Myelination and long diffusion times alter diffusion-tensor-imaging contrast in myelin-deficient shiverer mice

Diffusion tensor imaging (DTI) using variable diffusion times (tdiff) was performed to investigate wild-type (wt) mice, myelin-deficient shiverer (shi) mutant mice and shi mice transplanted with wt neural precursor cells that differentiate and function as oligodendrocytes. At tdiff = 30 ms, the diffusion anisotropy “volume ratio” (VR), diffusion perpendicular to the fibers (λ⊥), and mean apparent diffusion coefficient () of the corpus callosum of shi mice were significantly higher than those of wt mice by 12 ± 2%, 13 ± 2%, and 10 ± 1%, respectively; fractional anisotropy (FA) and relative anisotropy (RA) were lower by 10 ± 1% and 11 ± 3%, respectively. Diffusion parallel to the fibers (λ//) was not statistically different between shi and wt mice. Normalized T2-weighted signal intensities showed obvious differences (27 ± 4%) between wt and shi mice in the corpus callosum but surprisingly did not detect transplant-derived myelination. In contrast, diffusion anisotropy maps detected transplant-derived myelination in the corpus callosum and its spatial distribution was consistent with the donor-derived myelination determined by immunohistochemical staining. Anisotropy indices (except λ//) in the corpus callosum showed strong tdiff dependence (30-280 ms), and the differences in λ⊥ and VR between wt and shi mice became significantly larger at longer tdiff, indicative of improved DTI sensitivity at long tdiff. In contrast, anisotropy indices in the hippocampus showed very weak tdiff dependence and were not significantly different between wt and shi mice across different tdiff. This study provides insights into the biological signal sources and measurement parameters influencing DTI contrast, which could lead to developing more sensitive techniques for detection of demyelinating diseases.