCD sensor array. In this embodiment each of the 80 scanned areas is sensed by the entire array 19, which includes 752 pixels by 480 pixels. The optical array sensor 19 sends electrical signals indicative of the detected image to a microscope- controlled computer 32. The computer 32 stores the scanned images, including the top left X-Y stage coordinates for each of the 80 individual areas of the microscope slide. Each of the 80 scanned image areas' pixel locations are stored in a bit-mapped file (i.e., a file which contains a map of the location of each bit in the area) which corresponds to the layout of the individual images thereon. Thus, all of the pixels from the image tile derived from region A on FIG. 1A, which is the seventh from the left and in the top row, are individually assigned unique locations in the computer memory's bit-mapped file (FIG. 6), and are also stored in the data structure image tile file as shown in FIG. IB.
Each of the stored data image tiles is a standard image file with extension .bmp, and is of the order of one megabyte, i.e. each of the 752 x 480 pixels is stored as 3 bytes of red, green and blue image data (752 x 480 x 32 = 1,082,880 bytes) . Since the location of each image tile is known according to the bitmap, the complete microscope image can be recreated by painting (displaying) each image tile in accordance with its grid location.
To display the resulting image, the computer 32 calculates the appropriate portion to be displayed from each image tile depending upon the relative size of the display screen. Since the stored image data is usually greater than the size of the typical monitor, the viewer must scroll through the image on the window to view it entirely. However, an optional compression algorithm can be used to compress the entire image into the viewing window. The X-Y coordinate information is used by the viewing and manipulation program to reconstruct the image tiles into a complete image of the specimen. The resulting image is larger, and with better resolution than would be achieved if optics technology were able to construct a single lens capable of viewing the entire specimen in one field of view. In this example, each of the 80 image tiles has digital resolution of 752 x 480 pixels, with corresponding optical resolution of approximate .2 microns at 40X to approximately 6.4 microns at 1.25X.
After the macro or thumbnail images are digitally scanned and stored with their X-Y coordinate information, the user then examines the macro image or original specimen for significant details. Typically, the user will highlight with a marking pen the areas to be viewed at higher magnification. The user then changes the magnification of optics system 15 to the desired higher magnification, moves the scanning system to bring the selected region into view. The computer 32 then repeats the scanning and image tile creation process for the selected region, but at higher magnification and with a new grid system to locate the scanned selected regions. In the preferred embodiment example, the user has selected region B shown on FIG. 1A to perform a second view at a higher magnification. For example the user selects a 40X magnification. The computer 32 calculates the number of tiles needed to fill the selected area at 40X magnification and sets up a second grid.
It should be noted that region B crosses over several of the larger tiles in FIG. 1A. Because of the extremely precise 0.1 micron resolution of the instrument, locating such selected regions with high resolution is readily accomplished. As noted above, the computer 32 calculates the. size of the image portion, in this case as an example, X = 1500 and Y = 1200 stepping increments. Each image portion at the 40X resolution is detected by the optical sensor array, 752 by 480 pixels. Each resulting data file is stored in a separate, high magnification mapped area of memory so that the computer can easily recall the location of region B, or any of its 200 individual image tiles, when requested by a user. Once the user has completed selecting and having the computer controlled microscope system scan and store the digital images in image tiles, the computer 32 stores the mapped .bmp files along with their coordinate information and creates the slide image data structure 31 shown in FIG. 1. Slide image data structure 31 includes all of the bit-mapped image tile files at both magnifications (note that similarly, additional images could be stored at further magnifications, if desired), as well as X-Y coordinate information for the location of the various image tiles.
FIG. 7A is a file listing such as would be seen under a Windows 95 file manager showing the data files included in a data structure for a breast cancer specimen. Included in the file listing are FinalScan.ini and SlideScan.ini as well as sixty bit-mapped data files. Slidescan.ini is a listing of all the original bit-mapped (.bmp) files. The bit-mapped files represent the individual image tiles in the scan at, say, 1.25X magnifications. Slidescan.ini is set forth below in
Table 1 and describes the X-Y coordinates for each image tile file. When the data structure is viewed by a control program, the program uses the X-Y coordinates to display all the image tiles contiguously.
TABLE 1 — Slidescan.ini
[Header] [Ss2] x=278000 x=133571 y=142500 y=142500 lXStepSize=48143 [Ss3] lYStepSize-35800 x=37285 iScannedCount=37 y=106700
[Ssl] [Ss4] x=181714 x=85428 y=142500 y=106700 cπ ω ω IV) o o o o
X •— • X ■— >• X — • X — .» X --. »< X — ^ X — X r-.» X r-> * X — X ■"- > X -, l r-, l< ■—, > r- , l< X .— , >< _
II CO || II en II II C II II CO II II CO II II en II II co II CO || II en ii II co n n co n n co ιι ιι co n n co ιι ιι co n n co n n co ro co i ro ω co ro /i co μ-1 eo co t-1 CΛ co ∞ co ω ω oi I n -J i co -J LO CO -J oo co -J H ω -J μ-1 eo --j ro co μ-1 ro en i— -* en H μ co rO > -J -j ro cπ ro t-» (_π ro H cπ ω H (ji en p en -j H I— ' \-> O μ o -j o ^ μ o u o co ι_) θ M θ3 θ M -J o o) (i o ω uι ω H o ω o H iD uj H H co p ω -j μ Λ σi μ M (ji μ o ^ ω o ω ω M M W fc μ w ω o Φ ■ ■— ' Ω D σ> <_D ' σi ^ m ω
CD o o O 00 O -J ' — ' O Ui' — ' o to ' — ' O CO o oo o oo o oo o ro O Ui^ O -J O 03 - oo -j -j -J cπ
Cπ o O (_π o μ-1 o -J o oo o cπ O en O cπ o cπ o oo o μ-1 o Cπ o cπ o μ-1 O -J o co o -J O •£_> o μ-1
Cπ I x — * x — >< x .— .• x ■ • x — > x -— "< ^^< x <*<
.. .. co n II co II II en n ιι c ll ll CO || || co II II Co II II .. i oo eo i co ω i i en i i co i co eo i oo ω i -i u) i μ ra i co cπ ro co -j ro co μ-, ro -- μj ro -J -J ro -J cπ ro -J co ro -J oo ro -J
ChMD(ιN)ro(JιO --JO O m O M Ui O ^ ib O U O O o cπ ro Cπ oo cπ co o oo O CO ' — ' O CO ' — o π ' — ' o o o oo O cπ O Cπ CH Cπ co -J o o o oo CO
[Ss30] x=133571 y=-36500
[Ss31] x=181714 y=-36500
[Ss32] χ=229857 y=-36500
[Ss33] x=278000 y=-36500
[Ss34] x=278000 y=-72300
[Ss35] x=229857 y=-72300
[Ss36] x=181714 y=-72300
[Ss37] x=133571 y=-72300
Table 2 is a listing of the file FinalScan.ini, which is a listing the X-Y coordinates of the high magnification image tiles scanned and stored.
TABLE 2 - FinalScan.ini
[Header] dMagnification=40 tPatientID=mda027 lAnalysisImageCount=105 tAccession= lCalibrationImageCount=0 tOperatorID=jwb [DaO] tTimeOfScan=8/4/97 1:19:56 x=214532
PM y=65584 lXStageRef=278000 [Dal] lYStageRef-142500 x=212996 iImageWidth=752 y=65584 iImageHeight=480 [Da2] lXStepSize=1590 x-211460 lYStepSize=1190 y=65584 lXOffset=-1900 [Da3] lYOffset=-400 x=209924 y=65584 x=208388
[Da4] y=63216 x=208388 [Da21] y=65584 x=206852
[Da5] y=63216 x=206852 [Da22] y=65584 x=205316
[Da6] y=63216 x=205316 [Da23] y=65584 x=203780
[Da7] y=63216 x-203780 [Da24] y=65584 x=214532
[Da8] y=62032 x=214532 [Da25] y=64400 x=212996
[Da9] y=62032 x=212996 [Da26] y=64400 x=211460
[DalO] y=62032 x=211460 [Da27] y=64400 x=209924
[Dall] y=62032 x=209924 [Da28] y=64400 x=208388
[Dal2] y=62032 x=208388 [Da29] y=64400 x=206852
[Dal3] y-62032 x=206852 [Da30] y=64400 x=205316
[Dal4] y=62032 x=205316 [Da31] y=64400 x=203780
[Dal5] y=62032 x=203780 [Da32] y=64400 x=214532
[Dal6] y=60848 x=214532 [Da33] y=63216 x=212996 [Dal7] y=60848 x=212996 [Da34] y=63216 x=211460 [Dal8] y=60848 x=211460 [Da35] y=63216 x=209924 [Dal9] y=60848 x=209924 [Da36] y=63216 x=208388 [Da20] y=60848 -11
[Da37] y=58480 x=206852 [Da54] y=60848 x=205316 [Da38] y=58480 x=205316 [Da55] y=60848 x=203780 [Da39] y=58480 x=203780 [Da56] y=60848 x=180740 [Da40] y=82160 x=214532 [Da57] y=59664 x=179204 [Da41] y=82160 x=212996 [Da58] y=59664 x=177668 [Da42] y=82160 x=211460 [Da59] y=59664 x=176132 [Da43] y=82160 x=209924 [Da60] y=59664 x=174596 [Da44] y=82160 x=208388 [Daβl] y=59664 x=173060 [Da45] y=82160 x=206852 [Da62] y=59664 x=171524 [Da46] y=82160 x=205316 [Da63] y=59664 x=180740 [Da47] y=80976 x=203780 [Da64] y=59664 x=179204 [Da48] y=80976 x=214532 [Da65] y=58480 x=177668 [Da49] y=80976 x=212996 [Da66] y=58480 x-176132 [Da50] y=80976 x=211460 [Da67] y=58480 x=174596 [Da51] y=80976 x=209924 [Da68j y=58480 x=173060 [Da52] y=80976 x=208388 [Da69] y=58480 x=171524 [Da53] y=80976 x=206852 [Da70] x=180740 [Da87] y=79792 x=176132 [Da71] y=77424 x=179204 [Da88] y=79792 x=174596 [Da72] y=77424 x=177668 [Da89] y=79792 x=173060 [Da73] y=77424 x=176132 [Da90] y=79792 x=171524 [Da74] y=77424 x=174596 [Da91] y=79792 x=180740 [Da75] y=76240 x=173060 [Da92] y=79792 x=179204 [Da76] y=76240 x=171524 [Da93] y=79792 x=177668 [Da77] y=76240 x=180740 [Da94] y=78608 x=176132 [Da78] y=76240 x=179204 [Da95] y=78608 x=174596 [Da79] y=76240 x=177668 [Da96] y=78608 x=173060 [Da80] y=76240 x=176132 [Da97] y=78608 x=171524 [Da81] y=76240 x=174596 [Da98] y=78608 x=180740 [Da82] y=75056 x=173060 [Da99] y=78608 x=179204 [Da83] y=75056 x=171524 [DalOO] y=78608 x=177668 [Da84] y=75056 x=180740 [DalOl] y=77424 x=176132 [Da85] y=75056 x=179204 [Dal02] y=77424 x=174596 [Da86] y=75056 x=177668 [Dal03] y=77424 x=173060 y=75056 [Dal04] x=171524 y=75056
Computer 32 can also use the scanned image files to create a self-executing data structure. By compressing the .bmp images to .jpg and adding a dynamic, self-executing program which enables the user to view, reconstruct and manipulate the image tiles, the user can use the data structure as a virtual microscope slide of the original specimen. Preferably, the dynamic, self- executing program is a Java applet, such as shown on FIG. 7B. Computer 32 can provide the slide image data structure 31 directly or via an intranet browser 33 to local viewer 34, or via an Internet server 38. Slide image data structure 37 is shown as being directly accessible from Internet server 38. Alternatively, a user can download the slide image data structure on his own computer 39, use an internet browser 43 and view the reconstructed images. Another alternative is for computer 32 to store the slide image data structure on a CD-ROM, Jazz drive or other storage medium. To view slide image data structure 31 or 37, the
- user, who for example, has acquired the data structure via a CD-ROM, first installs the CD-ROM in the CD-ROM drive of his computer. Then the user opens up a browser or other applications program which can read the Java applet installed on the CD-ROM with the image tiles.
Note that in some instances no separate browser program may be required. In some case, the CD-ROM may include the complete applications program for viewing, reconstructing and manipulating the image tiles. In the instant example, the user will then select the icon or file listing for the slide image data structure and the control program will display the data files.
FIG. 2 is a screen view of a system embodying the present invention showing a low magnification image 24 of a specimen on a microscope slide in one window, a high magnification image 26 of a portion of the low magnification image selected by a region marker 30 and a control window 28. FIG. 3 is a view of a display screen of the apparatus embodying the present invention showing the control window 28, a low magnification window 24 having a plurality of high magnification micro image regions 310 delineated therein and a high magnification window 26 including one or more of the micro image regions 310, 314, 316. FIG. 4 is a view of a macro image of an actual breast cancer specimen displayed at 1.25X as seen on a computer monitor. FIG. 5 is a view of the grid portion of FIG. 4 outlining a region of interest selected by a pathologist displayed at 40X magnification.
Recall that region A in FIG. 1A was about 4.8mm by 3.5mm. This area creates 752 by 480 pixels of sensed data, or 360,930 pixels of information. Each pixel sends information about its location and the image it sensed to the computer. The computer stores this information in a series of data files (typically .bmp format, but .tif or .gif could also be used) . Thus, it can be seen that several more pixels of sensed data are available for viewing on a computer monitor operating at 640 by 480. To view the entire image, the user must scroll through the 'image tiles. However, scrolling need not be done on a tile, by tile basis. Rather, the user scrolls by pointing to a pixel on the monitor.
Figure 6 is a block diagram showing how the control program locates and scrolls through the stored image tiles. Using the example from Figure la, a complete data structure has been created. When the user loads the data structure (of the microscope slide) into his personal computer or views it from an Internet browser, the control program recreates a bit map of the stored data. The bit map of the entire slide is shown in Figure 6. Image tile A is also high-lighted. This bit map enables a user to point to or otherwise reference a location on the slide. The X-Y coordinate information specified in the data structure enables X-Y translation of the specific image tiles and specific pixels within the image tile. When the control program first loads the image, because this image file is so large, only a small number of the available tiles are displayed in the active window on the user's monitor. The user uses his mouse or pointing device to scroll through the active window to view the entire macro image. The X-Y coordinate information selected by the mouse translates into specific image tiles or portions therein. The computer takes the mouse pointer information and retrieves the image data from the series of stored tile images and displays them on the monitor for viewing the by user.
Because of the large amount of CCD pixel information stored, actual CCD pixel information can be recreated in the viewing window. The entire system operates in a loop, where the user inputs a mouse location, the computer translates the mouse location from the screen coordinates (screen pixels) to the X-Y coordinates on the bit map.
Similarly, the user may select the high magnification data images. These are outlined by a dark grid, indicating the areas stored. The user operates the mouse in the same manner as described above. The control program locates the stored X-Y coordinates and retrieves the selected parts of the image, CCD stored pixel by CCD stored pixel. As mentioned above, to save storage space, computer 32 can perform a data compression on each of the image tile files. A preferred data compression is JPEG, which is readily transferred and recognized by most Internet browser programs. Also, JPEG allows flexibility in the amount of data to be compressed, from 20 to 80 percent. FIG. 8 is file listing such as would be seen under Windows 95 file manager showing the data files included in an alternate data structure, one in which the data files have been compressed or converted to JPEG (-jpg) format for a breast cancer specimen. The file index. html (shown in Table 3) is the listing which contains the X-Y coordinate information for these data files. This is the information that is read by the dynamic, self-executing program for viewing, reconstructing and manipulating the image tiles into the macro and micro views.
TABLE 3 — index.html
<HTML>
<TITLE>
DCIS_02 7 - Web Slide
</TITLE>
<BODY>
<APPLET CODE=WebSlide/BliWebSlide . class NAME=DCIS_027
WIDTH=3384 HEIGHT=960 HSPACE=0 VSPACE=0 ALIGN=Middle>
<PARAM NAME "tPatientID" VALUE = "mda027
<PARAM NAME "tAccession" VALUE = ir It
<PARAM NAME "tOperatorlD" VALUE = "jwb">
<PARAM NAME "tTimeOfScan" VALUE = "8/4/97 1 19:56 PM">
<PARAM NAME "IXStageRef" VALUE = "278000">
<PARAM NAME "lYStageRef" VALUE = "142500">
<PARAM NAME "ilmageWidth" VALUE = "752"> <PARAM NAME ilmageHeight" VALUE = "480"> <PARAM NAME lXStepSize" VALUE = "1590"> <PARAM NAME lYStepSize" VALUE = "1190"> <PARAM NAME lXOffset" VALUE = "-1900"> <PARAM NAME lYOffset" VALUE = "-400"> <PAPAM NAME dMagnification" VALUE = "40"> <PARAM NAME ilmageCount" VALUE = "105"> <PARAM NAME IXSsStepSize" VALUE = "48143"> <PARAM NAME lYSsStepSize" VALUE = "35800"> <PARAM NAME iScannedCount" VALUE = "37"> <PARAM NAME lStartX" VALUE = "278000"> <PARAM NAME lStartY" VALUE = "142500"> <PARAM NAME Ssl_X" VALUE = " 18171 "> <PARAM NAME Ssl_Y" VALUE = "142500"> <PARAM NAME Ss2_X" VALUE = "133571"> <PARAM NAME Ss2_Y" VALUE = "142500"> <PARAM NAME Ss3_X" VALUE = "37285"> <PARAM NAME Ss3_Y" VALUE = "106700"> <PARAM NAME Ss4_X" VALUE = " 85428 "> <PARAM NAME Ss4_Y" VALUE = "106700"> <PARAM NAME Ss5_X" VALUE = "133571"> <PARAM NAME Ss5_Y" VALUE = "106700"> <PARAM NAME Ss6_X" VALUE = "181714"> <PARAM NAME Ss6_Y" VALUE = "106700"> <P RAM NAME Ss7_X" VALUE = "229857"> <PARAM NAME Ss7_Y" VALUE = "106700"> <PARAM NAME Ss8_X" VALUE = "229857"> <PARAM NAME Ss8_Y" VALUE = "70900"> <PARAM NAME Ss9_X" VALUE = "181714"> <PARAM NAME Ss9_Y" VALUE = "70900"> <PARAM NAME Ssl0_X" VALUE = "133571"> <PARAM NAME Ssl0_Y" VALUE = "70900"> <PARAM NAME Ssll_X" VALUE = "85428"> <PARAM NAME Ssll_Y" VALUE = "70900"> <PARAM NAME Ssl2_X" VALUE = "37285"> <PARAM NAME Ssl2_Y" VALUE = "70900"> <PARAM NAME Ssl3_X" VALUE = "-10858"> <PARAM NAME Ssl3_Y" VALUE = "70900"> <PARAM NAME Ssl4_X" VALUE - "-10858"> <PARAM NAME Ssl4_Y" VALUE = "35100"> <PARAM NAME Ssl5_X" VALUE = "37285"> <PARAM NAME Ssl5_Y" VALUE = "35100"> <PARAM NAME Ssl6_X" VALUE = "85428"> <PARAM NAME Ssl6_Y" VALUE = "35100"> <PARAM NAME Ssl7_X" VALUE = "133571"> <PARAM NAME Ssl7_Y" VALUE = "35100"> <PARAM NAME Ssl8_X" VALUE = "181714"> <PARAM NAME Ssl8_Y" VALUE = "35100"> <PARAM NAME Ssl9_X" VALUE = "229857"> <PARAM NAME Ssl9 Y" VALUE = "35100"> <PARAM NAME = ''Ss20 X" VALUE = ''278000 ">
<PARAM NAME = ' Ss20 Y" VALUE - ' *-700">
<PARAM NAME = ' 'Ss21 X" VALUE = ' '229857">
<PARAM NAME = ' Ss21 Y" VALUE = ' '-700">
<PARAM NAME = ' 'Ss22 X" VALUE = ' 181714 ">
<PARAM NAME = ' 'Ss22 Y" VALUE = ' '-700">
<PARAM NAME = ' 'Ss23 X" VALUE = ' '133571">
<PARAM NAME = ' 'Ss23 Y" VALUE = ' '-700">
<PARAM NAME = ' 'Ss24 X" VALUE = ' '85428">
<PARAM NAME = ' 'Ss24 Y" VALUE = ' '-700">
<PARAM NAME = ' 'Ss25 X" VALUE = ' '37285">
<PARAM NAME = ' 'Ss25 Y" VALUE = ' '-700">
<PARAM NAME = ' 'Ss26 X" VALUE = ' '-10858">
<PARAM NAME = ' 'Ss26 Y" VALUE = ' '-700">
<PARAM NAME = ' 'Ss27 X" VALUE = ' '-10858">
<PARAM NAME = ' 'Ss27 Y" VALUE = ' '-36500">
<PARAM NAME = ' Ss28 X" VALUE = ' '37285">
<PARAM NAME = ' 'Ss28 Y" VALUE = ' '-36500">
<PARAM NAME = ' 'Ss29 X" VALUE = ' '85428">
<PARAM NAME = ' 'Ss29 Y" VALUE = ' '-36500">
<PARAM NAME = ' 'Ss30 X" VALUE = ' '133571">
<PARAM NAME = ' 'Ss30 Y" VALUE = ' '-36500">
<PARAM NAME = ' 'Ss31 X" VALUE = ' 181714 ">
<PARAM NAME = ' 'Ss31 Y" VALUE = ' '-36500">
<PARAM NAME = ' 'Ss32 X" VALUE = ' *229857">
<PARAM NAME = ' 'Ss32 Y" VALUE = ' '-36500">
<PARAM NAME = ' 'Ss33 X" VALUE - ' 278000">
<PARAM NAME = ' 'Ss33 Y" VALUE = ' '-36500">
<PARAM NAME = ' 'Ss34 X" VALUE = ' '278000">
<PARAM NAME = ' 'Ss34 Y" VALUE = ' '-72300">
<PARAM NAME = ' 'Ss35 X" VALUE = ' '229857">
<PARAM NAME = ' 'Ss35 Y" VALUE = ' '-72300">
<PARAM NAME = ' 'Ss36 X" VALUE = ' '181714 ">
<PARAM NAME = ' 'Ss36 Y" VALUE = ' '-72300">
<PARAM NAME = ' 'Ss37 X" VALUE = ' 133571">
<PARAM NAME = ' 'Ss37 Y" VALUE = ' '-72300">
<PARAM NAME = ' 'DaO X" VALUE = " _14532">
<PARAM NAME = ' 'DaO Y" VALUE = "( 55584">
<PARAM NAME = ' 'Dal X" VALUE = " : _12996">
<PARAM NAME = ' 'Dal Y" VALUE = "( 55584">
<PARAM NAME = ' 'Da2 X" VALUE = " _11460">
<PARAM NAME = ' 'Da2 Y" VALUE = ". 55584">
<PARAM NAME = ' Da3 X" VALUE = n .09924">
<PARAM NAME = ' 'Da3 Y" VALUE = "( _5584">
<PARAM NAME = ' 'Da4 X" VALUE = " >08388">
<PARAM NAME = ' 'Da4 Y" VALUE = "( 55584">
<PARAM NAME = ' 'Da5 X" VALUE = "2 _06852">
<PARAM NAME = ' 'Da5 Y" VALUE = "( _5584">
<PARAM NAME = ' *Da6 X" VALUE = '• >05316">
<PARAM NAME = ' 'Da6 Y" VALUE = ". 55584"> ' <PARAM NAME = 'Da7 X" VALUE = '203780">
<PARAM NAME = Da7 Y" VALUE = 65584">
<PARAM NAME = 'Da8 X" VALUE = _ '214532">
<PARAM NAME = 'Da8 Y" VALUE = '64400">
<PARAM NAME = 'Da9 X" VALUE = '212996">
<PARAM NAME = 'Da9 Y" VALUE = '64400">
<PARAM NAME = DalO X' VALUE = "211460">
<PARAM NAME = DalO Y' VALUE = "64400">
<PARAM NAME = 'Dall X' VALUE = "209924">
<PARAM NAME = 'Dall Y' VALUE = "64400">
<PARAM NAME = 'Dal2 X' VALUE = "208388">
<PARAM NAME = 'Dal2 Y' VALUE = "64400">
<PARAM NAME = Dal3 X' VALUE = "206852">
<PARAM NAME = Dal3 Y' VALUE = "64400">
<PARAM NAME = Dal4 X' VALUE = "205316">
<P RAM NAME = 'Dal4 Y' VALUE = "64400">
<PARAM NAME = 'Dal5 X' VALUE = "203780">
<PARAM NAME = Dal5 Y' VALUE = "64400">
<PARAM NAME = 'Dal6 X' VALUE - "214532">
<PARAM NAME = 'Dal6 Y' VALUE = "63216">
<PARAM NAME = 'Dal7 X' VALUE = "212996">
<PARAM NAME = Dal7 Y' VALUE = "63216">
<PARAM NAME = 'Dal8 X' VALUE = "211460">
<PARAM NAME = Dal8 Y' VALUE = "63216">
<PARAM NAME = 'Dal9 X' VALUE = "209924">
<PARAM NAME = Dal9 Y' VALUE = "63216">
<PARAM NAME = 'Da20 X' VALUE = "208388">
<PARAM NAME = 'Da20 Y' VALUE = "63216">
<PARAM NAME = Da21 X' VALUE = "206852">
<PARAM NAME = Da21 Y' VALUE = "63216">
<PARAM NAME = 'Da22 X' VALUE = "205316">
<PARAM NAME = 'Da22 Y' VALUE = "63216">
<PARAM NAME = 'Da23 X' VALUE = "203780">
<PARAM NAME = 'Da23 Y' VALUE — "63216">
<PARAM NAME = 'Da24 X' VALUE = "214532">
<PARAM NAME = 'Da24 Y' VALUE = "62032">
<PARAM NAME = 'Da25 X' VALUE = "212996">
<PARAM NAME = 'Da25 Y' VALUE = "62032">
<PARAM NAME = 'Da26 X' VALUE = "211460">
<PARAM NAME = 'Da26 Y' VALUE = "62032">
<PARAM NAME = 'Da27 X' VALUE = "209924">
<PARAM NAME = 'Da27 Y' VALUE = "62032">
<PARAM NAME = 'Da28 X' VALUE = "208388">
