Is digital pathology ready for use in routine histopathology?

Dr David SneadUniversity Hospitals of Coventry and

Warwickshire NHS TrustCoventry UK

Pathologists and microscopes. 1850

• Rudolph Virchow (1821-1902), by many regarded as the greatest figure in the history of pathology

•Johannes Müller (1801–1858).

Müller was the source from which both histology and cellular pathology arose. He was one of the first to use the microscope in tissue analysis.

Pathologists 2010

Introduction

• The transition of glass slides to computerisedviewing platforms

• Whole slide imaging, telemicroscopy, virtual microscopy

• Based on streaming digital information of images from computer server to a remote viewer

• Just another way of viewing slides?

Charged couple device

Digital microscopy• Charged couple device (CCD)• Tile stitching• Line scanning• Area scanning• x20, x40, x60 magnification• Resolution depends on numerical aperture: • d=l/2NA• Microns per pixel

• UK providers: GE Healthcare (Omnyx), Hamamatsu, Phillips, Leica (Aperio), Roche, 3D Histec

Digital Pathology

• Partially proven

• Additional laboratory steps to convert slides to digital data

• Stability dependent on multiple factors

• Poor image quality on some older systems

• Limited to the most common applications

• High set-up and running costs

• High level of maintenance and support needed to ensure the service

Requirements of a digital pathology solution

• Rapid scanning

• Integration with the laboratory LIMS

• Stable

• Fast data transfer for real time reporting

• Validation - proven equity to light microscopy

• Value added tools

• International standard for digital archiving

UHCW activity data

• 27,000 surgicals

• 120,00 slides

Digital pathology at UHCW

• Innovation

• Local pathology network needs

• Academic potential

• Synergy with UoW computer science

• Enthusiastic consultant workforce

• Training opportunities

Immediate challenges

• Cost and return in investment• Improved efficiency, grant income, and market

opportunities• Validation• FDA decreed not class 1 exempt. Pre-market

testing required• CPA require validation against existing technology• None inferiority study designed• Audit meeting variations used as benchmark

Validation study power calculation

Validation study design

• Double reporting

• Glass first digital second

• Minimum of 3 week washout period

• Compare reports to detect differences

• Steering group meets weekly to assess and classify differences

• 3014 cases

Validation study data

• 3050 cases

• Slides scanned @ 40x: 10,138

• Slides scanned @ 60x: 1,384

• Data 2.45 TB

• Annual data size predicted 22TB

Validation study

• Scanned 3050 cases• Double reported 2952• Pathologists don’t remember cases• Difficult cases are no easier on digital• Bugs (H pylori, gram positive cocci) need x60 scans• Z stack not so important on histology cases• Renal Biopsies x60• Differences in diagnosis, so far, mainly due to interpretation• Grading low grade dysplasia may be more difficult on digital

than glass• Measurements more accurate on digital

Challenges for routine practice

• Front and back end interface with LIMS needed• Develop scanning rules• Re-work laboratory protocols• Improve section quality and tissue mounting• Maintain streaming speed within the

departmental security protocol• Some things will still need glass

• Polarisation• Over sized blocks• Low grade dysplasia• X100 oil (scanty organisms)

Problems

• Speed of streaming

• LIMS interface

• Tiles out of focus

• High quality sections work best

Positives

• Scan speed excellent mean around 90 seconds per slide

• Image quality excellent

• Workflow software excellent

• Very easy to use system

• Fits well in laboratory workflow

• Stable

• Excellent support

What does digital pathology offer?

• Economic advantages• Increase efficiency of pathologists

• Reduce turn around time to report cases

• Improved review of cases including MDT/Tumour board review

• Quality advantages• Reduced error rate

• Increased subspecialisation

• IHC scoring and indexing

• Tumour grading / dysplasia grading

• Cancer finder

Workflow Opportunities13.4% (0:43:09)

Slide Review36.0% (1:56:13)

Other16.0% (0:51:43)

Reporting34.6% (1:51:38)

Pathologist T&M Study ResultsBreakdown of Time Working Cases

Slide Review36.0% (1:56:13)

Other16.0% (0:51:43)

Reporting34.6% (1:51:38)

Organizing Cases 24.1% (0:10:25)

Querying for Cases 18.5% (0:07:59)

Waiting for Delivery 11.2% (0:04:49)

Matching 10.5% (0:04:32)

Searching for Cases 9.4% (0:04:04)

Transporting Cases 9.2% (0:03:58)

Other 17.0% (0:07:21)

Workflow Opportunities

100% (0:43:09)

13.4%

Pathologist T&M Study ResultsBreakdown of Workflow Opportunities

Pre-allocation of specimensPush system

Laboratory

Pathologist A

Subspecialty 1

Subspecialty 3

General Pool

Pathologist B

Subspecialty 1

General Pool

Pathologist C

Subspecialty 1

Pathologist D

Subspecialty 2

Subspecialty 4

General Pool

Pathologist E

Subspecialty 2

Subspecialty 4

General Pool

Pathologist F

Subspecialty 3

General Pool

Pathologist G

Subspecialty 3

General Pool

Pathologist H

Subspecialty 4

General Pool

Improved workflow efficiencyPull system

Server

Sub-specialist bench 1

Pathologist A

Pathologist B

Pathologist C

Sub-specialist bench 2

Pathologist D

Pathologist E

Pathologist F

Sub-specialist bench 3

Pathologist G

Pathologist A

Pathologist F

Sub-specialist bench 4

Pathologist E

Pathologist H

Pathologist D

General Pool bench

All except Pathologist C

Algorithms in development

• Improved accuracy and patient safety• Cancer grading tool prostate, breast, and bladder

cancers • Cancer finding tool, region of interest alert• Alerts for slides or tissue samples not examined• Overlay tool intelligently identifies regions of interest in

sequentially cut sections• Automation downstream quantitative ICC e.g ER, PR,

Ki67, HER2• Quantification of tumour volume for molecular analysis

Warwick digital pathology centreof excellence

• Mitotic count tool 3rd AMIDA Grand Challenge Nagoya 2013

• Nuclear grading tool 1st MITOS-Atypia 2014 Challenge

• Tumour grading tool

• Cancer finding tool

• IHC slides with quantitative scores

• Resection margin, depth of invasion exported directly to report

KorsukSirinukunwattanaNasir Rajpoot Adnan Mujahid

VioletaKovacheva Nick Trahearn

Remote Laser Capture Microscopy - RELCAM