Digital Pathology and Tissue-based Diagnosis. How do they differ?
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1 Digital Pathology and Tissue-based Diagnosis. How do they differ? P. Hufnagl Institute of Pathology (Rudolf-Virchow-Haus). Humboldt University, Berlin?
2 Structure of the talk Possible workflow routine diagnostic diagnostic support Which scanner? Quantification / image analysis Conclusions
3 Structure of the talk Possible workflow routine diagnostic diagnostic support Which scanner can we trust? Quantification / image analysis Conclusions
4 The Conventional Workflow Tissue Lab: Cutting, Staining, Coverslip Clinical request HIS PLIMS Report Physician: Dictation, Images, Physician: Assignment, diagnosing, Annotation consultation
5 The Digital Workflow Tissue Lab: Cutting, Staining, Coverslip Slide Scanner: Registration, Digitalisation PACS: Storage, Image streaming Clinical request HIS PLIMS Report Physician: Dictation, Images, Physician: Assignment, diagnosing, Image analysis: marker quantification Annotation consultation
6 The Digital Workflow Missing link between cover slipper and scanner Tissue Lab: Cutting, Staining, Coverslip Missing Slide Scanner: link between Registration, scanner Digitalisation and PLIS PACS: Storage, Image streaming Clinical request HIS PLIMS Report Physician: Dictation, Images, Physician: Assignment, diagnosing, Image analysis: marker quantification Annotation consultation
7 Advantages of Virtual Microscopy User Viewer Slide Server No glass transportation, no glass archive (?) Previous slides are always available Microscopic diagnostic - anytime anywhere - Parallel viewing of different stainings, positions Viewing and handling parallel at different locations Facilitated second opinion - online Quantification and image analysis just in time Annotations are simple to be handled much more.. Slide Scanner
8 Problems of the digital workflow Disadvantages Additional process step: Digitalisation Huge and continuous hardware and software investments Training of personnel Diagnosis on the monitor is unfamiliar for pathologists Legal Problems
9 Strategy Start with a less critical application Biobanking Introduce VM to applications with most effects Tumour board Second opinion in-house Solve all problems along the workflow LIMS integration Sure barcode identification Establishing of continuous testing
10 ZEBANC CHARITÉ BIOBANK CVK CCM CBF
11 CURRENTLY OFFERED SERVICES Aliquotation Quality documentation (SPREC) WSI generation TMA generation and WSI* based analysis Automatic DNA- extraction DNA Sequencing... *whole slide image 11
12 VALUE OF A SAMPLE Sample Clinical Data Whole Slide Images Quantification of Morphology V A L U E Next Generation Sequencing Data Data generated during experiments...
13 ZEBANC AND VM Digitalisation established for samples from frozen section labs Technical quality control implemented Infrastructure for block-centric navigation established Medical quality control in use (prototype tumor area detection) TMA as sample array in CentraXX integrated Several quantification procedures implemented to generate additional sample features Virtual studies on virtual slides instead of real samples Virtual microscopy has a huge potential for services in the context of a biomaterial bank
14 Clinical Pathology Second Opinion, Studies, Marker Quantification Medical Workstation - All Information in One View
15 Workflow of Tumor Board Meetings Set bookmarks and make annotations Browse slides and move to annotations Before meeting On meeting
16 Quantification
17 Structure of the talk Possible workflow routine diagnostic diagnostic support Which scanner? Quantification / image analysis Conclusions
18 Requirements on Slide Scanning Correct slide information is present Completeness of tissue Image sharpness Color fidelity
19 VIRTUAL MICROSCOPY SCANNER CONTEST P. Hufnagl 1,2, N.Zerbe 2 1 University of Applied Science Berlin, Berlin, German 2 Institute for Pathology, Charité Berlin, Germany 2 nd International Scanner Contest technology meets pathology
20 MISSION 2 nd International Scanner Contest technology meets pathology Determination of the state of the art in slide scanning Support of pathologists and scientists to find the appropriate scanner for their applications Support of vendors to understand the needs of pathologists Determination of quality of WSI within the context of pathology Development of a set of standard features for the characterization and comparison of scanning devices
21 DISCIPLINES 2 nd International Scanner Contest technology meets pathology High Throughput Quality Fluorescence Image Analysis Technical
22 2 nd International Scanner Contest QUALITY EVALUATION TERMINALS technology meets pathology
23 VENDORS. 2 nd International Scanner Contest technology meets pathology
24 2 nd International Scanner Contest TECHNICAL COLOUR & GEOMETRY AIMS & MATERIAL technology meets pathology Aims: Measurement of colour fidelity and colour resolution of devices Determination of true effective pixel size Detection of image distortions Material: IT8.7/1 Colour Target mounted on glas slide 264 colour & 24 grey value fields known absorption spectra and colourimetric coordinates Grid pattern glas slide overall size: 1 x 3 (25mm x 75mm) image area: 20mm x 50mm clear aperture: 8.5 µm² opaque lines: 1.5 µm² pitch: 10 µm
