digital pathology - use in breast pathology reporting · snead, rajpoot et al., histopathology (jun...
TRANSCRIPT
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Digital pathology - Use in breast pathology reporting
Professor D SneadUHCW NHS Trust Coventry
andUniversity of Warwick
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Disclaimer
• Philips computational pathology board
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Digital Pathology
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UHCW Digital Pathology Validation Study
Validation of digital pathology imaging for routine primary diagnosisSnead, Rajpoot et al., Histopathology (Jun 2016)
35,000 cases reported on digital pathology to date
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Dear colleagues,PHE is aware of rapid progress in clinical evaluation of digital pathology, and that several trusts are planning large scale implementation of this technology.This is a very interesting development that may well offer future advantages for screening programme delivery. However, prior to implementation in a screening programme context, we need to be sure that it is at least equivalent to current methods. Therefore further evaluation, discussion and specification are required.Please be aware that primary reporting of breast, bowel and cervical screening pathology specimens from a scanned slide should not currently be used.Further guidance on implementation will follow as soon as possible.
Memo from Public Health England15 Sept 2016
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J Pathol Inform 2017;8:12.
240 breast cases4 sets of 601 slide per case
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Histopathology 2017
1.2% non concordance rate
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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• Cytology• Over sized blocks• Low grade dysplasia• X100 oil (scanty organisms)
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Interfacing
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Crisis in pathology staffing• 26% consultant posts vacant at the
moment• 32% of consultants over 55 (615 due to
retire in next 5 years)• Many departments already send away
cases• Complexity of early cancer detection• Escalation of molecular testing and
companion diagnostics• Number of octogenarians is set to
double in next 10 years
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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
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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
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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
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Remote reporting• Workstations fitted with remote access to VPN • RSA token remote login• Ultra and Omnyx accessed through VPN• Dragon voice recognition installed on
workstation• Backlogged cases available to report• Report entered in and authorised• Additional requests made via LIS
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Breast cancer pathway outline
Diagnosis MDT Surgery MDT Oncology
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Breast core biopsies by result category
N=233
16.3
37.2
8.53.1
34.9
Summary of Biopsy Results by classification
1 2 3 4 5
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Indeterminate core biopsies
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Breast core biopsy time to final report
0
5
10
15
20
25
30
1 3 5 7 9 11 13 15 17 19 21 23 25 27 29 31 33 35 37 39 41 43 45 47 49 51 53 55 57 59
Fre
qu
en
cy
Number of Days
Core Biopsy
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PathCAD Systems
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Digital pathology algorithms – main applications
• IHC Biomarker assessment• ER, PR, HER2 & Ki67
• Disease quantification and grading tools• Cancer grading tools bladder, breast and prostate cancer• Dysplasia grading tools cervix, head and neck
• Rare event detection tools• Prostate template biopsies• Sentinel lymph node biopsies
• Automation• IHC Biomarker assessment• Endoscopic biopsies
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The Digital Pathology Market2012 Æ $2.1 bn, 2013 Æ $2.2 bn, … 2018 Æ $4.5 bn
(14.7% compound annual growth)
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1. Glandular probability map
2. Nuclei vertices
H&E-stained image
Evidence
Bayesian inference of polygons
Tubule formationThe Random Polygons Model
Sirinukunwattana et al., IEEE Trans Med Imaging (Nov 2015)US patent application number
61452293
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H&E-stained image ground truth Farjam et al.
Naik et al. Nguyen et al. RPM
Experiment: Warwick-QU Dataset (moderately & poorly differentiated tumor samples)
Experimental Results
Sirinukunwattana et al., IEEE Trans Med Imaging (Nov 2015)
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Stain Normalization
A non-linear mapping approach to stain normalisationKhan et al., IEEE Transactions on Biomedical Engineering (2014)
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Stain Normalization ToolboxPublicly available toolbox consisting of some of the leading algorithms (including our own) for normalization of stain colors in histology images
http://www.warwick.ac.uk/bialab/software/sntoolbox
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Mitosis algorithm
Khan et al., CMIG special issue on Breakthrough Technologies in Digital Pathology(2015)
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MITOS-ATYPIA Challenge Contest
Winner of the MITOS-ATYPIA Grand Challenge Contest at ICPR’2014http://mitos-atypia-14.grand-challenge.org/results2/
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Automated Her2 Scoring
http://www.warwick.ac.uk/TIAlab/Her2Contest
Qaiser et al., Histopathology (in press)
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Her2 Scoring – Man vs Machine
Rank Team Name Score Bonus Score+Bonus
1 Team Indus 220 12.5 232.5
2 Pathologist 2 210 20.5 230.5
3 Visilab 212.5 15 227.5
4 MUCS (Ireland) 205 20.5 225.5
5 Pathologist 1 185 10 195
6 Pathologist 3 180 13 193
http://www.warwick.ac.uk/TIAlab/Her2contest/
Qaiser et al., Histopathology (in press)
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• Most of the tumor slides were exhaustively annotated
• The average time for annotating each slide was 1 hour
Camelyon16 dataset
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Locating Metastasis in Breast LNBs
Qaiser, Rajpoot et al., submitted
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The White House Takes Took Note
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Pathologist + Algorithm
Aeffner et al., Arch Path Lab Med (Sep 2017)
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Detection of uNK+Stromal Cells
• Ratio of uNK to stromal cells is a good indicator of recurrent miscarriages
• Women with high numbers of uNK cells are more likely to have a live birth if given glucocorticoids in lieu of placebo
• Endometrial biopsy slides stained with Hematoxylin and DAB for CD56 to label the uterine Natural Killer (uNK) cells
Quenby et al., J Clin End Met 2013
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Automated ER & PR scoring
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Multi-IHC Analyser
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Trahearn, Rajpoot et al., submitted
Multi-IHC Analyser
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Blur report tool
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Deep Learning - Profiling Tumour Microenvironment
Sirinukunwattana et al., IEEE Trans Medical Imaging special issue on Deep Learning in Medical Imaging (May 2016)
• Cell recognition in large sets of whole-slide images
• Analytics for profiling the tumor micro-environment
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Invasive Tumour Fronts
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Acknowledgements
Dr AdnanKhan (ICR)
Dr VioletaKovacheva
(ICR)
DrGuannan
Li (Startup)
TalhaQaiser
Dr ShanRaza
(Warwick)
Dr KorsukSirinukunwattana
(Harvard)
Mike Song
Nicholas Trahearn
Prof NasirRajpoot
Prof Ian Cree (UHCW)
Dr Yee WahTsang
(UHCW)
Prof David Epstein FRS(Warwick)
Dr Mike Khan
(UHCW)
Dr HeshamEldaly
(Addenbrookes)