<PARAM NAME = 'Da28 Y' VALUE = "62032">
<PARAM NAME = 'Da29 X' VALUE = "206852">
<PARAM NAME = 'Da29 Y' VALUE = "62032">
<PARAM NAME = 'Da30 X' VALUE = "205316">
<PARAM NAME = 'Da30 Y' VALUE = "62032">
<PARAM NAME = 'Da31 X' VALUE = "203780">
<PARAM NAME = 'Da31 Y' VALUE = "62032"> <PARAM NAME = 'Da32 X" VALUE = "214532">
<PARAM NAME = 'Da32~ Y" VALUE = "60848">
<PARAM NAME — 'Da33~ X" VALUE = "212996">
<PARAM NAME = 'Da33" Y" VALUE = "60848">
<PARAM NAME = 'Da34" X" VALUE = "211460">
<PARAM NAME = 'Da34~ Y" VALUE = "60848">
<PAR7M NAME = 'Da35~ X" VALUE = "209924">
<PARAM NAME = 'Da35~ Y" VALUE = "60848">
<PARAM NAME = 'Da36~ X" VALUE = "208388">
<PARAM NAME = 'Da36~ Y" VALUE = "60848">
<PARAM NAME = 'Da37~ X" VALUE = "206852">
<PARAM NAME = 'Da37~ Y" VALUE = "60848">
<PARAM NAME = 'Da38~ X" VALUE = "205316">
<PARAM NAME = 'Da38~ Y" VALUE = "60848">
<PARAM NAME = 'Da39~ X" VALUE = "203780">
<PARAM NAME = 'Da39~ Y" VALUE = "60848">
<PARAM NAME = 'Da40~ X" VALUE = "214532">
<PARAM NAME - 'Da40~ Y" VALUE = "59664">
<PARAM NAME = 'Da41~ X" VALUE = "212996">
<PARAM NAME = Da4l" Y" VALUE = "59664">
<PARAM NAME = Da42" X" VALUE = "211460">
<PARAM NAME = Da42" Y" VALUE = "59664">
<PARAM NAME = 'Da43~ X" VALUE = "209924">
<PARAM NAME = 'Da43~ Y" VALUE = "59664">
<PARAM NAME = 'Da44~ X" VALUE = "208388">
<PARAM NAME = 'Da44~ Y" VALUE = "59664">
<PARAM NAME = 'Da45~ X" VALUE = "206852">
<P RAM NAME = 'Da45~ Y" VALUE = "59664">
<PARAM NAME = 'Da46~ X" VALUE = "205316">
<PARAM NAME = 'Da46~ Y" VALUE = "59664">
<PARAM NAME = 'Da47~ X" VALUE = "203780">
<PARAM NAME = 'Da47~ Y" VALUE = "59664">
<PARAM NAME = rDa48" X" VALUE = "214532">
<PARAM NAME = 'Da48~ Y" VALUE = "58480">
<PARAM NAME = 'Da49~ X" VALUE = "212996">
<PARAM NAME = Da49" Y" VALUE = "58480">
<PARAM NAME = 'Da50" X" VALUE = "211460">
<PARAM NAME = 'Da50" Y" VALUE = "58480">
<PARAM NAME = 'Da5l" X" VALUE = "209924">
<PARAM NAME = 'Da5l" Y" VALUE = "58480">
<PARAM NAME = 'Da52" X" VALUE = "208388">
<PARAM NAME = 'Da52" Y" VALUE = "58480">
<PARAM NAME = 'Da53~ X" VALUE = "206852">
<PARAM NAME = 'Da53" Y" VALUE = "58480">
<PARAM NAME = 'Da54" X" VALUE = "205316">
<PARAM NAME = 'Da54" Y" VALUE = "58480">
<PARAM NAME = 'Da55" X" VALUE = "203780">
<PARAM NAME = 'Da55" Y" VALUE = "58480">
<PARAM NAME = 'Da56" X" VALUE = "180740">
<PARAM NAME = 'Da56" Y" VALUE = "82160"> <PARAM NAME = 'Da57 X' VALUE = "179204">
<PARAM NAME = 'Da57~ Y' VALUE = "82160">
<PARAM NAME = 'Da5δ~ X' VALUE = "177668">
<PARAM NAME = 'Da5β~ Y' VALUE = "82160">
<PARAM NAME = 'Da59~ X' VALUE = "176132">
<PARAM NAME = 'Da59~ Y' VALUE = "62160">
<PARAM NAME = "Da6θ" X' VALUE = "174596">
<PARAM NAME = 'Da60~ Y' VALUE = "82160">
<PARAM NAME = Da6l" X' VALUE = "173060">
<PARAM NAME = 'Da61~ Y' VALUE = "82160">
<PARAM NAME = 'Da62~ X' VALUE = "171524">
<PARAM NAME = 'Da62~ Y' VALUE = "82160">
<PARAM NAME = 'Da63~ X' VALUE = "180740">
<PARAM NAME = 'Da63~ Y' VALUE = "80976">
<PARAM NAME = 'Da64~ X' VALUE — "179204">
<PARAM NAME = 'Da64~ Y' VALUE = "80976">
<PARAM NAME = Da65" X' VALUE = "17766δ">
<PARAM NAME = 'Da65~ Y' VALUE = "δ0976">
<PARAM NAME = 'Da66~ X' VALUE = "176132">
<PARAM NAME = 'Da66~ Y' VALUE = "80976">
<PARAM NAME = 'Da67~ X' VALUE = "174596">
<PARAM NAME = Da67" Y* VALUE = "80976">
<PARAM NAME = 'Da68~ X' VALUE = "173060">
<PARAM NAME = 'Da68" Y' VALUE = "80976">
<PARAM NAME = 'Da69~ X' VA.LUE — "171524">
<PARAM NAME = 'Da69~ Y' VALUE = "80976">
<PARAM NAME =_ 'Da70~ X' VALUE = "180740">
<PARAM NAME = 'Da7θ" Y' VALUE = "79792">
<PARAM NAME = 'Da71~ X' VALUE = "179204">
<PARAM NAME = 'Da71~ Y' VALUE = "79792">
<PARAM NAME = Da72" X' VALUE = "17766δ">
<PARAM NAME = 'Da72~ Y' VALUE = "79792">
<PARAM NAME = Da73~ X' VALUE = "176132">
<PARAM NAME = 'Da73~ Y' VALUE = "79792">
<PARAM NAME = 'Da74~ X' VALUE = "174596">
<PARAM NAME = Da74" Y' VALUE = "79792">
<PARAM NAME = 'Da75~ X' VALUE = "173060">
<PARAM NAME = 'Da75~ Y* VALUE = "79792">
<PARAM NAME = Da76" X' VALUE = "171524">
<PARAM NAME = Da76" ~Y' VALUE = "79792">
<PARAM NAME = 'Da77_ ~X' VALUE = "160740">
<PARAM NAME = Da77" ~Y' VALUE = "7δ60δ">
<PARAM NAME = 'Da78_ "x1 VALUE = "179204">
<PARAM NAME = 'Da78_ "Y1 VALUE = "7δ608">
<PARAM NAME = Da79" _X' VALUE = "177668">
<PARAM NAME = 'Da79_ Y' VALUE = "7860δ">
<PARAM NAME = 'Da80_ X' VALUE = "176132">
<PARAM NAME = 'Da80_ Y' VALUE = "7δ60δ">
<PARAM NAME = 'Da8l" _X' VALUE = "174596">
<PARAM NAME = 'Da8l" ~Y* VALUE = "78608"> <PARAM NAME 'Da82_X" VALUE == "173060"> <PARAM NAME 'Da82_Y" VALUE == "7860δ"> <PARAM NAME Da83_X" VALUE == "171524"> <PARAM NAME Daδ3_Y" VALUE == "76608"> <PARAM NAME τDaδ4_X" VALUE == "180740"> <PARAM NAME 'Daδ4_Y" VALUE == "77424"> <PARAM NAME 'Da65_X" VALUE == "179204"> <PARAM NAME 'Da85_Y" VALUE == " 7742 "> <PARAM NAME 'Da86_X" VALUE == "177666"> <PARAM NAME 'Da86_Y" VALUE := "77424"> <PARAM NAME 'Da87_X" VALUE ^= "176132"> <PARAM NAME 'Da67_Y" VALUE ■■= "77424"> <PARAM NAME Daδ8_X" VALUE == "174596"> <PARAM NAME Da88_Y" VALUE == "77424"> <PARAM NAME 'Da89_X" VALUE := "173060"> <PARAM NAME 'Daδ9_Y" VALUE -= "77424"> <PARAM NAME Da90_X" VALUE == "171524"> <PARAM NAME Da90_Y" VALUE := "77424"> <PARAM NAME 'Da91_X" VALUE == "160740"> <PARAM NAME TDa91_Y" VALUE := "76240"> <PARAM NAME 'Da92_X" VALUE == "179204"> <PARAM NAME 'Da92_Y" VALUE == "76240"> <PARAM NAME 'Da93_X" VALUE == "177668"> <PARAM NAME Da93_Y" VALUE == "76240"> <PARAM NAME 'Da94_X" VALUE := "176132"> <PARAM NAME 'Da94_Y" VALUE ■ ■= "76240"> <PARAM NAME Da95_X" VALUE == "174596"> <PARAM NAME 'Da95_Y" VALUE := "76240"> <PARAM NAME 'Da96_X" VALUE := "173060"> <PARAM NAME 'Da96_Y" VALUE == "76240"> <PARAM NAME Da97_X" VALUE == "171524"> <PARAM NAME Da97_Y" VALUE ■■= "76240"> <PARAM NAME 'Da96_X" VALUE = -- "180740"> <PARAM NAME Da98_Y" VALUE == "75056"> <PARAM NAME Da99_X" VALUE == "179204"> <PARAM NAME 'Da99_Y" VALUE == "75056"> <PARAM NAME 'DalOO_X " VALUE = "17766δ"> <PARAM NAME 'DalOO_Y " VALUE = "75056"> <PARAM NAME 'Dal01_X " VALUE = "176132"> <PARAM NAME 'Dal01_Y " VALUE = "75056"> <PARAM NAME 'Dal02_X " VALUE = "174596"> <PARAM NAME 'Dal02_Y " VALUE = "75056"> <PARAM NAME 'Dal03_X " VALUE = "173060"> <PARAM NAME 'Dal03_Y " VALUE = "75056"> <PARAM NAME 'Dal04_X " VALUE = "171524"> <PARAM NAME 'Dal04 Y " VALUE = "75056"> </APPLET> </BODY> </HTML> Referring now to the drawings, and especially to FIGS. 9A, 9B and 10, apparatus for synthesizing low magnification and high magnification microscopic images is shown therein and generally identified by reference numeral 10. The system includes a computer 12 which is a dual Pentium Pro personal computer in combination with a Hitachi HV-C20 video camera 14 associated with a Zeiss Axioplan 2 microscope 16. The computer system 12 is able to receive signals from the camera 14 which captures light from the microscope 16 having a microscope slide 18 positioned on an LUDL encoded motorized stage 20. The encoded motorized stage 20 includes a MAC 2000 stage controller for controlling the stage in response to the computer 12. A microscope slide 18 includes a biological specimen 21 which is to be viewed by the microscope and whose image is to be digitized both at low magnification and at high magnification as selected by a user. The low magnification digitized image is then displayed on a 21 inch liyama video display monitor 22 having resolution of 1600 by 1200 to provide display screens of the type shown in FIGS. 1 through 3 including a low magnification image 24, for instance, at 1.25 power, a high magnification image 26, for instance at 40X power and a control window or image 28. The low magnification image may have identified therein a region 30 which is reproduced at high magnification in high magnification screen or window 26 so that a pathologist or other operator of the system can review architectural regions of interest in low magnification image 24 and simultaneously view them in high magnification in the high magnification screen or window 26 to determine whether the cells forming a portion of the architectural feature need be examined further for cancer or the like or not. The computer 10 is constructed around a PCI system bus 40 and has a first Pentium Pro microprocessor 42 and a second pentium pro microprocessor 44 connected thereto. The system bus 40 has connected to it a PCI bus 50 and an ISA bus 52. The PCI bus 50 has a SCSI controller 60 connected thereto to send and receive information from a hard disk 62. The hard disk 62 also is coupled in daisy chain SCSI fashion to a high capacity removal disk and to a CD Rom drive 66. The hard disks 62 contains the programs for operating the system for controlling the microscope 16 and for processing the images as well as for doing a quantitative analysis of the selected portions of the histological specimens being viewed on the slide 18. The system bus 40 also has connected to it a random access memory 70 within which portions of the program being executed are stored as well as a read only memory 72 for holding a bootstrap loader as well as portions of the basic input/output operating system. A floppy disk controller 74 is coupled to the system bus 40 and has connected to it a floppy disk drive 76 for reading and writing information to a floppy disk as appropriate. A mouse controller 60 is coupled to the system bus and has a mouse 82 which operates as a pointing device for controlling manipulations on the screen 22 and within the windows 24, 26 and 28. A keyboard controller 90 is connected to the system bus and has a keyboard 92 connected thereto. The keyboard 92 may be used to send and receive alpha numeric signals to other portions of the computer. An audio controller 100 has a plurality of speakers 102 and a microphone 104 connected thereto for audio input and output and is coupled to the system bus 40. A network interface, such as a network interface card 104, is connected to the system bus and can provide signals via a channel 106 to other portions of a network or internet to which the system may be connected. Likewise, signals can be sent out of the system through a modem 110 connected to the ISA bus 52 and may be sent via a channel 112, for instance, to the internet. A printer 116 is connected via a parallel I/O controller 118 to the system bus in order to provide printouts as appropriate of screens and other information as it is generated. A serial I/O controller 122 is connected to the system bus and has connected to it a camera controller 124 which is coupled to CCD sensors 126 in the cameras. The CCD sensors 126 supply pixel or image signals representative of what is found on the slide 18 to an Epix pixci image acquisition controller 130 coupled to the PCI bus 50.
The microscope 16 includes a base 140 having a stage 20 positioned thereon as well as an objective turret 142 having a plurality of objectives 144, 146 and 148 thereon. The objective 144, for instance, may be of 1.25x objective. The objective 146 may be a 20X objective. The objective 148 may be a 40X objective. Signals from the camera sensors and controller are supplied over a bus 128 to the image acquisition system where they are digitized and supplied to the PCI bus for storage in RAM or for backing storage on the hard disk 62.
When a specimen is on the slide 18 the stage 20 may be manipulated under the control of the computer through a stage controller 160 coupled to the serial I/O controller 122. Likewise, a microscope controller 162 controls aspects of the microscope such as the illumination, the color temperature or spectral output of a lamp 16δ and the like. For instance, in normal operation, when a specimen is placed on the slide, specimen slide 18 is placed on the stage 20 in a step 200, as shown in FIG. 14, the processors 42 or 44 send a command through the system bus to cause the serial I/O controller 122 to signal the microscope controller to change magnification to 1.25X in a step 202. This is done by rotating the objective turret of the Axioplan 2 microscope to select the objective 144. Likewise, the controller sets the color temperature of the lamp 168, sets a pair of neutral density filter wheels 170 and 172 and sets a field diaphragm 174 for the correct illumination. A condenser diaphragm 176 is also controlled and a color filter wheel 180 may also be controlled to apply the appropriate filter color to the CCD censors 126 in the camera. The entire slide is then scanned in a step 204. The images are tiled and melded together into the overall image 24 supplied on the screen 22 to provide the operator in the step 206 with a visually inspectable macro image of relevant regions of the slide of interest.
In order to provide the magnified image, the mouse may be moved to identify a marker segment or region which, for instance, may be a rectangular region which will cause the microscope to change magnification as at step 208 to 4x, 20x, 40x, etc., by rotating the turret to bring the appropriate objective lens system into viewing position.
Next the user, in a step 209a, uses the mouse to select the region on the macro image in order to select the micro image to be viewed on the screen 22. In a step 209b a test is made to determine whether the user has commanded continued inspection. If the user has, a test is made in a step 209c to determine if the magnification is to be changed by changing the selected objective. In the event the magnification is to be changed control is transferred to the step 208. If the magnification is to remain unchanged control is transferred to the step 209a. In the event inspection is not to continue the region selected is outlined for higher magnification scan in a step 209d. In a step 209e, a . command may be received to scan or acquire the higher magnification image for display in screen 26. The image may then be archived for later analysis, displayed or analyzed immediately.
In order to perform the magnification called for in step 208, the overall illumination and control of the microscope will be controlled so that in a step 210 the objective turret 142 will be rotated to place the higher power objective above the slide 16. In a step 212 voltage to the lamp will be changed to adjust the lamp 168 to provide the proper illumination and color temperature as predetermined for the selected objective. In a step 214, the condenser diaphragm 176 will have its opening selected as appropriate to provide the proper illumination for that objective. In a step 216, the filter turret 180 will select the proper light wavelength filter to be supplied to the camera sensors. For instance, a red, blue or green filter, as appropriate, particularly if the specimen has been stained. In a step 218 the field diaphragm 174 will have its opening changed. In a step 220 the neutral density filter wheel 170 will select a neutral density filter and in a step 222 the neutral density filter wheel 172 will also select a neutral density filter. In a step 224 the X, Y and Z offsets will be used for reconstruction of the recorded image at the magnification and in a step 226 the current position will be read from encoders in the stage which are accurate to .10 micron.
In order to identify the selected region the mouse is moved to that area of the region in a pointing operation in a step 240 as shown in FIG. 14. The mouse may be moved to draw a box around the region selected. In a step 242 the X and Y screen points are computed for the edges of the regions selected and the computed image or pixel points are translated to stage coordinate points in order to control the stage of the microscope. In a step 244 a list of all of the X fields for positioning the stage for the objective is stored in random access memory and may be backed up on the hard disk. The information from the X offsets for the objective and the stage offsets is used as well as the size of the field to position the slide properly under the objective to capture the micro image.
When the slide has been positioned properly, as shown in FIG. 15 in a step 250 the stage is positioned for each of the X and Y coordinate values in stage coordinate values and the digitized image is captured by the cameras and stored in RAM and backed up on the hard disk. The image may be then analyzed quantitatively in various manners such as those set forth in the previously-identified United States application.
Optionally the image may be stored for archival purposes in a step 254.
In order to override the specific control functions that take place as shown in FIG. 12, a screen is provided as shown in FIG. 13 wherein the X-Y step size can be edited, the X, Y and Z offset can be edited, the lamp voltage can be selected, the neutral density filter can be selected as well as the opening of the field diaphragm and several other microscopic characteristics. FIG. 13 is a view of the settings of the microscope objective properties of the Axioplan 2, computer- controlled microscope. The X and Y positioning is specifically carried out as shown in FIG. 16 where the slide 18 is shown with a slide boundary 270, 272, 274 and 276. Stage boundary for limits of the stage travel for purposes of the stage the stage can be moved all the way from an upper left hand corner of travel 276 to a lower right hand corner of travel 280. At the upper left hand bounded corner of travel 276 limits which a signal that the end of travel has been reached and the stage is then translated a short distance 262 in the extra action and a short distance 284 in the Y direction to define the first tile 288 in terms of a reference point 290 at its upper left hand corner. Since the size of the macro image tile 288 is known, the next macro image tile 292 may be placed contiguous with it by moving the stage appropriately and by measuring the location of the stage from the stage in counters without the necessity of performing any image manipulation. The image tiles 288 and 292 may be abutted without any substantial overlap or they may be overlapped slightly, such as a one pixel with overlap, which is negligible insofar as blurring of any adjacent edges of abutted image tiles. The upper left hand corner 300 of the tile 292 defines the rest of 292 and other tiles can be so defined. Micro image tiles can likewise be defined so that they are contiguous but not substantially overlapping, as would interfere with the composite image. This avoids the problems encountered with having to perform extended computations on digital images in a frame storer or multiple frame storage in order to match or bring the images into contiguity without blurriness at the edges of contiguous image tiles. It may be appreciated that the low power image 24 has a plurality of micro images defined therein which are tiled and which are shown in higher magnification as individual tiles
312, 314, 316 and the like. In addition, the region 310 when magnified as shown in the window 26 may exceed the bounds of the window and thus the window may include scroll bars or other means for allowing the image 310 which is larger than the window 26 to be examined from within the window 26.
The stage 200 is best seen in FIG. 16A and includes the X 'and Y stepper motors 279 and 281 with their respective encoders, which provide a closed loop system to give the .1 micron accuracy versus the usual 5 or 6 micron accuracy of most microscope stages without a closed loop system. This closed loop system and this very high accuracy allow the abutting of the tile images for both high magnification and low magnification images without the substantial overlap and the time-consuming and expensive software currently used to eliminate the overlap and blurriness at the overlapping edges of adjacent image tiles. With the precisely positioned stage and by using the tiling system described in connection with FIG. 16, where the slide is precisely positioned relative to a center point CP for the slide, and the known position of point 278 is always taken from the same point, the tiles may be positioned precisely in a horizontal row and precisely in vertical rows to reconstruct the macro image and the micro image. This reconstruction is done without the use, as in the prior art, of extensive software manipulation to eliminate overlapping image tiles, horizontally or vertically or the haphazard orientation of image tiles.
The present invention also includes the facility for allowing remote observation to occur by being able to couple the system either over a network communication facility to an intranet, for instance via the network interface, or via a modem or other suitable connection, to an internet so that once the image has been scanned and stored in memory on hard disks or other storage, remote users may be able to access the low magnification image as well as the high magnification image and move around within both images to make determinations as to the histological characteristics of the samples.
An additional feature of the system includes a plurality of networked workstations coupled to a first computer console 12 having a display screen 22 connected to the microscope 14. Satellite work stations 350 and 352 are substantially identical to the work station 12 including respective computers 354 and 356 coupled to displays 358 and 360. The devices can be manipulated through input devices 360 and 362 which may include a keyboard, mouse and the like. Also a third device can be connected including a work station 370, having a display 372, a computer 374 and an input device 376. Each of the devices is connected over respective network lines 380,
382, 384 to the computer 12 which transmission may be via either net or the like. Each of the different operators at the physically separate viewing stations can locate regions from the view of entire tissue cross sections via a macro view and label the regions for subsequent scanning and/or quantitative analysis. A single operator at the instrument station 12 can locate regions to view the entire tissue cross section. Those regions can be labeled for subsequent scanning and/or quantitative analysis with subsequent review and physically remote viewing stations, for instance, in an operating room or in individual pathologists ' signout areas in order to review analysis results while still maintaining and reviewing the entire macro view of the tissue and/or the individual stored images from which the quantitative results were obtained. The viewing stations 350, 352 and 370 can comprise desk top computers, laptops, etc. There is no need for a microscope at the network stations 350, 352 and 370.
