WO2003096228A1 - 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 - Google Patents
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 Download PDFInfo
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- WO2003096228A1 WO2003096228A1 PCT/US2003/014583 US0314583W WO03096228A1 WO 2003096228 A1 WO2003096228 A1 WO 2003096228A1 US 0314583 W US0314583 W US 0314583W WO 03096228 A1 WO03096228 A1 WO 03096228A1
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- H—ELECTRICITY
- H04—ELECTRIC COMMUNICATION TECHNIQUE
- H04N—PICTORIAL COMMUNICATION, e.g. TELEVISION
- H04N1/00—Scanning, transmission or reproduction of documents or the like, e.g. facsimile transmission; Details thereof
- H04N1/32—Circuits or arrangements for control or supervision between transmitter and receiver or between image input and image output device, e.g. between a still-image camera and its memory or between a still-image camera and a printer device
- H04N1/32101—Display, printing, storage or transmission of additional information, e.g. ID code, date and time or title
- H04N1/32106—Display, printing, storage or transmission of additional information, e.g. ID code, date and time or title separate from the image data, e.g. in a different computer file
- H04N1/32112—Display, printing, storage or transmission of additional information, e.g. ID code, date and time or title separate from the image data, e.g. in a different computer file in a separate computer file, document page or paper sheet, e.g. a fax cover sheet
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- G—PHYSICS
- G02—OPTICS
- G02B—OPTICAL ELEMENTS, SYSTEMS OR APPARATUS
- G02B21/00—Microscopes
- G02B21/36—Microscopes arranged for photographic purposes or projection purposes or digital imaging or video purposes including associated control and data processing arrangements
- G02B21/365—Control or image processing arrangements for digital or video microscopes
- G02B21/367—Control 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
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- G—PHYSICS
- G06—COMPUTING; CALCULATING OR COUNTING
- G06F—ELECTRIC DIGITAL DATA PROCESSING
- G06F16/00—Information retrieval; Database structures therefor; File system structures therefor
- G06F16/50—Information retrieval; Database structures therefor; File system structures therefor of still image data
- G06F16/54—Browsing; Visualisation therefor
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- H—ELECTRICITY
- H04—ELECTRIC COMMUNICATION TECHNIQUE
- H04N—PICTORIAL COMMUNICATION, e.g. TELEVISION
- H04N1/00—Scanning, transmission or reproduction of documents or the like, e.g. facsimile transmission; Details thereof
- H04N1/04—Scanning arrangements, i.e. arrangements for the displacement of active reading or reproducing elements relative to the original or reproducing medium, or vice versa
- H04N1/0402—Scanning different formats; Scanning with different densities of dots per unit length, e.g. different numbers of dots per inch (dpi); Conversion of scanning standards
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- H—ELECTRICITY
- H04—ELECTRIC COMMUNICATION TECHNIQUE
- H04N—PICTORIAL COMMUNICATION, e.g. TELEVISION
- H04N1/00—Scanning, transmission or reproduction of documents or the like, e.g. facsimile transmission; Details thereof
- H04N1/04—Scanning arrangements, i.e. arrangements for the displacement of active reading or reproducing elements relative to the original or reproducing medium, or vice versa
- H04N1/0402—Scanning different formats; Scanning with different densities of dots per unit length, e.g. different numbers of dots per inch (dpi); Conversion of scanning standards
- H04N1/0408—Different densities of dots per unit length
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- H—ELECTRICITY
- H04—ELECTRIC COMMUNICATION TECHNIQUE
- H04N—PICTORIAL COMMUNICATION, e.g. TELEVISION
- H04N2201/00—Indexing scheme relating to scanning, transmission or reproduction of documents or the like, and to details thereof
- H04N2201/32—Circuits or arrangements for control or supervision between transmitter and receiver or between image input and image output device, e.g. between a still-image camera and its memory or between a still-image camera and a printer device
- H04N2201/3201—Display, printing, storage or transmission of additional information, e.g. ID code, date and time or title
- H04N2201/3225—Display, printing, storage or transmission of additional information, e.g. ID code, date and time or title of data relating to an image, a page or a document
- H04N2201/3247—Data linking a set of images to one another, e.g. sequence, burst or continuous capture mode
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- H—ELECTRICITY
- H04—ELECTRIC COMMUNICATION TECHNIQUE
- H04N—PICTORIAL COMMUNICATION, e.g. TELEVISION
- H04N2201/00—Indexing scheme relating to scanning, transmission or reproduction of documents or the like, and to details thereof
- H04N2201/32—Circuits or arrangements for control or supervision between transmitter and receiver or between image input and image output device, e.g. between a still-image camera and its memory or between a still-image camera and a printer device
