Applications of Telepathology and Whole Slide Imaging In Practice Today

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Applications of Telepathology and Whole Slide
Imaging In Practice Today
Anil V Parwani, MD., PhD Department of
Pathology Division of Pathology Informatics UPMC
Shadyside Hospital University of Pittsburgh
Medical Center Pittsburgh, PA
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Session Objectives

• Define Telemicroscopy and its applications
• Gain an understanding of the common and proven
  uses of telemicroscopy including whole slide
  images in routine pathology practice
• Provide an overview of telepathology at an
  academic institute
• Proven uses of whole slide imaging.
• Summary and future challenges

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VISUAL INFORMATION IS CENTRAL TO PATHOLOGY
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Telemicroscopy is the TOOL
Once the image is acquired, it can be transferred
to a REMOTE site for viewing.
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TELEMICROSCOPY
101101101000101001001000101010101000000010101
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Telemicroscopy results in digital images

• Static Images
• Non-robotic telepathology for expert/subspecialist
  consultation
• Robotic telepathology for full pathology services
• Whole-Slide Scanning for
• Distance education
• Telepathology
• QA/QC, CME, proficiency testing.
• Primary Diagnosis

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Proven Uses for Telemicroscopy

• Tele-education
• CPC conferences
• QA/QC
• Publications
• Image-enhanced reporting
• Tele-Consultation
• Telepathology Store and Forward
• Retrospective case review assisting diagnosis
• Primary diagnosis
• Advanced image analysis

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APPLICATIONS OF TELEMICROSCOPY

• Telepathology
• Teleconsultation
• Tele-education
• Teleconferencing

Telemicroscopy
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• Telepathology
• Transmittal of Pathology information for helping
  a health care professional at a remote location,
  who needs expert advice at a distant location.
• Subspeciality of Telemedicine
• Relies on telemicroscopy

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Telepathology

• Non-Robotic Microscope and Camera is controlled
  by the referring pathologists who sends
  snapshots to the consultant through a network
  (many vendors)
• Robotic Microscope and Camera is controlled by
  the consultant. (Apollo, Trestle, Nikon
  Coolscope)
• Both systems can be used effectively in limits
  situations

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History

• 1973 Washington, DC pathologists diagnosed
  lymphosarcoma/leukemia via satellite in a patient
  on a ship docked in Brazil
• 1986 telepathology coined by Weinstein
• 1990 A network of telepathology workstations was
  established in Norway to provide frozen section
  service to five remote hospitals.
• By the mid 1990s, with the increasing use of PCs,
  low cost telepathology systems were produced and
  the use of telepathology expanded.

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Telepathology Studies

• Many telepathology studies have been done in the
  last 20 years.
• These include static, dynamic or hybrid or WSI
  systems
• Focus has been broad and include frozens,
  cytology, general surgical pathology, prostate,
  GI, bronchial etc.
• Concordance rates with gold standards have been
  variable with ranges from 81 to 100

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A CLINICAL TRIAL FROM 2008
Assessment of diagnostic accuracy and feasibility
of dynamic telepathology in China Xinxia Li
PhDa, b, Encong Gonga, Michael A. McNutt MDa,
Jianying Liu PhDa, Feng Li MDb, Ting Li MD, PhDc,
Virginia M. Anderson MDd and Jiang Gu MD, PhDa,
d,    ,   
Hum Pathol. 2008 Feb39(2)236-42.
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Methods

• 600 cases covering a wide spectrum of lesions
  from 16 organ systems were tested.
• The gold standard was established as a consensus
  by 2 experienced pathologists.
• The cases were first examined by 4 pathologists
  at different levels of experience with dynamic
  telepathology.
• Cases were then reviewed by the same pathologists
  using light microscopy in a blinded fashion 3
  weeks to 2 months later.
• Dynamic telepathology with a remotely controlled
  microscope was used for viewing glass slides over
  the LAN in this study. This system used a Motic
  remotely controlled microscope (Motic Corp,
  Xiamen, China) equipped with 4, 10, 20, 40,
  and oil 100 objectives.

