Biomedical Informatics Research Network
to Improve Understanding of Brain Disorders

eading neuroscientists at centers across the country will soon share high-resolution brain images and other biological data over a high-speed communications network as part of a new $20 million research program. The Biomedical Informatics Research Network (BIRN) project, recently funded by the National Center for Research Resources (NCRR) of the National Institutes of Health, will inaugurate a new mode of scientific collaboration. “With advanced networking and data mining technology, we expect to demonstrate new ways to make exciting advances in the study of brain disorders,” said neurobiologist Mark H. Ellisman of UC San Diego, one of the principal investigators for BIRN.

Mouse Brain Section

Images of Alzheimer’s Disease

SHARING DATA

Many research groups at medical schools and universities in the United States have projects in neuroscience involving studies of the brains of humans and animals in health and disease. The projects use a variety of experimental and imaging techniques and focus at scales from the molecular to the whole brain. For individual studies, the sample sizes are small and restricted to limited populations. What has never been attempted is the directed cross-correlation of such studies. To do this, groups of neuroscientists must be ready to account for differences in technique and population focus in order to overcome the challenges of accessing and sharing large data sets. BIRN represents the first attempt to develop a protocol for this kind of collaborative research among neuroscientists and medical scientists.

The program relies on the new computational and networking technologies developed to bring researchers together over the Internet. It also incorporates still newer technologies for federating data from multiple sources. It depends even more on the social integration of the scientific groups that will be sharing their data and, ultimately, making their collective results public.

BIRN PROJECT STRUCTURE

UCSD will establish the BIRN Coordinating Center with expertise from NPACI, SDSC, UCSD’s Center for Research in Biological Structure (CRBS), and the newly formed California Institute for Telecommunications and Information Technology (Cal-(IT)2). The BIRN Coordinating Center at UCSD will work with Duke University, Massachusetts General Hospital (MGH), Brigham and Women’s Hospital (BWH), Caltech, UCSD’s School of Medicine, and UCLA to establish large-scale network connections and data-sharing facilities for the BIRN research projects. The coordinating center is a major extension of a current grant to the National Biomedical Computational Resource (NBCR), an NCRR-supported resource at UCSD/CRBS and SDSC that develops and deploys computational tools to benefit the biomedical community.

Initially, data from ongoing experiments will be shared by two major BIRN subprojects: the Mouse BIRN Project and Brain Morphology BIRN Project. G. Allan Johnson, director of the Center for In Vivo Microscopy at Duke University, leads the mouse project. Mouse BIRN will collaborate with Ellisman’s National Center for Microscopy and Imaging Research (NCMIR) at UCSD; the Laboratory of Neuro Imaging, directed by Arthur Toga at UCLA; and the Biological Imaging Center’s Magnetic Resonance Imaging division, directed by Russell Jacobs at Caltech’s Beckman Institute. These collaborators will extend studies by using two mouse models of human disease, one that develops a neurological disorder similar to multiple sclerosis and another in which a gene involved in regulating the level of dopamine in the brain has been altered. Changes in brain dopamine levels occur in Parkinson’s disease, schizophrenia, and several other brain disorders (Figure 1).

The Brain Morphology BIRN Project will be based on studies of human subjects. A major goal of this project is to develop technologies for enabling seamless interoperability of algorithms and computational tools for analysis and visualization of structural brain imaging data. The initial clinical focus of the project will be on depression and Alzheimer’s disease (Figure 2). The Brain Morphology BIRN Project will be led by Bruce Rosen, director of the MGH/MIT/Harvard Medical School Athinoula A. Martinos Center for Functional and Structural Biomedical Imaging in Cambridge, Massachusetts, and colleague Anders Dale. The project will rely on collaborators led by Ferenc Jolesz and Ron Kikinis of Harvard’s Center for Neuroimaging Technologies at Brigham and Women’s Hospital, Toga’s group at UCLA, and three groups at NCRR-supported General Clinical Research Centers. They are at Duke, led by Ranga Krishnan; Massachusetts General Hospital, where the BIRN projects will be led by David Nathan and Randy Gollub; and at the UCSD School of Medicine, which includes clinical investigators in the departments of psychiatry, neurosciences, and radiology, led by Edward Holmes, vice chancellor for health sciences and dean of the School of Medicine.

