Objects The diffusion‐based spherical mean technique (SMT) provides a novel model to relate multi‐b‐value diffusion magnetic resonance imaging (MRI) data to features of tissue microstructure. We propose the first clinical application of SMT to image the brain of patients with multiple sclerosis (MS) and investigate clinical feasibility and translation. Methods Eighteen MS patients and nine age‐ and sex‐matched healthy controls (HCs) underwent a 3.0 Tesla scan inclusive of clinical sequences and SMT images (isotropic resolution of 2 mm). Axial diffusivity (AD), apparent axonal volume fraction (Vax), and effective neural diffusivity (Dax) parametric maps were fitted. Differences in AD, Vax, and Dax between anatomically matched regions reflecting different tissues types were estimated using generalized linear mixed models for binary outcomes. Results Differences were seen in all SMT‐derived parameters between chronic black holes (cBHs) and T2‐lesions (P ≤ 0.0016), in Vax and AD between T2‐lesions and normal appearing white matter (NAWM) (P < 0.0001), but not between the NAWM and normal WM in HCs. Inverse correlations were seen between Vax and AD in cBHs (r = −0.750, P = 0.02); in T2‐lesions Dax values were associated with Vax (r = 0.824, P < 0.0001) and AD (r = 0.570, P = 0.014). Interpretations SMT‐derived metrics are sensitive to pathological changes and hold potential for clinical application in MS patients.

Background and Purpose Axonal injury is a key player of disability in persons with multiple sclerosis (pwMS). Yet, detecting and measuring it in vivo is challenging. The neurite orientation dispersion and density imaging (NODDI) proposes a novel framework for probing axonal integrity in vivo. NODDI at 3.0 Tesla was used to quantify tissue damage in pwMS and its relationship with disease progression. Methods Eighteen pwMS (4 clinically isolated syndrome, 11 relapsing remitting, and 3 secondary progressive MS) and nine age‐ and sex‐matched healthy controls underwent a brain MRI, inclusive of clinical sequences and a multi‐shell diffusion acquisition. Parametric maps of axial diffusivity (AD), neurite density index (ndi), apparent isotropic volume fraction (ivf), and orientation dispersion index (odi) were fitted. Anatomically matched regions of interest were used to quantify AD and NODDI‐derived metrics and to assess the relations between these measures and those of disease progression. Results AD, ndi, ivf, and odi significantly differed between chronic black holes (cBHs) and T2‐lesions, and between the latter and normal appearing white matter (NAWM). All metrics except ivf significantly differed between NAWM located next to a cBH and that situated contra‐laterally. Only NAWM odi was significantly associated with T2‐lesion volume, the timed 25‐foot walk test and disease duration. Conclusions NODDI is sensitive to tissue injury but its relationship with clinical progression remains limited.

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