1. Field of the Invention
The present invention generally relates to digital microscopy and more specifically relates to the processing and analysis of digital slides.
2. Related Art
In the growing field virtual microscopy, the first challenges to be overcome were related to the digital imaging of microscope slides (“scanning”). Conventional image tiling is one approach that is widely prevalent in the virtual microscopy industry. The image tiling approach to scanning microscope slides employs a square or rectangular camera called a fixed area charge coupled device (“CCD”). The CCD camera takes hundreds or thousands of individual pictures (“image tiles”) of adjacent areas on the microscope slide. Then the thousands of image tiles are each separately stored as a bitmap (“bmp”) or a JPEG (“jpg”) file on a computer. An index file is also required in order to identify the name of each image tile and its relative location in the overall image. As would be expected, the taking of thousands of individual pictures and storing each picture as an image tile along with creation of the index files takes a significantly long time. A conventional image tiling approach is described in U.S. Pat. No. 6,101,265. Although slow and cumbersome, conventional image tiling solutions did succeed in scanning microscope slides to create a digital slide.
Once the digital slide was present in a computer system, computer assisted image analysis became possible. Two significant drawbacks of processing image tiles are the computational expense of aligning tiles and correlating overlaps, and the presence of image artifacts along the seams between tiles. These problems each prevented practical application of automated image analysis to digital slide images. It has also proved difficult to maintain accurate focus for each of thousands of tiles in a digital slide produced in this way, reducing image quality.
A radical change in the virtual microscopy field has recently been developed by Aperio Technologies, Inc. that uses a new line scanning system to create a digital slide in minutes. It also creates the digital slide as a single TIFF file. This revolutionary line scanning system employs a line scan camera (i.e., called a linear-array detector) in conjunction with specialized optics, as described in U.S. Pat. No. 6,711,283 entitled “Fully Automatic Rapid Microscope Slide Scanner,” which is currently being marketed under the name ScanScope®.
In addition to rapid data capture and creating a single file digital slide, the line scanning system also benefits from several advantages that ensure consistently superior imagery data. First, focus of the linear array can be adjusted from one scan line to the next, while image tiling systems are limited to a single focal plane for an entire image tile. Second, because the linear array sensor in a line scanning system is one-dimensional (i.e., a line), there are no optical aberrations along the scanning axis. In an image tiling system, the optical aberrations are circularly symmetric about the center of the image tile. Third, the linear array sensor has a complete (100%) fill factor, providing full pixel resolution (8 bits per color channel), unlike color CCD cameras that lose spatial resolution because color values from non-adjacent pixels must be interpolated (e.g., using a Bayer Mask).
The creation of a single file digital slide is an enormously significant improvement. Managing a single image file for a digital slide requires significantly less operating system overhead than the management of thousands of individual image tiles and the corresponding index file. Additionally, alignment of component images may be computed once, then re-used many times for automated processing.
Therefore, introduction of the superior line scanning system for creating single file digital slides has created a need in the industry for efficient digital slide image analysis systems and methods that meet the unique needs imposed by the new technology.