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RESULTS

• Diagnostic accuracy by telepathology was 94.8
  (569/600), 93.3 (560/600), 91.6 (550/600), and
  97 (388/400) for pathologists A, B, C, and D,
  respectively.
• Telepathologic diagnosis was concordant with the
  gold standard and with direct microscopy, with a
  mean of 94.2 and 99.26, respectively.
• Most cases (510 or 85) were diagnosed in 15 to
  40 minutes by telepathology, with a mean of 17.0
  minutes.
• The time needed to review a slide by
  telepathology was 3 to 4 times longer than that
  of standard light microscopy.
• The authors concluded that robotic telepathology
  is sufficiently accurate for primary diagnosis in
  surgical pathology, but modifications in
  laboratory protocols, telepathology hardware, and
  internet speed are needed to reduce the time
  necessary for diagnosis by telepathology before
  this method may be deemed suitable for use in a
  busy practice.

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MULTIPLE APPLICATIONS OF DIGITAL IMAGES IN OUR
ENVIRONMENT
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The UPMC Health System

• Diversified environment ( academic hospitals,
  community hospitals)
• 19 hospitals with another 18 affiliations
• 2 million outpatient visits per year

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University of Pittsburgh Medical
Centerwww.upmc.com
29 Western PA Counties 19 Hospitals 40 Cancer
Center Locations
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Pathology Centers of Excellence (COEs) at UPMC
UPMC Presbyterian ENT/Thyroid Pathology Gastrointe
stinal Pathology Hematopathology Neuropathology Th
oracic/Mediastinal Pathology Transplant Pathology
UPMC Shadyside Pathology Informatics Dermatopathol
ogy Genitourinary Pathology Bone/Soft
Tissue/Melanoma Pathology
UPMC Magee-Womens Hospital Breast
Pathology Gynecologic Cytopathology Obstetric/Gyne
cologic Pathology
UPMC Childrens Hospital Pediatric Pathology
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Case Documentation
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Case Documentation
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TELEEDUCATION Conferences
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TELEEDUCATION Online Conferences
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TELE-EDUCATION Online Conferences
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TELE-EDUCATION Teaching Case
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TELE-CONSULTATION Quality Assurance
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TELE-CONSULTATION
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Publications
Echinococcal cyst of the liver . Diagn
Cytopathol. 2004 Aug31(2)111-2.
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HARDWARE CAMERAS

• Most microscopic image capture workstations
  utilize SPOT Insight digital cameras (various
  models, Diagnostic Instruments, Sterling Heights,
  MI)
• Sony analog video cameras (Sony Corp., New York,
  NY).

• Features include
• 2 or 4 MP resolution
• High quantum efficiency Kodak 2020/4020 CCD
• Up to 14 bit image capture
• 20 Mhz readout
• FireWire interface
• SPOT software

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CAPTURE OF GROSS AND MICROSCOPIC IMAGES

• Gross images are captured at different locations
  including in gross rooms and autopsy suites.
• Microscopic images are captured at more than
  thirty sites including pathologists sign-out
  rooms and offices.
• Image acquisition is performed within the LIS
  software.
• Once acquired, the image is converted into JPEG
  2000 format then the file is copied to an image
  server.
• Finally, a link to the file is added to the LIS
  database.
•  

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CAPTURE OF GROSS AND MICROSCOPIC IMAGES

• Image application and hardware support is
  provided by specialist personnel but is
  integrated with the general LIS support network.
  
• A departmental networking team supports image
  server maintenance and backup.
•  

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MULTIPLE GROSS AND MICROSCOPIC IMAGES ARE
ACQUIRED EVERYDAY AND STORED IN THE IMAGE SERVERS
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• Integration of Images in Pathology Reports
• Images can be imported directly into the LIS via
  TWAIN driver or indirectly as image files
  (including images captured by almost any digital
  camera).
• Image capture workstations are standard pathology
  PC configurations (Pentium 4, 512MB RAM, Windows,
  etc.) that are specifically licensed for imaging
  functionality with our LIS vendor (PicsPlus
  imaging module and CoPathPlus, Cerner
  Corporation, Kansas City, MO).

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Pathology Gross Images Uploaded into Radiology
System

• Pathology images are uploaded directly into
  Stentor by a process in which the .JPG image
  files and a .txt file are detected and processed
  on a Radiology server directory with the
  reference file name of the image files.
• Within seconds the text file and JPG filenames
  that follow the naming convention are processed
  automatically.   