- H04N2201/3201—Display, printing, storage or transmission of additional information, e.g. ID code, date and time or title
- H04N2201/3225—Display, printing, storage or transmission of additional information, e.g. ID code, date and time or title of data relating to an image, a page or a document
- H04N2201/3253—Position information, e.g. geographical position at time of capture, GPS data
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- H—ELECTRICITY
- H04—ELECTRIC COMMUNICATION TECHNIQUE
- H04N—PICTORIAL COMMUNICATION, e.g. TELEVISION
- H04N2201/00—Indexing scheme relating to scanning, transmission or reproduction of documents or the like, and to details thereof
- H04N2201/32—Circuits or arrangements for control or supervision between transmitter and receiver or between image input and image output device, e.g. between a still-image camera and its memory or between a still-image camera and a printer device
- H04N2201/3201—Display, printing, storage or transmission of additional information, e.g. ID code, date and time or title
- H04N2201/3274—Storage or retrieval of prestored additional information
- H04N2201/3277—The additional information being stored in the same storage device as the image data
Definitions
- the present invention relates generally to the acquisition and analysis of digital images of objects and areas of interest located on a microscopic slide, and more particularly to a system and method capable of providing various digital views ofthe same areas of interest to a user, where each view provides digital images with different information for use in quantitative and qualitative analysis of the objects on the microscopic slide.
- Microscopic analysis is a widely used research tool in the field of cellular biology and pathology. Specifically, tissue samples and cell preparations are visually inspected by pathologists under several different conditions and test procedures with use of microscopes. Based on these visual inspections, determinations concerning the tissue or cellular material can be deduced. For example, in the area of cancer detection and research, microscopic analysis aids in the detection and quantification of genetic materials that appear related to the cause and progression of cancer, such as genes or messenger RNA, or the expression of this genetic information in the form of proteins such as, for example, through gene amplification, gene deletion, gene mutation, messenger RNA molecule quantification, or protein expression analyses.
- microscopic analysis of tissue samples is typically an iterative process.
- the pathologist or other user usually begins with a low-resolution magnification setting on the microscope in which they are able to see a larger area ofthe sample. From this low-resolution view, the user determines areas ofthe sample that require closer inspection. These areas are then typically further analyzed using higher magnification levels.
- the user may wish to alternate between the various magnification levels to determine which magnification level provides a desired and informative view ofthe selected area of the tissue sample.
- the user must make a mental note ofthe current view at one magnification and compare it to the views at the other magnifications to determine which provides the best level of detail and resolution.
- the user after each area is inspected, the user must typically return to the low-resolution setting to collect his/her bearings in the sample and to look for a next area ofthe sample for inspection. This procedure may cause the user to become confused as to what areas have and have not been inspected in the sample.
- the task consists of identifying the cancer areas in the tissue section based on the tissue morphology and quantitatively or qualitatively assessing the marker expression within these areas versus the expression in normal regions.
- the marker presentation is often separated from the morphology through the use of different illumination methods, such as, for example, bright field versus dark field illumination (for the radiometric ISH assay) or bright field versus fluorescence microscopy, or different contrast methods such as, for example, phase contrast, differential interference contrast, etc.
- these data files are provided to a pathologist or other user for viewing.
- the files are stored on a computing system that can be accessed either locally or remotely via either an Intranet or the Internet connection.
- the advantage of these conventional virtual slide viewers over more conventional methods of inspection with a microscope is that these virtual slide viewers allow a user to view both a low-resolution "big picture" view ofthe slide, while also allowing the user to view magnified images of selected areas ofthe slide.
- the files containing the scans of a slide can either be transmitted to or accessed by the user from a remote location.
- Figure 1 illustrates a typical monitor display of data from a conventional virtual slide viewer.
