Microscopy Goes Virtual--and Global

Image: Courtesy of Aperio Technologies VIRTUAL SLIDE comprising 38,000 x 43,500 pixels, scanned at 108,000 pixels/ inch. Selected views show a thumbnail (top), an intermediate-resolution image (middle), and a small region of the full-resolution virtual slide (bottom). Robert Cardiff has thought a lot about virtual microscopy. As chair of the pathology committee for the National Cancer Institute's Mouse Models of Human Cancer Consortium, Cardiff is charged with creating an image archive of both murine and human histological samples. As professor of pathology at the University of California, Davis' Center for Comparative Medicine, he helps run the medical school's pathology course as well. It is an expensive operation: "We spend an enormous amount of money making glass slide sets, maintaining the slide sets, handing them out each year, [and] renting microscopes." The solution to both of these problems is virtual slides--digital representations of histological samples at diagnostic resolution. Several companies offer hardware to create virtual slides, but they all suffer from one major drawback: time. Because they use image tiling--capturing hundreds or thousands of individual images that are then assembled into a single, contiguous picture--most scanners require hours to process a single slide, making them practically unusable for applications like clinical diagnostics. Several years ago, a former colleague walked into Cardiff's office and asked, "What if you could acquire virtual slides in minutes?" As Cardiff recalls, "I think I expressed some disbelief." Nevertheless, Cardiff contacted Vista, Calif.-based Aperio Technologies. He liked what he saw, becoming Aperio's first beta site, and ultimately, a client. Aperio's core technology is the ScanScope™ slide scanner. Instead of using the standard image-tiling approach, the ScanScope works like a fax machine, says company CEO Dirk Soenksen, producing images nearly 20 times faster than its competitors. The ScanScope T108 performs brightfield imaging. Using either a 20x/0.75 or 40x/0.95 objective, it scans at up to 108,000 pixels per inch. At that resolution, the system scans about 10 mm2 per minute, tackling a 15-mm x 15-mm area in less than 15 minutes. Users can opt to compress the resulting 11-gigabyte TIFF output file, producing a 560-MB JPEG2000 file (20:1 compression). The system includes a PC with controller software and ImageScope™, Aperio's virtual slide-viewing software. Aperio also offers server software to enable remote access. "An institution could host a library of virtual slides, and anybody who has an Internet connection can then log onto that file server and view images, really the same way that you would look at a slide under a microscope," explains Soenksen. Alternatively, users can view virtual slides using a Web browser. (Aperio offers a demonstration of this capability at www.scanscope.com; Cardiff's virtual slides are available at ccm.ucdavis.edu/imagearchive/.) Remote users do not download multigigabyte datasets; they download only portions of files. This is like browsing a large corporate Web site, says Soenksen as you only download the few pages you want to view. "The same concept applies to viewing a multigigabyte image," explains Soenksen. "You're only able to really show on your computer monitor a portion that corresponds to however many pixels your monitor can display." The server therefore transmits only the piece of information that the user can see at any one time. Virtual slide technology offers several benefits. First, students can trade their expensive slide sets and microscopes for DVDs containing digital histological images. Second, virtual slides enable telepathology, allowing pathologists to examine slides from remote locations. Finally, this technology aids bioinformatics by allowing researchers to extract data from the slides. For example, Dako Cytomation is developing software to scour virtual slides stained with the company's Her-2/neu probes for abnormal, possibly cancerous cells. A pathologist would then review the results of such an analysis. Aperio is currently developing a fluorescence-capable ScanScope (slated for release next year), plus software to simplify tissue microarray analysis. The slide scanner, computer, and ImageScope software cost $70,000 (US); the optional server software costs $10,000.

Microscopy Goes Virtual--and Global

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	Image: Courtesy of Aperio Technologies
	VIRTUAL SLIDE comprising 38,000 x 43,500 pixels, scanned at 108,000 pixels/ inch. Selected views show a thumbnail (top), an intermediate-resolution image (middle), and a small region of the full-resolution virtual slide (bottom).