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Abstract
The recent introduction of advanced magnetic resonance (MR) imaging techniques to
characterize focal and global degeneration in multiple sclerosis (MS), like the Composite
Hindered and Restricted Model of Diffusion, or CHARMED, diffusional kurtosis imaging
(DKI) and Neurite Orientation Dispersion and Density Imaging (NODDI) made available
new tools to image axonal pathology non-invasively in vivo. These methods already
showed greater sensitivity and specificity compared to conventional diffusion tensor-based
metrics (e.g., fractional anisotropy), overcoming some of its limitations. While previous
studies uncovered global and focal axonal degeneration in MS patients compared to
healthy controls, here our aim is to investigate and compare different diffusion MRI
acquisition protocols in their ability to highlight microstructural differences between
MS and control tissue over several much used models. For comparison, we contrasted
the ability of fractional anisotropy measurements to uncover differences between lesion,
normal-appearing white matter (WM), gray matter and healthy tissue under the same
imaging protocols. We show that: (1) focal and diffuse differences in several microstructural
parameters are observed under clinical settings; (2) advanced models (CHARMED, DKI
and NODDI) have increased specificity and sensitivity to neurodegeneration when compared
to fractional anisotropy measurements; and (3) both high (3 T) and ultra-high fields
(7 T) are viable options for imaging tissue change in MS lesions and normal appearing
WM, while higher b-values are less beneficial under the tested short-time (10 min
acquisition) conditions.