In a still further alternative embodiment, remote workstations 400, 402, 404, 406 and 408 may be connected through a server 410 which may be supplied via a packet switched network. The server 410 and may be a hypertext transport protocol based server of the type used for the World Wide Web or may be a telnet type server as used previously in internet remote operation applications. The server 410 communicates via a communications channel 414 with a local computer 416 having a display 418 associated therewith, the local computer 416 being connected to the microscope 420. Each of the remote work stations 400, 402, 404, 406 and 408 may perform the same operations as the stations 350, 352 and 370 although they do it from nearby buildings or even from around the world, thus providing additional flexibility for others to make use of the specimen obtained and being viewed under the microscope 420. In addition, stored images may be disseminated through the server 410 to the remote servers 400 through 408 for further analysis and review. The server was designed to interact with either a thin client browser or with a Java applet viewer, operating through an HTML browser such as Netscape or the Microsoft Internet Explorer.
The server runs on a standard PC under a Windows operating system. It uses HTTP Internet communication protocols. The computer has stored on its storage media already collected data files having the data structure disclosed above. This data structure consists of "tiled" sets of digital images, with x, y information organized to aid the viewer program to "reconstruct" and spatially align physically-contiguous images, at multiple resolutions. The server responds to HTTP "Get" requests from multiple thin client browsers or other browsers with embedded Java applet viewers. As such, it uses a "listening socket" and a number of short-lived "threads" which handle "Get" requests independently and simultaneously, as shown in FIG. 28.
After initial logic, as shown in FIG. 29, to determine whether the HTTP request is valid and, if so, whether it is a Java request for a thin client request, the server generates a response thread, depending upon the request as detailed in Table 1, to send back the requested information to the client. Large numbers of these requests can be handled at one time.
The server 12 was designed to interact with a client having either a thin client browser or with a Java applet viewer, operating through an HTML browser such as Netscape Navigator or Microsoft Internet Explorer. The server 12 runs on a standard PC under a Windows operating system. It uses the HTTP communication protocol. The computer 12 has stored on its storage media already collected data files of with the data structure disclosed in U.S. application no. 09/032,514, filed February 27, 1998, which is incorporated herein by reference. This data structure consists of "tiled" sets of digital images, with x, y information organized to aid the viewer program to "reconstruct" and spatially align physically-contiguous images, at multiple resolutions. The server responds to HTTP "GET" requests from multiple thin client browsers or other browsers with embedded Java applet viewers. As such, it uses a "listening socket" and a number of short-lived "threads" which handle "GET" requests independently and simultaneously, as shown in FIG. 19.
After initial logic, as shown in FIG. 20, to determine whether the HTTP request is valid and, if so, whether it is a Java request or a thin client request, the server generates a response thread, depending upon the request as detailed in Table 4, to send back the requested information to the client. Large numbers of these requests can be handled at one time.
Table 4. Client - Server "GET" Interactions
Figure imgf000043_0001
Figure imgf000044_0001
In addition to the tiled image data, and the x, y coordinate lists for each tile of the image data, as set forth in Table 5 below there are several small reconstructed images that are stored in the individual folder, or on the server. These facilitate bringing image content to the client viewing screen rapidly, and can be used as an aid m determining what viewing options to choose in the various viewing programs. 90
o
! _
H U α.
tn Di t- Di Di Di U Di H tn tJi α. .n α α & . α α α α α. a cπ π
Figure imgf000045_0001
Q. -n -rπ -n -m -r— i -n -r~ι -r— i •<— i £__, J_L, Qj Li S-L. ϋ. J-Li Cπ Ol i— i (M n ' ιι «. r~ o oι
CM CM CM CM CM CM CM CNJ CM CM cO cO cO cG co cO cO cO cO
Figure imgf000045_0002
Q Q Q Q Q Q Q Q Q
Figure imgf000045_0003
I en I ^r1 ^r σi r~ o ro o o co oo oo oo vu _n r~ m vo "=r co co o en co _n r~ r~ oo m o oo o o ^r t— _n _n rH l-O D _n o co co cn vo -n oo in r— r- D vo r— r~ r- vD r- r r- co
Figure imgf000045_0004
r~ r-
Figure imgf000045_0005
-n vo r- oo cri o cO cO cfl co co Q Q Q Q Q Q Q Q Q Q Q Q Q
Figure imgf000045_0006
o O
O 00 co
Da20 JPG 69 , 762 Da20 pg
Da21 JPG 79 ,036 Da21 ipg
Da22 JPG 80 ,779 Da22 Dpg
Da23 JPG 38 ,576 Da23 Dpg
Da24 JPG 65 ,975 Da24 upg
Da25 JPG 73 ,812 Da25 Dpg
Da26 JPG 80 , 660 Da26 Dpg
Figure imgf000046_0001
Da28 JPG 88 ,332 Da28 ]pg
Da29 JPG 66 , 672 Da29 Dpg
Da3 JPG 78 399 Da3.;jpg
Da30 JPG 29 , 994 Da30 Dp
Da 31 JPG 57 465 Da31 Dpg
Da32 JPG 74 , 006 Da32 ipg
Da33 JPG 78 ,765 Da33 ipg
Da34 JPG 54 120 Da34 ]pg
Da35 JPG 82 550 Da35 :pg
Da36 JPG 63 735 Da36 ]pg
Da37 JPG 41 253 Da37 ipg
Da38 JPG 69 759 Da38 jpg
Da39 JPG 49 376 Da39 jpg
Da4 JPG 77 922 Da4. ipg
Da40 JPG 52 514 Da40 ipg
Da41 JPG 68 291 Da41 Dpg
Da42 JPG 69 726 Da42 Dpg
Da43 JPG 79 840 Da43 ]pg
Da44 JPG 80 526 Da44 ]pg
Da45 JPG 84 245 Da45 Dpg
Da46 JPG 50 315 Da46 upg
Da47 JPG 73 069 Da47 Dpg
Da48 JPG 73 188 Da48 :pg
Da49 JPG 69 155 Da49 Dpg
Da5 JPG 69 257 Da5. ηpg
Da50 JPG 69 087 Da50 ]pg
Da51 JPG 74 156 Da51 jpg
Da52 JPG 82 847 Da52 jpg
Da53 JPG 74 838 Da53 ipg
Da54 JPG 69 003 Da54 ]pg
Da55 JPG 73 524 Da55 ]pg
Da56 JPG 65, 242 Da56 upg
Da57 JPG 67, 796 Da57 upg
Da58 JPG 70, 367 Da58 pg
Da59 JPG 39, 998 Da59 ipg
Da6 JPG 68, 210 Da6. ηpg
Da60 JPG 14, 487 Da60 3pg
Da61 JPG 76, 801 Da61 Dpg Da62 JPG 74 394 Da62 ipg
Da63 JPG 69 446 Da63 pg
Da64 JPG 63 296 Da64 upg
Da65 JPG 17 568 Da65 ipg
Da66 JPG 71 935 Da66 :pg
Da67 JPG 71 736 Da67 :pg
Da68 JPG 67 406 Da68 ipg
Da69 JPG 74 488 Da69 ]pg
Da7 JPG 69 660 Da7. ηpg
Da70 JPG 45 382 Da70 ]pg
Da71 JPG 69 849 Da71 ]pg
Da72 JPG 12 009 Da72 Dpg
Da73 JPG 62 862 Da73 :pg
Da74 JPG 68 522 Da74 Dpg
Da75 JPG 67 734 Da75 ]pg
Da76 JPG 60 510 Da76 Dpg
Da77 JPG 28 689 Da77 ipg
Da78 JPG 68 839 Da78 ipg
Da79 JPG 67 137 Da79 ipg
Da8 JPG 71 914 Da8.; ]pg
Da80 JPG 65 232 Da 80 pg
Da81 JPG 78 365 Da81 Dpg
Da82 JPG 63 535 Da82 :pg
Da83 JPG 74 889 Da83 Dpg
Da84 JPG 71 895 Da84 ]pg
Da85 JPG 65 744 Da85 jpg
Da86 JPG 76 849 Da86 ipg
Da87 JPG 74 373 Da87 ]pg
Da 88 JPG 73 449 Da 88 Dpg
Da89 JPG 69 255 Da 89 ]pg
Da9 JPG 74 054 Da9.; ]pg
Da90 JPG 65 637 Da90 :pg
Da91 JPG 62 566 Da91 :pg
Da92 JPG 75 703 Da92 upg
Da93 JPG 70 315 Da93 ipg
Da94 JPG 63 884 Da94 :pg
Da95 JPG 62 949 Da95 pg
Da96 JPG 69 046 Da96 ]pg
Da97 JPG 77 595 Da97 Dpg
Da98 JPG 71 528 Da98 Dpg
Da99 JPG 58 862 Da99 Dpg
Each image has a PreviewSlide.jpg image contained m its data structure. This is a "thumbnail" image reconstructed from all of the tiles from the low magnification, 1.25x slide view image tiles. The reconstructed composite image has been digitally reduced to an image size of 454 x 240. During server startup, for each data structure found as described below, this
Preview Slide image is further converted to an additional thumbnail image of 232 x 120. The use of the Preview STide and thumbnail images will be described below. Also, if specific HTML Java applet views have been chosen, four reconstructed .jpg images from each view, corresponding to four different magnifications have also been stored on the server, as described in detail below under the Java applet creator description and image viewer descriptions. FIGS. 21A, 21B and 22 illustrate two different virtual microscope slide viewing implementations. These suit two different needs. The thin client browser has three screens and many more functions. As described in more detail below, there is a main screen that displays the thumbnail Preview Slide image, and uses a tabbed interface to implement different functionalities to the browser. Some of these important functionalities are: (1) a SlideTray tab, which allows for the selection of any of the stored images hosted on the server computer; (2) a server tab, which allows coordination of views and chats with multiple other clients all logged-in at the same time; and (3) an Applet Creation tab to select specific region views for HTML applets viewed by the Java Applet viewer. The other two windows, Slide View and Field View, allow viewing of low-magnification tiled images and high-magnification tiled images with scrolling and coordination between the two views. The thin client browser is more suited to secondary opinion expert pathology consultations, and sophisticated professional pathology users m departmental pathology practice, for review of cases and as archival backup virtual slide records. In operation, the browser program is loaded separately, once on a client computer. After that it can be used to access any number of servers, as described below, by simply typing in the Internet address of the server. It is faster than the JAVA applets because it comprises code which is already compiled, and is not based upon interpreted applet execution. It is unnecessary to load the thin client browser for every virtual microscope slide viewed. During creation of the image, only smaller regions of specific diagnostic material need be scanned at high magnification, thus saving time during the scanning process .
The HTML applet viewer is simpler than the thin client browser, and may be used in medical student, dental student, veterinary and undergraduate biology teaching situations. Advantage is taken of the fact that most students are familiar with an HTML browser. Instructors can easily add course "content" text to provide different descriptions of the virtual microscope slide images. Since the virtual microscope slides will often be used for longer periods, and since there is no premium on speed of scanning, entire specimens can be scanned offline at high magnification which takes a longer time. In this viewer simply acts as a "portal," or a small window, in a fixed position on a specific HTML page.
As described below, each applet instance relates to a specific image on a specific server computer. There are two parts to the view, the upper part of the portal is a display of the Preview Slide image. The bottom part of the portal initially shows a selected view from that image at one of four magnifications. A plurality of radio button choices loaded on a bar between the views allows for additional magnification choices in the bottom view. The bottom view is also scrollable, and can be changed by pointing the mouse to a region on the Preview Slide image. It will be appreciated that this viewer is simpler to learn initially and to operate than the thin client browser. It has the disadvantage of being slower and of only addressing one image at a time. It has an advantage of being simple, having various types of explanatory text right next to the image, and of being cross platform with regard to operating system, computer type and HTML browser type. These are all helpful in the educational market .
The Slide Tray concept is used in the server and the browser programs and is central to providing an organizational construct to collections of images. It is set forth in Table 6 below.
Table 6.
FINALS- -1 INI 3,902 FinalScan. ini
PREVIE' -1 JPG 6,210 PreviewSlide . jpg
SLIDES' -1 INI 654 SlideScan. ini
SSI JPG 10,285 SSI. jpg
S SSS1100 J JPPGG 63,150 SS10. jpg
SS11 JPG 70, 838 SS11. jpg
SS12 JPG 15,535 SS12. jpg
SS13 JPG 12, 071 SS13.jpg
SS14 JPG 73, 847 SS1 . jpg
S SSS1155 J JPPGG 70,783 SS15. ipg
SS16 JPG 25, 178 SS16. jpg 5517 JPG 2,983 SS17.jpg
5518 JPG 9,035 SS18.jpg
5519 JPG 15,629 SS19.jpg
552 JPG 25,194 SS2.jpg SS20 JPG 4,200 SS20.jpg
553 JPG 9,936 SS3.jpg
554 JPG 10,118 SS4.jpg
555 JPG 4,559 SS5.jpg SΞ6 JPG 35,961 SS6.jpg SS7 JPG 86,933 SS7.jpg
558 JPG 16,212 SS8.jpg
559 JPG 33,872 Ss9.jpg [Header] tPatientID=Prostate tAccession= tOperatorID= tTime0fScan=9/17/98 4:56:31 PM lXStageRef=278000 lYStageRef=142500 iImageWidth=752 iImageHeight=480 lXStepSize=1588 lYStepSize=1184 lXOffset=0 lYOffset=0 dMagnification=40 tImageType= . jpg iFinalImageQuality=60 lAnalysisImageCount=130 lCalibrationImageCount=0 iiTotalBytes=9221691 tFolder=Test STP
[DaO] x=164208 y=45264
[Dal] x=162672 y=45264 [Da2] x=161136 y=45264
[Da3] x=159600 y=45264
[Da4] x=158064 y=45264
[Da5] x=156528 y=45264
[Da6] x=154992 y=45264
[Da7] x=164208 y=44080
[Da8] x=162672 y=44080
[Da9] x=161136 y=44080
[DalO] x=159600 y=44080
[Dall] x=158064 y=44080
[Dal2] x=156528 y=44080
[Dal3] x=154992 y=44080
[Dal4] x=164208 y=42896
[Dal5] x=162672 y=42896
[Dal6] x=161136 y=42896
[Dal7] x=159600 y=42896
[Dal8] x=158064 y=42896
[Dal9] x=156528 y=42896 [Da20] x=154992 y=42896 [Da21] x=164208 y=41712 [Da22] x=162672 y=41712 [Da23] x=161136 y=41712 [Da24] x=159600 y=41712 [Da25] x=158064 y=41712 [Da26] x=156528 y=41712 [Da27] x=154992 y=41712 [Da28] x=164208 y=40528 [Da29] x=162672 y=40528 [Da30] x=161136 y=40528 [Da31] x=159600 y=40528 [Da32] x=158064 y=40528 [Da33] x=156528 y=40528 [Da34] x=154992 y=40528 [Da35] x=164208 y=39344
[Da36] x=162672 y=39344
[Da37] x=161136 y=39344
[Da38] x=159600 y=39344
[Da39] x=158064 y=39344
[Da40] x=156528 y=39344
[Da41] x=154992 y=39344
[Da42] x=164208 y=38160
[Da43] x=162672 y=38160
[Da44] x=161136 y=38160
[Da45] x=159600 y=38160
[Da46] x=158064 y=38160
[Da47] x=156528 y=38160
[Da48] x=154992 y=38160
[Da49] x=164208 y=36976
[Da50] x=162672 y=36976
[Da51] x=161136 y=36976
[Da52] x=159600 y=36976
[Da53] x=158064 y=36976
[Da54] x=156528 y=36976
[Da55] x=154992 y=36976
[Da56] x=130160 y=48076
[Da57] x=128624 y=48076
[Da58] x=127088 y=48076
[Da59] x=125552 y=48076
[Da60] x=124016 y=48076
[Da61] x=130160 y=46892
[Da62] x=128624 y=46892
[Da63] x=127088 y=46892
[Da64] x=125552 y=46892
[Da65] x=124016 y=46892 [Da66] x=130160 y=45708
[Da67] x=128624 y=45708
[Da68] x=127088 y=45708
[Da69] x=125552 y=45708
[Da70] x=124016 y=45708
[Da71] x=130160 y=44524
[Da72] x=128624 y=44524
[Da73] x=127088 y=44524
[Da74] x=125552 y=44524
[Da75] x=124016 y=44524
[Da76] x=130160 y=43340
[Da77] x=128624 y=43340
[Da78] x=127088 y=43340
[Da79] x=125552 y=43340
[Da80] x=124016 y=43340
[Da81] x=130160 y=42156
[Da82] x=128624 y=42156
[Da83] x=127088 y=42156
[Da84] x=125552 y=42156
[Da85] x=124016 y=42156
[Da86] x=130160 y=40972
[Da87] x=128624 y=40972
[Da88] x=127088 y=40972
[Da89] x=125552 y=40972
[Da90] x=124016 y=40972
[Da91] x=130160 y=39788
[Da92] x=128624 y=39788
[Da93] x=127088 y=39788
[Da94] x=125552 y=39788
[Da95] x=124016 y=39788
[Da96] x=130160 o
! _
H U α.
I
VD
_n
I
^ o . — . o
^r ^r _n , — , , — . o o o , — , o , — , o . — , • r- oo r , — , oo ^r , — , o , — , o o o o o o o co oo r- oo o o o r- r— σ-ι vo o o r— o m ^r o ^r n r- en o en o en oo r- en en co r r- r~ r r- •^ oo co o oo o oo co co co oo oo P
II P II II P II II P II II P II II P II II P II II P II II P II II P II II P II II '' II II P II 11 Q II II P II II Q II II
>. X >, X >, L— • X ' — ' X X X ' — ' X X ' — ' X >, •—• X ' — ' X •— ' X >! ' — ' X X 1 — ' X o O o o sr
[Dall2] x=145776 y=23804
[Dall3] x=144240 y=23804
[Dall4] x=148848 y=22620
[Dall5] x=147312 y=22620
[Dall6] x=145776 y=22620
[Dall7] x=144240 y=22620
[Dall8] x=148848 y=21436
[Dall9] x=147312 y=21436
[Dal20] x=145776 y=21436
[Dal21] x=144240 y=21436
[Dal22] x=148848 y=20252
[Dal23] x=147312 y=20252
[Dal24] x=145776 y=20252
[Dal25] x=144240 y=20252
[Dal26] x=148848 y=19068
[Dal27] -5£ x=147312 y=19068
[Dal28] x=145776 y=19068
[Dal29] x=144240 y=19068
It provides a flexible filing structure, whether the images are located in multiple places on a computer running a server program, or are collections held on removable storage media such as CD-ROMs and are ;just being viewed locally. The image data structure includes two modifiable text string byte arrays which are used to hold the file name and the folder name that identifies an individual image. When the server program is initiated, it searches all of its available storage (indicated in a setup file) , finds any images present, reads the folder names and the file names of all of the images and creates URL path extensions for each one.
When the image browser initially starts its Main Window looks like FIG. 24. This is before a Login request has been initiated. The browser first sends a client Login Request using a specific server Internet address, such as shown in the address line of FIG. 20, and as indicated in Table 4. After the Login Request has been acknowledged, the browser then sends a Slide Tray Request. The server response to this is to send the list of image names and header text, their associated file folders, and the URL path extensions depending upon various image data structure storage locations on the server. The browser then constructs and displays m the Slide Tray tab of its main window a file folder tree structure display such as shown in FIG. 25. This is a dynamic display, such that a mouse click on the file folder opens up the file and displays its contained images. The browser responses are set forth m Tale 7 below.
TABLE 7. tResponse = tResponse + IntToStrO^O + & ' tResponse = tResponse + FrmMam Client 3. . tUserName + ' & ' , tResponse = tResponse + FrmMain Client ]] . tN ckName + ' & ' , tResponse = tResponse + FrmMam Client : ] . tEmail + ' & ' ; tResponse = tResponse + FrmMain Client . 3 ] . tTraylndex + ' & ' , tResponse = tResponse + FrmMain Client . 3 ] . tSlide + ' & ' ; tResponse = tResponse + FrmMain Client ■ 3 1 . tSlideZoomLevel + ' & ' ; tResponse = tResponse + FrmMain Client . 3 ] . tSlideXRef + ' & ' ; tResponse = tResponse + FrmMain Client . 3 ] . tSlideYRef + ' & ' ; tResponse = tResponse + FrmMain Client . 3 ] . tFmalZoomLevel + ' & ' ; tResponse = tResponse + FrmMain Client '. 3 ] . tXRe f + ' & ' ; tResponse = tResponse + FrmMain Client :D] . tYRef + ' & ' ; tResponse = tResponse + FrmMain Client :DI .tSlideScanMode + ' & ' ; tResponse = tResponse + FrmMain Client . 3 ] . tPomterX + ' & ' ; tResponse = tResponse + FrmMain Client [ 3 ] . tPointerY + ' & ' ; if FrmMam .bLogoffClients then tResponse = tResponse + ' Server logo Ef issued ... & ' else tResponse := tResponse + FrmMain. Client [ [3] . tStatus + ' & ' ;
Inc (iCount ) ; end; end;
A mouse click on a specific image file name activates a client Image Request to the server, and the server sends back the requested thumbnail image which is displayed m the tab image area, as shown m FIG. 25. If one of the virtual microscope images is of further interest for more detailed observation, it can be retrieved by further mouse clicks, either on the thumbnail image or by a double click on the Slide Tray tree structure file name. In this case, the client browser sends a Select Slide Request. As indicated m Table 1, the server then sends the larger Preview Slide image along with the x, y coordinate list of all image tiles associated with that virtual slide. The tab changes from the Slide Tray to the image tab and the Preview Slide image is displayed in the image display area, as shown in FIG. 26.
One of the advantages of this virtual slide tray organizational design is that the folder names are carried as part of the image data set structure. This is different from a standard file structure where the file name is created and files are moved into the created folder. In a virtual microscope slide environment, collections of slides may come from different sources, e.g., on CD-ROMs or other storage media. This method carries the file folder information with the slide. The server can then automatically organize, on startup, all of the file folders depending upon the media in place at that time. For read/write media, the folder names can be edited to put specific images into different folders. This method also allows for automatic folder generation during the image creation process, which reduces the possibility of mixup for collections of slides that go together.
As described above, the image data set is created initially by scanning the microscope slide at two different magnifications. The initial scan, which is referred to as the Slide View scan, is performed with a 1.25x objective lens and can potentially use as many as 8 x 10, or 80 tiles, to cover the region of tissue or cells deposited on the slide. The second, higher-magnification scan is referred to as the Field View scan, and can occupy variable regions. These regions are mapped to the Slide View regions, and can be shown as overlaid areas. As shown in FIG. 22, there are a number of overlays in the image tab of the main image browser window that can be used as aids in navigating the images. Two of these are shown there. They indicate potential regions that could have been scanned and those that were actually scanned on the specimen. Clicking on one of these regions, using the mouse as a pointer, instructs the browser to bring up the Slide Scan window, as shown in FIG. 27. Depending upon the size of the Slide View window and the location point specified in the Preview Slide image, the browser program can use the x, y image list and associated URL information that was transferred in response to the Select Slide Request to determine which Slide View scan image tiles are necessary. The browser then issues an Image Request for each image tile and paints in the received -tiles to fill in the image display area in the window. There are optional navigation overlays for this window also. The illustrated overlay shows regions where higher-magnification image tiles exist in the image data structure. By clicking in the region of one of these tiles, the browser is instructed to bring up its third window, the Field View window, shown overlain on top of the other two windows in FIG. 28. It uses the same procedure, e.g., the size of the Field View window to determine which high-magnification image tiles to request. The size of the Field View and Slide View windows can be changed to suit the user, for example, to fill the available viewing screen, and the browser program will request and fill in the necessary tiles to fill the viewing area.
