BRAIN DEVELOPMENTAL STUDY BY DIFFUSION TENSOR IMAGING

Johns Hopkins University, Baltimore MD

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Abstract

DESCRIPTION: (adapted from applicant's abstract) The overall goal of this project is to study child developmental defects with a newly developed MRI (magnetic resonance imaging) technique. This technique, so-called diffusion tensor imaging, non-invasively provides two types of data that have previously been inaccessible. First, it enables investigators to visualize the 3-dimensional (3D) structure of axonal fiber projections. Second, maturation of myelination can be studied qualitatively. By combining the two sets of data it is also possible to quantify the degree of maturation of each individual fiber tract. Projections of axonal fibers have been studied in the past with one of the tracer techniques that require invasive in vivo animal experiments. Because these methods can not be applied to human subjects, comparable human data, especially during the development process, are necessarily much more limited. Study of normal and abnormal development by this new technique will lead to further understanding of the mechanism of human brain development and its defects. The method is expected to be a new powerful diagnostic tool for evaluating developmental defects. With this new technique, the directionality (anisotropy) of water diffusion in the brain will be measured using the diffusion MRI technique. Recently investigators have succeeded in the 3D reconstruction of numerous brain fiber tracts both in vivo and ex vivo using animal models. Using this new technique, it is now possible to study the time-evolution of human brain fiber structures. In this project, the following three aims will be pursued. Aim 1: As the first step toward the overall goal, the normal development process of axonal projections will be studied in detail using animal models. The effect of brain maturation on the diffusion MRI parameters will be investigated by comparing the MRI and histology findings in detail. Aim 2: Normal development of human axonal fiber structures will be studied using postmortem tissues. This study will establish the normal fiber structures at each developmental stage of human brain. Aim 3: Human postmortem tissues with various developmental defects will be scanned by this technique. Two important questions will be answered by this study; first, is the technique sensitive enough to define the abnormalities and second can it describe the time-evolution of the abnormality? Although this technique has a potential to detect many white matter related abnormalities, the initial effort for Aim 3 will be focused on the study of leukodystrophies through collaboration with Dr. Hugo Moser.