- the conventional slide viewer displays a low-resolution view 12 ofthe slide on a display 10.
- the low-resolution view consists of a series of tiles 14 that each represents a scan of a portion ofthe slide.
- the tiles 14 are pieced together to provide a view of either all or most ofthe slide.
- the user selects an area of interest in the slide.
- a separate window 16 on the display provides the user with higher magnified images ofthe selected area.
- the display includes a control window 18 typically indicating all or part of the information about the presentation mode, presentation options, the displayed virtual slide 12 and the magnified view 16.
- the biological samples must first undergo specific detection and revelation preparations based on the analysis to be performed on the slide. These preparations may involve the addition of markers and dyes to the tissue sample. In some instances, a first dye is added to the sample and observations are made ofthe slide. The sample is then removed, destained and then restained with another dye for a second observation. As such, several different observations of a sample with different preparations can be made during an analysis of a sample.
- the preparation of samples for detection may involve different types of preparation techniques that are suited to microscopic image analysis, such as, for example, hybridization-based and immunolabeling-based preparation techniques.
- detection techniques may be coupled with appropriate revelation techniques, such as, for example, fluorescence-based and absorbance color reaction-based techniques.
- Colorimetric, Radiometric and Fluorescent In Situ Hybridization are detection and revelation techniques used, for example, for detection and quantification in genetic information amplification and mutation analyses.
- CISH, RISH and FISH can be applied to histological or cytological samples. These techniques use specific complementary probes for recognizing corresponding precise sequences.
- the specific probe may include a colorimetric (CISH), radiometric (RISH) or a fluorescent (FISH) marker, wherein the samples are then analyzed using a transmitted light microscope with bright filed or dark field illumination or a fluorescence microscope, respectively.
- CISH colorimetric
- RISH radiometric
- FISH fluorescent
- the use of a colorimetric, radiometric or fluorescent marker depends on the goal ofthe user; each type of marker having corresponding advantages over the other in particular instances.
- immunohistochemistry 'THC
- immunocytochemistry ICC
- IHC is the application of immunochemistry to tissue sections
- ICC is the application of immunochemistry to cultured cells or tissue imprints after they have undergone specific cytological preparations such as, for example, liquid-based preparations.
- Immunochemistry is a family of techniques based on the use of a specific antibody, wherein antibodies are used to specifically target molecules inside or on the surface of cells. The antibody typically contains a marker that will undergo a biochemical reaction, and thereby experience a change of color, upon encountering the targeted molecules.
- signal amplification may be integrated into the particular protocol, wherein a secondary antibody, that includes the marker stain, follows the application of a primary specific antibody.
- a secondary antibody that includes the marker stain
- chromagens of different colors are used to distinguish among the different markers.
- the coordinate system ofthe subsequent scan ofthe tissue sample will be somewhat offset from the coordinate system of scans occurring prior to removal ofthe slide. This, in turn, makes it difficult, if not impossible, to positionally correlate the various scans of the same area of interest.
- the present invention provides a multi-view virtual slide viewing system that provides a display capable of illustrating multiple viewing windows containing different scans of an area of interest.
- the views may be either different magnifications of a selected area or different scans ofthe slide taken under different conditions.
- the slide viewing system ofthe present invention may display a scan ofthe slide taken in with bright field illumination in one window and a scan ofthe same view with dark field illumination in another window ofthe display.
- the slide viewer ofthe present invention is able to display a unitary low-resolution scan ofthe slide taken with a cost efficient flat bed scanner, as opposed to a display formed of tiles, and combine it in a correlated way with the image presentation of a tiled high resolution scan of the same slide taken with another scan platform.
- the low-resolution display does not require processing to blend tiles together nor does it experience problems with resolution at tile boundaries.
- An additional advantage consists in the ability to add the high resolution scan at a later time and only on demand. In that respect a flat bed scanner can be used as a cost efficient pre scan device.
- the multi- view virtual slide viewer can also present additional views of a slide derived from an original scan via image analysis, such as displaying certain features via false color presentation and look up tables or images derived from chromagen separation.
- the chromagen separation is able to digitally separate the different chromagens such as markers labeled with certain stains, the counter stain, etc. and present them individually in separate images. Chromagen separation is described in patent applications filed by the Assignee ofthe present application. These patent applications are 1) U.S.
