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

Abstract

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 × 75 μm² in-plane resolution, 1-mm-slice thickness, and radial DWI using b_max = 42,890 s/mm² . 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 × 10^-3 mm² /s. However, as expected with less myelination, the signal-b of shiverer mouse cords behaved monoexponentially with significantly greater D_H = 0.162 × 10^-3 , 0.142 × 10^-3 , and 0.164 × 10^-3 mm² /s at anterodorsal, posterodorsal, and lateral columns, respectively. The axial DWI signals of all mouse cords behaved monoexponentially with D = (0.718-1.124) × 10^-3 mm² /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.

Keywords: Ultrahigh-b diffusion-weighted imaging; diffusion kurtosis imaging; diffusion-weighted imaging; electron microscopy; multiple sclerosis; optical microscopy; shiverer mice; spinal cord; white matter.