Abstract
Introduction
Virtual slide technology consists of creating a digital replica of the content of a whole glass microscope slide and displaying and manipulating it on the computer, so that it closely emulates looking at a slide with a traditional microscope. Advantages of virtual microscopic slides over digital photomicrographs stems from the fact that virtual slides can be moved in 2 dimensions and through multiple magnifications. In addition the technology to annotate virtual slides by overlaying with arrows, lines and text; compare immunohistochemistry and fluorescence microscopy side-by-side with H&E; evaluate tissue micro-arrays; and do computer assisted image analysis has further augmented the advantages of virtual slides even over the traditional microscope and glass slides. To date a majority of the practical applications for virtual microscopy have been in the field of education in histology and histopathology (Harris et al., 2001; Dick (Dee), 2001; Dee et al., 2003; Blake et al., 2003, Dee & Heidger, 2005; Krippendorf & Lough, 2005).
At Iowa we have developed a number of educational resources. Some of these are completed and others are under construction (see http://www.path.uiowa.edu/virtualslidebox/). More recently, application to service pathology has begun at a number of institutions (Molnar et al., 2003; Gagnon et al., 2004; Helin et al., 2006; Dee et al., in press).
Finally, it is likely that virtual microscopy will play a significant role in morphology-based research both for clinically applied and basic science investigation, and dissemination of research findings. For example, the explosion of new animal histopathologic phenotypes will require investigators to have ready access to annotated cancers and normal histology from humans and other species for comparison and classification of their new findings (see the Visible Mouse at http://tvmouse.compmed.ucdavis.edu/histology/).
Development of a Comparative Pathology Research Resource
The University of Iowa Department of Pathology has been funded by the National Center for Research Resources of the NIH to develop a Virtual Slidebox of Comparative Cancer Pathology using virtual slide technology purchased from www.aperio and www.microbrightfield. This web-accessible research-related resource will increase the knowledge of the biomedical research community about individual cancer sub-types across species including a comparison with human cancer. Its content will include spontaneous, as well as induced, and genetically engineered animal cancers. The project has been piloted with a unit on hematopoietic neoplasms with an emphasis on lymphomas (see http://www.path.uiowa.edu/virtualslidebox/cancer_pathology/index.html).
In addition to displaying cancers from laboratory animals, the site also displays animal cancer from other species such as the dog and cat, that are not as heavily utilized as the mouse model for understanding human disease. This will give the research community a concept of the breadth and diversity of lymphomas in vertebrates, and this increased awareness may lead to new routes of investigation that have not yet been explored. This approach will also contribute to cancer research in clinical veterinary medicine.
Although lymphomas are not as high on the list of human cancers as breast, lung, and prostate, they represent a good model for a pilot because they are very well characterized in humans, and also are present in a wide variety of animals. Lymphomas in vertebrates may not be precisely the same genotypic diseases as those in humans; however, if animal models are to be useful for understanding human cancer, correlation as closely as possible with the human World Health Organization classification, while acknowledging any differences, is imperative (Jaffe et al., 2001).
The Iowa pilot project will not only be a resource for the lymphoma research community, but will also serve as a model for other investigators to: 1) create derivative virtual slide databases for other disease systems or animal models such as are under way with the mouse and zebrafish, and 2) create databases for web-based publishing of extended visual materials in the form of annotated virtual slides. Acceptance of virtual slides as a surrogate for traditional microscopy and photomicrography to disseminate knowledge about cancer will be a slow and initially expensive evolutionary process. However, virtual slide technology has the potential to eventually revolutionize the way microscopic morphology is viewed and disseminated by the biomedical research community.