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

Diffusion tensor imaging (DTI) using variable diffusion times (t _diff) 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 t_diff = 30 ms, the diffusion anisotropy "volume ratio" (VR), diffusion perpendicular to the fibers (λ_⊥), and mean apparent diffusion coefficient (<D>) 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 T ₂-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 t_diff dependence (30-280 ms), and the differences in λ_⊥ and VR between wt and shi mice became significantly larger at longer t_diff, indicative of improved DTI sensitivity at long t_diff. In contrast, anisotropy indices in the hippocampus showed very weak t_diff dependence and were not significantly different between wt and shi mice across different t _diff. 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.