Utilization of Virtual Microscopy in a Cooperative Group Setting

Transcription

1 Utilization of Virtual Microscopy in a Cooperative Group Setting The Research Institute at Nationwide Children s Hospital Research Informatics Core Biopathology Center Tom Barr Bill Beyer Dave Billiter Agenda Overview of the Biospecimen Core Purpose of Cooperative Cancer Groups Pathological Evaluation Electronic Pathology Molecular Based Methods Medicine for Gen XI 1

2 Research Informatics Core Mission The Research Informatics Core of The Research Institute at Nationwide Children s Hospital, under the vision of Dr. Stephen J. Qualman and direction of Dr. Nilsa Ramirez, is an informatics application development team dedicated to increasing cure rates and decreasing side effects in therapy through innovation of information technology. Informatics Core Team Dave Billiter, PMP- Informatics Development Manager Tom Barr- Imaging Manager Bob Neville- Senior Software Developer Scott Hargrose- Software Developer/DBA Bill Beyer- Software Developer/Business Analyst Heather Bao- Software Developer Heather Day- Quality Assurance/Tech Writer/PM Subha Krishnamachary- Software Developer Andy Fox- Software Developer Mark Plaskow- Software Architect Eric Kramer- Data Architect 2

3 Informatics Core Technology Microsoft.NET Framework (.NET Suite) MS SQL Server 2000/2005 (6.5/7) MS Access 97/2000/2003/2007 MS Team Foundation Server MySQL ColdFusion Java Ruby/Ruby On Rails Aperio ScanScope and Image Software Linux/Apache/PHP/JSP Freezerworks Biopathology Center (BPC) Non-profit organization whose primary objective is the long-term acquisition and storage of cancer-related tissues to support cutting edge research (also normal and non-cancerous tissue) Largest pediatric specimen bank in nation Began accruing specimens in 1989 Directed by Dr. Nilsa Ramirez 3

4 Biopathology Center Specimen Management Services for: Pediatric Cooperative Human Tissue Network (pchtn) Children s Oncology Group (COG) Gynecologic Oncology Group (GOG) Childhood Cancer Survivor Study (CCSS) Clinical Trials Evaluation Program (CTEP) The Cancer Genome Atlas (TCGA) Strategic Partnering for the Evaluation of Cancer Signatures (SPECS) BPC by the Numbers Over 650,000 specimens currently in bank Receive tissues from over 500 hospitals from the US, Canada, New Zealand, the Netherlands, Australia and Switzerland 90% pediatric solid tumor cancer cases diagnosed in US and Canada 90% of the nation s childhood leukemia cases Receive and process 100 cases or 500 aliquots each day Distribute over 25,000 specimens annually to over 130 academic and commercial researchers 4

5 BPC Our function is to ensure the proper collection of, storage of, and access to, high quality well annotated human specimens, collected from representative patient populations and entered into NCI funded clinical treatment trials. Prepare specimen collection kits, receives specimens, prepares liquid samples, banks specimens (frozen, liquid, and paraffin specimens), Prepares nucleic acids, organizes pathology review, develops informatics systems and software to support enriching the repository with easily tracked and retrievable inventory and clinical data, distributes tissue, and constructs tissue microarrays (TMAs) Biopathology Center Components Biospecimen Repository Specimen management, quality control, expert pathology review Core Morphology Histology services Molecular Genetics High Throughput Genotyping and Sequencing Core ALL Reference Laboratory for the COG Digital Imaging Core Performs image acquisition of histologic slides for QC and review purposes 5

6 Digital Imaging Core Supports multiple investigators and cooperative groups for pathology review including QC review of tissue quality and pathology review by the expert pathologists to make certain that the patients qualify for a specific protocol Education Technology has been endorsed to improve turnaround time for rapid review and to train junior pathologists in the review process. The goal is to employ Virtual Microscopy as Training and Educational Tool While Not Delaying Turnaround Time for Protocol Diagnostic and Data Review Pathology Training Pathology Teaching Sets rare tumors Difficult Case Reviews Allied Health fields Biology 6

