The overall aim of this study is to demonstrate the feasibility to generate computerized human white matter tract maps based on a newly developed magnetic resonance imaging (MRI) technique, called diffusion tensor imaging (DTI). Knowledge of neuronal connections by the white matter tracts is of critical importance for the understanding of normal brain functions and abnormalities of function. However, to date most approaches have relied on invasive in vivo techniques and, necessarily, human data have been severely limited. In the DTI technique, the directionality (anisotropy) of water diffusion in the brain is measured. This technique provides two types of data that have previously been inaccessible. First, as we have demonstrated recently, it enables us to reconstruct the 3-dimensional (3D) structure of white matter tracts. Second, it provides a unique contrast called anisotropy map that indicates how anisotropic the water diffusion is and is believed to reflect the degree of fiber density and myelination. In this proposal, DTI measurements will be performed on postmortem tissues, which allow the acquisition of ultra high-resolution 3D DTI data. The long-term goals of this project are two-fold. First, these unique capabilities of the DTI technique provide novel opportunities to study neuroanatomy of human whiter matter and its variations due to individual, gender, normal and abnormal development/aging processes and other diseases. Second, the study will provide vital information for the future application of this novel technology to clinical studies, such as the range of normal deviation and nature and extent of expected white matter abnormalities in terms of DTI findings in each disease. Use of postmortem tissues also allows histology studies to explore the precise meanings of the DTI findings. To achieve these goals and as a Phase I feasibility study for Human Brain Project, this project is designed to build systems for data acquisition, fiber reconstruction, statistical analysis, and visualization. Toward this end, we propose four principal aims. 1) to acquire ultra high-resolution 3D DTI data of normal brains, 2) to develop fiber reconstruction technology, 3) to develop statistical tools to study individual variations in white matter structures, and 4) to develop tools to visualize 3D white matter architectures/creation of electric white matter atlas.
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