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AJNR - American Journal of Neuroradiology

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American Journal of Neuroradiology 22:1572-1576 (9 2001)
© 2001 American Society of Neuroradiology

ARTICLE

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.

BACKGROUND AND PURPOSE: Previously, we showed that diffusion-weighted MR imaging depicts evidence of directionally preferential water motion in white matter structures of developing rat brain before and after myelination, and considerably earlier than conventional imaging strategies. Present data augment these imaging and corresponding histologic findings with electron-microscopic corroboration. We additionally report the findings of a 10-day-old rat pup tested functionally by administration of the sodium-channel blocker, tetrodotoxin.

METHODS: In two rat pups, drawn from the population reported previously, MR estimates of diffusion anisotropy of the optic nerves and chiasm were compared with histologic and electron microscopy results. To test the hypothesis that "premyelination" directional preference of water motion in white matter structures relates to sodium-channel activity, MR imaging was performed in a 10-day-old rat pup treated with the sodium-channel blocker, tetrodotoxin, and findings were compared with data from an age-matched control.

RESULTS: Although diffusion anisotropy was present in optic structures of the youngest animal, myelin-sensitive histologic staining did not show myelin before 12 days; electron microscopy confirmed lack of any myelin or its precursors during the earliest maturational stage. Administration of tetrodotoxin to the 10-day-old rat-pup led to loss of diffusion anisotropy.

CONCLUSION: Our findings provide two pieces of supporting data for the hypothesis that nonstructural changes are responsible for early anisotropic diffusion: electron microscopy shows no evidence of myelin despite diffusion anisotropy, and inhibiting the sodium-channel pump appears to remove the directional preference of water motion. Visualization of nonstructural "premyelination" consequences with diffusion-weighted imaging emphasizes its sensitivity and potential in studying early processes of brain development.

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