The purpose of this work was to evaluate the feasibility and reproducibility of the spherical mean technique (SMT), a multi‐compartmental diffusion model, in the spinal cord of healthy controls, and to assess its ability to improve spinal cord characterization in multiple sclerosis (MS) patients at 3 T. SMT was applied in the cervical spinal cord of eight controls and six relapsing‐remitting MS patients. SMT provides an elegant framework to model the apparent axonal volume fraction v ax , intrinsic diffusivity D ax , and extra‐axonal transverse diffusivity D ex_perp (which is estimated as a function of v ax and D ax ) without confounds related to complex fiber orientation distribution that reside in diffusion MRI modeling. SMT's reproducibility was assessed with two different scans within a month, and SMT‐derived indices in healthy and MS cohorts were compared. The influence of acquisition scheme on SMT was also evaluated. SMT's v ax , D ax , and D ex_perp measurements all showed high reproducibility. A decrease in v ax was observed at the site of lesions and normal appearing white matter ( p < 0.05), and trends towards a decreased D ax and increased D ex_perp were seen. Importantly, a twofold reduction in acquisition yielded similarly high accuracy with SMT. SMT provides a fast, reproducible, and accurate method to improve characterization of the cervical spinal cord, and may have clinical potential for MS patients.
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