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• THE SYSTEM CAN TRANSFER ANY TYPE OF STATIC IMAGE
  TO THE RADIOLOGY SYSTEM.
• AT PRESENT ONLY GROSS IMAGES ARE TRANSMITTED TO
  THE RADIOLOGY SYSTEM

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Multimedia
Electronic Medical Record
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Telemicroscopy results in digital images

• Static Images
• Non-robotic telepathology for expert/subspecialist
  consultation
• Robotic telepathology for full pathology services
• Whole-Slide Scanning for
• Distance education
• Telepathology
• QA/QC, CME, proficiency testing.
• Primary Diagnosis

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Expert
1101000101010101001010111010
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Store and forward
Telepathologist
Capture and digitalization of a group of
macroscopic and/or microscopic images selected by
a pathologist, which are then transmitted through
electronic means to a telepathologist.
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Dynamic Robot
2x 4x 10x 20x 40x 60x X Y Z Brighter Darker Con
denser
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Automated, High Speed, High Resolution Whole
Slide Imaging

• To provide the digital view of the complete slide
  in context, several new technologies have emerged
  using Whole Slide Imaging.
• Whole Slide images are digital images of the
  entire block face or slide. These digitized
  images are captured, compressed and viewed on any
  browser over the internet.
• Using WSI for telepathology
• Speed
• Quality (focus issues)
• Archiving

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Whole Slides Images
2x 4x 10x 20x 40x 60x X Y Z Brighter Darker Con
denser
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Slide scanners
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Digital PathologyWhole Slide Imaging
Digital Slide and Virtual Microscope
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ScanScope CS System
http//www.zeiss.com
http//www.aperio.com
http//www.dmetrix.net
i-SCAN
http//sales.hamamatsu.com
http//www.bioimagene.com
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Applications of WSI

• Education
• Clinical Conferences
• Quality Assurance
• Precious slides (cytopathology, frozen sections)
• Proficiency testing
• Other Clinical Applications
• Archival of rare cases before they are sent out.
• Consultation
• Tumor Boards

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Educational Conferences Using Whole Slide Imaging

• Slides are scanned at Shadyside
• Links are added to presenters handout
• Electronic handout posted to residents web site

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Image
(link to this sheet)
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SL-4 Slide Loader System Microscope Site(4
systems at UPMC) Standard PCInternet
ConnectionMicroscopeMotorized Stage Focus
ControlDigital CameraDigitizer
MedMicroscopy Application
Viewer SiteStandard PCInternet Connection
UPMC FIREWALL
Java-based viewer from the Internet through UPMC
Citrix
SL50 Slide Loader System Microscope Site (3
systems at UPMC) Standard PCInternet
ConnectionMicroscopeMotorized Stage Focus
ControlDigital CameraDigitizer
DSS Server on IIS attached to SAN. Pulls images
from SL-4 and SL-50, serves for local and public
Java-based viewer for the Internet
Ishtiaque Ahmed, DPIG, UPMC http//dpig.upmc.com
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Pathology Centers of Excellence (COEs) at UPMC
UPMC Presbyterian ENT/Thyroid Pathology Gastrointe
stinal Pathology Hematopathology Neuropathology Th
oracic/Mediastinal Pathology Transplant Pathology
UPMC Shadyside Pathology Informatics Dermatopathol
ogy Genitourinary Pathology Bone/Soft
Tissue/Melanoma Pathology
UPMC Magee-Womens Hospital Breast
Pathology Gynecologic Cytopathology Obstetric/Gyne
cologic Pathology
UPMC Childrens Hospital Pediatric Pathology
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CASE STUDY 1 TELEPATHOLOGY OF NEUROPATHOLOGY
INTRAOPERATIVE CONSULTATIONS AT OUR INSTITUTE
Telepathology for Intraoperative Neuropathologic
Consultations at an Academic Medical Center A
5-Year Report Craig Horbinski, MD, PhD, Jeffrey
L. Fine, MD, Rafael Medina-Flores, MD, Yukako
Yagi, PhD, and Clayton A. Wiley, MD, PhD
J Neuropathol Exp Neurol Volume 66, Number 8,
August 2007
SLIDES PROVIDED BY DR. CRAIG HORBINSKI,
UNIVERSITY OF PITTSBURGH
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NEUROPATHOLOGY FROZENS

