High Volume Slide Scanning Architecture and Applications Picture: First (?) Leitz photo microscope, 1950. Museum Boerhave, Leiden, The Netherlands Dr. André Huisman Department of pathology UMC Utrecht, The Netherlands a.huisman-4@umcutrecht.nl

Department of pathology UMCU UMC Utrecht >1,000 beds >10,000 employees Department of pathology: 20.000 surgical pathology cases 156.000 glass slides (histology, cytology, IHC) 15 pathologists, 10 residents

Digital pathology - advantages Digital Archiving Instant access from multiple locations by multiple people No searching for slides Constant quality Telepathology Consultations, revisions and panels Education Research Automated image processing Difference between

Project background Clinico pathological conferences: 900 meetings every year No (multi headed) microscope needed Quicker preparation of meetings No retrieval of glass slides from archive

Digitize all diagnostic slides we have (prospectively) Aim (2007) Digitize all diagnostic slides we have (prospectively)

Challenges Scanners Image size: up to 1 GB x 500 slides per day No existing infrastructure present for storage of this size at our facility Image presentation and software integration Logistics

Scanners Different manufacturers: Speed Focusing method Acquisition technique z-stack acquisition File format policy Application integration 2007: 3D Histech (Zeiss), Aperio, Hamamatsu, Olympus (US: Dmetrix, BioImagene) 2010: Leica, Menarini, Philips, Omnyx, BioImagene

Scanning logistics 3 Aperio XT scanners (120 slides per scanner) Morgue assistants Mark slides after scanning 6 Hours per run at 20x magnification (~3 minutes/scan)

Storage – HSM HSM = Hierarchical Storage Management Sun Microsystems (Oracle) 6 TB available on very fast fibre channel disks 120 TB available on tape (750 GB each) 2 Tape drives Completely transparent archiving and retrieval (robot) Access time from tape: 1 - 3 minutes

Linking systems 1D Barcodes U-DPS: reporting system LMS: Laboratory Management System Spectrum: Aperio’s image management solution Storage system Own development: integration layer

Scanner workflow LIS Image / Data server U-DPS Scanning Database Other images (e.g. macro) Scanning Order form scanner Database LIS Image / Data server U-DPS Speech recognition HSM 120 TB on tape 6 TB fast disks Storage pathology users

Validation Aim: validate diagnostic use of digital slides Method: reevaluate diagnosis with same pathologist on scanned slide after washout period (1 year) for several organs Gold standard: original diagnosis using ‘traditional’ microscopy

Preliminary results validation GI tract (%) Skin (%) Same 92 94 Similar 7 5 Discrepant 1 GI tract discrepancy Different interpretation of abnormality Glass slide and WSI contained same information Skin discrepancy Clinical information not used for interpreting digital slide

Pitfalls of digital archive Costs Huge storage needs – 40 TeraByte per year (over 57,000 CDs) Largest storage in the UMCU Logistics of scanning up to 500 slides per day Currently scanning almost 24 / 7 Place of scanning in process Speed of image retrieval Image compression (JPEG 2000?) Backup

Education All students view the same “best slide” Slide images can be integrated with Annotations Questions Macroscopic images Other multimedia Most UMCU microscopy practical sessions are digital Student satisfaction is high

Teleconsultation Place (small) slide scanners at different labs Upload digital slides to UMC Utrecht Aurora mScope Clinical www.pathoconsult.com Upload new media

Digital slide panel discussions

Image processing research Image processing applications on virtual slides: Detecting mitotic figures in breast cancer slides Use texture features Establishing histological grade in breast cancer Segmentation of individual nuclei (on H&E stained slides) Detect points of interest Use marker-controlled watershed segmentation Post processing

Conclusions Routine scanning is possible and makes sense Future of pathology is digital Digital pathology is expensive Digital pathology is just starting.. Together we are shaping Pathology 2.0

Discussion Limitations current system Cytology Speed Magnification (20x / 40x incidental) Backup Quality Control

Discussion Archive heavily used Educational use still growing Teleconsultation network growing (www.slideconsult.com) Need for standards DICOM / JPEG 2000 Images, annotations and reports Mixing scanners and integration with other software platforms (middleware?) Image management central in workflow for pathologist? Other platforms = LIS, PACS, HER, reporting software, speech recognition

Questions?! a.huisman-4@umcutrecht.nl Huisman et al., Creation of a fully digital pathology slide archive by high-volume tissue slide scanning, Human Pathology, 2010 May; 41(5): 751-7 a.huisman-4@umcutrecht.nl