- the multi-view virtual slide viewer ofthe present invention is intended for display of scans of an area of interest at different magnifications and different focal planes. It is also contemplated for display of scans taken with different sample preparations, scan platforms, or microscope settings such as the following list which only names a few examples:
- TMA tissue micro arrays
- the present invention provides a virtual slide viewing system connected to a database stored in a storage device.
- the database includes at least one set of data related to a particular tissue or cytology sample.
- the data set includes a low-resolution scan of either all or a substantial portion ofthe slide. This scan can be acquired using a flat bed scanner or similar device capable of scanning the entire slide. It also can be derived from subsampling the data ofthe high resolution scan.
- the data set can include various scans ofthe tissue sample taken under different conditions and/or sample preparations.
- the database may include scans taken at different levels of resolution of different areas ofthe sample. It may also include scans taken with different microscope illumination and/or contrast settings and scans taken with different sample preparations.
- the slide prior to the slide being scanned for the first time, the slide is provided with a zero point, i.e., (0, 0), for its coordinate system.
- This zero point is placed on the slide as a fiducial, typically in the form of an ink dot. All subsequent scans ofthe tissue sample are referenced from this zero point.
- the coordinate system for the new position ofthe slide is calibrated to the original zero point so that subsequent scans can be positionally correlated with the previous scans.
- the microscope is first checked for calibration differences. The slide is then placed on the microscope and aligned with the microscope using the previously marked zero point on the slide.
- each scan is stored in one or more separate files in the database.
- a descriptive header file is included in the data set. The header includes the zero origin coordinate information for the slide. Furthermore it contains resolution information ofthe scans i.e.
- each scan file also includes a header describing the size ofthe scan in pixels. It may also include text information related to the scan, such as scanner hardware information, scanning date, preparation used for the scan, etc.
- the multi-view virtual slide viewer ofthe present invention further includes a computing system with a display.
- the computing system is connected either physically to the database or remotely via an Intranet, Internet, or other connection.
- the computing system ofthe present invention controls the display such that multiple views ofthe sample can be displayed simultaneously. Specifically, during an analysis session, the computing system first retrieves the data for a low-resolution scan display and presents this on the screen.
- the computing system further provides a position indicator, such as an arrow, window box, etc., superimposed over the low-resolution scan. This position indicator can be manipulated by the user ofthe computing system to select different areas of interest on the slide.
- the computing system is also capable of displaying various additional windows on the terminal.
- Some ofthe windows are used to display selected scans chosen by the user.
- One ofthe windows is a text window. This window may include information associated with each scan selected for viewing by the user.
- the text window may also allow the user to enter and store notes associated with a scan. These annotations can be associated with a complete scan or with individual selected locations within a scan. Additionally, the computing system allows the user to toggle between the various scans for the chosen area if desired.
- the computing system is also capable of displaying a single full window view of a particular scan. Specifically, the user may select to view a scan full screen. In this instance, the computing system will hide the low-resolution scan and text window and will display the selected screen full screen.
- a navigation guide such as keyboard shortcuts or pointers, is made available to the user to navigate within the scan.
- the computing system ofthe present invention is also capable of superimposing the images of slides over each other such that the user may view corresponding pixels from all stored scans for a selected area.
- the user may wish to view one scan but be able to click on an area ofthe scan and see views ofthe same area from other scans.
- the user may wish to view the bright field scan and select areas ofthe scan and see the corresponding dark field pixels for the selected area.
- the user could view a scan of one magnification and by selecting a particular area of the scan see pixels of a higher magnification scan for the selected area. This would be similar to placing a magnifying glass over one section ofthe scan.
- the computing system ofthe present invention first displays a scan selected by the user.
- the computing system provides selection tools, such as a pointer, window box, etc. that allow the user to select a portion of the scan.
- the computing system provides information to the user about what other scans are available in a pop-up box.
- the computing system uses the coordinates ofthe selection made by the user, retrieves the data related to these coordinates from the scan file associated with the scan selected by the user, and replaces the current data displayed within the box with the data from the selected scan.
- the computing system will retrieve data from the scan file associated with the dark field scan and will replace the data in the window selected by the user with the dark field scan data, thereby providing the user with a complementary view with new information ofthe same scan in the selected area.
