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

2

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

16

Image from: http://rosaicollection.org/

Whole Slide Imaging

17

Image from: http://rosaicollection.org/

Whole Slide Imaging

18

Image from: http://rosaicollection.org/

Whole Slide Imaging

19

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?