Digital Pathology at John Hopkins Practical Research and Clinical Considerations Alexander Baras Presented at the Digital Pathology Congress: USA. For more information visit: www.global-engage.com.

1. Digital Pathology at Johns Hopkins
Practical Research and Clinical Considerations
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
July 10, 2017

2. 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

3. 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

4. Digital Pathology
• What are the use cases?
– Education
– Research
– Publication
– Telepathology / Conferences
• And now primary diagnosis!

5. Digital Pathology - Overview
Software
Hardware
Slide scanner
Whole slide image
Slide handling
Slide scanning
Optics
Detection
Acquisition software
Compression
File format
Viewers & Analytics
Digital slide repository/server
Digital slide viewer
Image Analysis

6. 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…

7. 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

8. 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

9. 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

10. 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

11. 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)

12. Digital Slide File Format
Level 0 (full resolution)
Level 1 (1/2 resolution)
Level 2 (1/4 resolution)
Level 4 (1/8 resolution)
Level 5 (1/16 resolution)
HighermagnificationLowermagnification

13. 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

14. 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

15. 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

16. Research & Education
https://digital.pathology.johnshopkins.edu/

17. Research & Education

18. Research & Education

19. Research & Education

20. Research & Education

21. Research & Education

22. Research & Education

23. Clinical - Overview

24. Clinical - Accessioning

25. Clinical - Interfacing

26. Clinical - Interfacing

27. Clinical - Tumor Boards

28. Clinical - Case Searching

29. Clinical - Case Searching

30. Clinical - Slide Annotations

31. Clinical - Slide Annotations

32. Clinical - Slide Annotations

33. Clinical - Consult Colleague

34. Clinical - Quality Assurance

35. Digital Pathology - Tele/Live
• Conferences Across Hopkins Networks
– No scanning required

36. 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)

37. 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

38. 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

39. Questions?