BIRN NETWORKING

Advanced networking for BIRN will be developed using the Internet 2/Abilene high-speed infrastructure. Eventually, BIRN will use the large-scale, distributed data and supercomputing resources of the TeraGrid, a $53 million national computational infrastructure established by NSF under the Partnerships for Advanced Computational Infrastructure program.
“The BIRN project exemplifies the kind of scientific project for which the TeraGrid is designed,” said Fran Berman, director of SDSC and NPACI and co-principal investigator of the TeraGrid. “It will combine computational and data-intensive projects and develop the infrastructure for a new mode of collaborative scientific research.”

The initial configuration links the BIRN-associated laboratories over Internet 2 from the Abilene backbone, with the collaboration of the CalREN-2 network in California and similar networks in Massachusetts and North Carolina. This will involve “last-mile” linkage for some of the laboratories, although all the institutions belong to Internet 2. A BIRN Network Operations Center will be located at SDSC. The bandwidth will be upgraded after 18 months, from OC-3 (135 Mbps) to OC-12 (622 Mbps).
While the computer platforms at each site will vary, the BIRN operations center will have a mirror of each site’s configuration and will specify network interface services. An important component of the data-sharing network will be the Storage Resource Broker developed at SDSC, middleware for integrating disparate data repositories.

BIRN will develop and deploy a “virtual data grid” across the equipment, which will be a state-of-the-art configuration similar to others in operation or under development to study particle physics, earthquake engineering simulations, and other projects. The grid will allow researchers affiliated with the project to share the large volume of data being developed.
The data from each of the university sites involved in the Mouse BIRN Project (Duke, UCLA, Caltech, and UCSD/NCMIR) are expected to total 4 terabytes (TB) in the first year, 15 TB in the second, and 30 TB in the third year, with continuous deposition rates of 3-5 gigabytes a day and much higher “burst” deposition rates. The Brain Morphology BIRN Project will assemble similar amounts of data. Each partner site will retain complete autonomy over access to its data and resources, and data will be available only to authenticated users until it is placed in the public domain. Close collaboration between information engineers at the partner sites and the BIRN Coordinating Center will enable the development of “fusion” data models that combine inputs from the various sites and from publicly accessible databases.

“We’re eager to start on this challenging project,” said Randy Gollub, a Brain Morphology BIRN project participant who is assistant director of psychiatric neuroimaging at MGH and an assistant professor at Harvard Medical School. The project will allow robust clinical research involving imaging across multiple sites simultaneously. “This means that trials can be done more quickly and we’ll have a better ability to conduct longitudinal studies,” she said. “It will also advance the development of structural and functional analysis tools, which can then play an ever-increasing diagnostic and prognostic role.” —MM

BIRN COORDINATING CENTER
Mark H. Ellisman
NCMIR, UCSD/SDSC, CRBS, Cal-(IT)2

Maryann E. Martone
NCMIR

Phil Papadopoulos
UCSD/SDSC, Cal-(IT)2

Bertram Ludäscher
UCSD/SDSC

Peter Arzberger
NBCR, CRBS, NPACI

Kim K. Baldridge
NBCR, SDSC

Amarnath Gupta, Chaitan Baru
UCSD/SDSC

Arthur Olson
TSRI

MOUSE BIRN PROJECT
G. Allan Johnson
Duke University

Arthur M. Toga
UCLA

Russell Jacobs
Caltech

Mark H. Ellisman
NCMIR

BRAIN MORPOLOGY BIRN PROJECT
Bruce Rosen, Anders Dale
Martinos Center, MGH/MIT/HMS

Ferenc Jolesz, Ron Kikinis
BWH

Ranga Krishnan
Duke University

Arthur M. Toga
UCLA

Randy Gollub
MGH

David M. Nathan
MGH-GCRC

Edward Holmes
UCSD-GCRC

Gregory Brown
UCSD School of Medicine