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Overview of Changes in HistologyTechniques, Tools, & Workflow
John Gilbertson MD
Associate Chief of PathologyDirector of Pathology InformaticsMassachusetts General Hospital
Associate ProfessorHarvard Medical School
HARVARDMEDICAL SCHOOL
The Executive War CollegeApril 29, 2010
New Orleans, Louisiana
Disruptive Technologies in Histology & Digital Pathology
John Gilbertson: Thursday, April 29, 2010 Executive War College, New Olreans LA
Disruptive Technologies in Histology & Digital Pathology
• John Gilbertson– Massachusetts General Hospital
• Roberta Provencal– Catholic Medical Center,
Manchester, NA
• Mary Anne Haynes– Children’s National Medical
Center, Washington, DC
• Lu Anne Lupfer– Leica Microsystems
• Katja Lehmann– Sakura Finetek
• Theresa Ford– Milestone Medical
• Marco Bellini– Ventana Medical Systems
• Kelsi Currier– Tucson, Az
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John Gilbertson: Thursday, April 29, 2010 Executive War College, New Olreans LA
Conflicts
• I have no personal financial relationship with any company*
• However, I am Associated Chief of Pathology and Director of Pathology Informatics in a Department that does significant research and co-development with industry
• The Laboratory for Pathology Imaging Research and The Laboratory for Pathology Operations Research
• All are disclosed and compliant with Partners and Harvard ethics rules
• Names that we work with and I might mention today include Kurabo, Sony, Olympus, NEC, 3D Histech, Corista, Barco, Bioimagene, Philips, Hamamatsu and Sunquest*
*see next slide
John Gilbertson: Thursday, April 29, 2010 Executive War College, New Olreans LA
MGH & Sunquest
• On August 24, 2009 the Massachusetts General Hospital, Partners Healthcare System and Sunquest Information Systems Corporation signed a ten year collaboration agreement to co-create modules of a next generation AP LIS as part of an modular AP CP LIS to be marketed and commercialized by Sunquest
• As part of this agreement, both MGH and Sunquest are committing resources to the co-development. MGH will receive a royalty streamback from Sunquest. The size of which will depending on the commercial success of each module and the amount of MGH resources used in its creation
• I am Sunquest advisory boards (unpaid)
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John Gilbertson: Thursday, April 29, 2010 Executive War College, New Olreans LA
MGH PathologyInformatics
Gudewicz Dighe Yagi Wilbur Happel Lewandrowski
• Le• Garniss• Badizadegan• Flood• Higgins• Michaelson
• Misdraji• Tearney• Beckwith*• Kim*• Kuo*
John Gilbertson: Thursday, April 29, 2010 Executive War College, New Olreans LA
Pathology Informatics 2010Westin Hotel, Copley PlaceBoston, MassachusettsSeptember 19-22, 2010
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John Gilbertson: Thursday, April 29, 2010 Executive War College, New Olreans LA
• I am a pathologist
• The stained slide is the best, most powerful way medicine has to interrogate the nature of disease in tissue
Histopathology
Foundation of knowledge
John Gilbertson: Thursday, April 29, 2010 Executive War College, New Olreans LA
Disruptive Technologies in Histology & Digital Pathology
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John Gilbertson: Thursday, April 29, 2010 Executive War College, New Olreans LA
Histopathology
John Gilbertson: Thursday, April 29, 2010 Executive War College, New Olreans LA
How histology labs will save the world
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John Gilbertson: Thursday, April 29, 2010 Executive War College, New Olreans LA
This is not an implemented system!
