Overview of Digital Pathology’s Current State: Technologies ......•Michigan Medicine creates...
Transcript of Overview of Digital Pathology’s Current State: Technologies ......•Michigan Medicine creates...
Overview of Digital Pathology’s Current State: Technologies, Systems, Capabilities, Limitations,
and OpportunitiesDavid McClintock, MD
Executive War College Post-Conference Workshop – Digital Pathology
Disclosures
Philips Digital Pathology: Member, Scientific Advisory Board
XIFIN: Member, Medical Advisory Board
Any products or vendors mentioned today are for
presentation and information purposes only and they do not
represent any form of endorsement on the speaker's part
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Who Am I??
David S. McClintock, MD
Director, Digital Pathology
Associate Chief Medical Information Officer, Michigan Medicine
Associate Director, Pathology Informatics
Associate Professor, University of Michigan, Dept. of Pathology
President, Association for Pathology Informatics (API)
Learning Objectives
• What is Digital Pathology?
• Current state of Digital Pathology systems
• Digital Pathology and Primary Diagnosis
• Limitations of Digital Pathology / Barriers to Adoption
• Opportunities in Digital Pathology
What is Digital Pathology?
Digital Pathology - Definition
• Digital Pathology Association (DPA):
• A dynamic, image-based environment that enables the
acquisition, management and interpretation of pathology
information generated from a digitized glass slide. Often used
interchangeably with “Virtual Microscopy.”
Imaging in Pathology
• Gross imaging
• Microscopic imaging
• Whole slide imaging
• Electron microscopy
• Immunofluorescence
Digital Pathology - Definition
• My definition:
• Subspecialty of Pathology Informatics involving the acquisition,
management, and distribution of pathology and clinical
laboratory digital images and their associated data, generally
including modalities such as whole slide imaging,
telepathology, gross imaging, and microscopic imaging
Digital Pathology and Pathology Informatics
• Whole Slide Imaging (WSI) is a
subset of Digital Pathology (DP),
which is a subset of Pathology
Informatics (PI)
• For some, PI ≅ DP NOT TRUE!!
• For many, DP WSI NO!!
Pathology
Informatics
Digital
Pathology
Whole
Slide
Imaging
Current State of Digital Pathology Systems
Recreates the glass
slide as a virtual image
object
A “pyramid” with a
thumbnail on top and
high resolution on the
bottom
Whole Slide Imaging
Zoomed In
Zoomed Out
Illustration (modified) courtesy of Toby Cornish, MD
WSI File pyramid structure
Level 0 (full resolution)
Level 1 (1/2 resolution)
Level 2 (1/4 resolution)
Level 4 (1/8 resolution)Level 5 (1/16 resolution)
Hig
her
mag
nif
icati
on
Lo
wer
mag
nif
icati
on
Illustration (modified) courtesy of Toby Cornish, MD
Each Level is Composed of Tiles
Illustration (modified) courtesy of Toby Cornish, MD
Retrieving WSI Views
A viewer client connects to the
Digital Slide Repository (DSR)
The viewer requests the area of the
image being displayed (green) at a
particular zoom level
The DSR then sends only the tiles
needed to fulfill the request
Saves on bandwidth, allows fast
viewing of images
Illustration (modified) courtesy of Toby Cornish, MD
Whole Slide Imaging
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Image from: http://rosaicollection.org/
Whole Slide Imaging
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Image from: http://rosaicollection.org/
Whole Slide Imaging
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Image from: http://rosaicollection.org/
Whole Slide Imaging
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Image from: http://rosaicollection.org/
Whole Slide Imaging
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Image from: http://rosaicollection.org/
Whole Slide Imaging Systems
• Leica (Aperio)
• Philips
• 3D Histech/ThermoFisher
• Roche (Ventana/Bioimagene)
• MikroScan
• Motic
• Huron Digital Pathology
• Hamamatsu
• Olympus
• Nikon
• Zeiss
• TissueGnostics
• Sakura
• ViewsIQ (Panoptic)
• Others…
Whole Slide Imaging Systems
WSI Devices – Common Parameters
• Slide capacity/storage, batched: from 1 to 1000 slides
• Small WSI devices: 1 to 12 slides, 4-6 common
• Large WSI devices: 150-1000 slides, 150-400 common
• Slide size: standard size or whole mount?