A number of other viewing options are available, including changing the digital image magnification, i.e., lowering from 40x to 5x . In this case, more tiles are requested to fill in the available viewing area. The combination of the ability to change the various windows position and size, and the digital magnification (zoom) allows for full inspection of the virtual microscope specimen at high and low magnifications throughout the entire specimen. As additional image tiles are requested, they are cached locally so that additional inspection becomes quicker.
FIG. 29 is a flow chart of typical usage to further illustrate the above. This flow chart is shown as a sequence of related steps since some should occur before others and this is a typical sequence. However, it should be appreciated that the browser is multithreaded as well as event driven. Most of the time, for example, the Update Request process is running on its own thread concurrently with client user event-driven processes, a shown in FIG. 29.
Referring back to FIGS. 18 and 19, Table 4 and the server description, it is clear that multiple clients can be logged-in at one time. All such clients independently view the same or different images. The design of the total combined system or all components is more powerful than that, however, through the use of the Update Request indicated in Table 1. Update Requests are generated by each user logged in the client browser at one-second intervals. Through the use of these Update Requests, the server is essentially functioning as a total system
"state machine" for all of the logged-in users. Since each user is assigned an ID number upon login, the server can pass information regarding all of the other logged-in users, with regard to which slide they are viewing, where on that slide they are looking, the status of any pointer locations, etc. This all happens at one-second intervals for all logged-in clients. The browser then can use this information if desired to view the same images seen by other clients. This essentially means that the network of client viewers operates as a virtual multi-headed microscope, letting each other simultaneously view the same virtual slide. Additional features of the browser, as shown in
FIG. 30, enhance this capability. The server tab in the main browser window, shown in FIG. 30, is used to activate a multi-headed virtual microscope function. A browser logged onto a server initially displays only the current user's information in the server tab. As Update Requests are serviced, if additional clients log onto the same server that information is also displayed in the Server tab, using additional login lines.
FIG. 30 shows two users logged into the same server. Also shown are buttons "Display another's view" and "Sync with another's view." After point and click highlighting of one of the logged-in user lines, the current user can then, for example, click on the button "Display another's view" and the browser will use the last update information on that user to send a Select Slide Request, and whatever Image Tile requests are necessary to display the same image view that the user is looking at. In a similar manner, if the user clicked on "Sync with another's view," then the browser would continue to use the update requests to change fields, zoom levels, etc. In the meantime, the various clients involved could communicate through the chat screen about the specimen under consideration.
As shown in FIG. 28, a pointer may be drawn at any x, y location on an image screen view. A right click mouse event on an image where the pointer is desired activates program code which creates a pop-up menu, as shown in FIG. 31. When the "Set the Pointer" menu option is chosen, the position of the pointer is computed in x, y stage coordinate units and those position values are put in the main window Pointer tab and kept in memory to pass along to the server on the next update. Also, a pointer is placed on the image, as shown in FIG. 32. when another client, logged on at the same time, activates "Display another's view" (as shown in FIG. 30) for the client displaying the pointer, then that second client's browser would use the Update Request transferred x, y pointer position from the first client to put a pointer on the second client's image, after any Image Requests to the server were satisfied. In this way, two clients can pass arrows back and forth.
This is additionally facilitated by the right click mouse menu that each can use when she has the same image in front of her. Usually, this occurs when both parties are on the telephone, using the Internet and talking to each other while they move pointers back and forth, or synchronize on each other's views as desired. They can also communicate through the Chat process using the Server tab, as shown in FIG. 28, or through e- mail through the Server tab. It should be appreciated that more than two clients may be logged on and participate in this process. This provides a multi- headed virtual microscope environment with pointers for multiple client users simultaneously.
One of the most important technological improvements in the "tiling" methodology is the improved resolution of image capture and display compared to previous methods of capturing images and transferring them over the Internet. The reason for this relates to microscopy optical resolution compared to digital camera sensor resolution, and the limited "field of view" imposed by the aperture sizes of the microscopy system. In order to match the optical resolution to the digital sensor resolution at high magnification with readily- available sensors, only a small part of the specimen can be captured at one time. Attempting to capture a larger view, e.g., with a lower magnification (and as a result lower optical resolution) objective microscope lens onto digital camera sensor, and then digitally magnifying the resulting captured image, results in "pixelated, " "false' magnification. Tiled images can be captured at a matching pixel and optical resolution, and displayed seamlessly by the present invention, to achieve true virtual images. The same method automatically overcomes the limited "field of view" issue to preserve high resolution over large areas in the original high- magnification image plane of the microscope specimen. The method of retrieving and displaying these tiles as a coherent connected image is depicted in the flow diagram of FIG. 33. This flow diagram is relevant for choosing by a point and click, an image point in the Preview Slide image of the main browser window to open and display the Slide View window (or to choose another region to display in an already open Slide View window) , or to open and display at a higher magnification the Field View window from a point in the Slide View window, or to display image areas not already pre-loaded in the Java applet portal window in an HTML browser page. An important factor in accomplishing seamless tiled image display according to the methods of this invention is to maintain an image x, y pixel reference to the original mechanical stage x, y coordinate reference. In the preferred embodiment, the x, y stage resolution is .1 micrometers per step. Each image tile is a known number of pixels, in this instance 752 x 480 pixels. Through calibration setup procedures during instrument construction, the number of stage coordinate steps per pixel is determined. This varies slightly from system to system and is different for each microscope objective. It is therefore recorded as part of each image data set. Table 8 shows some typical examples of one system.
Table 8. Example Stage x, y Coordinates per Image Tile Pixel
Figure imgf000068_0001
Using the values from Table 8, if a Slide View image data set consisted of a full component of 8 x 10 image tiles, then there would be 7,520 pixels along the x direction and 3,840 pixels in the y direction. This would result in an x, y coordinate system for this slide of 518,880 x coordinate values and 264,960 y coordinate values. This, in effect, creates a virtual coordinate reference system for each tiled image data set. As each tile is collected, the initial upper left starting pixel location in stage coordinate values is stored in a separate subfile list as part of the image data structure file, along with, of course, that .jpg tile image. They are associated with each other by the name of the image tile being used as the name in the list associated with the x, y coordinates. In this way, each data structure has contained in it a list of x, y coordinate positions. The x, y coordinate position list is transferred to a specific client in response to the client issuing a Select Slide Request.
Referring again to FIG. 33, the initial step is to translate the starting display image size in pixels into the virtual stage coordinates. For example, if the image is the 452 x 240 Preview Slide image then each x pixel increments by 1,148 x virtual stage coordinates and each y pixel increments by 1,104 virtual stage coordinates. A given mouse click resulting in an x, y pixel location can then be easily translated into a known virtual image x, y location. Next, the new display image window, in this case the Slide View image, -is opened, and some of the possible 8 x 10 1.25x image tiles may be displayed. This window will either have a present initial size or will have been set by a previous call. In either case the size of the window in pixels can be determined from the associated windows properties parameter's, accessible to the program. The size and placement of this window can then be calculated in the virtual coordinate space. The program assumes that the pixel point chosen in the previous window is associated with the center of the new window to do this.
Next, the image stage coordinate list is searched. The image stage coordinate list was previously transferred to find all candidate tiles which should be displayed according to size of the window.
As shown in FIG. 33, the tiles can be two types; they may already have been viewed and are there, and are therefore cached and available locally, or they exist on the server. If they are on the server, a Send Image Request is initiated and the server sends back the requested tile. Otherwise, they are read from the cache. It should be appreciated again in the case of the program's execution, shown in the flow chart of FIG. 33, that the program is event driven and multi-threaded. The final operation is to fill in the display window with the chosen tile. This same, or an analogous method of filling in tiles for display images is used in scrolling, zooming in and out, and in retrieving tiles for the Field View window (coming from the Slide View window) , and in retrieving image tiles from the server for the fixed size Java applet viewer.
Even though in many instances these five images would be sufficient, the additional approach of this invention is to make available to the applet, the entire virtual slide. This is accomplished using the techniques already described for the browser. In this instance, the upper panel Preview Slide Image can be used by a mouse point and click, to locate an x, y position. This is translated into x, y virtual stage coordinates, and the needed tiles are requested through an Image Request to the server. If the magnification choices are used the operation of this application is handled by the same methods of zoom and calling for images as in the browser, all relating to the size of the window and which image tiles are needed from what virtual x, y location to fill in the window. In a similar way, the lower portion of the portal window is also enabled for scrolling. So the virtual slide advantage of scrolling and zooming in and out are available but in a limited size window. They are accessible, however, from an HTML document that has embedded content.
An additional feature of this approach, as shown by comparing FIGS. 21A, 21B and 22, is that the controlling HTML web-page code may be calling the content for the page from a computer other than the image computer. The advantage of this is that it decouples the text content from the image collections. In a teaching environment this enables many different users to create their own course content, using standard HTML methods, and simply provides a call to the server at appropriate places in the HTML code.
As indicated in FIGS. 18 and 19, and as discussed previously, the server also interacts with a second type of viewer, an HTML embedded applet, in this case written in the Java programming language, as set forth in Table 9 below.
TABLE 9.
<APPLET CODEBASE="http://209.100.40.94/" CODE="WebSlide" ALIGN="m iddle" HEIGHT="590" NAME="Histology06a" WIDTH="464" ALT=" ebSlide"> <PARAM NAME="lslidexrefpos" VALUE="82458 "> <PARAM NAME=" ebslideurl"
VALUE="http://209.100.40.94/ ebSlides/ Histology06a/">
<PARAM NAME="izoomlevel" VALUE="2"> <PARAM NAME="lyrefpos" VALUE="23768 "> <PARAM NAME="lxssstepsize" VALUE="48062 ">
<PARAM NAME="lxrefpos" VALUE=" 92237 "> <PARAM NAME="instance" VALUE="Histology06a "> <PARAM NAME="lyssstepsize" VALUE="35892 "> <PARAM NAME="lslideyrefpos" VALUE="17177 "> This browser does not support Java vl .1 applets1
</APPLET>
The interaction of this viewer with the server is also shown in FIG. 22. This viewer is simpler, and used for different purposes than the browser, but uses many of the same techniques of transferring image tiles.
FIG. 34 illustrates the layout and features of the HTM] portal window created by this applet. This viewer consists of two views; a low-magnification view (which is the Preview Slide image discussed above) shown as an upper portion in FIG. 34, and a higher-magnification view shown in the lower portion. The two views are separated by a menu bar with four magnification choices. As described below, there is an HTML applet creation process which is another browser tab portion. This enables the creation of both the HTML code to generate a Java applet request and additional pre-configured images for the applet to use when it runs.
In an application of interest for this type of viewer, specific regions are identified in the image which are of primary interest, and the need is to see this region as quickly as possible and to change between magnifications rapidly. In order to enable this the applet creation process enables the location of a specific view on a given image, i.e., it specifies a center x, y position for the region and specifies a final view window size, of the same size as the lower portion of the portal window, and assembles from the tiled data structure four zoom level views corresponding to the menu bar magnification options. The zoom levels start with the highest Field View magnification level, usually 40x or 20x, and the viewer creates a lower-magnification image of each tile by using every other pixel at each lower zoom magnification. Additional tiles are brought in and assembled from the image data structure as needed to fill in the fixed field size of the lower HTML portal window. These four assembled images are referred to as Preview images, are given specific names in the creation process and are stored in a file accessible to the server program, on the same computer that the related image is located.
The first thing the Java applet does then after it is loaded is to send a Login and Virtual Slide Request as indicated in Table 1. If the slide name and server identity is correct, the server response is to send the Preview Slide image for the upper panel, the four Preview images that will be used for the lower panel, and the x, y list of all image tiles m the associated data structure. The HTML applet generation process specified which of the magnification choices would be loaded first. The other are available to the applet through the radio button event generated from the menu bar.
The advantage of this approach, of using the pre-stored Preview Slide and Preview images, is that they are small and can be transmitted relatively rapidly, essentially only five tiles, and are m essence pre-cached, m terms of the relationship to the browser description. One problem with applets is that they are interpreted rather than compiled; hence, they are slower than native machine code such as that used m the browser. Thus, this approach helps to overcome that. In addition, for many purposes, e.g., m an educational setting, these views are all that are needed to achieve the initial purpose. For the presentation of a microscope specimen, especially in anatomic pathology or histology, an overall view of the specimen, such as that shown m the upper portion, and localization of a specific region, with the ability to zoom in and out is sufficient.
The virtual slide link is set forth m Table 10 below.
TABLE 10.
[WebSlide Link] tWebSlιdeURL=http://209.100.40.94/ ιMamTop=0 iMamLeft=0 tScanFιlename=Prost- z2 ιMamOverlays = l bGratιcles=l bScanArea=l bMult Mag=l bTιleLoctιon=0 bSlιdeVιew=l bFιeldVιew=l ιSlιdeVιewTop=0 ιSlιdeVιewLeft=600 ιSlιdeVιewHeιght=478 ιSl deVιewWιdth=1000 iSlideViewWindowState=l bDisplayTileLocationOverlay=l iSlideViewZoomLevel=l lSlideXRefPos=44397 lSlideYRefPos=55668 iFieldViewTop=478 iFieldViewLeft=0 iFieldViewHeight=402 i FieldViewWidth=472 iFieldView indowState=l iFieldViewZoomLevel=l lFieldViewXRefPos=58436 l FieldViewYRe fPos=55520 tSlideScanMode=0
In order to perform the multiheaded microscope function of emulation, a plurality of clients are logged on, which might include a client A and a client B . After having logged on, client B elects to consult with logged on client A and highlights client A' s name in logged on l ist in a step 800 , as shown in FIG . 35A . The client B then selects a synchroni zation and user function by cl icking on the sync on user button and a thin cl ient browser enters a synchroni zation state keyed on signal s from client A in a step 802 .
During the one-second interval update command for the browser, client B monitors cl ient A' s update state variables , as set forth in the l isting in Table 6 , and uses the variables necessary to display the same location and magni f ication of the slide data set that cl ient A is currently viewing . A plurality of the state variables include state variable values that indicate whether those variables are disabled, for instance 999999999 . Otherwise , the variable state is considered to contain active data and, during the one-second interval update, decisions are made by the state variables by client B, as set forth in step 804 . Control is then transferred to a step 806 to determine whether the chat messenger index on the server is greater than the current state variable index . I f it is , control is transferred to a step 808 to request each missing chat message from the server and displayed in the chat window at the client until the chat message index on the server is equal to the state variable index following which the routine returns in a step 810 to a test in a step 812 to determine whether the state variables have been placed in sync mode. If they have not, control is transferred back to the step 806, as shown in FIG. 35D.
If the system is in sync mode, a test is made in a step 814, as shown in FIG. 35A, to determine whether the virtual slide image selected from the slide tray data collection is the same as the one that is currently displayed. If it is not, the position in the slide tray is updated in a step 816. If it is, control is transferred either from step 814 or 816 to a step 818 where a test -is made to determine whether the low-magnification x, y position location state variables are in the disabled state. If they are, control is transferred back to step 814. If they are not, the slide view window is displayed and updated for the low-magnification view to t-he lower-magnification position previously selected by client A using client A's current magnification state variable in step 820 in order to synchronize the views.
A test is then made in a step 822 similar to the step 818 to determine whether the high-magnification x, y location state variables are in the disabled state in a step 822. If they are disabled, control is transferred back to step 814. If they are not, control is transferred to a step 824 which displays the field view window on the client and/or updates the high-magnification view to synchronize with client A's x, y high-magnification selected position also using client A's current magnification state variables. The slide scan mode state variable indicates whether what is being displayed is the low-magnification or high-magnification data and each of the data's associated coordinate systems in field of view. Control is then transferred to a step 830, as shown in FIG. 35C, where a test is made to determine the mouse pointer or display pointer x, y position state variables in the disabled state or not. If they are not disabled, the pointer is displayed at the location selected by client A and control is transferred to step 814. If the state variables are disabled, control is transferred directly to step 814.
It should be appreciated that the updating function from the client A variables may take place not just with one client, client B, but over multiple clients in order to provide image coherency from the client, in this example client A, which in effect controls the command token for the virtual multiheaded microscope remote emulation.
While there has been illustrated and described a particular embodiment of the present invention, it will be appreciated that numerous changes and modifications will occur to those skilled in the art, and it is intended in the appended claims to cover all those changes and modifications which fall within the true spirit and scope of the present invention.