Staining Optics &Digitization
Workflow and Dataflow Infrastructure (LIS)
Cutting &Adhesion
Processing& Embedding
ImageAnalysisossing Interpreta
Pathology Imaging Engine
John Gilbertson: Thursday, April 29, 2010 Executive War College, New Olreans LA
• Imaging begins in Histology• WSI digitizes it• WSI is one of many AH robots
Histology and imaging are one…
Staining &Drying
Optics &Digitization
Workflow and Dataflow Infrastructure (LIS)
Cutting &Adhesion
Processing& Embedding
ImageAnalysisossing Interpreta
Pathology Imaging Engine
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John Gilbertson: Thursday, April 29, 2010 Executive War College, New Olreans LA
Whole Slide Imaging
• If we could digitize all of our slides, rapidly, easily and at high resolution, then we could apply computational power and network connectivity – the drivers of efficiency, communication and discovery in the modern world - to the study of morphologic biology and practice of anatomic pathology
John Gilbertson: Thursday, April 29, 2010 Executive War College, New Olreans LA
We took the Slide (histology) for granted: Skill and Variance
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John Gilbertson: Thursday, April 29, 2010 Executive War College, New Olreans LA
John Gilbertson: Thursday, April 29, 2010 Executive War College, New Olreans LA
Things that were never a problem for the human hand and pathologist’s eye were problems for the robotic actuator and the digital camera
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John Gilbertson: Thursday, April 29, 2010 Executive War College, New Olreans LA
Upstream and Downstream
We found that some of the most important problems/failures of WSI devices (tissue finding, focusing, etc), had root causes in
histology
Accessioning Grossing Histology Sign out
Surgery Report
WSI
John Gilbertson: Thursday, April 29, 2010 Executive War College, New Olreans LA
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John Gilbertson: Thursday, April 29, 2010 Executive War College, New Olreans LA
John Gilbertson: Thursday, April 29, 2010 Executive War College, New Olreans LA
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John Gilbertson: Thursday, April 29, 2010 Executive War College, New Olreans LA
John Gilbertson: Thursday, April 29, 2010 Executive War College, New Olreans LA
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John Gilbertson: Thursday, April 29, 2010 Executive War College, New Olreans LA
5um3um
John Gilbertson: Thursday, April 29, 2010 Executive War College, New Olreans LA
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John Gilbertson: Thursday, April 29, 2010 Executive War College, New Olreans LA
Upstream and Downstream
Accessioning Grossing Histology Sign out
Surgery Report
WSI
WSI developers spend a lot of effort compensating for upstream variations (technical problems in slides). Upstream variation caused trouble in Slide Handling, Tissue Finding and Focus whichlimited Capture Speed, Image Quality and Device Throughput
John Gilbertson: Thursday, April 29, 2010 Executive War College, New Olreans LA
• A robot for every step – could we minimize the variance at the source?• Better slides better images with less effort…
Better, faster, cheaper imagers?
Staining Optics &Digitization
Workflow and Dataflow Infrastructure (LIS)
Cutting &Adhesion
Processing& Embedding
ImageAnalysisossing Interpreta
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John Gilbertson: Thursday, April 29, 2010 Executive War College, New Olreans LA
High slide quality, low variance
John Gilbertson: Thursday, April 29, 2010 Executive War College, New Olreans LA
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John Gilbertson: Thursday, April 29, 2010 Executive War College, New Olreans LA
John Gilbertson: Thursday, April 29, 2010 Executive War College, New Olreans LA
Yagi et al
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John Gilbertson: Thursday, April 29, 2010 Executive War College, New Olreans LA
John Gilbertson: Thursday, April 29, 2010 Executive War College, New Olreans LA
Higher Quality Images
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John Gilbertson: Thursday, April 29, 2010 Executive War College, New Olreans LA
• Better images Better Slides• Quantitative QA
Staining Optics &Digitization
Workflow and Dataflow Infrastructure (LIS)
Cutting &Adhesion
Processing& Embedding
ImageAnalysisossing Interpreta
Bautista PA, Yagi YDetection of tissue folds in whole slide images.Conf Proc IEEE Eng Med Biol Soc. 2009:3669-72.