• Scan magnification: 20X vs 40X objectives
• Scan resolution:
• ~0.25μm/pixel @40X,
• ~0.5 μm/pixel @20X
WSI Devices – Common Parameters
• Scan times: defined at either 20X or 40X
• 20X: 30 sec – 5 min, but most around 1-2 min
• 40X: 45 sec – 6 min, bimodal mostly (60-90 sec, 4-5 min)
NOTE: All speeds are
according to manufacturer
15 mm x 15 mm scan area
Th
e
“sta
nd
ard
”
WSI re
fere
nce
tiss
ue s
ize 1
5 m
m
15 mm
1 in
ch (
2.5
cm
)
3 inch (7.6 cm)
WSI Devices – Common Parameters
• Designed for clinical use
• One button operation: Load and walk away, automatic tissue detection
• Continuous scanning: Load and unload slides without disrupting the
scanning process
• Positive patient identification: can ID barcoded slide and match to patient
record
• Integrated vs separate PC
• On-board PC with touchscreen (typical of automated systems)
• Separate PC that controls scanner (typical of earlier systems,
education/research systems)
WSI Devices – Common Parameters
• Z-stacking (multiple focal planes)
• Dynamic focusing
• Ability to adjust focusing to tissue irregularities
• Other imaging modalities
• Fluorescence
• Oil immersion @ 100X
• Cost (device only)
• $10K to $300K
• Small scanners typically <$75K, Large scanners $150-$300K
Components of a WSI System
• Slide Scanning Device / Instrument
• Workstation
• Monitor
• Image management system
• Digital slide repository
• Pixel pipeline
Complete Whole Slide Imaging System
Digital Pathology and Primary Diagnosis
Digital Pathology and the FDA
• It’s has been a long, somewhat rocky road
• Long history between Digital Pathology Association (DPA) and FDA
Center for Devices and Radiological Health
• However…on April 12, 2017…SUCCESS!!!
• FDA clears first whole slide imaging system for primary diagnosis
• Philips IntelliSite Pathology Solution (PIPS)
• Comprises the Image Management System (IMS), the Ultra Fast Scanner (UFS)
and Display
• NOTE: I am not endorsing Philips here…they are literally the only FDA-
cleared system we can talk about
PIPS – Indications for Use
• Intended for in vitro diagnostic use as an aid to the pathologist to review and interpret digital images of surgical pathology slides prepared from formalin-fixed paraffin embedded (FFPE) tissue
•The PIPS is NOT intended for use with frozen section, cytology, or non-FFPE hematopathologyspecimens.
PIPS – Indications for Use
•The PIPS is for creation and viewing of digital
images of scanned glass slides that would
otherwise be appropriate for manual visualization
by conventional light microscopy
• It is the responsibility of a qualified pathologist to
employ appropriate procedures and safeguards to
assure the validity of the interpretation of images
obtained using PIPS
Whole Slide Imaging Systems
• For regulatory purposes, WSI systems contain two integrated subsystems• Image acquisition subsystem (the slide scanner) that converts the
content of a glass slide into a virtual image object (the digital image file)
• Pathology workstation environment, including the display, for viewing digital images
• Vendors are required to submit their manufactured device to the FDA as one system that encompasses the entire pixel pathway
• The technical and clinical performance of these combined subsystems must be validated as a whole
FDA Cleared WSI System = CLOSED SYSTEM
• Per FDA:• Cannot decouple the two imaging subsystems
• Doing so does not ensure the safety and effectiveness for their intended use
• Closed system = combined setup of image acquisition plus workstation environment• Following FDA clearance, the cleared version of the system,
including all of its components and software configurations for its particular intended use, become a “locked down” device
Complete Whole Slide Imaging System
FDA Medical Device – 510(k) submission
• Uses a substantially equivalent (predicate) device for
comparison
Comparison of FDA Device Submissions
From: Abels E, Pantanowitz L. Current state of the regulatory trajectory for whole slideimaging devices in the USA. J Pathol Inform. 2017;8(1):23-25
FDA and Digital Pathology - Summary
• WE HAVE A WSI SYSTEM FDA CLEARED FOR PRIMARY
DIAGNOSIS!!