Claims

What is claimed is:
1. A method for viewing virtual microscope slides comprised of sets of digitized tiled images over a common communication channel, the method comprising: providing a transmitting station connected to the common communication channel and accessible by a number of remote receiving stations connected to the common communication channel; storing a plurality of sets of virtual microscope, digitized slide images at the transmitting station; transmitting control information to the requesting computer for use in aligning the transmitted sets of digitized tiled images to form a composite, coherent, seamless digitized, virtual microscope, slide image from a set of digitized tiled images; displaying on a viewer at a remote receiving station a thumbnail view of a specimen or portion thereof on the virtual microscope slide; displaying on the viewer at the remote receiving station an aligned set of digitized tiled images at a higher resolution than the resolution of the thumbnail view; and zooming by the viewer back and forth between the thumbnail view and the higher resolution set of digitized tiled images.
2. A method in accordance with claim 1 further comprising: providing a plurality of digitized tiled images each at a different resolution and each a higher resolution than the thumbnail view; and zooming back and forth between the plurality of higher resolution images as well as with the thumbnail image.
3. A method in accordance with claim 2 further comprising operating a magnification selector at the receiving station to change between the plurality of higher resolution images .
4. A method in accordance with claim 3 further comprising: transmitting from the transmitting station an entire set of digitized slide images of several resolutions from the transmitting station to the receiving station; and operating the magnification selector at the remote station to select from the stored digitized slide images at the receiving station those images of the selected magnification.
5. A method in accordance with claim 1 wherein transmitting a control program comprises downloading a control program as an applet.
6. A method in accordance with claim 5 further comprising transmitting a dynamic, self-executing program for viewing, manipulating, and reconstructing image tiles.
7. A method of viewing virtual microscope slides in accordance with claim 1 further comprising displaying to the viewer descriptive text about the composite digitized tiled slide image being viewed by the viewer at the remote station.
8. A method in accordance with claim 1 further comprising using an HTML browser and a personal computer at the remote viewing station for receiving the control program and set of digitized, slide images.
9. A method in accordance with claim 1 further comprising changing tiled sets of digital images from a smaller size to a larger size.
10. A method in accordance with claim 7 further comprising: providing viewing windows of different sizes each for viewing a set of digitized, tiled images; and filling each of the windows of different sizes with a different number of reconstructed, digitized tiled images.
11. A method in accordance with claim 1 further comprising: changing the size and position of viewing windows for viewing of sets of digitized tiled images; and changing the image magnification to allow zooming between high and low magnifications of the sets of digitized tiled images.
12. A method in accordance with claim 1 further comprising: selecting a region of a displayed image to be viewed at a higher resolution; determining the size of the window and selecting the image tiles which are needed for filling the window at the requested resolution; and displaying the selected higher-resolution digitized image tiles and filling the window therewith.
13. A method in accordance with claim 1 further comprising scrolling along the displayed image to remove some image tiles from the window and to add other image tiles to the window for viewing.
14. A method m accordance with claim 1 further comprising transmitting a set of low-magnification, digitized tiled images for reconstruction into the thumbnail view.
15. A method for viewing virtual microscope slide specimen image views at different magnifications using sets of digitized, image tiles comprised of a predetermined number of pixels per tile, comprising: scanning and digitizing a field of view taken through a microscope; providing a microscope stage travel having a resolution greater than a resolution of the pixels; translating the digitized pixel resolution into a stage X, Y coordinate system of a known resolution; storing a point of reference for each tile as part of a data structure for the slide image view; assembling a plurality of tiles using the X, Y stage coordinates into a seamless image as a first view at a first magnification on a display device; selecting a region on the first, tiled image view for viewing at a second higher magnification; using the selected region as a reference point for image tiles to be used to form a higher magnification second view of the selected region; opening a display window for the higher magnification second view of a known size and translating the window size into the X, Y stage coordinate system; using the X, Y stage coordinate system and the reference point to select the tiles to be used for the view; and using the X, Y stage coordinate system for assembling and displaying on the display device the selected tiles to form a seamless image for the second view of the selected region and at the higher magnification.
16. A method in accordance with claim 15 further comprising : providing a common communication channel; transmitting digitized image tiles from a first station to a remote requesting station at which the views are displayed; and storing as part of a transmitted data structure at the remote station tiles for use in assembling into the selected view of the selected region and at a higher magnification.
17. A method in accordance with claim 16 further comprising: searching tiles cached at the data structure to determine whether the desired tiles have already been transmitted and stored; and requesting the desired cached tiles from the transmitting station that are needed and that were not previously transmitted and stored at the receiving station.
18. A method in accordance with claim 16 further comprising transmitting all of the tiles needed for the first and second views at their respective first and second magnifications as part of the data structure transmitted to the receiving station.
19. A method in accordance with claim 16 further comprising: opening a view window of a known size for the second view; and using an X, Y coordinate list of tiles when selecting the image tiles needed to fill the window in order to display the selected region at a higher magnification for the second view.
20. A method in accordance with claim 19 further comprising using the reference point as an appropriate center of the window and selecting tiles from the X, Y coordinate list of tiles located about the reference point to fill the window.
21. A method in accordance with claim 15, wherein the resolution of stage travel relative to pixel resolution comprises : more than one stage step per pixel for a higher magnification pixel; and more than one hundred stage steps per pixel for a lower magnification pixel.
22. A method in accordance with claim 21, wherein there are 500 or more stage steps per pixel at the lower magnification.
23. A method in accordance with claim 15 further comprising scrolling the higher magnification view and using the stage X, Y coordinate system to remove image tiles and to select new image tiles for addition to the currently-displayed image tiles.
24. A method in accordance with claim 15 further comprising : providing a third view comprised of image tiles taken at a third magnification using a third resolution of stage steps per pixel; and zooming in and out between the first, second and third views.
25. A method in accordance with claim 15 further comprising : storing in stage X, Y coordinate system the location of a corner of a tile; and measuring the stage movements in counters from the respective tile corners in the X and Y directions to form tiles of a uniform size for a view at a given magnification.
26. A method in accordance with claim 25 further comprising using a closed loop microscope image stage on the microscope to provide stage steps of .1 micrometer or less.
27. A method in accordance with claim 15 further comprising using a reduced percentage of the pixels from the original microscope scan and digitized field of view tile.
28. , method in accordance with claim 27 comprising providing a thumbnail view of the specimen using digitally de- magnified tiles of the scanned and digitized field of view- tile.
29. A method of providing tiled, digitized image tiles of specimens over a common communication channel to viewers at remote locations, comprising: storing at a central location data for sets of digitized image tiles of a plurality of specimens; requesting over the common communication channel access to the data for the stored, digitized image tiles of at least one specimen of the stored image tiles; sending back over the common communication channel information to the remote location to aid in the selection of a digitized image tile for viewing by the remote user; using the sent information for selecting at the remote location and requesting a transmission of specific digitized image tiles from those stored at the central location; sending from the central station the stored data for the selected digitized image tiles over the common communication channel to the remote location; and making available at the remote location the digitized image tiles requested for viewing the specimen or a portion thereof.
30. A method in accordance with claim 29, wherein sending the information back over the common communication channel to remote locations further comprises: presenting to the viewer thumbnail views of specimens as information for use in selecting; and requesting transmission of a specific digitized image for the selected specimen.
31. A method in accordance with claim 29 wherein the sending of the stored data further comprises: transmitting a data structure having a self- executing program and digitized image tiles to the receiving station; and wherein making available the digitized images further comprises selecting stored digitized image tiles from
32. A method in accordance with claim 29 wherein making available the digitized image tiles for viewing the specimen further comprises transmitting over the common communication channel sets of digitized image tiles for different resolutions and for different regions of the specimen.
33. A method in accordance with claim 29, wherein sending back information over the common communication channel to the remote location further comprises presenting to the viewer a thumbnail digitized image of a specimen and an enlarged preview, digitized image of the specimen and an x, y list image tiles.
34. A method in accordance with claim 29 further comprising: using a personal computer to communicate over the common transmission channel; and using a Windows operating system for displaying on a screen of the personal computer the transmitted, digitized image tiles.
35. A method in accordance with claim 29, wherein the storing of digitized image tiles and the sending of information to the remote location comprises: providing a server at the central location; and providing at the server data structures having tiled sets of digitized images with x, y information to aid the viewer program to reconstruct, to spatially align, physically contiguous images at multiple resolutions.
36. A method in accordance with claim 29, wherein an HTML browser is installed at the remote user's personal
37. A method in accordance with claim 29 further comprising providing descriptive text with the digitized tiled image to instruct about the specimen being viewed.
38. A method in accordance with claim 35 further comprising: storing a plurality of digitized image tiles of different resolutions on the server; and selecting at the remote location different resolution image tiles to be transmitted from the server to the remote location.
39. A method in accordance with claim 29 further comprising: providing at the remote location a plurality of folders having a virtual microscope slide comprised of digitized image tiles therein in an organized system; and selecting at the remote location one of the folders from the organized set of folders for transmission of its associated virtual microscope slide.
40. A method in accordance with claim 39 further comprising : providing three screens on a viewing device for viewing of virtual microscope slides; presenting a thumbnail view of the specimen on one screen; presenting a larger preview view comprised of digitized, image tiles of the specimen on a second screen for selection of a higher resolution, segment of the preview image; and presenting the selected higher magnification region comprised of digitized image tiles on a third screen to the viewer .
41. A method in accordance with claim 40 further comprising changing the size of the window and changing the magnification to allow a full inspection of the specimen at higher and lower magnifications.
42. A method in accordance with claim 29 further comprising : providing a digitized, tiled image of a portion of a specimen at a first predetermined resolution; and overlaying a digitized, tiled image of the specimen at a lower resolution than the predetermined resolution.
43. A method in accordance with claim 29, wherein the making available at the remote location of the digitized tiled image comprises: changing the size of a viewing window; and filling the necessary digitized image tiles to fill the viewing windows of different sizes.
44. A method in accordance with claim 43 further comprising : requesting a lowered resolution of the digitized image tiles at a first higher resolution presented on the window; and using more digitized image tiles to fill the window at a second lower resolution than used to fill the window at the higher resolution.
45. A method in accordance with claim 29, wherein at the remote location the user is provided with the options of: selecting a folder associated with a given digitized image tiles from an organized set of folders; selecting to interact with other multiple users on the same digitized tiled image; or selecting an HTML applet of a specific digitized tiled image of a specific region of a specimen.
46. A method in accordance with claim 29 further comprising: selecting spaced points on the digitized, tiled image; and measuring the distance between the selected spaced points and reporting the distance to a viewer.
47. A method in accordance with claim 29 further comprising selecting from a plurality of collected data files stored at the first station the requested virtual microscope slides for transmitting over the common communication channel to the viewer.
48. A method in accordance with claim 29 further comprising: providing a server at the first station; and selecting by the server from RAM and CD media the stored digitized, image tiles for transmission.
49. A method in accordance with claim 29 further comprising loading a browser program onto computers at the multiple receivers at the receiving stations for assistance in assembling the digitized tiled images.
50. A method in accordance with claim 29 further comprising : providing a plurality of first stations each capable of transmitting virtual microscope slides over the common communication channel; and addressing one of the plurality of stations and requesting a desired virtual microscope slide therefrom.
51. A method of providing a virtual, multiheaded microscope allowing a plurality of viewers at remotely located different stations to simultaneously view the same virtual microscope slide comprised of tiled digital images comprising: providing a common communication channel; transmitting over the common communication channel a virtual microscope slide to a first receiving station for viewing by a first viewer; transmitting over the common communication channel the same virtual microscope slide to a second viewing station for viewing by a second viewer; and indicating by the first of the users an area on the virtual microscope slide at the first receiving station for discussion and transmitting from the first station information for locating the same area on the virtual microscope slide being viewed at the second station for discussion of the same indicated area between the first and second viewers; and communicating over a carrier between the first and second viewers about the indicated area on the virtual microscope slides being displayed simultaneously to both of the first and second viewers.
52. A method in accordance with claim 51 further comprising: placing one of the first and second viewers in control and allowing this viewer to change the sets of tiled images to be viewed simultaneously by each of the viewers at their* respective receiving stations; allowing one of the viewers to change the magnification between tiled images of high and lower resolutions; and transmitting from a central station the newly changed resolution tiled images to the respective first and second receiving stations.
53. A method in accordance with claim 51 further comprising passing control of an indicator from the first viewer to the second viewer to allow the second viewer to shift the indicator to a region that the second viewer wants to discuss with the first viewer.
54. A method in accordance with claim 53 further comprising indicating with a pointer controlled by a computer controller device.
55. A method in accordance with claim 54 further comprising using a mouse as the computer control device for shifting the pointer on the virtual microscope slide.
56. A method in accordance with claim 51 wherein, the communicating between the first and second viewer is by speaking over a telephone.
57. A method in accordance with claim 51 wherein, the communicating between the first and second viewer is by written messages over an Internet common communication
58. A method of providing a virtual, multiheaded microscope allowing a plurality of viewers at remotely located different stations to simultaneously view the same virtual microscope slide view comprised of digital image tiles, comprising: providing a common communication channel; storing at a common repository sets of digitized image tiles at a central station connected to the common communication channel for transmission of digitized image tiles to multiple users connected to the common communication channel ; transmitting over the common communication channel digitized image tiles to a first receiving station to provide a view for viewing by a first viewer; transmitting over the common communication channel the same digitized image tiles to a second viewing station to provide a view for viewing by a second viewer; the first viewer causing a change in the side image being viewed by sending a request for a subset of new digitized image tiles to be transmitted from the central station and the central station responding by sending the subset of digitized image tiles to both the first and second stations; and communicating over a common communication channel between the first and second viewers about the virtual microscope slide views being displayed simultaneously to both of the first and second viewers.
59. A method in accordance with claim 58 further comprising: the first user initiating requests for changes in views and resolutions and of the specimen slide images; and the central station receiving the requested changes and transmitting a packet of image tiles to both the first user and second user for the change resolution and changed views .
60. A method in accordance with claim 58 further comprising : moving a pointer on the virtual microscope slide image to a new location; transmitting the pointer's new location from the first station to a central station; transmitting from the central station to the second station the new location of the pointer; and moving the pointer at the second station to the same new location on the slide image.
61. A method in accordance with claim 58 further comprising: providing a central station with a central repository having a stored, plurality of digitized tiles for substantially the entire image of the specimen; and selecting from the stored digitized image tiles a subset of the digitized image tiles and transmitting the subset of digitized image tiles to both the first and second users for viewing of the same image simultaneously at their respective stations.
62. A method in accordance with claim 61 further comprising providing a digitized image tile comprising an image analysis digitized image that corresponds substantially to a single field of view taken through an objective view of a microscope .
63. A method in accordance with claim 61 further comprising using a reduced percentage of the corresponding microscope single field of view for transmission as a digitized image tile for transmission from the central station.
64. A method of using a filing structure for organizing virtual microscope slide images to be requested by and transmitted to a requester from a server at a server station over a common carrier, comprising: transmitting a request from a requester at requesting station to the server station; transmitting a slide tray request to the server station; transmitting slide tray information from the server station to the requesting station; displaying to the requester slide tray information comprising a list of virtual microscope slide names on a display device at the requesting station; selecting from the slide tray information a microscope slide name to cause an image request for the selected slide to be sent to the server station; and transmitting from the server station a set of tiled digitized images comprising the slide specimen or a portion thereof for viewing on the display device at the requesting station .
65. A method of providing virtual microscope slides each having at least a portion of a specimen associated therewith and identified by name from a central station to remote stations comprising: storing data at a central location for use in for use in providing and assembling digitized image tiles for viewing a virtual microscope slide at multiple resolutions; connecting one or more remote stations over a common communication channel to the central station; transmitting a request from the remote station for information about the virtual microscope slides available for transmission to the requesting remote station; transmitting from the central station a list of names of virtual microscope slides in response to the request form the remote station; selecting a virtual microscope slide from the list of names by a viewer at the remote station; displaying a thumbnail image of the specimen on the virtual microscope slide to the viewer at the remote station; selecting a region from the thumbnail image to be displayed at higher resolution; and assembling the digitized image tiles at the higher resolution and making them available for viewing at the higher resolution the selected region of the specimen.
66. A method in accordance with claim 65, wherein the selecting of a region from thumbnail image comprises displaying at the remote station a preview image larger in size than the thumbnail image and selecting from the preview image the region to be viewed at the higher resolution.
67. A method in accordance with claim 66 further comprising indicating on the preview image those regions where digitized image tiles are available for assembling into the higher resolution view.
68. A method in accordance with claim 67 further as a dynamic display such that the selection thereof activates a request to the central station to transmit the thumbnail image tiles to the remote station.
69. A method in accordance with claim 65, wherein selecting of a region on the thumbnail image causes a request to the central station and a responsive transmission of a larger preview slide image and a list of tiles for the higher magnification image in an X, Y coordinate system.
70. A method in accordance with claim 66 further comprising overlaying on the display device the thumbnail image, the preview image, and the higher magnification view.
71. A method in accordance with claim 65 further comprising : changing the size and position of a viewing window for the selected region; and zooming between several resolutions of the specimen when analyzing the specimen on the selected virtual microscope slide .
72. A method in accordance with claim 66 further comprising: transmitting from the central station multiple image tiles at a higher resolution than the thumbnail image for viewing as a slide view image at the remote station; and selecting from the slide view image and requesting from the central station multiple image tiles at a resolution higher than the side view image to provide a field view of specimen.
73. A method m accordance with claim 65 further comprising overlaying on the virtual specimen an overlay showing the regions of the specimen actually scanned and available for viewing and showing the regions of the specimen that have not been scanned and are not available for viewing.
74. A method in accordance with claim 65 wherein the selecting of a virtual microscope slide from the list of names comprises sending a request to the central station which results in transmission of a dynamic self-executing control program having stored multiple resolution tiles for the selected slide to the receiving station.
75. A method in accordance with claim 74 further comprising sending and assembling the stored multiple resolution tiles from the dynamic, self-executing program at a viewer to provide the higher resolution view of the region.
76. A method in accordance with claim 74 further comprising adding descriptive text for the microscope slide by a user at a remote station for use by another viewer.
77. A method in accordance with claim 76 further comprising storing the descriptive text on a computer separate from the stored image tiles so that different users at different stations may access the slides with respectively associated, descriptive texts and update their separate texts.
78. A method in accordance with claim 75 further comprising using the self-executing program to provide multiple resolution tiles to show substantially the entire specimen at each of the predetermined resolutions.
79. A method in accordance with claim 78 further comprising transmitting from the central station a prestored thumbnail image slide for the specimen and prestored preview images for each of the resolutions that are available.
80. A method in accordance with claim 79 further comprising digitally reducing from the highest resolution the other resolutions for the respective prestored image tiles.
81. A method in accordance with claim 78 further comprising: transmitting a thumbnail view of substantially the entire specimen to the requesting station for display; and selecting from the thumbnail view a region to be viewed at a higher magnification and sending a select slide request to the server station to obtain a high-magnification set of digitized image tiles of the selected region.
82. A method in accordance with claim 81 further comprising transmitting from the server station a high- magnification preview image in response to the select slide request .
83. A method in accordance with claim 82 further comprising : selecting from the higher-magnification preview image an area thereon for viewing at higher magnification; and displaying the selected areas as a field view.
84. A method in accordance with claim 83 further comprising the viewer changing the resolution of the field view images to zoom back and forth there between durinσ a diagnosis by a pathologist of the specimen on the virtual microscope slide.
85. A method in accordance with claim 81 further comprising : providing a dynamic display of virtual microscope names and the thumbnail view; and using a control device to select the name and region from these dynamic displays.
86. A method in accordance with claim 64 wherein the displaying to the requester of slide tray information comprises displaying a file folder tree display in a window of the requester's display device.
87. A method of operating a display drive to display sets of tiled digitized images of portions or of a specimen to a viewer comprising: storing at a central location sets of tiled digitized images at different resolutions; displaying to the viewer a thumbnail view of the specimen at a first resolution; selecting by the viewer from the thumbnail view an area to be viewed at a second resolution higher than the first resolution of the thumbnail view; displaying to the viewer a set of tiled digitized images of the selected area at the second resolution; selecting by the viewer from the set of digitized, tiled images at the second resolution an area for viewing at a third resolution higher than the second resolution; and displaying simultaneously to the viewer another set of digitized, tiled images at the third higher resolution and
88. A method m accordance with claim 87 further comprising forming and displaying the thumbnail view form a plurality of digitized, tiled images at the first resolution.
89. A method m accordance with claim 87 further comprising providing a grid on at least one of the sets of digitized, tiled images showing the tile boundaries for selecting a tile as an area for viewing at a higher resolution.
90. A method m accordance with claim 87 further comprising: providing a grid on the thumbnail view to aid in selecting the area to be viewed at the second resolution; and providing a grid on the second resolution digitized tiled image to aid m selecting the area to be viewed at the third resolution.
91. A method m accordance with claim 87 wherein each of the three views shown simultaneously with there being an overlapping of the views being shown simultaneously.
92. A method m accordance with claim 87 further comprising: changing the size and locations of the displayed views on the display device; and changing the magnification to allow zooming between different magnifications for viewing a suspicious area of a specimen.
93. A method m accordance with claim 87 further comprismσ: providing a first window on the display device for viewing the thumbnail view; providing a second window on the display device for viewing a set of digitized tiled images which are filling the second window; and providing a third window on the display device for viewing at the third resolution a set of digitized tiled images, which are filling the third window.
94. A method of providing tiled, digitized image tiles of specimens over a common communication channel to viewers at remote locations, comprising: storing at a central location data for sets of digitized image tiles of a plurality of specimens; requesting over the common communication channel access to the data for the stored, digitized image tiles of at least one specimen of the stored image tiles; sending back over the common communication channel information to the remote location to aid in the selection of a digitized image tile for viewing by the remote user; using the sent information for selecting at the remote location and requesting a transmission of specific digitized image tiles from those stored at the central location; sending from the central station the stored data for the selected, digitized image tiles over the common communication channel to the remote location; providing an applet for transmitting from the central station to a browser at a remote location for viewing, manipulating and reconstructing the digitized image tiles into a composite view; using a previously-installed control program at the remote station for viewing, manipulating and reconstructing the digitized image tiles into a composite view; and making available at the remote location the digitized, image tiles requested for viewing the specimen or a portion thereof while using one of the applet or previously- installed control program.
95. A method of providing a text file created by a first user for a second user of a virtual microscope slide comprised of a set of digitized image tiles comprising: providing a common communication channel having a provider station that provides virtual microscope slides; transmitting a virtual microscope slide to the first user at a first station connected to the common communication channel ; creating text at the first station for instructing the second user with respect to evaluating the virtual microscope slide transmitted to the first station from the provider station; and transmitting the text over the common communication channel from the first station to the second user at the second station to provide instructions to the second user to aid in the second user's review of the virtual microscope slide .
96. A method in accordance with claim 95 further comprising: identifying the virtual microscope slide to the second user in the transmitted text; and the user requesting and receiving the identified virtual microscope slide over the common communication channel
97. A method in accordance with claim 95 further comprising: instructing in the text the second user as to a region of the virtual microscope slide to view; and instructing the second user as to what to observe in the selected region.
98. A method in accordance with claim 95 further comprising providing instructions in the text as to resolutions to be used in viewing a region on the virtual microscope slide.
99. A method m accordance with claim 95 further comprising providing a virtual microscope slide to the first and second users wherein each of the digitized image tiles corresponds substantially to a view shown through an objective lens of a microscope.
100. A method in accordance with claim 95 further comprising using a reduced percentage of a corresponding original microscope image for transmission as a digitized image tile.
101. A method for viewing a virtual microscope slide specimen views comprised of sets of digitized image tiles transmitted over a common communication channel comprising: providing a transmitting station connected to the common communication channel and accessible by a number of remote receiving stations connected to the common communication channel; storing virtual microscope digitized image tiles at the transmittinσ station; transmitting a control program to the requesting computer for use in obtaining and aligning the transmitted sets of digitized image tiles to form a composite, coherent, seamless digitized, virtual microscope, slide view from a set of digitized tiled images; selecting by the user of a region at a desired resolution of the slide specimen for viewing; requesting by the control program of the specific tiles needed for a tiled, image view of the specimen region at the desired resolution; transmitting from the remote station the requested tiles for the region to the receiving station; and assembling and displaying the transmitted tiles for the region using the control program to form the view of the region of the specimen at the desired resolution without having transmitted all of the sets of tiles for the specimen to the receiving station.
102. A method in accordance with claim 101 further comprising transmitting a group of requested tiles to the receiving station.
103. A method in accordance with claim 101 further comprising: caching the transmitted tiles under the control of the control program; and first searching the user's cached tiles for tiles to be used to satisfy the user's request and, secondly, requesting from the transmitting station those tiles not found in the cache, to satisfy the request.
1 04 A mpthnH i n a rrnrrlsnrp w th r l a i m i m fn rrh pr storing at the transmitting station a large quantity of tiles for a substantive portion of one specimen at several resolutions; and transmitting only the tiles requested which may be a small portion of the total stored quantity of tiles for the one specimen.
105. A method in accordance with claim 104 further comprising : identifying the tiles using an X, Y stage coordinate system; providing a list of the identified tiles; and searching the list for the requested tiles to be used to display the requested region.
106. A method in accordance with claim 101 further comprising: providing tiles that are represented by data acquired by scanning and digitizing a field of view of the specimen through a microscope; and compressing the data to provide the digitized image tile used for transmission.
PCT/US2001/001782 2000-01-21 2001-01-18 Method and apparatus for internet, intranet, and local viewing of virtual microscope slides WO2001054052A1 (en)

