Abstract Details

Cervical spinal cord (CSC) damage from demyelinating disease, as would occur in multiple sclerosis (MS), compression or trauma can lead to severe disabilities. Unfortunately, there is a lack of sensitive imaging biomarkers for evaluating CSC injuries. Fortunately, our UHb-rDWI is a powerful tool to quantitate disease progression and monitor treatment responses in various CSC diseases. In this abstract, we present UHb-rDWI evaluations correlated with histological analyses of (de)myelinated mouse spinal cords to validate UHb-rDWI.

To perform a quantitative evaluation of myelination on myelin-deficient (shiverer) and WT mouse spinal cords using UHb-DWI.

UHb-rDWI experiments were performed on ex-vivo mouse spine columns at a 7T small-bore MRI system, using an in-house developed specimen RF coil and 3D ms-DWSTEPI with 75 x 75 μm² in-plane resolution and 1-mm slice thickness, and b_max of 42,890 s/mm². After MRI experiments, histologic slides were prepared at the upper thoracic section for electron and optical microscopy studies. EM analyses were performed using a Transmission Electron Microscopy.

EM study showed SHR mice to have noticeably thinner myelin, consistent with a significant increase in water permeability at the membrane. The white-matter (WM) signal-b curves of WT mouse cords behaved biexponentially with high-b diffusion coefficient D_H < 0.020x10^-3mm²/s. However, as expected with lower myelination, the signal-b curves of SHR mouse cords behaved monoexponentially with significantly greater D_H of 0.162x10^-3, 0.142x10^-3, and 0.164x10^-3 mm²/s at dorsoanterior, dorsoposterior, and lateral columns, respectively. Therefore, D_H is directly related to the myelination. UHb-rDWI results were consistent with the histology, confirming D_H as a biomarker with high specificity for quantitative evaluation of WM myelination.

UHb-DWI provides quantitative differences in myelination of spinal cords from myelin-deficit shiverer and wild-type mice. UHb-DWI shows great promise to become a powerful tool to evaluate myelination in demyelinating disease models that may translate to human diseases, including MS.