Ultrahigh-b diffusion-weighted imaging for quantitative evaluation of myelination in shiverer mouse spinal cord

Purpose To perform a quantitative evaluation of myelination on WT and myelin-deficient (shiverer) mouse spinal cords using ultrahigh-b diffusion-weighted imaging (UHb-DWI). Methods UHb-DWI of ex vivo on spinal cord specimens of two shiverer (C3HeB/FeJ-shiverer, homozygous genotype for MbP(shi)) and six WT (Black Six, C3HeB/FeJ) mice were acquired using 3D multishot diffusion-weighted stimulated-echo EPI, a homemade RF coil, and a small-bore 7T MRI system. Imaging was performed in transaxial plane with 75 x 75 mu m(2) in-plane resolution, 1-mm-slice thickness, and radial DWI using b(max) = 42,890 s/mm(2). Histological evaluation was performed on upper thoracic sections using optical and transmission electron microscopy. Numerical Monte Carlo simulations (MCSs) of water diffusion were performed to facilitate interpretation of UHb-DWI signal-b curves. Results The white matter ultrahigh-b radial DWI (UHb-rDWI) signal-b curves of WT mouse cords behaved biexponentially with high-b diffusion coefficient D-H < 0.020 x 10(-3) mm(2)/s. However, as expected with less myelination, the signal-b of shiverer mouse cords behaved monoexponentially with significantly greater D-H = 0.162 x 10(-3), 0.142 x 10(-3), and 0.164 x 10(-3) mm(2)/s at anterodorsal, posterodorsal, and lateral columns, respectively. The axial DWI signals of all mouse cords behaved monoexponentially with D = (0.718-1.124) x 10(-3) mm(2)/s. MCS suggests that these elevated D-H are mainly induced by increased water exchange at the myelin sheath. Microscopic results were consistent with the UHb-rDWI findings. Conclusion UHb-DWI provides quantitative differences in myelination of spinal cords from myelin-deficit shiverer and WT mice. UHb-DWI may become a powerful tool to evaluate myelination in demyelinating disease models that may translate to human diseases, including multiple sclerosis.