This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Magnetic Resonance Histology (MRH), the use of MRI for the study of tissue microstructure, is a rapidly evolving investigational technique with enormous potential to advance our understanding of the complex structure and function of the brain. MRH has several desirable characteristics including: 1) it is non-destructive and performed in situ, 2) it is inherently 3 dimensional and allows simultaneous imaging in any arbitrary plane, and 3) it provides multiple proton contrasts each of which uniquely illuminates the state of water in tissues. One proton contrast of particular interest is diffusion-weighted contrast, which probes the thermal motion of water within the surrounding cytoarchitecture. Diffusion Tensor Imaging (DTI) uses a series of diffusion-weighted images to calculate a 3x3 tensor at each voxel, allowing 3-dimensional tractography of structures with highly directional diffusion, such as white matter tracts. Here we discuss a multi-contrast MRH atlas of the developing rat brain. Our goal is to use MRH and DTI to characterize brain development in the rat from birth to adulthood. Diffusion-weighted contrast is well suited for this application because it changes significantly during development and has an intuitive physiological correlate (the movement of water along axons). This normative atlas will provide a unique window for studying a wide range of disease processes including toxicologic (fetal alcohol syndrome), traumatic (diffuse axonal injury), and vascular insults (hypoxic ischemic encephalopathy) among others. The atlas will include 25 micron isotropic resolution T2*-weighted anatomical volumes and 50 micron isotropic DTI volumes acquired from five specimens at each of eight different time points between birth and adulthood. DTI calculations and white matter tractography will be performed using a custom-made DTI pipeline developed for both internal and collaborator use. Initial results have demonstrated feasibility and confirm many expected changes in structure, diffusion contrast and white matter tractography during development.
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