The Visible Embryo Project: A Metacomputing Resource Center for Developmental Biology

PROPOSAL OUTLINE (DRAFT)

Introduction

Sets of serial microscopic cross-sections through human embryos, within the collection of the National Museum of Health and Medicine, will be digitized and processed to create volumetric reconstructions of normal human embryonic anatom .During the five years of this initial project, a significant portion of the Museum's Carnegie Collection of Human Embryology, over 600 embryos in all, will be digitized, reconstructed and archived, together with case histories, scientific articles, research notes, didactic descriptions, and other data contained within the collection. This massive database will be housed at the Museum at Washington D.C., while teams of researchers at more than 20 universities around the United States will develop software tools, educational materials, virtual reality simulations, basic science investigations, and clinical research projects based upon the data contained within the collection.

Project Structure

a) Data Acquisition and Archiving (P.D.: Eric Allely)

1) Digital Image Data (Eric Allely)

• Photography
• Digitizing
• Storage
• Networking

• Case histories
• Articles
• Didactic descriptions
• Scientists' notes

b) Software Tools Development (P.D.: Jay Udupa)

• This will involve development of hybrid object-oriented, relational and hypertext database management tools, which will be distributed among a host of physical locations, linked by multi-gigabit-speed networking.

• We will produce multidimensional visualization tools that access data from distributed sources and can distribute computational tasks among several networkedvectorizing and massively parallel supercomputers at NCSA.

• Methdologies and software tools will be developed to allow the statistical comparisons of embryological shape across populations of embryos within the database. User-researchers will be able to query the database with respect to morphology, to extract new knowledge from the collection about the patterns and processes of human development.

• Tools will be developed to facilitate the development of distributed workgroups of collaborating scientists using common data from the database. Specialized multimedia e-mail, bulltein board systems, and multiple-simultaneou -user visualization tools will allow dynamic collaborations among researchers irrespective of their physical locations.

c) Educational Applications (P.D.: Cornelius Rosse)

• We will develop a complete medical school curriculum in human embryology that can be taught entirely through online access to the database.

• Virtual reality applications will be developed for two purposes: surgical simulation and a museum exhibit. A VR simulator will be developed for training physicians in laparoscopic techniques for intrauterine fetal surgery. Several VR embryology demonstrations will be developed for the "CAVE" virtual reality environment, to be incorporated into a public exhibit at the new National Museum of Health and Medicine, which will open on the mall in D.C. in 1995.

• Both permanent and traveling exhibits on human development will be designed and produced exploiting the new visualization and virtual reality technologies to be developed during this project.

d) Basic and Clinical Science Applications (P.D.: Paul Lauterbur)

• Brain mapping (Ray Gasser)
  • The Hooker Humphries developmental neuroanatomy collection will be used to create topologically-correct morphologic maps of central nervous system pathways within human embryos.
  2) Magnetic Resonance Microscopy
  • High resolution imaging
  (Brad Smith, Dale Huff)
  • Very-high-resolution techniques will be developed for magnetic resonance microscopy of human embryos from the Carnegie Collection. Slice resolutions on the order of 1024x1024 voxels will ultimately be produced.
  • Ligand-specific contrast marker development (Paul Lauterbur)
    • Novel agents will be developed to alow ligand-specific imaging of individual cell and tissue types, in-vivo and in-vitro, within developing mouse embryos.
    3) Genome Research (Scott Baldwin)
    • The Lauterbur lab's novel MRM contrast media will be adapted for MRM resolvable in-situ hybridization, in order to create a morphological map of gene expression, initially in mouse embryos, but later applied to human embryos newly submitted to the Carnegie Collection. This will allow genetic information generated by the Human Genome project to be correlated with embryological anatomy data within the Visible Embryo database.
    4) Pediatrics
    • Several projects will explore the uses of this database to improve diagnosis and treatment of developmental defects.
      • Pediatric Otolaryngology
      (Mike Dunham)
    • Pediatric Cardiology (Scott Baldwin)

    Budget

    • Approximately $20 million to $100 million over a 5 year period

      This proposal will be submitted to NIH as a P41 Resource Center Grant totalling approximately $20 million over a 5 year period. An additional application will be submitted to ARPA's HPCC grant program to extend the scope of the supercomputing and high-speed networking aspects of the project. The lead institutions will be the Registry of Human Embryology within the American Registry of Pathology, Armed Forces Institute of Pathology, and the Center for Knowledge Management, at the University of California, San Francisco. Subcontracts will be made with the other collaborating institutions.

    Advisory Board

    • Board Members of the Human Developmental Anatomy Center, National Museum of Health and Medicine, Armed Forces Institute of Pathology
    • Many others yet to be invited

    Demonstrations:

    • MPEG movie of rotating embryo model

    See Also:

    Doyle, M. D., et. al. Processing cross-sectional image data for reconstruction of human developmental anatomy from museum specimens. SIGBIO Newsletter, the Journal of the ACM Special Interest Group for Biological Computing, 13/1 (1993).