• Neuropathology CoE _at_ Presbyterian (PUH)
• Neurosurgery _at_ PUH, Childrens, and Shadyside
  (SYS)
• 18 city blocks between PUH and SYS
• 1 hour total transit time

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Clincial SituationWhat happens when a
neurosurgeon at the remote hospitals needs an
intraoperative consult from neuropathology?
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Coolscope at UPMC (2 at UPMC, Telapthology LAB
and Shadyside Frozen Section)
Java-based viewer direct from Coolscope
Java-based viewer direct from Coolscope through
UPMC Citrix
UPMC FIREWALL
Ishtiaque Ahmed, DPIG, UPMC http//dpig.upmc.com
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Intraoperative cases, 2002-2006
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2007-Present
Medmicroscopy system
Pateint in the OR
Prepare Slides
Rapid Frozen section
Remote Viewing Station
Telepathologist
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Conclusions from neuropathology studies

• Similar discrepant rates
• Similar overall concordant rates
• More exact concordant diagnoses via
  conventional
• Similar types of problem cases
• Longer turnaround time for diagnoses (anecdotal)
• Validated method for cost-effective expansion of
  neuropathology coverage

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Case Study 2Cytological Evaluation of
Image-Guided Fine Needle Aspiration Biopsy via
Robotic Microscope
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Background

• FNAB has been increasing recognized as the choice
  of diagnostic tool in the management of
  superficial or deep-seated masses.
• On-site immediate assessment is a key component
  in the FNAB, which assures adequate sampling,
  guides specimen triage for appropriate work-up
  and in some cases renders a diagnosis for
  immediate therapeutic intervention.
• As compared to traditional hematoxylin-eosin
  tissue sections, the cells of interest on the
  aspirate smears are three-dimensional and are
  often present as clusters, which may add to the
  technical complexity of the tele-pathology.
• In this pilot study, we examine the feasibility
  of cytological evaluation of image-guided FNAB
  via a robotic microscopy tele-pathology.

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Study Design

• 40 cases of image-guided FNAB of lung, liver,
  pleural, or mesentery masses were included in
  this study.
• Representative Diff-Quick and Papanicolaou-stained
  slides were reviewed via a robotic microscopy
  followed by real slide assessment.
• The cytological evaluations included sampling
  adequacy assessment and cytological diagnosis.
• The results were compared between the robotic
  imaging approach and real slide assessment and
  between the individual cytopathologists.
• The intra- and inter-observer discrepancies were
  analyzed and resolved by a follow-up conscience
  conference.

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SL-4 Slide Loader System Microscope Site(4
systems at UPMC) Standard PCInternet
ConnectionMicroscopeMotorized Stage Focus
ControlDigital CameraDigitizer
MedMicroscopy Application
Viewer SiteStandard PCInternet Connection
UPMC FIREWALL
Java-based viewer from the Internet through UPMC
Citrix
SL50 Slide Loader System Microscope Site (3
systems at UPMC) Standard PCInternet
ConnectionMicroscopeMotorized Stage Focus
ControlDigital CameraDigitizer
DSS Server on IIS attached to SAN. Pulls images
from SL-4 and SL-50, serves for local and public
Java-based viewer for the Internet
Ishtiaque Ahmed, DPIG, UPMC http//dpig.upmc.com
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Adequacy Assessment

• Adequacy assessment
• Satisfactory
• Suboptimal
• Unsatisfactory

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Cytologic Diagnosis

• Benign
• Atypical cells
• Suspicious
• Neoplasm Epithelial, Mesenchymal, Others
• Malignant
• Epithelial (adenocarcinoma, squamous cell
  carcinoma, non-small cell carcinoma, carcinoma)
• Mesenchymal (low grade sarcoma, high grade
  sarcoma)
• Others (metastatic melanoma)
• Comments Favor, Suggestive of, With ?
  Differentiation/features

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TABLE 1. Malignant Cytology Diagnosis of the
Image-Guided Fine-Needle Aspiration Biopsy via
Robotic Microscopy vs. Real Slide Review
CP, Cytopathologist CA, Carcinoma excluding
neuroendocrine carcinoma and hepatocellular
carcinoma NE, neuroendocrine carcinoma HCC,
hepatocellular carcinoma Sarc, sarcoma Mel,
melanoma.
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Case A

• A 65-year-old woman with history of ovarian
  cancer with metastasis to peritoneum presented
  with a liver mass.

