Digital Pathology at Johns Hopkins Practical Research and Clinical Considerations July 10, 2017 Alexander Baras, MD, PhD Assistant Professor of Pathology, Urology, and Oncology Associate Director of Pathology Informatics Director of Precision Medicine Informatics, Sidney-Kimmel Comprehensive Cancer Center Johns Hopkins School of Medicine
Agenda Discuss applications of digital pathology First steps vs next steps Describe decision points in implementation Hardware Basic Infrastructure vs Analytics Clinical applications for digital pathology
Digital Pathology Whole slide imaging Creation of a single, high magnification digital image of an entire microscopic slide Live imaging from microscope Live video feed of what is screen at the microscope
Digital Pathology What are the use cases? Education Research Publication Telepathology / Conferences And now primary diagnosis!
Digital Pathology - Overview Image Analysis Digital slide viewer Software Viewers & Analytics Digital slide repository/server File format Compression Whole slide image Acquisition software Detection Optics Hardware Slide scanning Slide handling Slide scanner
Scanner Considerations Manufactures Phillips Ventana Leica Olympus Nikon Zeiss Hamamatsu MikroScan 3D Histech TissueGnostics Perkin Elmer/Cri/Caliper Motic Huron Digital Pathology Sakura Omnyx Others
Scanner Considerations Capabilities vary widely: Brightfield only vs Fluorescence only vs Both Capacities from 1 slide to 400 or more slides Various slide handling mechanisms
Scanner Considerations Capabilities vary widely: 1 x3 only vs. 1 x3 and 2 x3 (whole mount) Single plane scan vs. z-stacking (vs. limited z-stacking) 4x, 10x, 20x, 40x, 60x, 100x, oil immersion
Scanner Considerations Software that drives the scanner Wide range of capability and maturity here Robustness to a problem with a single slide for a batch of slides Ease of user interface Needs to be normalized by the experience level of the intended operator
Scanner Considerations Brightfield scanners The most common type of scanner By far the least complicated & least expensive Images are acquired and stored as color images Use: H&E, IHC, CISH, other visible stains
Digital Slide File Format Most WSI files contain an image pyramid Zoom levels are pre-calculated and stored in the file The image at each zoom level is broken into small tiles (e.g. 256 x 256 px)
Higher magnification Lower magnification Digital Slide File Format Level 5 (1/16 resolution) Level 4 (1/8 resolution) Level 2 (1/4 resolution) Level 1 (1/2 resolution) Level 0 (full resolution)
Digital Slide File Size WSI These files are relatively large 100s of MBs to multi GB (same scale as genomics) Compression is effectively required Lossless is likely the ideal target Resolution considerations Magnification vs micron/pixel (mpp) Optics vs digital capture technology
Research vs Clinical Two very different use cases Research (educational) Provide a simple web-based resource for viewing and annotating whole slide images Foster a collaborative environment around digital pathology Common infrastructure for analytics Open source software
Research vs Clinical Clinical Need to accession a digital case Cases for which only WSI files are sent Most EMRs will want to point to a case Provide pathologists with simple web-based platform Viewing and annotating whole slide images Reporting and sign-out Consulting with other pathologists (collaboration) Eventual integration into EMR
Research & Education https://digital.pathology.johnshopkins.edu/
Research & Education
Research & Education
Research & Education
Research & Education
Research & Education
Research & Education
Clinical - Overview
Clinical - Accessioning
Clinical - Interfacing
Clinical - Interfacing
Clinical - Tumor Boards
Clinical - Case Searching
Clinical - Case Searching
Clinical - Slide Annotations
Clinical - Slide Annotations
Clinical - Slide Annotations
Clinical - Consult Colleague
Clinical - Quality Assurance
Digital Pathology - Tele/Live Conferences Across Hopkins Networks No scanning required
Implementation Strategies Around one million slides per year Full conversion is not a good fit for us now Target areas Secondary consultation (international) Both submitted cases & a regular review program Conferences (tumor boards, QC/QA) Stain controls, central lab for 3 sites Autopsy (targeting primary diagnosis)
Analytics Focus infrastructure first Largely will be more in the research space What has stuck in radiology? Quantitation and visualization Obvious applications for IHC/CISH with existing biomarkers (ER, PR, Ki67, HER2, etc) Hybrid model probably best Approaches that make pathologists more efficient Screening technologies with ~ 0% false negative rate
Summary Implementation of both WSI and Live/Tele Targeted vs Full adoption Scanners, Analytics, Viewers, and Informatics Focus on infrastructure first with common framework for analytics For Clinical Applications: Case Review, Primary Diagnosis, Consultation, and Continual quality assurance/monitoring
Questions?