• More systems will be cleared over the next 1-3 years
• Expect additional de novo and 510(k) submissions
Limitations of Digital Pathology / Barriers to Adoption
Adding Value to Surgical Pathology
Generic Surg Path Workflow – with Imaging
Accessioning/ registration
Specimen triage
ProcessingEmbedding
Microscopic analysis
Microtomy
Staining, coverslipping,
& labeling
Case post-processing and
archival
GrossingTAKE A
PICTURE?
TAKE A PICTURE?
SCAN/TAKE A PICTURE?
Workflow and Time Considerations
• No matter how you slice it, adding DP ADDS TIME!!
• Effects on histology workflow can be estimated
• Goal is to estimate appropriate number of scanners required to
have a minimal effect on TAT, however…
• Goal is to not spend too much money??
• Pathologist time signing out
• With full adoption, expect to see more comprehensive data
examining this aspect
• Current consensus…it goes up
Image Data Storage at an Academic Hospital
• ~150TB total storage for Radiology
• ~30TB total for Cardiology
• ~10TB total for Interventional Cardiology
• Backup is through server replication• Replicate off-site for Radiology (through vendor)
• Replicate on-site for Cardiology (in hospital data center)
• Total storage, replicated, ~400 TB (includes ALL imaging from beginning of time)
DP - Storage as the Limiting Factor
• Current estimates:
• For primary dx, Philips UFS: ~1.25 GB/slide
• Michigan Medicine creates ~11,000 slides per week
• Annual slide volume ~570,000
• Average estimated storage for clinical use ~715,000 GB = 715 TB
• Requires production system redundancy…so yotta, yotta, yotta...
• GRAND TOTAL PER YEAR: ~1.43 PB required
Storage Costs are the Lowest Ever!
30 GB in 2000 $125
3TB in 2015 $105
350 TB in 2030 $100-$125 ????
Image from : https://community.spiceworks.com/topic/1993877-future-tech-storage-capacity-in-the-year-2030-and-beyond
The Michigan Medicine Example - Costs
• Minimally:• Assuming $0.025/GB currently
• 1,430,000 GB x $0.025/GB = $37,500/year
• CHEAP!!!• Except…that is assuming I am buying my
storage from Costco…
• And setting it up in my office???
Data Center Storage Costs
• Data center costs include:
• Building space
• Cooling
• Power (UPS + Generator)
• Fire Suppression
• Security
• Equipment maintenance (hard drives/servers ~5 year lifespan)
• FTE maintenance (need people to run the data center, 24x7x365)
• Networking (Can I have a 10Gb/s line please??)
Actual Storage Costs are MUCH MORE
• Low estimates of cost in a data center are ~$0.15 –
$0.25/GB (industry estimate)
• ~$215,000 to $375,000 per year…not so cheap anymore
• Networking speeds from data center may need
upgrading
• Also need to look at physical cabling in building where
signout will occur
• Laying fiber ain’t cheap either…
Opportunities in Digital Pathology
Adding Value to Surgical Pathology
Digital Pathology Has Great Potential for Data Integration
Digital Pathology
System
EMR/
CPOEDigital Slide
Scanner
Image Repository
Image Viewer
Image Analysis Engine
Asset Tracking Systems
Other Digital
Imaging
CP LIS
AP LIS
Illustration (modified) courtesy of Toby Cornish, MD
DICOM in Pathology
• DICOM Connectathons
• First one in post-FDA clearance
era at Path Visions 2017
• Next one at Pathology
Informatics Summit 2018
• Digital Pathology vendors use
DICOM to successfully
exchange images in a
VENDOR NEUTRAL WAY!!!