7 Research Integrating a virtual microscopy service into the research workflow Systems acts as a catalyst to advance collaborative pediatric and gynecologic pathology research Image Analysis Image Warehouse Whole slide images, gross images, radiology images Sifting mechanism across multiple data sets to return data for specific users and diseases. Answers specific questions from different perspectives. Pathology, computer science, biology, statistician Further research in image analysis Necrosis, Anaplasia & Neuroblastoma Agenda Overview of the Biospecimen Core Purpose of Cooperative Cancer Groups Pathological Evaluation Electronic Pathology Molecular Based Methods Medicine for Gen XI 7

8 Cooperative Cancer Group Funded primarily by the National Cancer Institute (NCI) Large network of researchers, physicians, and health care professionals at public and private institutions Work together to treat a large number of people in the same way so that new treatment can be tested quickly Treatment Protocols Treatment instruction for a specific disease and stage of that disease Defines requirements for pathology review including microscopic visual examination of tissues, with special stains and immunohistochemistry employed to visualize specific proteins and other substances in and around cell 8

9 Children s Oncology Group Over 5,000 pediatric cancer specialists located at 240 pediatric medical centers in the United States, Canada and Australia Over 150 concurrent studies of leukemia, brain tumors and the other principal cancers of children Over 90% of pediatric cancer cases diagnosed in US and Canada Gynecologic Oncology Group 50 principal centers, most of which are academic centers, and over 160 affiliate institutions Over 2,100 gynecologic oncologists, medical oncologists, pathologists, radiation oncologists, nurses, statisticians, basic scientists, quality of life experts, data managers, and administrative personnel Over 3,300 patients are registered each year to GOG research trials To date, GOG has completed over 300 clinical trials and contributed over 550 manuscripts to the peer reviewed medical literature 9

10 Agenda Overview of the Biospecimen Core Purpose of Cooperative Cancer Groups Pathological Evaluation Electronic Pathology Molecular Based Methods Medicine for Gen XI 10

11 Pathology Review Provide expert pathology review to ensure correct diagnoses of case material for protocol assignment, clinical and biological correlative studies and tissue banking There is an appreciable misdiagnosis rate by local pathologists (20 to 40%), underscoring the value of review prior to protocol enrollment and entry of biospecimens into the tumor repository Agenda Overview of the Biospecimen Core Purpose of Cooperative Cancer Groups Pathological Evaluation Electronic Pathology Molecular Based Methods Medicine for Gen XI 11

12 Digital Pathology The technique of digitizing microscope slides with common objective magnifications Equivalent to original glass slides on microscopes Provides diagnostic image quality Digital Images may be more valuable than glass slides.. Caveats of Digital Pathology Introduction of a new technology to an established work group Costs associated related to image scanners, hardware (storage), and software (management) Limitations in the technology Image size Bandwidth requirements Scan times 12

13 Benefits of Digital Pathology Reproducible diagnosis as compared to glass reviews Eliminates distribution of glass slides, logistical issues with rapid turnaround times, and costs of tracking and lost or broken slides Support image analysis Better quality than static images Accessible anytime via the Internet Why Digital Pathology? Improve patient care by reducing review times Reduces use of precious research material Reduces costs associated with cutting multiple slide sets, shipping costs, broken glass slides Accessible anytime via the Internet Educational Potential much improved over traditional teaching sets Support image analysis Easy retrieval of pathology images 13

14 Digital Pathology Business Process A significant achievement has been the coordination of central pathology review using virtual microscopy. Imaging Hardware Aperio ScanScope XT (2) Viewing Station in Anatomic Pathology NAS Device 1 Tb 6 Tb local storage cluster Virtual Slide Repository 14

15 Pathology Review Workstation Industry Partners 10 Tb storage cluster at the Ohio Supercomputer Center (OSC) Serve images from the OSC GB connection Beta testing site for Aperio OSC HPC Microsoft Life Sciences 15