- a data set for a tissue sample will include a large amount of data representing different scans using different lighting and contrast settings, magnification, and sample preparations.
- the computing system ofthe present invention allows the user to save individual views ofthe sample in a snap shot gallery.
- the user may indicate that they wish to save a particular scan.
- the computing system ofthe present invention saves the scan in a separate file or creates a link to the file in the main header.
- the computing system may also associate a thumbnail ofthe scan on the viewing screen so that the user can more easily recall the scan.
- the computing system ofthe present invention may also allow the user to annotate a scan with particular notes or information.
- the annotations can be in text form or they may be graphic information, such as lines, circles, etc., that hi-light parts ofthe scan.
- the computing system also allows the user to perform certain measurements. These could be measurements related to the geometrical dimensions ofthe section or parts ofthe section, features describing the morphology and neighborhood relationships of cells within the tissue, single cell features, measurements such as the amount of dye absorbed by a cell, combined measurements ofthe same objects or areas in different scans ofthe same slide, etc.
- Figure 1 is an illustration of a display from a monitor illustrating operation of a conventional virtual slide viewer.
- Figure 2A is an illustration of a basic microscope set up for bright field and fluorescent microscopy.
- Figure 2B is an illustration of a basic microscope set up for dark field and bright field illumination.
- Figure 2C is an illustration ofthe correlation of positions on a slide when moved to different stands according to one embodiment ofthe present invention.
- Figure 3 is schematic block diagram of the virtual slide viewing system according to one embodiment ofthe present invention.
- Figure 4A is an illustration of data displayed by the virtual slide viewing system ofthe present invention illustrating display of multiple scans for a selected area according to one embodiment ofthe present invention.
- Figure 4B is an illustration of data displayed by the virtual slide viewing system ofthe present invention illustrating display of a full screen view of a scan of interest according to one embodiment ofthe present invention.
- Figure 4C is an illustration of data displayed by the virtual slide viewing system ofthe present invention illustrating pixels from one scan superimposed on a first scan according to one embodiment ofthe present invention.
- Figure 4D is an illustration of data displayed by the virtual slide viewing system ofthe present invention illustrating pixels from one scan superimposed on a first scan according to another embodiment ofthe present invention.
- Figure 4E is an illustration of data displayed by the virtual slide viewing system ofthe present invention illustrating storing of scans of interest in a thumbnail gallery.
- the microscope includes first and second light sources, 20 and 22, and first and second shutters, 24 and 26.
- the first light source is positioned to provide light to the slide 28 via a dichroic beamsplitter 30 when the first shutter is opened.
- the second light source 22 provides a back light source to the slide when the second shutter 26 is open.
- the slide is viewed through the objective 32 by an observer 34.
- By closing the first shutter 24 and opening the second shutter 26 a bright field image is taken ofthe field of view.
- opening the first shutter 24 and closing the second shutter 26 enables the system to take the fluorescent image ofthe same field of view.
- FIG. 2A An example for a bright field/fluorescence microscope as described in Figure 2A is the Axioskop 2 Mot from Zeiss with two (2) additional integrated automatic shutters.
- FIG. 2B An example is shown in Figure 2B and is the same device with an integrated automatic dark field condenser 36 having a change mechanism 38, which can be automatically switched between a bright field condensor 40 and the dark field condensor 42.
- a third example can be an integrated automated interferometer, such as for example, the Spectracube system from Applied Spectral Imaging, which allows the acquisition of multiple images with very narrow bandwidth spectral characteristics ofthe same field of view. Only when all these different images are taken does the system move to the next field of view and the process is repeated.
- one way of stitching these images together to seamless virtual slides with a one-to-one pixel relation between the different views could be the use ofthe tiling parameters derived from the bright field scan. This is especially important as the precise tiling normally depends on the correlation between the overlap of adjacent images. As there is usually very little information in images derived from dark field or fluorescent settings, (most of the images is just black), correlation between adjacent images would not work in these specific settings and the tiling parameters have to be gained from elsewhere such as for example the bright field scan. The disadvantage of this method is the time it will take to switch between the different microscope settings per field. Therefore this method is only feasible for low throughput scanning and for specialty high precision scans.