Priority Applications (4)

Application Number Priority Date Filing Date Title
CA2398736A CA2398736C (en) 2000-01-21 2001-01-18 Method and apparatus for internet, intranet, and local viewing of virtual microscope slides
EP01942762A EP1252604A4 (en) 2000-01-21 2001-01-18 Method and apparatus for internet, intranet, and local viewing of virtual microscope slides
AU2001229630A AU2001229630A1 (en) 2000-01-21 2001-01-18 Method and apparatus for internet, intranet, and local viewing of virtual microscope slides
HK03101687.3A HK1049723A1 (en) 2000-01-21 2003-03-07 Method and apparatus for internet, intranet, and local viewing of virtual microscope slides

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US17755000P 2000-01-21 2000-01-21
US60/177,550 2000-01-21
US09/592,561 2000-06-12
US09/592,561 US6396941B1 (en) 1996-08-23 2000-06-12 Method and apparatus for internet, intranet, and local viewing of virtual microscope slides

Publications (1)

Publication Number Publication Date
WO2001054052A1 true WO2001054052A1 (en) 2001-07-26

Family

ID=26873422

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2001/001782 WO2001054052A1 (en) 2000-01-21 2001-01-18 Method and apparatus for internet, intranet, and local viewing of virtual microscope slides

Country Status (6)

Country Link
US (6) US6396941B1 (en)
EP (1) EP1252604A4 (en)
AU (1) AU2001229630A1 (en)
CA (1) CA2398736C (en)
HK (1) HK1049723A1 (en)
WO (1) WO2001054052A1 (en)

Cited By (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1341023A2 (en) * 2002-02-20 2003-09-03 Leica Microsystems Heidelberg GmbH Method for training a user of a scanning microscope, scanning microscope, and software for said training
WO2003096228A1 (en) * 2002-05-10 2003-11-20 Tripath Imaging, Inc. Video microscopy system and multi-view virtual slide viewer capable of simultaneously acquiring and displaying various digital views of an area of interest located on a microscopic slide
WO2007138369A1 (en) * 2006-05-26 2007-12-06 3Dhistech Kft. Method and system for digitizing a specimen with fluorescent target points
WO2010133375A1 (en) * 2009-05-22 2010-11-25 Leica Microsystems Cms Gmbh System and method for computer-controlled execution of at least one test in a scanning microscope
WO2012024627A1 (en) * 2010-08-20 2012-02-23 Sakura Finetek U.S.A., Inc. Digital microscope
EP2469434A1 (en) * 2010-12-27 2012-06-27 Siemens Aktiengesellschaft Method and device for displaying medical image data
GB2492218A (en) * 2011-06-16 2012-12-26 Leeds Teaching Hospitals Nhs Trust Display of virtual slide images with different magnification regions
EP2804145A1 (en) * 2013-05-14 2014-11-19 Olympus Corporation Microscope system and stitched area decision method
EP2871513A1 (en) * 2013-11-12 2015-05-13 Olympus Corporation Microscope system
US9310598B2 (en) 2009-03-11 2016-04-12 Sakura Finetek U.S.A., Inc. Autofocus method and autofocus device
US10007102B2 (en) 2013-12-23 2018-06-26 Sakura Finetek U.S.A., Inc. Microscope with slide clamping assembly
US10269094B2 (en) 2013-04-19 2019-04-23 Sakura Finetek U.S.A., Inc. Method for generating a composite image of an object composed of multiple sub-images
US11193950B2 (en) 2019-03-29 2021-12-07 Sakura Finetek U.S.A., Inc. Slide identification sensor
US11280803B2 (en) 2016-11-22 2022-03-22 Sakura Finetek U.S.A., Inc. Slide management system