25 2 nd International Scanner Contest TECHNICAL COLOUR & GEOMETRY TASK technology meets pathology General Conditions: All participants had to scan the same slide Any manual interaction was allowed Rescan of slide was allowed 1h time limit Evaluation: Colour difference calculation to CIEDE2000 average inside middle 50% of each field low-resolution scan Measurements inside whole slide images Inside sensor field (no stitching) 9 sensor fields 18 measurements each
26 2 nd International Scanner Contest technology meets pathology TECHNICAL COLOUR TEST METHOD Fidelity test: average de over 144 fields de avg = Σ de(c * mes, c ref ) /144 mix-colours matrix for fidelity test Colour difference calculation to CIEDE2000 colour step wedges
27 2 nd International Scanner Contest TECHNICAL COLOUR SOFTWARE technology meets pathology
28 COMPLETENESS OF SCAN 2 nd International Scanner Contest technology meets pathology
29 2 nd International Scanner Contest technology meets pathology HIGH THROUGHPUT AIMS & MATERIAL 29
30 2 nd International Scanner Contest technology meets pathology HIGH THROUGHPUT AIMS & MATERIAL 30
31 2 nd International Scanner Contest DIGITALISATION - SCANMASTER technology meets pathology Sample identifikation (barcode / OCR) Sharpness assessment + Completeness of particles
32 2 nd International Scanner Contest FOCUS QUALITY ASSESSMENT technology meets pathology Green: quality sufficiant Red: not sharp, possible artefacts
33
34 2 nd International Scanner Contest technology meets pathology
35 2 nd International Scanner Contest technology meets pathology VIEWING ON A VIRTUAL MICROSCOPE
36 RESOLUTION 2 nd International Scanner Contest technology meets pathology MAGNIFICATION IS NOT RESOLUTION AND OPTICAL RESOLUTION IS NOT DIGITAL RESOLUTION!
37 Several Positions in Test Leap Motion over the table Leap Motion under acryl glass pane
38 Leap Motion Stereo imaging based on infrared cameras (
39 Handling Possible workflow
40 Gesture Control Next/ previous slide Zoom in/ out
41 Histological Image Registration Goal Inter-Modal Registration (Stain-To-Stain) Applications WSI Navigation Support Virtual Staining 3D Reconstruction Approach Intensity Based Multi-Resolution Similarity Measure Mutual Information Transformation Models Rigid: Rotation + Translation Affine: Linear Transformation + Translation Free Form Deformation: B-Splines Optimization Gradient Descent
42 Registration Of Renal Images: Reference Image (H&E) Template Image (SFOG)
43 Reference Image (H&E)
44 Template Image (SFOG)
45 Coarse to Fine Image Registration: Rigid, Affine, Free Form Model
46 Rigid Registration
47 Affine Registration
48 Free Form Registration
49 Reference Image
50 Structure of the talk Possible workflow routine diagnostic diagnostic support Which scanner? Quantification / image analysis Conclusion
51 The strong reputation of pathology is becoming weaker.. if trust is gone, you almost never get it back
52 Standardized Quantification in Tumor Pathology Nat J Inst., preprint November
53 . At the St. Gallen cutoff of 13.5 % there are 32.3 % high Ki67 by Lab A while Lab B would call the same cases low Ki
54 Optical Illusions Not always funny, sometimes really critical
55 Human brain: Square a is lighter than square b! Reality: Both are identical
56 Simulated Ki67 15%
57 Estimation of variation of Ki67 scoring
58 FEATURE BASED MULTIRESOLUTION CORRESPONDENCE Combined tumor annotations Individual tumor annotations Annotated as tumor by 10 pathologists By 4 pathologists By 2 pathologists tumor non-tumor by no pathologist
59 CLASSIFICATION RESULTS Gastric Cancer (HER2) Transmission to HE Learning Sample 59
60 Structure of the talk Possible workflow routine diagnostic diagnostic support Which scanner? Quantification / image analysis Conclusions
61 Summary on Relevance of VM Workflow routine diagnostic diagnostic support Which scanner? Quantification / image analysis In routine path not yet active on a broad level Excellent instruments exist, but they have to be integrated properly Will become very important in personalized medicine Clinical-pathological tumorconferences (tumor board) Is already very important Biobanking Is important in research institutions
62 Most important requirements on VM Clinical data (LIMS) are correctly connected to WSI Completeness of tissue Image sharpness Color fidelity Compression is adequate Resolution and quality of the monitor is sufficiant Test continously!
63 Let s go virtual 13th European Conference on Digital Pathology Berlin May 25. /
64 Acknowledgement Team Norman Zerbe, Karsten Schlüns, Sebastian Lohmann, Mario Domhardt, Björn Lindequist, Daniel Heim, Stephan Wienert, Kai Saeger, Thorsten Knape, Arend Müller, Wolfram Schädel, Uwe Brunner, Thomas Schrader, Manfred Dietel 2 nd International Scanner Contest technology meets pathology
Second Announcement Call for Participation. (Evaluation Criteria added)
Second Announcement Call for Participation 2 nd International Scanner Contest (ISC) (Evaluation Criteria added) P. Hufnagl 1, T. Schrader 1, 2, M.G. Rojo 3, A. Laurinavicius 4, G. Kayser 5, Y. Yagi 6 1
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