- the system completes a scan with one microscope setting and only switches to a new setting at the end ofthe scan to run the slide again with the new setting.
- the precision ofthe correlation ofthe different views ofthe scans is obviously limited by the precision ofthe mechanics ofthe scanning stage that the automated microscope is using. The mechanics will determine with what precision it is possible to go back to the same starting point ofthe first scan.
- Examples are slides which are scanned with one preparation, destained, restained and scanned with the new preparation again; or consecutive histological sections, where section one is prepared in one way and section two in a different way; or slides which went through a fast cost effective low resolution pre scan, for example on a flat bed scanner, for a first investigation and where a high resolution scan is ordered as a consequence ofthe first investigation later on, the high resolution scan being run on a different platform.
- the slides have to be marked with at least two (2) fiducials in diagonally opposing corners ofthe slide, for example upper left and lower right corner.
- the fiducials can be inserted using an ink dotter. From the number of pixels in the x and y direction between the two fiducials, determined in the images ofthe two (2) different scans the ratios nx and ny ofthe dimensions in x- and y- direction can be computed as referenced in Figure 2C:
- an area of interest selected in the display of scan 1 in the multi-view virtual slide viewer can be related to the corresponding area in scan 2:
- the coordinates are preferably related to one ofthe fiducial locations as zero point, as it cannot be guaranteed that some ofthe devices used for the scans will not truncate the left or the right end ofthe slide.
- the multi-view virtual slide viewer of the present invention remedies this problem.
- the virtual slide viewer ofthe present invention can provide more information to the user in analyzing the slide.
- the present invention can use a flat bed scanner to take the low magnification scan ofthe slide and other scanners for higher magnification scans.
- the virtual slide viewer ofthe present invention allows the virtual slide viewer ofthe present invention to provide a unitary low magnification scan to the user, as opposed to a tiled view.
- the separation into a low resolution scan being done on one device and the high resolution scan being acquired on an other device at a later time may have several advantages.
- the more expensive high-resolution scan may only be ordered if the investigation ofthe low-resolution scan indicates the need for it, i.e. scanning of TMAs.
- the low resolution scan may be used in an interactive labeling station to mark areas of interest which later can be relocated in the high resolution virtual slide image, which was acquired by an automatic scanning platform at an earlier time, for further investigation.
- Figure 3 a generalized view ofthe multi-view virtual slide viewer ofthe present invention is illustrated. Specifically, Figure 3 illustrates an embodiment ofthe present invention in a networked system.
- the slide viewer 50 includes one or several computing systems 52 each containing general processors.
- the computing systems importantly include display monitors 54.
- Each computing system is connected to a network 56, which could be an Intranet, Internet, or other network connection.
- a file server 58 located on the network is Also located on the network.
- the files representing the various scans of a tissue sample are stored on the file server. These files are then accessed by one ofthe computing systems 52 via the network 56.
- the slide viewer ofthe present invention provides a low-magnification scan 60 of either all or portions of a slide.
- This low-magnification scan is used as a visual and navigational aid to the user.
- a navigational guide such as a moveable window 62, pointer, etc.
- the display also includes either one or several windows, 64 and 66. These windows are used to display various scans ofthe slide. These scans may be either scans at various magnifications, or scans made using different microscope illumination and contrast settings, or scans ofthe sample using different preparations.
- the scans displayed in these windows correlate to the position ofthe navigation guide 62 on the low-magnification scan.
- the user can view the various saved scans for various locations on the slide.
- An additional window 68 may also be used to display text data concerning each scan. The user can also use this window to add text concerning a scan.
- the multi-view slide viewer system ofthe present invention includes tools 74 allowing the user to draw graphic information on the scans to highlight areas of interest on the slide.
- the present invention first includes a header file in the data set of scans.
- This header file contains the zero origin, (i.e., 0, 0) ofthe coordinate system for the low-magnification scan. It further includes an array containing the location of pixels in the low-magnification scan.
- the header includes a pointer or call out ofthe file name containing the actual data for low-magnification scan. Further, in the array, under each pixel location is listed the file names ofthe scans that were taken at these pixel positions, such that by selecting a pixel location in the low magnification scan, all ofthe scan files related to this pixel location can be accessed.