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SMALL CELL CARCINOMA
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Case C

• A 71-year-old man with history of ocular melanoma
  presented with a 3.5-cm mass with FDG uptake in
  the liver.

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METASTATIC MELANOMA
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VirtuPath

• Facilitation of access to and increased
  utilization of WSI resources
• Establishment of a solid contact point for COEs
  and individual faculty who wish to create or
  expand WSI resources

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Advantages for Academic Practice

• Internet-based educational resources have
  enhanced pathology resident education at UPMC for
  more then ten years
• Residents may virtually attend conferences that
  would otherwise be unavailable
• A web portal (VirtuPath) can facilitate access
  to these resources

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Other Benefits

• Digital archive of FS slides
• Protects original slides from handling
• Permits viewing by many simultaneously
• No transportation costs
• Slides widely available at all campuses for
  residents and faculty

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Justification

• QA is a high priority
• Cost effectiveness poorly understood
• Equipment and personnel already in place
• Eases funding transition from research to
  operational
• Low volume application

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Quality assurance is a suitable application for
WSI
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Slide Archival

• Rapid review of prior pathology case
• No time or courier costs for retrieval
• Increased compliance with this basic QC procedure
  (enhanced patient care)
• Retention of outside pathology material
• Archival of precious slides
• Frozen sections, cytopathology slides, etc.
• Access for conferencing, education, research, or
  consultation

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Image Analysis

• Immunohistochemistry and FISH
• WSI not required but could decrease manual labor
  associated with imaging step of image analysis
• Potential revenue
• Other Computer-Assisted Diagnosis (CAD) activities

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Conclusions 1 Digital Pathology

• In an academic pathology practice, digital
  imaging provides a fast, high quality, cost
  effective, and secure solution for acquiring,
  managing, and distributing pathology images.
• Integration with the LIS is important and
  facilitates utilization of and access to images,
  as well as streamlines provision of end-user
  support via established mechanisms.
• Standardization of imaging workstations and
  hardware greatly improves deployment and support
  of these activities.
• Pathology imaging support can include scanned
  documents, persistent archives of supplemental
  images associated with departmental academic
  publications, and whole slide images.

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Conclusions 2 WSI

• WSI and telepathology are increasingly being used
  in a academic pathology
• Many areas of pathology including education,
  clinical pathology, anatomic pathology and
  informatics are creating and utilizing digital
  imaging applications using WSI.
• Pathologists current routines will change and be
  impacted by WSI.
• We need to be in the forefront to embrace and
  evaluate this technology and make it work for
  us!!!

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FUTURE CHALLENGES

• New Hospitals entering the network
• Connectivity with other information systems
• Maintaining digital archives of the images
• Robotic vs. WSI
• Regulatory Issues

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Acknowledgements

• Jeff Fine
• Jonhan Ho
• John Gilbertson
• Drazen Jukic
• Ishtiaque Ahmed and Jon Duboy (Telepathology)
• Tony Piccoli
• Ralph Anderson
• Craig Horbinski (Providing Neuropathology Slides)
• Guoping Cai (Providing TeleCytology Slides)

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References

• Sinard, John. Practical Pathology Informatics.
  2006.Springer, New York, NY.
• Becker RL et al. Human Pathology 24(8) 909-911,
  1993.
• Dunn BE et al. Telemedicine Journal 5(4)
  323-337, 1999.
• Horbinski C et al. J Neuropathol Exp Neurol
  Volume 66, Number 8, August 2007
• Riggs RS et al. JAMA 228(5) 600-602, 1974.
• Szymas J et al. Human Pathology 32(12)
  1304-1308, 2001.
• Weinstein RS. Human Pathology 17(5) 433-434,
  1986.

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QUESTIONS??????? COMMENTS?????