John Gilbertson: Thursday, April 29, 2010 Executive War College, New Olreans LA
Quantitative QA
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John Gilbertson: Thursday, April 29, 2010 Executive War College, New Olreans LA
• Lower Variance, Quantitative QA• Better slides Images• Faster image capture speed
Staining Optics &Digitization
Workflow and Dataflow Infrastructure (LIS)
Cutting &Adhesion
Processing& Embedding
ImageAnalysisossing Interpreta
• Lower variances – faster focus• Lower variance – fewer failures
(unacceptable focus, tissue finding or mechanical failure)
John Gilbertson: Thursday, April 29, 2010 Executive War College, New Olreans LA
Throughput
Continuous Flow
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John Gilbertson: Thursday, April 29, 2010 Executive War College, New Olreans LA
5:00 AM 4:00 PM
2400 Slides / Day
Sign out
3 Devices1 Minute / Slide / Device
Batch Mode(then image)
Cases are collectedthe day before
John Gilbertson: Thursday, April 29, 2010 Executive War College, New Olreans LA
4:00 PM
2400 slides / day
Sign out
WSI3 Devices
1 Slide / Minute / Device
Histology3 Lines
1 Slide / Minute / Line
~ 13 hours ~ 1 Additional Minute
Cases are collectedand entered in the process
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John Gilbertson: Thursday, April 29, 2010 Executive War College, New Olreans LA
John Gilbertson: Thursday, April 29, 2010 Executive War College, New Olreans LA
Pathology on the right side of Moore’s Law…
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John Gilbertson: Thursday, April 29, 2010 Executive War College, New Olreans LA
• Lower Variance, Quantitative QA• Better Slides Better Images • Minimal Impact on Throughput
Staining Optics &Digitization
Workflow and Dataflow Infrastructure (LIS)
Cutting &Adhesion
Processing& Embedding
ImageAnalysisossing Interpreta
• Ubiquitous, high quality digital slides on which we can apply growing computational power and network connectivity
John Gilbertson: Thursday, April 29, 2010 Executive War College, New Olreans LA
Conclusions
• For most people histology is about getting slides to pathologists and automated histology is about containing or decreasing cost
• But there is more, it as also a area though which we can change the dynamic of the field (pathology)
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John Gilbertson: Thursday, April 29, 2010 Executive War College, New Olreans LA
Conclusions
• Without digitization, what pathology can do will be limited by our ability to physically manipulate and distribute slides and the time (and eyes) of our pathologist
• Molecular Medicine• Personalized Medicine• Baby Boomers• Global Opportunities
John Gilbertson: Thursday, April 29, 2010 Executive War College, New Olreans LA
• What if the rest of the medicine is taking advantage of growing computational power and network connectivity and pathology isn’t?
… It will not end well
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John Gilbertson: Thursday, April 29, 2010 Executive War College, New Olreans LA
• Imaging is part of histology• Better Slides Better digitization
Staining Optics &Digitization
Workflow and Dataflow Infrastructure (LIS)
Cutting &Adhesion
Processing& Embedding
ImageAnalysisossing Interpreta
• Ubiquitous digital slides• A new dynamic in pathology
Conclusions
John Gilbertson: Thursday, April 29, 2010 Executive War College, New Olreans LA
Staining Optics &Digitization
Workflow and Dataflow Infrastructure (LIS)
Cutting &Adhesion
Processing& Embedding
ImageAnalysisossing Interpreta
More
Surgery Collection Transport AccessioningArchive Research
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John Gilbertson: Thursday, April 29, 2010 Executive War College, New Olreans LA
Intel 1965
• The goal this morning was to connect automated histology to digital pathology
• To give a prediction of how histopathology might look in 5 – 10 years
• We are thinking about this…
John Gilbertson: Thursday, April 29, 2010 Executive War College, New Olreans LA
• We are stable, strong…• We are not “agile”• We are worried about disruptive
technologies…
“Ether Dome”, MGH
Will we be displaced?
Will we have the cycles totake advantage?
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John Gilbertson: Thursday, April 29, 2010 Executive War College, New Olreans LA
• We are stable, strong…• We are not “agile”• We are worried about disruptive
technologies…
“Ether Dome”, MGH
Will we be displaced?
Will we have the cycles totake advantage?
John Gilbertson: Thursday, April 29, 2010 Executive War College, New Olreans LA
Staining Optics &Digitization
Workflow and Dataflow Infrastructure (LIS)
Cutting &Adhesion
Processing& Embedding
ImageAnalysisrossing Interpreta
Surgery Collection Transport Accessioning
Archive Research
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John Gilbertson: Thursday, April 29, 2010 Executive War College, New Olreans LA
Clinic
Clinic
Clinic
Clinic
50%
Specially Clinics
Ord
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ntry
& C
olle
ctio
n
Expr
ess
Acce
ssio
n
RoboticGrossing
AutomatedHistology
ColorNumberShapeSize
CameraDocumentation
MGH Laboratory forPathology Operations
John Gilbertson: Thursday, April 29, 2010 Executive War College, New Olreans LA
Staining Optics &Digitization
Workflow and Dataflow Infrastructure (LIS)
Cutting &Adhesion
Processing& Embedding
ImageAnalysisossing Interpreta
This is not “real”
We have an R&D facility that examines the technology,but this is not in our clinical lab
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John Gilbertson: Thursday, April 29, 2010 Executive War College, New Olreans LA
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