In vivo tensor-valued diffusion MRI of focal demyelination in white and deep grey matter of rodents

Background: Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease leading to damage of white matter (WM) and grey matter (GM). Magnetic resonance imaging (MRI) is the modality of choice to assess brain damage in MS, but there is an unmet need in MRI for achieving higher sensitivity and specificity to MS-related microstructural alterations in WM and GM. Objective: To explore whether tensor-valued diffusion MRI (dMRI) can yield sensitive microstructural read-outs for focal demyelination in cerebral WM and deep GM (DGM). Methods: Eight rats underwent L-alpha-Lysophosphatidylcholine (LPC) injections in the WM and striatum to introduce focal demyelination. Multimodal MRI was performed at 7 Tesla after 7 days. Tensor-valued dMRI was complemented by diffusion tensor imaging, quantitative MRI and proton magnetic resonance spectroscopy (MRS). Results: Quantitative MRI and MRS confirmed that LPC injections caused inflammatory demyelinating lesions in WM and DGM. Tensor-valued dMRI illustrated a significant decline of microscopic fractional anisotropy (mu FA) in both LPC-treated WM and DGM (P < 0.005) along with a marked increase of isotropic kurtosis (MKI) in DGM (P < 0.0001). Conclusion: Tensor-valued dMRI bears considerable potential for microstructural imaging in MS, suggesting a regional mu FA decrease may be a sensitive indicator of MS lesions, while a regional MKI increase may be particularly sensitive in detecting DGM lesions of MS.