Families Citing this family (284)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7467137B1 (en) 1994-09-02 2008-12-16 Wolfe Mark A System and method for information retrieval employing a preloading procedure
US6215892B1 (en) * 1995-11-30 2001-04-10 Chromavision Medical Systems, Inc. Method and apparatus for automated image analysis of biological specimens
US6718053B1 (en) * 1996-11-27 2004-04-06 Chromavision Medical Systems, Inc. Method and apparatus for automated image analysis of biological specimens
US6396941B1 (en) * 1996-08-23 2002-05-28 Bacus Research Laboratories, Inc. Method and apparatus for internet, intranet, and local viewing of virtual microscope slides
US6272235B1 (en) * 1997-03-03 2001-08-07 Bacus Research Laboratories, Inc. Method and apparatus for creating a virtual microscope slide
US6182127B1 (en) * 1997-02-12 2001-01-30 Digital Paper, Llc Network image view server using efficent client-server tilting and caching architecture
US6535878B1 (en) * 1997-05-02 2003-03-18 Roxio, Inc. Method and system for providing on-line interactivity over a server-client network
US8626763B1 (en) 1997-05-22 2014-01-07 Google Inc. Server-side suggestion of preload operations
US7257604B1 (en) 1997-11-17 2007-08-14 Wolfe Mark A System and method for communicating information relating to a network resource
US6606413B1 (en) * 1998-06-01 2003-08-12 Trestle Acquisition Corp. Compression packaged image transmission for telemicroscopy
US20040083085A1 (en) * 1998-06-01 2004-04-29 Zeineh Jack A. Integrated virtual slide and live microscope system
JP2000194726A (en) * 1998-10-19 2000-07-14 Sony Corp Device, method and system for processing information and providing medium
US6670934B1 (en) * 1999-02-03 2003-12-30 William H. Gates, III Method and system for distributing art
US6487718B1 (en) * 1999-03-31 2002-11-26 International Business Machines Corporation Method and apparatus for installing applications in a distributed data processing system
US6847729B1 (en) 1999-04-21 2005-01-25 Fairfield Imaging Limited Microscopy
US7424543B2 (en) * 1999-09-08 2008-09-09 Rice Iii James L System and method of permissive data flow and application transfer
US6700589B1 (en) * 2000-02-17 2004-03-02 International Business Machines Corporation Method, system, and program for magnifying content downloaded from a server over a network
JP2001281554A (en) * 2000-03-29 2001-10-10 Nikon Corp Digital camera for microscope and microscope system equipped with the same
US20030163031A1 (en) * 2000-06-26 2003-08-28 Adlabs, Inc. Method and system for providing centralized anatomic pathology services
KR100405060B1 (en) * 2000-08-24 2003-11-07 휴먼드림 주식회사 Enlarged Digital Image Providing Method and Apparatus Using Data Communication Networks
IL138123A0 (en) * 2000-08-28 2001-10-31 Accuramed 1999 Ltd Medical decision support system and method
US7130458B2 (en) * 2000-10-24 2006-10-31 Affymetrix, Inc. Computer software system, method, and product for scanned image alignment
ATE454845T1 (en) 2000-10-30 2010-01-15 Gen Hospital Corp OPTICAL SYSTEMS FOR TISSUE ANALYSIS
US9295391B1 (en) 2000-11-10 2016-03-29 The General Hospital Corporation Spectrally encoded miniature endoscopic imaging probe
US7027628B1 (en) 2000-11-14 2006-04-11 The United States Of America As Represented By The Department Of Health And Human Services Automated microscopic image acquisition, compositing, and display
US6876759B2 (en) * 2001-02-01 2005-04-05 Fuji Photo Film Co., Ltd. Image transmitting system, image transmitting method and storage medium
US7885448B2 (en) * 2001-03-19 2011-02-08 Dmetrix, Inc. Diagnostic scanning microscope for information-enriched qualitative histopathology
US7020775B2 (en) * 2001-04-24 2006-03-28 Microsoft Corporation Derivation and quantization of robust non-local characteristics for blind watermarking
DE10297689B4 (en) 2001-05-01 2007-10-18 The General Hospital Corp., Boston Method and device for the determination of atherosclerotic coating by measurement of optical tissue properties
JP2002345745A (en) * 2001-05-22 2002-12-03 Olympus Optical Co Ltd Endoscopic system
AU2002346211B2 (en) 2001-06-27 2008-06-12 Sony Corporation Integrated circuit device, information processing device, information recording device memory management method, mobile terminal device, semiconductor integrated circuit device, and communication method using mobile terminal device
CA2455118C (en) * 2001-08-03 2012-01-17 Nanosphere, Inc. Nanoparticle imaging system and method
US20040146917A1 (en) * 2001-08-03 2004-07-29 Nanosphere, Inc. Nanoparticle imaging system and method
US7119811B2 (en) * 2001-08-10 2006-10-10 Pixia Corp. Image display system
US6912695B2 (en) * 2001-09-13 2005-06-28 Pixia Corp. Data storage and retrieval system and method
WO2003023757A1 (en) * 2001-09-13 2003-03-20 Pixia Corp. Image display system
US20040205459A1 (en) * 2001-10-26 2004-10-14 Green Brett A. Browser-controlled scanning system and method
US7549129B2 (en) * 2001-10-31 2009-06-16 Microsoft Corporation Computer system with enhanced user interface for images
JP2003135371A (en) * 2001-10-31 2003-05-13 Olympus Optical Co Ltd Endoscopic system
US7355716B2 (en) * 2002-01-24 2008-04-08 The General Hospital Corporation Apparatus and method for ranging and noise reduction of low coherence interferometry LCI and optical coherence tomography OCT signals by parallel detection of spectral bands
US7107331B2 (en) * 2002-03-25 2006-09-12 Kabushiki Kaisha Toshiba System and method for configuring digital image devices
DE10224948A1 (en) * 2002-06-05 2004-05-27 Egner, Steffen, Dr. Device and method for examining images
AU2003304298A1 (en) * 2002-09-18 2005-01-21 Dmetrix, Inc. Method for referencing image data
JP2004153462A (en) 2002-10-29 2004-05-27 Keyence Corp Magnifying observation apparatus, operating method of the magnifying observation apparatus, magnifying observation apparatus operating program, and computer-readable recording medium
US20040105000A1 (en) * 2002-11-29 2004-06-03 Olymlpus Corporation Microscopic image capture apparatus
US7643153B2 (en) 2003-01-24 2010-01-05 The General Hospital Corporation Apparatus and method for ranging and noise reduction of low coherence interferometry LCI and optical coherence tomography OCT signals by parallel detection of spectral bands
GB2398196B (en) 2003-02-05 2005-06-01 Fairfield Imaging Ltd Microscope system and method
JP4498770B2 (en) * 2003-03-10 2010-07-07 株式会社リコー Image forming apparatus for data distribution and information processing apparatus for acquiring data from the image forming apparatus
EP1611470B1 (en) 2003-03-31 2015-10-14 The General Hospital Corporation Speckle reduction in optical coherence tomography by path length encoded angular compounding
EP2008579B1 (en) 2003-06-06 2016-11-09 The General Hospital Corporation Process and apparatus for a wavelength tuned light source
WO2005010495A2 (en) * 2003-07-22 2005-02-03 Trestle Corporation System and method for generating digital images of a microscope slide
US8068988B2 (en) 2003-09-08 2011-11-29 Ventana Medical Systems, Inc. Method for automated processing of digital images of tissue micro-arrays (TMA)
US20050136509A1 (en) * 2003-09-10 2005-06-23 Bioimagene, Inc. Method and system for quantitatively analyzing biological samples
US20050058330A1 (en) * 2003-09-16 2005-03-17 Sysmex Corporation Method of displaying smear image and retrieving method employing the same, surveillance method, system of displaying smear image, program for displaying smear image and recording medium recording the program
US7882132B2 (en) 2003-10-09 2011-02-01 Oracle International Corporation Support for RDBMS in LDAP system
JP5567246B2 (en) 2003-10-27 2014-08-06 ザ ジェネラル ホスピタル コーポレイション Method and apparatus for performing optical imaging using frequency domain interferometry
DE10355529A1 (en) * 2003-11-21 2005-07-07 Carl Zeiss Jena Gmbh stereomicroscope
US7458030B2 (en) * 2003-12-12 2008-11-25 Microsoft Corporation System and method for realtime messaging having image sharing feature
DE10361150A1 (en) * 2003-12-22 2005-07-21 Leica Microsystems Imaging Solutions Ltd. Microscope system, includes digital camera, for input of image data, and computer system with display and storage unit
US7925070B2 (en) * 2004-03-30 2011-04-12 Sysmex Corporation Method for displaying virtual slide and terminal device for displaying virtual slide
DE102004016736A1 (en) * 2004-04-05 2005-11-10 Carl Zeiss Image recording system, image reproduction system and image recording / reproducing system
US7226167B2 (en) 2004-05-25 2007-06-05 Eastman Kodak Company Autostereoscopic display apparatus
JP5134365B2 (en) * 2004-05-27 2013-01-30 アペリオ・テクノロジーズ・インコーポレイテッド System and method for generating and visualizing a three-dimensional virtual slide
EP1754016B1 (en) * 2004-05-29 2016-05-18 The General Hospital Corporation Process, system and software arrangement for a chromatic dispersion compensation using reflective layers in optical coherence tomography (oct) imaging
US7653260B2 (en) * 2004-06-17 2010-01-26 Carl Zeis MicroImaging GmbH System and method of registering field of view
WO2006014392A1 (en) 2004-07-02 2006-02-09 The General Hospital Corporation Endoscopic imaging probe comprising dual clad fibre
JP2006039315A (en) * 2004-07-28 2006-02-09 Hamamatsu Photonics Kk Automatic focusing device and microscope using the same
JP4542386B2 (en) * 2004-07-30 2010-09-15 シスメックス株式会社 Image display system, image providing apparatus, image display apparatus, and computer program
EP1782020B1 (en) 2004-08-06 2012-10-03 The General Hospital Corporation Process, system and software arrangement for determining at least one location in a sample using an optical coherence tomography
US7792338B2 (en) * 2004-08-16 2010-09-07 Olympus America Inc. Method and apparatus of mechanical stage positioning in virtual microscopy image capture
KR20070058523A (en) 2004-08-24 2007-06-08 더 제너럴 하스피탈 코포레이션 Method and apparatus for imaging of vessel segments
ATE538714T1 (en) 2004-08-24 2012-01-15 Gen Hospital Corp METHOD, SYSTEM AND SOFTWARE ARRANGEMENT FOR DETERMINING THE ELASTIC MODULE
EP1787105A2 (en) 2004-09-10 2007-05-23 The General Hospital Corporation System and method for optical coherence imaging
US7165842B2 (en) * 2004-09-13 2007-01-23 Eastman Kodak Company Autostereoscopic display apparatus having glare suppression
EP1804107B1 (en) * 2004-09-22 2018-10-24 Nikon Corporation Microscope system and image processing method
JP4997112B2 (en) 2004-09-29 2012-08-08 ザ ジェネラル ホスピタル コーポレイション Apparatus for transmitting at least one electromagnetic radiation and method of manufacturing the same
US7113625B2 (en) * 2004-10-01 2006-09-26 U.S. Pathology Labs, Inc. System and method for image analysis of slides
EP2278265A3 (en) 2004-11-24 2011-06-29 The General Hospital Corporation Common-Path Interferometer for Endoscopic OCT
EP1816949A1 (en) 2004-11-29 2007-08-15 The General Hospital Corporation Arrangements, devices, endoscopes, catheters and methods for performing optical imaging by simultaneously illuminating and detecting multiple points on a sample
US8774560B2 (en) * 2005-01-11 2014-07-08 University Of Central Florida Research Foundation, Inc. System for manipulation, modification and editing of images via remote device
WO2006076432A2 (en) * 2005-01-11 2006-07-20 University Of Central Florida Interactive multiple gene expression map system
JP4504824B2 (en) * 2005-01-13 2010-07-14 オリンパス株式会社 Microscope camera
US7551182B2 (en) * 2005-01-18 2009-06-23 Oculus Info Inc. System and method for processing map data
US20060159325A1 (en) * 2005-01-18 2006-07-20 Trestle Corporation System and method for review in studies including toxicity and risk assessment studies
WO2006078928A2 (en) * 2005-01-18 2006-07-27 Trestle Corporation System and method for creating variable quality images of a slide
ES2337497T3 (en) 2005-04-28 2010-04-26 The General Hospital Corporation EVALUATION OF CHARACTERISTICS OF THE IMAGE OF AN ANATOMICAL STRUCTURE IN IMAGES OF TOMOGRAPHY OF OPTICAL COHERENCE.
US20060291042A1 (en) * 2005-05-17 2006-12-28 Alfano Robert R Optical scanning zoom microscope with high magnification and a large field of view
US7587671B2 (en) * 2005-05-17 2009-09-08 Palm, Inc. Image repositioning, storage and retrieval
EP1889037A2 (en) 2005-06-01 2008-02-20 The General Hospital Corporation Apparatus, method and system for performing phase-resolved optical frequency domain imaging
US7796815B2 (en) * 2005-06-10 2010-09-14 The Cleveland Clinic Foundation Image analysis of biological objects
AU2006257622B2 (en) * 2005-06-13 2012-02-23 Tripath Imaging, Inc. System and method for re-locating an object in a sample on a slide with a microscope imaging device
US8164622B2 (en) 2005-07-01 2012-04-24 Aperio Technologies, Inc. System and method for single optical axis multi-detector microscope slide scanner
CN101238347B (en) 2005-08-09 2011-05-25 通用医疗公司 Apparatus, methods and storage medium for performing polarization-based quadrature demodulation in optical coherence tomography
US8914070B2 (en) * 2005-08-31 2014-12-16 Thomson Licensing Mobile wireless communication terminals, systems and methods for providing a slideshow
CN101304683B (en) 2005-09-29 2012-12-12 通用医疗公司 Method and apparatus for method for viewing and analyzing of one or more biological samples with progressively increasing resolutions
US7929738B2 (en) * 2005-10-11 2011-04-19 Olympus Corporation Microscope apparatus and microscope system
US20070088680A1 (en) * 2005-10-14 2007-04-19 Microsoft Corporation Simultaneously spawning multiple searches across multiple providers
WO2007047690A1 (en) 2005-10-14 2007-04-26 The General Hospital Corporation Spectral- and frequency- encoded fluorescence imaging
NO327155B1 (en) 2005-10-19 2009-05-04 Fast Search & Transfer Asa Procedure for displaying video data within result presentations in systems for accessing and searching for information
EP1971848B1 (en) 2006-01-10 2019-12-04 The General Hospital Corporation Systems and methods for generating data based on one or more spectrally-encoded endoscopy techniques
US8145018B2 (en) 2006-01-19 2012-03-27 The General Hospital Corporation Apparatus for obtaining information for a structure using spectrally-encoded endoscopy techniques and methods for producing one or more optical arrangements
US9087368B2 (en) 2006-01-19 2015-07-21 The General Hospital Corporation Methods and systems for optical imaging or epithelial luminal organs by beam scanning thereof
WO2007149602A2 (en) 2006-02-01 2007-12-27 The General Hospital Corporation Methods and systems for providing electromagnetic radiation to at least one portion of a sample using conformal laser therapy procedures
US9186066B2 (en) 2006-02-01 2015-11-17 The General Hospital Corporation Apparatus for applying a plurality of electro-magnetic radiations to a sample
JP5519152B2 (en) 2006-02-08 2014-06-11 ザ ジェネラル ホスピタル コーポレイション Device for acquiring information about anatomical samples using optical microscopy
US7982879B2 (en) 2006-02-24 2011-07-19 The General Hospital Corporation Methods and systems for performing angle-resolved fourier-domain optical coherence tomography
JP4917331B2 (en) * 2006-03-01 2012-04-18 浜松ホトニクス株式会社 Image acquisition apparatus, image acquisition method, and image acquisition program
JP4917329B2 (en) * 2006-03-01 2012-04-18 浜松ホトニクス株式会社 Image acquisition apparatus, image acquisition method, and image acquisition program
JP4917330B2 (en) * 2006-03-01 2012-04-18 浜松ホトニクス株式会社 Image acquisition apparatus, image acquisition method, and image acquisition program
EP2004041B1 (en) 2006-04-05 2013-11-06 The General Hospital Corporation Methods, arrangements and systems for polarization-sensitive optical frequency domain imaging of a sample
JP2009536740A (en) 2006-05-10 2009-10-15 ザ ジェネラル ホスピタル コーポレイション Process, configuration and system for providing frequency domain imaging of samples
WO2007133964A2 (en) 2006-05-12 2007-11-22 The General Hospital Corporation Processes, arrangements and systems for providing a fiber layer thickness map based on optical coherence tomography images
JP4890096B2 (en) * 2006-05-19 2012-03-07 浜松ホトニクス株式会社 Image acquisition apparatus, image acquisition method, and image acquisition program
US8249315B2 (en) * 2006-05-22 2012-08-21 Upmc System and method for improved viewing and navigation of digital images
US8126725B2 (en) * 2006-06-07 2012-02-28 Cerner Innovation, Inc. Coordinating anatomic pathology consultations and inventory tracking
US8131561B2 (en) * 2006-06-07 2012-03-06 Cerner Innovation, Inc. Inventory tracking for anatomic pathology consultations
JP2010501877A (en) 2006-08-25 2010-01-21 ザ ジェネラル ホスピタル コーポレイション Apparatus and method for improving optical coherence tomography imaging capabilities using volumetric filtering techniques
KR20080033027A (en) * 2006-10-12 2008-04-16 최해용 Educational entity brown rice imaging device
US8838213B2 (en) 2006-10-19 2014-09-16 The General Hospital Corporation Apparatus and method for obtaining and providing imaging information associated with at least one portion of a sample, and effecting such portion(s)
EP1925962A1 (en) * 2006-11-21 2008-05-28 Swiss Medical Technology GmbH Stereo video microscope system
US7675549B1 (en) * 2006-12-08 2010-03-09 Itt Manufacturing Enterprises, Inc. Imaging architecture for region and time of interest collection and dissemination
US8244021B2 (en) 2006-12-20 2012-08-14 Ventana Medical Systems, Inc. Quantitative, multispectral image analysis of tissue specimens stained with quantum dots
US8212805B1 (en) 2007-01-05 2012-07-03 Kenneth Banschick System and method for parametric display of modular aesthetic designs
EP2662674A3 (en) 2007-01-19 2014-06-25 The General Hospital Corporation Rotating disk reflection for fast wavelength scanning of dispersed broadbend light
US7911621B2 (en) * 2007-01-19 2011-03-22 The General Hospital Corporation Apparatus and method for controlling ranging depth in optical frequency domain imaging
US7738094B2 (en) * 2007-01-26 2010-06-15 Becton, Dickinson And Company Method, system, and compositions for cell counting and analysis
US8098956B2 (en) * 2007-03-23 2012-01-17 Vantana Medical Systems, Inc. Digital microscope slide scanning system and methods
WO2008118781A2 (en) 2007-03-23 2008-10-02 The General Hospital Corporation Methods, arrangements and apparatus for utilizing a wavelength-swept laser using angular scanning and dispersion procedures
US10534129B2 (en) 2007-03-30 2020-01-14 The General Hospital Corporation System and method providing intracoronary laser speckle imaging for the detection of vulnerable plaque
US8045177B2 (en) 2007-04-17 2011-10-25 The General Hospital Corporation Apparatus and methods for measuring vibrations using spectrally-encoded endoscopy
US8115919B2 (en) 2007-05-04 2012-02-14 The General Hospital Corporation Methods, arrangements and systems for obtaining information associated with a sample using optical microscopy
JP4296207B2 (en) * 2007-05-10 2009-07-15 日本分光株式会社 Microscopic measuring device
DK2156370T3 (en) 2007-05-14 2012-01-23 Historx Inc Compartment separation by pixel characterization using image data clustering
US20080292162A1 (en) * 2007-05-23 2008-11-27 David Thomas Gering Method and System for Generating a Collage to Summarize a Medical Dataset
HU0700409D0 (en) * 2007-06-11 2007-08-28 3D Histech Kft Method and system for accessing a slide from a remote workstation
WO2008156669A1 (en) * 2007-06-15 2008-12-24 Historx, Inc. Method and system for standardizing microscope instruments
JP5564421B2 (en) * 2007-06-21 2014-07-30 ザ・ジョンズ・ホプキンス・ユニバーシティ Operating device for navigating virtual microscope slides / digital images and associated methods.
WO2009011107A1 (en) * 2007-07-17 2009-01-22 Nikon Corporation Light stimulus apparatus and observation apparatus
WO2009018456A2 (en) 2007-07-31 2009-02-05 The General Hospital Corporation Systems and methods for providing beam scan patterns for high speed doppler optical frequency domain imaging
CA2604317C (en) 2007-08-06 2017-02-28 Historx, Inc. Methods and system for validating sample images for quantitative immunoassays
CA2596204C (en) * 2007-08-07 2019-02-26 Historx, Inc. Method and system for determining an optimal dilution of a reagent
US8203552B2 (en) * 2007-08-30 2012-06-19 Harris Corporation Geospatial data system for selectively retrieving and displaying geospatial texture data in successive additive layers of resolution and related methods
US8040608B2 (en) 2007-08-31 2011-10-18 The General Hospital Corporation System and method for self-interference fluorescence microscopy, and computer-accessible medium associated therewith
US7978258B2 (en) * 2007-08-31 2011-07-12 Historx, Inc. Automatic exposure time selection for imaging tissue
JP2011500173A (en) * 2007-10-12 2011-01-06 ザ ジェネラル ホスピタル コーポレイション System and process for optical imaging of luminal anatomical structures
US7933021B2 (en) 2007-10-30 2011-04-26 The General Hospital Corporation System and method for cladding mode detection
US20090112806A1 (en) * 2007-10-31 2009-04-30 Microsoft Corporation Query view inferred from datasource and query
JP5025457B2 (en) * 2007-12-28 2012-09-12 キヤノン株式会社 Image processing apparatus and method
US9418474B2 (en) * 2008-01-04 2016-08-16 3M Innovative Properties Company Three-dimensional model refinement
US20100311106A1 (en) * 2008-01-25 2010-12-09 Hartmann Lynn C Quantitation of lobular involution for breast cancer risk prediction
WO2009097494A1 (en) * 2008-01-30 2009-08-06 Rudolph Technologies, Inc. High resolution edge inspection
US8170698B1 (en) * 2008-02-20 2012-05-01 Mark David Gusack Virtual robotic controller system with special application to robotic microscopy structure and methodology
US20090244698A1 (en) * 2008-03-28 2009-10-01 Reto Zust Microscope comprising at least two components
JP5196181B2 (en) * 2008-04-14 2013-05-15 株式会社リコー Image processing system and storage medium
US7898656B2 (en) * 2008-04-30 2011-03-01 The General Hospital Corporation Apparatus and method for cross axis parallel spectroscopy
EP2274572A4 (en) 2008-05-07 2013-08-28 Gen Hospital Corp System, method and computer-accessible medium for tracking vessel motion during three-dimensional coronary artery microscopy
JP5795531B2 (en) 2008-06-20 2015-10-14 ザ ジェネラル ホスピタル コーポレイション Fused fiber optic coupler structure and method of using the same
US8064733B2 (en) 2008-06-24 2011-11-22 Microsoft Corporation Variable resolution images
US7933473B2 (en) * 2008-06-24 2011-04-26 Microsoft Corporation Multiple resolution image storage
US9254089B2 (en) 2008-07-14 2016-02-09 The General Hospital Corporation Apparatus and methods for facilitating at least partial overlap of dispersed ration on at least one sample
CA2737116C (en) * 2008-09-16 2019-01-15 Historx, Inc. Reproducible quantification of biomarker expression
US8290346B2 (en) 2008-09-25 2012-10-16 Pixia Corp. Large format video archival, storage, and retrieval system and method
US20100145613A1 (en) * 2008-12-05 2010-06-10 Electronics And Telecommunications Research Institute Apparatus for generating location information based on web map and method thereof
JP5731394B2 (en) 2008-12-10 2015-06-10 ザ ジェネラル ホスピタル コーポレイション System, apparatus and method for extending imaging depth range of optical coherence tomography through optical subsampling
WO2010090837A2 (en) 2009-01-20 2010-08-12 The General Hospital Corporation Endoscopic biopsy apparatus, system and method
US8097864B2 (en) 2009-01-26 2012-01-17 The General Hospital Corporation System, method and computer-accessible medium for providing wide-field superresolution microscopy
US8537181B2 (en) * 2009-03-09 2013-09-17 Ventana Medical Systems, Inc. Modes and interfaces for observation, and manipulation of digital images on computer screen in support of pathologist's workflow
WO2010105197A2 (en) 2009-03-12 2010-09-16 The General Hospital Corporation Non-contact optical system, computer-accessible medium and method for measuring at least one mechanical property of tissue using coherent speckle techniques(s)
US20100294821A1 (en) * 2009-05-20 2010-11-25 Laci Szabo Welding/cutting torch system holster
WO2010140999A1 (en) * 2009-06-03 2010-12-09 Thomson Licensing Method and apparatus for constructing composite video images
CN102469943A (en) 2009-07-14 2012-05-23 通用医疗公司 Apparatus, systems and methods for measuring flow and pressure within a vessel
US8891851B2 (en) * 2009-07-15 2014-11-18 Glenn F. Spaulding Home healthcare management system and hardware
US8463741B2 (en) * 2009-09-04 2013-06-11 Omnyx, LLC Digital pathology system
EP2993478B1 (en) 2009-10-19 2022-08-24 Ventana Medical Systems, Inc. Device and method for slide caching
JP2011113401A (en) * 2009-11-27 2011-06-09 Sony Corp Apparatus and method for processing information, computer program, and information processing server
JP5617233B2 (en) * 2009-11-30 2014-11-05 ソニー株式会社 Information processing apparatus, information processing method, and program thereof
JP5561027B2 (en) 2009-11-30 2014-07-30 ソニー株式会社 Information processing apparatus, information processing method, and program thereof
JP5573145B2 (en) * 2009-12-16 2014-08-20 ソニー株式会社 Image processing system, image processing apparatus, image processing method, and program
HUE052561T2 (en) 2010-03-05 2021-05-28 Massachusetts Gen Hospital Apparatus for providing electro-magnetic radiation to a sample
US8411970B2 (en) * 2010-03-16 2013-04-02 Pixia Corp. Method and system for determining statistical data for image pixels having a higher bit depth per band
JP5531750B2 (en) * 2010-04-16 2014-06-25 ソニー株式会社 Information processing apparatus, information processing method, program, and information processing system
US9069130B2 (en) 2010-05-03 2015-06-30 The General Hospital Corporation Apparatus, method and system for generating optical radiation from biological gain media
US20110289424A1 (en) * 2010-05-21 2011-11-24 Microsoft Corporation Secure application of custom resources in multi-tier systems
US9557154B2 (en) 2010-05-25 2017-01-31 The General Hospital Corporation Systems, devices, methods, apparatus and computer-accessible media for providing optical imaging of structures and compositions
JP5778762B2 (en) 2010-05-25 2015-09-16 ザ ジェネラル ホスピタル コーポレイション Apparatus and method for spectral analysis of optical coherence tomography images
EP2575591A4 (en) 2010-06-03 2017-09-13 The General Hospital Corporation Apparatus and method for devices for imaging structures in or at one or more luminal organs
BR112012031688A2 (en) 2010-06-15 2016-08-16 Koninkl Philips Electronics Nv method for processing a first digital image and computer program product for processing a first digital image
JP5663979B2 (en) 2010-06-29 2015-02-04 ソニー株式会社 Image management server, image display device, image providing method, image acquisition method, program, and image management system
JP5560966B2 (en) 2010-07-01 2014-07-30 ソニー株式会社 Microscope control apparatus, image management server, image processing method, program, and image management system
JP5703609B2 (en) 2010-07-02 2015-04-22 ソニー株式会社 Microscope and region determination method
JP5655557B2 (en) 2010-07-12 2015-01-21 ソニー株式会社 Microscope control device, image display device, image management server, focus position information generation method, image display method, image management method, and microscope image management system
CA2943966C (en) 2010-08-27 2019-02-19 The Board Of Trustees Of The Leland Stanford Junior University Microscopy imaging device with advanced imaging properties
US9407876B1 (en) 2010-09-14 2016-08-02 Pixia Corp. Method and system for encoding and decoding multiple wide-area surveillance area-of-interest video codestreams
US8532397B1 (en) 2010-09-16 2013-09-10 Pixia Corp. Method of creating a container file for large format imagery and organizing data within the container file
EP2616925A4 (en) 2010-09-16 2014-02-12 Omnyx LLC Histology workflow management system
US8542274B2 (en) 2010-10-18 2013-09-24 Olympus America Inc. Wide field microscopic imaging system and method
EP2632324A4 (en) 2010-10-27 2015-04-22 Gen Hospital Corp Apparatus, systems and methods for measuring blood pressure within at least one vessel
US8811695B2 (en) * 2010-12-14 2014-08-19 General Electric Company Methods, apparatus and articles of manufacture to adaptively reconstruct medical diagnostic images
US8705805B2 (en) * 2011-01-10 2014-04-22 Peter Alexander Forrest Secure portable token and systems and methods for identification and authentication of the same
US8917397B2 (en) * 2011-05-27 2014-12-23 Ferrand D. E. Corley Microscope illumination and calibration apparatus
JP2012252559A (en) * 2011-06-03 2012-12-20 Sony Corp Image processing device, image processing method, recording medium, and program
US8832690B1 (en) * 2011-06-21 2014-09-09 Google Inc. Multi-threaded virtual machine processing on a web page
JP2013029806A (en) * 2011-06-22 2013-02-07 Canon Inc Imaging apparatus
JP2013025466A (en) * 2011-07-19 2013-02-04 Sony Corp Image processing device, image processing system and image processing program
US9330092B2 (en) 2011-07-19 2016-05-03 The General Hospital Corporation Systems, methods, apparatus and computer-accessible-medium for providing polarization-mode dispersion compensation in optical coherence tomography
US9230153B2 (en) 2011-07-20 2016-01-05 Mikroscan Technologies, Inc. Networkbased pathology system with desktop slide scanner
US8774518B2 (en) 2011-08-02 2014-07-08 Nec Laboratories America, Inc. Digital pathology system with low-latency analytics
JP5859771B2 (en) * 2011-08-22 2016-02-16 ソニー株式会社 Information processing apparatus, information processing system information processing method, and program
US10241028B2 (en) 2011-08-25 2019-03-26 The General Hospital Corporation Methods, systems, arrangements and computer-accessible medium for providing micro-optical coherence tomography procedures
JP6035716B2 (en) 2011-08-26 2016-11-30 ソニー株式会社 Information processing system and information processing method
US20130067346A1 (en) * 2011-09-09 2013-03-14 Microsoft Corporation Content User Experience
WO2013052025A1 (en) * 2011-10-03 2013-04-11 Hewlett-Packard Development Company, L.P. Region selection for counterfeit determinations
EP2769491A4 (en) 2011-10-18 2015-07-22 Gen Hospital Corp Apparatus and methods for producing and/or providing recirculating optical delay(s)
FR2982384B1 (en) * 2011-11-04 2014-06-27 Univ Pierre Et Marie Curie Paris 6 DEVICE FOR VISUALIZING A VIRTUAL BLADE
EP3441142A1 (en) 2011-11-16 2019-02-13 Becton, Dickinson and Company Methods and systems for detecting an analyte in a sample
US8799358B2 (en) 2011-11-28 2014-08-05 Merge Healthcare Incorporated Remote cine viewing of medical images on a zero-client application
JP2013134574A (en) * 2011-12-26 2013-07-08 Canon Inc Image data generation device, image data display system, and image data generation method
JP2013178742A (en) * 2012-01-30 2013-09-09 Canon Inc Image processing device, image processing system, image processing method and program
JP2013167798A (en) * 2012-02-16 2013-08-29 Canon Inc Image forming device and control method thereof
JP2013200640A (en) * 2012-03-23 2013-10-03 Canon Inc Image processing device, image processing system, image processing method and program
TWI499309B (en) * 2012-03-28 2015-09-01 Albert Chang Image control system and method thereof
EP2833776A4 (en) 2012-03-30 2015-12-09 Gen Hospital Corp Imaging system, method and distal attachment for multidirectional field of view endoscopy
US11490797B2 (en) 2012-05-21 2022-11-08 The General Hospital Corporation Apparatus, device and method for capsule microscopy
JP6186775B2 (en) * 2012-05-31 2017-08-30 株式会社リコー Communication terminal, display method, and program
JP6222088B2 (en) * 2012-06-11 2017-11-01 ソニー株式会社 Information processing apparatus, information processing system, information processing method, and program
JP6019798B2 (en) * 2012-06-22 2016-11-02 ソニー株式会社 Information processing apparatus, information processing system, and information processing method
US9092455B2 (en) 2012-07-17 2015-07-28 Microsoft Technology Licensing, Llc Image curation
US9754560B2 (en) * 2012-08-20 2017-09-05 Open Invention Network, Llc Pooling and tiling data images from memory to draw windows on a display device
US9454298B2 (en) 2012-10-04 2016-09-27 Brigham Young University Methods and apparatus related to expanding or contracting representations of data
JP6296457B2 (en) 2013-01-11 2018-03-20 ベクトン・ディキンソン・アンド・カンパニーBecton, Dickinson And Company Low-cost clinical on-site assay device
JP6560126B2 (en) 2013-01-28 2019-08-14 ザ ジェネラル ホスピタル コーポレイション Apparatus and method for providing diffusion spectroscopy superimposed on optical frequency domain imaging
US10893806B2 (en) 2013-01-29 2021-01-19 The General Hospital Corporation Apparatus, systems and methods for providing information regarding the aortic valve
US11179028B2 (en) 2013-02-01 2021-11-23 The General Hospital Corporation Objective lens arrangement for confocal endomicroscopy
JP6378311B2 (en) 2013-03-15 2018-08-22 ザ ジェネラル ホスピタル コーポレイション Methods and systems for characterizing objects
JP6455829B2 (en) * 2013-04-01 2019-01-23 キヤノン株式会社 Image processing apparatus, image processing method, and program
US9829696B2 (en) * 2013-05-01 2017-11-28 Bio-Rad Laboratories, Inc. Adjustable digital microscope display
US9784681B2 (en) 2013-05-13 2017-10-10 The General Hospital Corporation System and method for efficient detection of the phase and amplitude of a periodic modulation associated with self-interfering fluorescence
US9439565B1 (en) 2013-07-08 2016-09-13 Dermatopathology Laboratory of Central States, Inc. Wireless viewing of digital pathology specimens
WO2015010133A1 (en) 2013-07-19 2015-01-22 The General Hospital Corporation Determining eye motion by imaging retina. with feedback
EP3692887B1 (en) 2013-07-19 2024-03-06 The General Hospital Corporation Imaging apparatus which utilizes multidirectional field of view endoscopy
EP3910282B1 (en) 2013-07-26 2024-01-17 The General Hospital Corporation Method of providing a laser radiation with a laser arrangement utilizing optical dispersion for applications in fourier-domain optical coherence tomography
DK2857841T3 (en) 2013-10-07 2021-07-26 Eppendorf Ag Laboratory apparatus for apparatus-controlled processing of at least one laboratory sample, and a method for configuring the laboratory apparatus by means of the configuration control
EP2857843A1 (en) 2013-10-07 2015-04-08 Eppendorf Ag System comprising at least two laboratory devices for processing a device controlled subtask in a treatment process comprising at least one laboratory sample, laboratory device and method
EP2857842B1 (en) * 2013-10-07 2022-09-21 Eppendorf SE Access control for a laboratory device, laboratory device with access control, and method for treatment of laboratory specimens controlled by devices
EP2857844B1 (en) 2013-10-07 2021-12-01 Eppendorf AG Laboratory device, system and method for device-controlled treatment of at least one laboratory sample using at least one consumable item
BR112016009958B1 (en) 2013-11-06 2021-08-03 Becton, Dickinson And Company MICROFLUIDIC DEVICE, METHOD, SYSTEM AND KIT
JP6518245B2 (en) 2013-11-13 2019-05-22 ベクトン・ディキンソン・アンド・カンパニーBecton, Dickinson And Company Optical imaging system and method using the same
CA2930411C (en) 2013-11-15 2022-05-03 Mikroscan Technologies, Inc. Geological scanner
US9733460B2 (en) 2014-01-08 2017-08-15 The General Hospital Corporation Method and apparatus for microscopic imaging
US10736494B2 (en) 2014-01-31 2020-08-11 The General Hospital Corporation System and method for facilitating manual and/or automatic volumetric imaging with real-time tension or force feedback using a tethered imaging device
US10176605B2 (en) 2014-03-26 2019-01-08 Brigham Young University Dynamic display of heirarchal data
WO2015153982A1 (en) 2014-04-04 2015-10-08 The General Hospital Corporation Apparatus and method for controlling propagation and/or transmission of electromagnetic radiation in flexible waveguide(s)
WO2015172025A1 (en) 2014-05-08 2015-11-12 The Cleveland Clinic Foundation Systems and methods for detection, analysis, isolation and/or harvesting of biological objects
ES2907287T3 (en) 2014-07-25 2022-04-22 Massachusetts Gen Hospital Apparatus for imaging and in vivo diagnosis
US10324733B2 (en) 2014-07-30 2019-06-18 Microsoft Technology Licensing, Llc Shutdown notifications
US9836464B2 (en) 2014-07-31 2017-12-05 Microsoft Technology Licensing, Llc Curating media from social connections
US9787576B2 (en) 2014-07-31 2017-10-10 Microsoft Technology Licensing, Llc Propagating routing awareness for autonomous networks
US10254942B2 (en) 2014-07-31 2019-04-09 Microsoft Technology Licensing, Llc Adaptive sizing and positioning of application windows
US10592080B2 (en) 2014-07-31 2020-03-17 Microsoft Technology Licensing, Llc Assisted presentation of application windows
US10678412B2 (en) 2014-07-31 2020-06-09 Microsoft Technology Licensing, Llc Dynamic joint dividers for application windows
US9414417B2 (en) 2014-08-07 2016-08-09 Microsoft Technology Licensing, Llc Propagating communication awareness over a cellular network
EP3485927B1 (en) 2014-10-14 2023-10-25 Becton, Dickinson and Company Blood sample treatment using open cell foam
BR122020024283B1 (en) 2014-10-14 2023-02-23 Becton, Dickinson And Company BLOOD TRANSFER DEVICE ADAPTED TO RECEIVE A BLOOD SAMPLE
WO2016069794A1 (en) 2014-10-28 2016-05-06 Mikroscan Technologies, Inc. Microdissection viewing system
CN104573362B (en) * 2015-01-06 2018-11-20 上海交通大学 More people's synchronous digitalization slice diagosis and consultation of doctors system and method
DE102016101546B4 (en) * 2015-02-10 2024-03-07 Siemens Healthcare Gmbh Method and system for processing electronic documents
WO2016145057A1 (en) 2015-03-10 2016-09-15 Becton, Dickinson And Company Biological fluid micro-sample management device
US10102219B2 (en) * 2015-05-22 2018-10-16 Box, Inc. Rendering high resolution images using image tiling and hierarchical image tile storage structures
US10073612B1 (en) * 2015-08-17 2018-09-11 Bentley Systems, Incorporated Fixed cursor input interface for a computer aided design application executing on a touch screen device
CA3109854C (en) 2015-09-01 2023-07-25 Becton, Dickinson And Company Depth filtration device for separating specimen phases
JP6333871B2 (en) * 2016-02-25 2018-05-30 ファナック株式会社 Image processing apparatus for displaying an object detected from an input image
FR3048524A1 (en) * 2016-03-07 2017-09-08 Datexim REMOTE DISPLAY SYSTEM OF MEDICAL IMAGE
US10025902B2 (en) * 2016-08-12 2018-07-17 Verily Life Sciences Llc Enhanced pathology diagnosis
US10371934B2 (en) * 2016-11-15 2019-08-06 Leica Instruments (Singapore) Pte. Ltd. Microscope arrangement comprising a plurality of microscopes, and method for operating a plurality of microscopes, in particular in a learning environment
US10712548B2 (en) 2017-06-08 2020-07-14 Microscope International, LLC Systems and methods for rapid scanning of images in digital microscopes
US10444486B2 (en) 2017-09-04 2019-10-15 Microscopes International, Llc Systems and methods for detection of blank fields in digital microscopes
JP2021505926A (en) 2017-11-30 2021-02-18 ライカ バイオシステムズ イメージング インコーポレイテッドLeica Biosystems Imaging, Inc. Systems and methods for managing multiple scanning devices in a high-throughput laboratory environment
WO2019165480A1 (en) 2018-02-26 2019-08-29 Caliber Imaging & Diagnostics, Inc. System and method for macroscopic and microscopic imaging ex-vivo tissue
US11112952B2 (en) 2018-03-26 2021-09-07 Microscopes International, Llc Interface for display of multi-layer images in digital microscopy
US11030968B2 (en) * 2018-07-11 2021-06-08 Nvidia Corporation Middle-out technique for refreshing a display with low latency
WO2020014296A1 (en) 2018-07-12 2020-01-16 Luminex Corporation Systems and methods for performing variable sample preparation and analysis processes
CN110825286B (en) * 2019-10-30 2021-09-03 北京字节跳动网络技术有限公司 Image processing method and device and electronic equipment
CN112232349B (en) * 2020-09-23 2023-11-03 成都佳华物链云科技有限公司 Model training method, image segmentation method and device
CN115953344B (en) * 2023-03-08 2023-05-30 上海聚跃检测技术有限公司 Image processing method, device, electronic equipment and storage medium

Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5297034A (en) * 1987-04-30 1994-03-22 Corabi International Telemetrics, Inc. Telepathology diagnostic network
US5793969A (en) * 1993-07-09 1998-08-11 Neopath, Inc. Network review and analysis of computer encoded slides
US5978804A (en) * 1996-04-11 1999-11-02 Dietzman; Gregg R. Natural products information system
US5993001A (en) * 1997-06-05 1999-11-30 Joslin Diabetes Center, Inc. Stereoscopic imaging system for retinal examination with remote examination unit
US6091930A (en) * 1997-03-04 2000-07-18 Case Western Reserve University Customizable interactive textbook
US6148096A (en) * 1995-09-15 2000-11-14 Accumed International, Inc. Specimen preview and inspection system
US6151405A (en) * 1996-11-27 2000-11-21 Chromavision Medical Systems, Inc. System and method for cellular specimen grading
US6155603A (en) * 1998-08-13 2000-12-05 Fox; Joshua L. Laboratory reporting system and labeling system therefor

Family Cites Families (57)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3999047A (en) 1972-09-05 1976-12-21 Green James E Method and apparatus utilizing color algebra for analyzing scene regions
US4150360A (en) 1975-05-29 1979-04-17 Grumman Aerospace Corporation Method and apparatus for classifying biological cells
US4199748A (en) 1976-11-01 1980-04-22 Rush-Presbyterian-St. Luke's Medical Center Automated method and apparatus for classification of cells with application to the diagnosis of anemia
US4175860A (en) 1977-05-31 1979-11-27 Rush-Presbyterian-St. Luke's Medical Center Dual resolution method and apparatus for use in automated classification of pap smear and other samples
US4213036A (en) 1977-12-27 1980-07-15 Grumman Aerospace Corporation Method for classifying biological cells
DE2903855A1 (en) 1979-02-01 1980-08-14 Bloss Werner H Prof Dr Ing METHOD FOR AUTOMATICALLY MARKING CELLS AND DETERMINING THE CHARACTERISTICS OF CELLS FROM CYTOLOGICAL MEASUREMENT DEVICES
US4742558A (en) 1984-02-14 1988-05-03 Nippon Telegraph & Telephone Public Corporation Image information retrieval/display apparatus
US4673988A (en) 1985-04-22 1987-06-16 E.I. Du Pont De Nemours And Company Electronic mosaic imaging process
FR2583545B1 (en) 1985-06-13 1987-08-07 Primat Didier IMPROVEMENT IN METHODS AND DEVICES FOR AUTOMATIC DIGITALIZATION OF A SCENE COMPRISING DISCRETE SIGNIFICANT ELEMENTS
US4741043B1 (en) 1985-11-04 1994-08-09 Cell Analysis Systems Inc Method of and apparatus for image analyses of biological specimens
US4777525A (en) 1985-12-23 1988-10-11 Preston Jr Kendall Apparatus and method for a multi-resolution electro-optical imaging, display and storage/retrieval system
GB8611554D0 (en) 1986-05-12 1986-06-18 Crosfield Electronics Ltd Image display
JP2686274B2 (en) 1988-03-24 1997-12-08 東亜医用電子株式会社 Cell image processing method and apparatus
US5544650A (en) 1988-04-08 1996-08-13 Neuromedical Systems, Inc. Automated specimen classification system and method
US4965725B1 (en) 1988-04-08 1996-05-07 Neuromedical Systems Inc Neural network based automated cytological specimen classification system and method
JP2813348B2 (en) 1988-04-22 1998-10-22 東亜医用電子株式会社 Cell image extraction storage processing device and method
US5163095A (en) 1988-04-22 1992-11-10 Toa Medical Electronics Co., Ltd. Processor for extracting and memorizing cell images, and method of practicing same
JP2671393B2 (en) 1988-06-21 1997-10-29 ソニー株式会社 Map information display device
US5072832A (en) * 1989-03-09 1991-12-17 Devon Industries, Inc. Multipurpose shaped pitcher and surgical kit and wrap system
US5252487A (en) 1989-05-19 1993-10-12 Cell Analysis Systems, Inc. Method and apparatus for determining the amount of oncogene protein product in a cell sample
US5073857A (en) 1989-06-01 1991-12-17 Accuron Corporation Method and apparatus for cell analysis
US5268966A (en) 1989-08-10 1993-12-07 International Remote Imaging Systems, Inc. Method of differentiating particles based upon a dynamically changing threshold
US5107422A (en) 1989-10-02 1992-04-21 Kamentsky Louis A Method and apparatus for measuring multiple optical properties of biological specimens
US5072382A (en) 1989-10-02 1991-12-10 Kamentsky Louis A Methods and apparatus for measuring multiple optical properties of biological specimens
US5313532A (en) 1990-01-23 1994-05-17 Massachusetts Institute Of Technology Recognition of patterns in images
US5123056A (en) 1990-02-02 1992-06-16 Siemens Medical Systems, Inc. Whole-leg x-ray image processing and display techniques
ATE178728T1 (en) 1990-11-07 1999-04-15 Neuromedical Systems Inc EXAMINATION CONTROL PROCEDURES FOR IMAGES SHOWN ON A DISPLAY
US5257182B1 (en) 1991-01-29 1996-05-07 Neuromedical Systems Inc Morphological classification system and method
US5784162A (en) 1993-08-18 1998-07-21 Applied Spectral Imaging Ltd. Spectral bio-imaging methods for biological research, medical diagnostics and therapy
US5218645A (en) 1991-03-29 1993-06-08 Cell Analysis Systems, Inc. Method and apparatus for separating cell objects for analysis
US5216500A (en) 1991-07-15 1993-06-01 Rj Lee Group, Inc. Simultaneously recording of video image and microscope stage position data
US5260871A (en) 1991-07-31 1993-11-09 Mayo Foundation For Medical Education And Research Method and apparatus for diagnosis of breast tumors
US5428690A (en) 1991-09-23 1995-06-27 Becton Dickinson And Company Method and apparatus for automated assay of biological specimens
CA2077781A1 (en) 1991-09-23 1993-03-24 James W. Bacus Method and apparatus for automated assay of biological specimens
JPH05303621A (en) 1992-04-24 1993-11-16 Fujitsu Ltd Method for displaying image information
JP3018733B2 (en) 1992-05-13 2000-03-13 株式会社ニコン Still image transmission device
JP3321197B2 (en) 1992-06-22 2002-09-03 オリンパス光学工業株式会社 Microscope still image transmission system
JP3448847B2 (en) 1992-07-29 2003-09-22 オリンパス光学工業株式会社 Microscope still image observation system
JPH06118307A (en) 1992-10-02 1994-04-28 Nikon Corp Microscopic examination assisting device
EP0610916A3 (en) 1993-02-09 1994-10-12 Cedars Sinai Medical Center Method and apparatus for providing preferentially segmented digital images.
JPH0715721A (en) 1993-06-28 1995-01-17 Nikon Corp Image transmitting device
US5625765A (en) 1993-09-03 1997-04-29 Criticom Corp. Vision systems including devices and methods for combining images for extended magnification schemes
US5505946A (en) 1994-04-01 1996-04-09 Trustees Of Univ Of Pa Bowman-birk inhibitor concentrate compositions and methods for the treatment of pre-malignant tissue
US5499097A (en) 1994-09-19 1996-03-12 Neopath, Inc. Method and apparatus for checking automated optical system performance repeatability
JPH08287218A (en) 1995-04-10 1996-11-01 Sharp Corp Image composing device
US6430309B1 (en) * 1995-09-15 2002-08-06 Monogen, Inc. Specimen preview and inspection system
US6418236B1 (en) * 1999-06-24 2002-07-09 Chromavision Medical Systems, Inc. Histological reconstruction and automated image analysis
AU3723697A (en) 1996-07-12 1998-02-09 Erim International, Inc. Mosaic construction, processing, and review of very large electronic micrograph composites
US6272235B1 (en) * 1997-03-03 2001-08-07 Bacus Research Laboratories, Inc. Method and apparatus for creating a virtual microscope slide
US6396941B1 (en) * 1996-08-23 2002-05-28 Bacus Research Laboratories, Inc. Method and apparatus for internet, intranet, and local viewing of virtual microscope slides
US5784163A (en) 1996-09-23 1998-07-21 International Business Machines Corporation Optical differential profile measurement apparatus and process
US5836877A (en) * 1997-02-24 1998-11-17 Lucid Inc System for facilitating pathological examination of a lesion in tissue
AU9476798A (en) * 1997-09-10 1999-03-29 Bellsouth Corporation Digital telepathology imaging system with bandwidth optimization and virtual focus control functions
AU1313699A (en) 1997-12-11 1999-06-28 Bellsouth Intellectual Property Corporation Digital telepathology imaging system programmed for identifying image regions ofpotential interest and anticipating sequence of image acquisition
US6424996B1 (en) * 1998-11-25 2002-07-23 Nexsys Electronics, Inc. Medical network system and method for transfer of information
US6535626B1 (en) * 2000-01-14 2003-03-18 Accumed International, Inc. Inspection system with specimen preview
US6711283B1 (en) * 2000-05-03 2004-03-23 Aperio Technologies, Inc. Fully automatic rapid microscope slide scanner

Patent Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5297034A (en) * 1987-04-30 1994-03-22 Corabi International Telemetrics, Inc. Telepathology diagnostic network
US5793969A (en) * 1993-07-09 1998-08-11 Neopath, Inc. Network review and analysis of computer encoded slides
US6148096A (en) * 1995-09-15 2000-11-14 Accumed International, Inc. Specimen preview and inspection system
US5978804A (en) * 1996-04-11 1999-11-02 Dietzman; Gregg R. Natural products information system
US6151405A (en) * 1996-11-27 2000-11-21 Chromavision Medical Systems, Inc. System and method for cellular specimen grading
US6091930A (en) * 1997-03-04 2000-07-18 Case Western Reserve University Customizable interactive textbook
US5993001A (en) * 1997-06-05 1999-11-30 Joslin Diabetes Center, Inc. Stereoscopic imaging system for retinal examination with remote examination unit
US6155603A (en) * 1998-08-13 2000-12-05 Fox; Joshua L. Laboratory reporting system and labeling system therefor

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See also references of EP1252604A4 *

Cited By (27)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1341023A3 (en) * 2002-02-20 2003-11-19 Leica Microsystems Heidelberg GmbH Method for training a user of a scanning microscope, scanning microscope, and software for said training
US7218762B2 (en) 2002-02-20 2007-05-15 Leica Microsystems Cms Gmbh Method for user training for a scanning microscope, scanning microscope, and software program for user training for a scanning microscope
EP1341023A2 (en) * 2002-02-20 2003-09-03 Leica Microsystems Heidelberg GmbH Method for training a user of a scanning microscope, scanning microscope, and software for said training
WO2003096228A1 (en) * 2002-05-10 2003-11-20 Tripath Imaging, Inc. Video microscopy system and multi-view virtual slide viewer capable of simultaneously acquiring and displaying various digital views of an area of interest located on a microscopic slide
AU2003237810B2 (en) * 2002-05-10 2008-01-24 Tripath Imaging, Inc. Video microscopy system and multi-view virtual slide viewer capable of simultaneously acquiring and displaying various digital views of an area of interest located on a microscopic slide
WO2007138369A1 (en) * 2006-05-26 2007-12-06 3Dhistech Kft. Method and system for digitizing a specimen with fluorescent target points
US9310598B2 (en) 2009-03-11 2016-04-12 Sakura Finetek U.S.A., Inc. Autofocus method and autofocus device
US10495867B2 (en) 2009-03-11 2019-12-03 Sakura Finetek U.S.A., Inc. Autofocus method and autofocus device
US9599804B2 (en) 2009-05-22 2017-03-21 Leica Microsystems Cms Gmbh System and method for computer-controlled execution of at least one test in a scanning microscope
CN102439506A (en) * 2009-05-22 2012-05-02 莱卡微系统Cms有限责任公司 System and method for computer-controlled execution of at least one test in a scanning microscope
WO2010133375A1 (en) * 2009-05-22 2010-11-25 Leica Microsystems Cms Gmbh System and method for computer-controlled execution of at least one test in a scanning microscope
CN102439506B (en) * 2009-05-22 2014-11-05 莱卡微系统Cms有限责任公司 System and method for computer-controlled execution of at least one test in a scanning microscope
US10139613B2 (en) 2010-08-20 2018-11-27 Sakura Finetek U.S.A., Inc. Digital microscope and method of sensing an image of a tissue sample
CN107255863B (en) * 2010-08-20 2020-06-05 美国樱花检验仪器株式会社 Digital microscope
EP2910993A1 (en) * 2010-08-20 2015-08-26 Sakura Finetek U.S.A., Inc. Digital microscope
EP3018520A1 (en) * 2010-08-20 2016-05-11 Sakura Finetek U.S.A., Inc. Digital microscope
WO2012024627A1 (en) * 2010-08-20 2012-02-23 Sakura Finetek U.S.A., Inc. Digital microscope
CN107255863A (en) * 2010-08-20 2017-10-17 美国樱花检验仪器株式会社 Digital microscope
EP2469434A1 (en) * 2010-12-27 2012-06-27 Siemens Aktiengesellschaft Method and device for displaying medical image data
GB2492218A (en) * 2011-06-16 2012-12-26 Leeds Teaching Hospitals Nhs Trust Display of virtual slide images with different magnification regions
US8970618B2 (en) 2011-06-16 2015-03-03 University Of Leeds Virtual microscopy
US10269094B2 (en) 2013-04-19 2019-04-23 Sakura Finetek U.S.A., Inc. Method for generating a composite image of an object composed of multiple sub-images
EP2804145A1 (en) * 2013-05-14 2014-11-19 Olympus Corporation Microscope system and stitched area decision method
EP2871513A1 (en) * 2013-11-12 2015-05-13 Olympus Corporation Microscope system
US10007102B2 (en) 2013-12-23 2018-06-26 Sakura Finetek U.S.A., Inc. Microscope with slide clamping assembly
US11280803B2 (en) 2016-11-22 2022-03-22 Sakura Finetek U.S.A., Inc. Slide management system
US11193950B2 (en) 2019-03-29 2021-12-07 Sakura Finetek U.S.A., Inc. Slide identification sensor

Also Published As

Publication number Publication date
US7856131B2 (en) 2010-12-21
US7149332B2 (en) 2006-12-12
US20110145755A1 (en) 2011-06-16
US6396941B1 (en) 2002-05-28
EP1252604A1 (en) 2002-10-30
EP1252604A4 (en) 2006-04-26
US20090210809A1 (en) 2009-08-20
CA2398736C (en) 2013-04-02
US7542596B2 (en) 2009-06-02
US20040141637A1 (en) 2004-07-22
HK1049723A1 (en) 2003-05-23
US6674881B2 (en) 2004-01-06
CA2398736A1 (en) 2001-07-26
US8306298B2 (en) 2012-11-06
AU2001229630A1 (en) 2001-07-31
US20020135678A1 (en) 2002-09-26
US20060188137A1 (en) 2006-08-24

Similar Documents

Publication Publication Date Title
CA2398736C (en) Method and apparatus for internet, intranet, and local viewing of virtual microscope slides
EP1686533B1 (en) Method and apparatus for creating a virtual microscope slide
US6674884B2 (en) Apparatus for remote control of a microscope
US6226392B1 (en) Method and apparatus for acquiring and reconstructing magnified specimen images from a computer-controlled microscope
WO1998044446A9 (en) Method and apparatus for acquiring and reconstructing magnified specimen images from a computer-controlled microscope
JP5600584B2 (en) Computer-readable recording medium storing data structure
WO1999013360A2 (en) Digital telepathology imaging system with bandwidth optimization and virtual focussing

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BY BZ CA CH CN CR CU CZ DE DK DM DZ EE ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NO NZ PL PT RO RU SD SE SG SI SK SL TJ TM TR TT TZ UA UG US UZ VN YU ZA ZW

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): GH GM KE LS MW MZ SD SL SZ TZ UG ZW AM AZ BY KG KZ MD RU TJ TM AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE TR BF BJ CF CG CI CM GA GN GW ML MR NE SN TD TG

121 Ep: the epo has been informed by wipo that ep was designated in this application
DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
WWE Wipo information: entry into national phase

Ref document number: 2398736

Country of ref document: CA

WWE Wipo information: entry into national phase

Ref document number: 2001942762

Country of ref document: EP

WWP Wipo information: published in national office

Ref document number: 2001942762

Country of ref document: EP

REG Reference to national code

Ref country code: DE

Ref legal event code: 8642

NENP Non-entry into the national phase

Ref country code: JP