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AJNR - American Journal of Neuroradiology

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Visualization of Nonstructural Changes in Early White Matter Development on Diffusion-Weighted MR Images: Evidence Supporting Premyelination Anisotropy

Daniela Prayer^a, A. James Barkovich^a, Daniel A. Kirschner^a, Lukas M. Prayer^a, Timothy P.L. Roberts^a, John Kucharczyk^a and Michael E. Moseley^a

^a From the Department of Radiology (D.P., L.M.P.), Section of Neuroradiology, University of Vienna, Austria; Department of Radiology (D.P., A.J.B., L.M.P., T.P.L.R., J.K.), Neuroradiology Section, University of California at San Francisco; Department of Biology (D.A.K.), Boston College, Chestnut Hill, Massachusetts; Department of Radiology (M.E.M.), Stanford University, Palo Alto, California.

View larger version (21K): [in a new window]   FIG 1. Maturation score defined according to anisotropic diffusion-weighted imaging and histologic sections, respectively, as a function of rat pup postnatal age. Anisotropy of diffusion precedes, by about 1 week, histologic evidence of myelin in the optic nerves, internal capsules, and corpus callosum

View larger version (93K): [in a new window]   FIG 2. Electron-microscopy preparation of the optic nerve of a 7-day-old rat pup (A) shows no evidence of myelin sheaths or significant structural changes within the oligodendrocytes. Oligodendroglial cells have large nuclei (black arrow). Electron-microscopy preparation of the optic nerve of a 21-day-old rat pup (B) shows myelin sheaths (black arrows) surrounding multiple axons

View larger version (66K): [in a new window]   FIG 3. Coronal diffusion anisotropy maps of 10-day-old rat pups, showing the effect of tetrodotoxin (TTX). The untreated animal (left) shows high signal intensity in the slightly myelinated optic structures (white arrows), and the unmyelinated internal capsules (white arrowheads) show diffusion anisotropy. In the TTX-treated animal (right), diffusion anisotropy is no longer visible in the unmyelinated internal capsule. However, anisotropy (hyperintensity) still is present in the partially myelinated optic nerves, presumably because the hydrophobic myelin sheath already constitutes a physical barrier to water diffusion. This suggests that the anisotropy present before myelin results from a physiological phenomenon, such as sodium diffusion, that is paralyzed by the TTX. Note that the intensity of the entire TTX-treated brain appears different from that of the untreated animal. This intensity change is attributed to TTX-induced global cytotoxic edema, restricting water motion in gray matter as well as white matter