Newswise — PHILADELPHIA—James C. Gee, PhD, director of the Penn Image Computing and Science Laboratory in the Department of Radiology at the Perelman School of Medicine at the University of Pennsylvania, has received two grants totaling $3.9 million from the National Institutes of Health to help develop a first-ever three-dimensional, cellular-resolution digital atlas of  brain cell types in collaboration with national colleagues from the Allen Institute for Brain Science, Broad Institute of MIT and Harvard, and University of California, San Diego.

The atlas will comprise a vast collection of data acquired by the BRAIN Initiative Cell Census Network, serving as a compendium of information, including location, structure, function, molecular properties, and connectedness to other cells,  for use in classifying and cataloging the diversity of cell types in the brain. In the human brain there are about 86 billion neurons and a similar number of non-neuronal cells. Ideally, every cell could be assigned to a unique type based on its characteristics, with the number of cell types being significantly smaller – and thus more manageable – than the aggregate number of cells themselves.

“An atlas of this kind is one of the most promising ways of advancing our understanding of both the healthy and diseased human brain by increasing comprehension of its components,” Gee said. “Researchers will gain access to an immense storehouse of information, much of which has been unknown or generally inaccessible. My fellow grant recipients and I are extremely grateful to the NIH for its support of this vital effort.”

Gee’s awards support the NIH’s ambitious goal of creating a foundational community resource for cell data from mouse, human and non-human primate brains as part of the BRAIN Initiative announced by President Obama in 2013 dedicated to enhancing understanding of the mind and improving methods for preventing, treating, and curing brain disorders.

“Three-dimensional mapping into a standard spatial coordinate framework such as we’ll be pursuing is essential for integrating the complex datasets that will be collected by the BRAIN Initiative Cell Census Network,” Gee said. “These kinds of common coordinate-based atlases have become well established for studying mouse and rat brains. But because of challenges arising from scale, clear-cut differences in individual human brains, and other difficulties, human-brain atlases are much less advanced in their development. The aim of this project is to accelerate the generation of methods and tools  that overcome these obstacles.”

As part of this process, in collaboration with Gee and other external partners, the Allen Institute will develop and house the BRAIN Cell Data Center, which will include a web-portal for sharing the new brain cell atlases, research tools, and findings among neuroscientists worldwide. The Center will also develop common data models, standards, and terminology, helping unify variations in technique and reporting of results among the diverse community of global neuroscience researchers. For example, since there are currently no generally-accepted location standards akin to latitude and longitude, such a protocol will be created for pinpointing brain anatomy, enabling researchers to precisely and consistently describe the locations of their research findings. Specifically, each position in a brain image will be assigned standard spatial coordinates and an anatomical name. Researchers will be able to identify the anatomical regions within which cells of interest reside and also determine where these cells are located in relation to other cells in the brain.

To develop the atlases, researchers from a number of member institutions of the BRAIN Initiative Cell Census Network will collect detailed brain-cell information that Gee will help map into and locate within a common coordinate framework that he and the Center will also help specify and construct. This effort builds on the research and development work Gee has been carrying out to establish the newest version of Waxholm Space, a community-defined common coordinate framework for the rodent brain. “Our results from the rodent atlasing project formed the basis of the new Center’s strategy for cell data integration,” Gee said. “We will be extending all of the tools and techniques from that atlas for use in the human and non-human primate versions.”

Funding for this study comes from the NINDS National Institute of Neurological Disorders and Stroke R01 NS096720 and National Institute of Mental Health U24 MH114827.

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U24 MH114827; R01 NS096720