Beyond the “Nuclear Option”: Sophisticated Digital Analysis Adds Value to Researchers’ Work and to a Core Lab’s Worth
Dr Clara E. Magyar
Manager, Translational Pathology Core Laboratory, Department of Pathology UCLA School of Medicine, Los Angeles, CA
The UCLA Translational Pathology Core Laboratory (TPCL) provides basic and sophisticated pathology services, including digital slide scanning and analysis, to support basic, translational and clinical research. Located in the Department of Pathology and Laboratory Medicine, this UCLA Jonsson Comprehensive Cancer Center Shared Facility serves both UCLA and non-UCLA academic and industry researchers. While we have offered image analysis services to researchers for five years, the addition of more robust software, such as Definiens, has allowed us to greatly enhance the complexity of our analysis. We are no longer limited to standard immunohistochemical (IHC) staining for quantitation (e.g. Ki67), but have been able to benefit from Tissue Studio’s flexibility by expanding the scope of our analyses, such as isolating and quantifying biochemically stained structures (e.g. Picrosirius red) from neighboring vasculature. Our core currently maintains an Aperio AT brightfield scanner, the Leica Ariol-SL-50 brightfield/fluorescence scanner and Definiens’ Tissue Studio and Developer. We scan over 7000 slides a year; approximately 10% are immunofluorescently stained slides. Our Definiens system consists of one dual engine workstation. Within the last 18 months, we have logged over 1500 hours of processing time from over 30 investigators. As our user base consists of researchers from varying disciplines, our image analysis projects encompass a wide range of interests. This has allowed us to employ much of the functionality available in Tissue Studio. For brightfield analyses of whole tissue sections and tissue microarrays we have used nuclear, cytoplasmic, membrane and vessel algorithms, with and without Composer, as well as incorporating pre-defined annotations from Aperio images. We have also used the flexibility of Tissue Studio to identify and quantitate more complex, unique regions of interest such as fibrotic liver tissue and multiple tumor sub-types. These types of analyses demonstrate strong correlations with manual scoring by trained pathologists, thereby validating the algorithmic approaches we have designed. To set up an analysis, users first undergo a consultation appointment to determine how best to approach their question. Depending upon interest of the user, either we perform the analysis for them, or we train the user on the system. Users can then access the workstation room 24 hours a day / 7 days a week through a coded access lock, allowing flexible scheduling. The versatility of the Definiens suite has allowed our core research laboratory to provide a unique and actively growing image analysis center at UCLA.