The goal of this project is to produce a high resoluation electronic atlas of the brain in three dimensions (3D). A number of technical problems are addressed, including how to minimize distortions during the processing of the brain through steps of hardening (fixation), embedding in a rigid support medium, sectioning and staining. Other problems relate to the massive computer database and memory requirements for the large number of images at the closely spaced intervals through the brain necessary for resolution of 1 um or less in all three planes of space (1 um isomorphic voxels). To solve these problems, we propose to make an atlas of the small brain of the mouse, as a prelude to tackling the human brain. We will begin at a voxel resolution of 10 um, and procede to 3 um and 1 um (greater than 550 GB of image data). Novel technical methods for whole brain embedding and sectionaing in epoxy resin and for confocal microscopy of stable 3D data space, and for partially automated volumetric segmentation of brains packed with hundreds of 3D structures, many with comples shapes. Images will be warped to a high resolution MRI standard of the intact fixed head (100 um digital """"""""slices"""""""" obtained with a 9.4 Tesla magnet). The uniquely high level of histological resolution in 3D will allow us to develop a new """"""""white matter anatomy"""""""" by tracing the exact trajectories of myelinated fiber groups that intermingle so intimately in the white matter that they have been impossible to sort out by previously available characterization of brain structures. Chemical, genetic, and pathological data will be superimposable digitally onto the basic cell and myelin atlas templates. For ease of data storage and transmission, the atlas images will be compressed with wavelet compression algorithms, with an added substraction method that will allow the origical focus on the elucidation of the genetic gases for individual differences in brain organization. Remote users with their own research, educational, and public welfare needs, will be able to obtain the entire database, including capabilities for rotations and digital """"""""resectioning"""""""" in any desired orientation, on new high capacity DVD disks, or will gain access to specific 2D and 3D images via a dedicated WWW page outfitted with a systematic and friendly query interface and VRML-based browser. Users needing to download atlas images will access the WWW pageover new high speed Asynchronous Transfer mode transmission lines.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
1R01NS036041-01A1
Application #
2461887
Study Section
Special Emphasis Panel (ZLM1-RWD-B (01))
Program Officer
Kitt, Cheryl A
Project Start
1997-07-01
Project End
2000-04-30
Budget Start
1997-07-01
Budget End
1998-04-30
Support Year
1
Fiscal Year
1997
Total Cost
Indirect Cost
Name
Harvard University
Department
Veterinary Sciences
Type
Schools of Medicine
DUNS #
082359691
City
Boston
State
MA
Country
United States
Zip Code
02115
Westlund, Karin N; Vera-Portocarrero, Louis P; Zhang, Liping et al. (2009) fMRI of supraspinal areas after morphine and one week pancreatic inflammation in rats. Neuroimage 44:23-34