16 Evolution of the Technology Create digital slides of blood smear, bone marrow, Gram stain, and other specimens using oil immersion on the ScanScope OS System Commercial Software SSH Communications Security SSH MathWorks MatLab Aperio ImageScope Aperio ImageServer Aperio WebViewer Aperio Digital Slide Conferencing Aperio Digital Slide Studio Aperio SpectrumPlus 16

17 Custom Application Development Virtual Pathology Image Analysis with the Image Dashboard DVD HTML Generator Scanner Scheduling System Virtual Microscopy Request System VIPER VM2M Image Dashboard Slide processor for cancerous diseases Allows users to query multiple images by morphologic characteristics Algorithms to detect and measure necrosis, anaplasia & mitotic index 17

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20 Virtual Imaging for Pathology, Education, and Research (VIPER) Web-based pathology review system that is extensible both for today and tomorrow s research needs Facilitates a more efficient and costeffective pathology review process of patient tissue submitted by member institutions Integration of a virtual microscopy service into the research workflow Acts as catalyst to advance collaborative pediatric and gynecologic pathology research and research in image analysis 20

21 Expert Reviewers and VIPER Online registration and request for password resets Notified via of new cases Personalized screen with list of cases and case status after authenticating into VIPER System monitors new cases, completed cases, and cases under review Ability to annotate images Online forms for completion notification of completed cases to the BPC User s manual available online BPC Operations and VIPER Assign Password Assign Cases and/or groups of cases Upload Pathology Reports Add Staff Accounts Add or Remove reviewers Manage Cases Manage Slides Manage Groups Manage Institutions Query for Case status by reviewer or protocol Image Directory Assignment Online User s Manual 21

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25 VIPER G3 In Development by the Research Informatics Core Ability to connect to multiple image data centers Voice recognition for online forms Online chat for Digital Slide Conferencing Algorithms for Image Quality 25

26 Rich Image Warehouse Currently populated with whole slide pathology images Supplement current image set with additional image types (radiology, cardiology, etc.) and correlated metadata Supports sifting through multiple data sets to return data for specific users and diseases providing data to answer specific questions from different perspectives Pathology, computer science, biology, statistician Further development of analysis algorithms for multiple image types Synergistic personalized healthcare medicine through expert systems and decisioning Integration with Personal Health Records/Electronic Medical Record/Laboratory Information Systems/Radiology Information Systems facilitating personalized medicine Agenda Overview of the Biospecimen Core Purpose of Cooperative Cancer Groups Pathological Evaluation Electronic Pathology Molecular Based Methods Medicine for Gen XI 26

27 Virtual Microscopy to Microarray (VM2M) Creates a system where Virtual Microscopy data is made available alongside microarray data for disease diagnosis and treatment Web-based system where a pathologist can search for tissue samples of interest Reviewer can inspect the corresponding digital image using a web based image viewer, with the ability to zoom and pan to the desired parts of the image Reviewer will also have the ability to access the micro- array data corresponding to the same tissue sample, along with results from an automated analysis of the digital image 27

28 VM2M Accomplishments Completion of first iteration, which includes the biology and molecular components of a COG IRSG (Rhabdo) study. 192 cel files; 146 images Complete framework designed and developed in a secure and flexible method, which allows for addition of future components (e.g. Radiology). 28

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32 Agenda Overview of the Biospecimen Core Purpose of Cooperative Cancer Groups Pathological Evaluation Electronic Pathology Molecular Based Methods Medicine for Gen XI VM2M G3 A clearer strategy for the development of novel strategies for high-risk disease, demonstrating the links between molecular pathology and therapy Increase number of studies with corresponding biology and molecular data Incorporate Electronic Lab Notebook functionality Add additional components to the framework of the application (Radiology, Proteomics, etc.) Increase overall search capabilities, reporting and export functionality, and other added features 32

33 High Dimension Data Analyzer A web-based, patient-driven, dashboard application which integrates data from disparate modalities, applications and data sources at one single point of entry. Acknowledgements Aperio Technologies Children s Oncology Group Gynecologic Oncology Group Microsoft Life Sciences Division Nationwide Children s Hospital Ohio Supercomputer Center 33

34 Questions Open Discussion 34