- the data set further includes the individual scan files for the slide.
- Each ofthe scan files also includes a local header followed by the actual scan data.
- the local header includes such information as the size ofthe file and the location on the slide where the scan was performed. Further, the header may include any text or graphical data entered at the time the scan was taken.
- the overall header includes the origin and size ofthe overall slide with callouts or pointers to each scan and the corresponding location ofthe scan on the slide and each scan includes the actual data and text and graphical information concerning the individual scan.
- the user will initially access either the local storage device on the computing system 52 or access the file server 58 via the network 56.
- the computing system initially sends information concerning its display size and other compatibility information to the server.
- the server formats the data ofthe scan so that it can be properly displayed by the client computing system.
- the computing system 52 accesses the main file header for the data set and with reference to Figure 4A, displays the low magnification scan in a window 60. Additionally, a window or other navigation device 62 is superimposed over the low magnification scan.
- the user moves the window 62 to the desired area using either a mouse or keyboard controls.
- the computing system notes the x, y coordinates ofthe area chosen by the user and accesses the main header file.
- the computing system accesses the array and determines the scans associated with the coordinate location chosen by the user.
- the names of these various scans are then provided in a popup selection box 70 to the user.
- the computing system will access the data for the selected scan and display it in one ofthe windows, 64 and 66.
- the computing system will access the header associated with the data and will display any text associated with the scan in the text window 68, such as scanner hardware information, scanning date, preparation used for the scan, etc. Further, if there is any graphical data, such as arrows, circles, pointers, etc., the computing system retrieves this data and displays it over the scan. For example, Figure 4A illustrates a circle 72 that has been drawn around an area of interest in the scan.
- the user may select another scan to be displayed in the next window 66. Further, the user may toggle between different scans. Additionally, the user may enter text information using the text window 68 to be saved with the scan.
- the computing system may also include a graphic toolbar 74 that allows the user to draw and save graphic images, such as circles, pointers, etc., on the scan.
- the multi-view virtual scan viewer ofthe ' present invention allows the user access not only to scans representing different magnifications, but also to various other scans associated with the sample.
- the multi-view virtual slide viewer ofthe present invention provides scans taken with different microscope illumination and contrast settings, different magnifications, and with different slide preparations. As such, all scanned information related to the sample is provided to the user for analysis.
- digitally created new views of acquired scans can be computed and presented in the multi-view virtual slide viewer. Such views for example may display just one marker digitally extracted via Chromagen Separation from the RGB image of a multi marker scan. It may display just the counter stain part ofthe scanned slide.
- the multiview virtual slide viewer can also be used to show views of additional scans which are positionally unrelated to the displayed initial scan, but are related in a sense of complementary information display, such as for example views of scans out of a reference database or a histology or cytology image atlas. These are only some examples of many possible embodiments. Because the user can view the various scans simultaneously for a selected area and can toggle between scans, the user can perfo ⁇ n a more complete analysis ofthe slide.
- the multi-view virtual slide viewer ofthe present invention provides additional features.
- the multi- view virtual slide viewer ofthe present invention may provide a full screen view of a scan of interest.
- the window 64 containing the scan is maximized and the remaining windows are hidden.
- the multi- view virtual slide viewer ofthe present invention may further provide keyboard shortcuts to allow the viewer to navigate within the scan.
- the multi- view slide viewer may include navigational guides such as directional arrows 76 that may be clicked with a mouse to navigate within the scan.
- the multi- view slide viewer may display the pop-up selection box 70 allowing the user to select or toggle to other scans.
- Figures 4C and 4D illustrate another important aspect ofthe present invention.
- the multi- view virtual slide viewer ofthe present invention is capable of superimposing the scanned pixels from one scan onto the pixels of another scan. This, in turn, allows the user to view one scan and toggle certain portions ofthe scan to see different scan views for a selected area ofthe scan.
- a classic example of this aspect ofthe present invention is to provide a virtual magnifying glass for the user.
- the user could display a scan 64 having a lower magnification.
- a selector 78 such as a window or other device, the user could select an area ofthe scan for further magnification.
