Multi-compartmental diffusion characterization of the human cervical spinal cord in vivo using the spherical mean technique

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 3T. 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.