Imaging Informatics and EIM
• EIM = Enterprise Image Management
• New functional unit of Clinical Informatics / Imaging
Informatics that aims to provide proper governance over
digital images across all medical disciplines
• Goal is to ultimately MANAGE all images used for clinical
purposes in a standardized, HIPAA compliant and patient
safe way!!
Enterprise Image Management
• Pathology will NEED to play a part in EIM
• With full adoption of WSI, will quickly become a big player in
the field
• Will generate petabytes of clinical image data, quickly eclipsing
Radiology and other clinical specialties
• Combined with molecular and clinical laboratory data –
Pathology will be THE major data player in clinical
diagnostics
ACADEMIC
CLINICAL
IMAGING
Future State
Do you see
Pathology?
55
Radiology PACS
Flash SAN NAS Tape
Enterprise Viewer
MiChartUHS, Urology,
Oral Surgery
US, Fluoroscopy,
General Imaging,
C-Arm
Clinical Imaging Devices
Pathology
Adult and Peds.
CardiologyDVUOphthalmologyOB/GYNSurgical Images ED
Smart Devices
Storage Virtualization and Data Lifecycle Management
Workflow Services (API, Web Services, Morphing, Routing)
DICOM HL7 Audit/ROIBusiness
Continuity
Non-DICOM
XDS-I
IHE
Database
Intelligence
Administrative
Tools
FHIR
WADO
VNA/ECM
Cloud Storage
EHR
Use Case: Clinical Decision Support in WSI
• Issue: Whole slide imaging, by itself, adds time and cost
to the typical surgical pathology clinical workflow
• Potential solution: With a completely digital workflow
(using WSI) , we can add value to the process, reduce
turn-around-time, improve quality, and increase case
volume to offset increased costs
Contextually Driven Workflow
• Use existing EMR and LIS data to identify contextually
relevant data that aids in working up pathology cases
• E.g. Part type = lung biopsy
• Gather all relevant chest radiology (X-ray, CT, MRI)
• Gather relevant prior surgical pathology cases (primary lung vs.
metastatic secondary)
• Compile specimen gross images (if available)
• Gather relevant laboratory data, molecular data
• Gather relevant clinical notes, op notes, etc.
Computational Pathology-Potential Benefits
• Automating Image Analysis/Computational Pathology• Contextually driven prior to virtual slide delivery to the pathologist
• Example: Prostate biopsies1. Image Analysis to detect potential tumor
2. If absent – prioritize and send to “negative for tumor” queue• Option – auto-verify and release negative result, similar to cytology and paps
3. If tumor detected, perform:• Computational analysis to quantify tumor volume (if present)
• Machine learning algorithms to estimate Gleason Grading
• Order IHC on ”questionable” cases
• Prefill relevant data into synoptic report
• Prioritize cases for pathologist
Plateau of ProductivitySlope of
Enlightenment
Trough of
Disillusionment
Peak
of
Infl
ate
d E
xp
ecta
tio
ns
Innovation
Trigger
Phase
The Digital Pathology Hype Cycle
Time
Expectations
Birth of
Slide
Scanning
Specific DP Reimbursement Models
Integration with AP-LIS systems
High Throughput Scanning
Digital Consultation Outreach
WSI
for
Ed
uca
tio
n
FDA Clearance for
Primary Diagnosis
FDA clearance for IHC scoring
WSI
for
Rese
arc
h
Proprietary Slide
Formats
Slow Adoption
of DICOM
FDA Class 3
WSI
& T
ele
path
olo
gy
All-digital Whole Slide Imaging Workflow
Cost
Computational
Pathology
Illustration (modified) courtesy of Ulysses Balis, MD
QUESTIONS?