- the virtual slide viewer Using the coordinates ofthe selected area, the virtual slide viewer will access a corresponding scan for the selected area and retrieve pixel data from the scan file corresponding a scan taken at higher magnification for the pixel location. These magnified pixel data is then superimposed over the lower magnification pixels within the selected window 78 to thereby provide a magnified view.
- This same concept would hold true for other types of scans. For example, the user may display a bright field scan and choose within the bright field scan to view corresponding dark field scan data, fluorescent data, spectral data, data derived from chromagen separation, etc.
- Figure 4D illustrates a similar concept, except that in this embodiment a slide bar 80 is used.
- One scan is displayed to, the left ofthe slide bar and a different scan is displayed to the right ofthe slide bar.
- a bright field scan is illustrated on the left and a dark field scan is located on the right.
- the slide bar represents the transition from one set of scan data to the other.
- the user can change the data display. Specifically, if the slide bar is moved left, the bright field scan pixels previously located on the left of the slide bar that are now on the right are superimposed by the virtual slide viewer with the corresponding pixels from the dark field scan. It is understood that this concept ofthe invention applies to all the different views.
- each side may be different magnifications, with the slide bar changing magnification as it is slid left or right. It may be used to view bright field data versus fluorescent data, different spectral data, different data derived from chromagen separation, etc.
- the virtual slide viewer ofthe present invention further allows the user to take snap shots ofthe scans. Specifically, while viewing the scans the user may flag particular scans of interest.
- the parameters ofthe flagged scan such as location, magnification, size and type of scan (bright field, dark field, etc.) are stored in the database, along with date, time and user identification.
- the user may add textual comment to the snapshots. These comments are also stored with date, time and user identification.
- the user may select to display her/his own snapshots only or the snapshots of all users.
- the saved scan may appear as a thumbnail 82 in a snap shot gallery 84 displayed on the monitor. This gallery may replace the low magnification map image 60. The user can review these saved images by clicking on the thumbnail. These saved scans can also be used to generate reports concerning the analysis ofthe tissue.
- the computing system ofthe present invention also allows the user to perform measurements. These could be measurements of large structural compounds ofthe slide, such as the dimensions of whole glands, tissue layers, large cell clusters etc., or of smaller compounds such as individual cells.
- the measurements can be related to individual cell features, such as the cell mo ⁇ hology, texture, amount of dye absorbed by the cells, or of more global features such as the neighborhood relationships between cells in a tissue section, etc.
- features can be extracted from multiple views ofthe same scan to create a feature set with a maximum of information.
- Features extracted from the scans can be presented and displayed in a graphical way as a new view ofthe scan in the multi- view virtual slide viewer.
Abstract
Description
Claims
Priority Applications (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
AU2003237810A AU2003237810B2 (en) | 2002-05-10 | 2003-05-09 | 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 |
JP2004504146A JP2005530225A (en) | 2002-05-10 | 2003-05-09 | Video microscope system and multi-view virtual slide viewer that simultaneously acquire and display various digital representations of a region of interest located on a microscope slide |
CA002485414A CA2485414A1 (en) | 2002-05-10 | 2003-05-09 | 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 |
EP03736572A EP1504379A1 (en) | 2002-05-10 | 2003-05-09 | 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 |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
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US10/143,735 | 2002-05-10 | ||
US10/143,735 US20030210262A1 (en) | 2002-05-10 | 2002-05-10 | 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 |
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WO2003096228A1 true WO2003096228A1 (en) | 2003-11-20 |
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PCT/US2003/014583 WO2003096228A1 (en) | 2002-05-10 | 2003-05-09 | 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 |
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US (2) | US20030210262A1 (en) |
EP (1) | EP1504379A1 (en) |
JP (1) | JP2005530225A (en) |
AU (1) | AU2003237810B2 (en) |
CA (1) | CA2485414A1 (en) |
WO (1) | WO2003096228A1 (en) |
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Also Published As
Publication number | Publication date |
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AU2003237810B2 (en) | 2008-01-24 |
US20090006969A1 (en) | 2009-01-01 |
CA2485414A1 (en) | 2003-11-20 |
AU2003237810A1 (en) | 2003-11-11 |
JP2005530225A (en) | 2005-10-06 |
EP1504379A1 (en) | 2005-02-09 |
US20030210262A1 (en) | 2003-11-13 |
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