Visualization of nonstructural changes in early white matter development on diffusion-weighted MR images: evidence supporting premyelination anisotropy

BACKGROUND AND PURPOSE: Previously, we showed that diffusion-weighted MR im aging 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 au gment these imaging and corresponding histologic findings with electron-mic roscopic corroboration. We additionally report the findings of a 10-day-old rat pup tested functionally by administration of the sodium-channel blocke r, tetrodotoxin. METHODS: In two rat pups, drawn from the population reported previously, MR estimates of diffusion anisotropy of the optic nerves and chiasm were comp ared with histologic and electron microscopy results. To test the hypothesi s that "premyelination" directional preference of water motion in white mat ter structures relates to sodium-channel activity, MR imaging was performed in a 10-day-old rat pup treated with the sodium-channel blocker, tetrodoto xin, and findings were compared with data from an age-matched control. RESULTS: Although diffusion anisotropy was present in optic structures of t he youngest animal, myelin-sensitive histologic staining did not show myeli n before 12 days; electron microscopy confirmed lack of any myelin or its p recursors during the earliest maturational stage. Administration of tetrodo toxin to the 10-day-old rat-pup led to loss of diffusion anisotropy. CONCLUSION: Our findings provide two pieces of supporting data for the hypo thesis that nonstructural changes are responsible for early anisotropic dif fusion: electron microscopy shows no evidence of myelin despite diffusion a nisotropy, and inhibiting the sodium-channel pump appears to remove the dir ectional preference of water motion. Visualization of nonstructural "premye lination" consequences with diffusion-weighted imaging emphasizes its sensi tivity and potential in studying early processes of brain development.