  Diffusion kurtosis imaging (DKI), is an imaging modality that yields novel
disease biomarkers and in combination with nervous tissue modeling, provides
access to microstructural parameters. Recently, DKI and subsequent estimation
of microstructural model parameters has been used for assessment of tissue
changes in neurodegenerative diseases and their animal models. In this study,
mouse spinal cords from the experimental autoimmune encephalomyelitis (EAE)
model of multiple sclerosis (MS) were investigated for the first time using DKI
in combination with biophysical modeling to study the relationship between
microstructural metrics and degree of animal dysfunction. Thirteen spinal cords
were extracted from animals of variable disability and scanned in a high-field
MRI scanner along with five control specimen. Diffusion weighted data were
acquired together with high resolution T2* images. Diffusion data were fit to
estimate diffusion and kurtosis tensors and white matter modeling parameters,
which were all used for subsequent statistical analysis using a linear mixed
effects model. T2* images were used to delineate focal
demyelination/inflammation. Our results unveil a strong relationship between
disability and measured microstructural parameters in normal appearing white
matter and gray matter. The changes we found in biophysical modeling parameters
and in particular in extra-axonal axial diffusivity were clearly different from
previous studies employing other animal models of MS. In conclusion, our data
suggest that DKI and microstructural modeling can provide a unique contrast
capable of detecting EAE-specific changes correlating with clinical disability.
These findings could close the gap between MRI findings and clinical
presentation in patients and deepen our understanding of EAE and the MS
mechanisms.
