To investigate the relationship between myelin density measured by q-space diffusional MRI (q-space myelin map; qMM) in normal-appearing white matter (NAWM) and clinical disability in multiple sclerosis (MS).

We previously developed the qMM method to depict myelin sheaths in vivo and visualize remyelination in demyelinating lesions of MS patients (Fujiyoshi, J Neurosci 2016). A method for evaluating NAWM using the qMM is needed.

Individuals diagnosed with MS according to the 2010 or 2017 McDonald Criteria were recruited at our hospital (April 2016-Sept. 2022). The Expanded Disability Status Scale (EDSS) and MRI including qMM were evaluated in all participants. The Processing Speed Test (PST) (Rao, Mult Scler 2017) was performed when possible. For a quantitative comparison of qMM modalities, we defined Myelin Index (MI) and calculated it between ROIs (selected regions) and a reference (cerebrospinal fluid) with the formula: GV_ROI/GV_REF, where GV indicates median gray value. The MI was assessed in NAWM at the corpus callosum (CC) (average of the CC’s genu and splenium), bilateral cerebral peduncles (CP), bilateral middle cerebellar peduncles (MCP), bilateral posterior limbs of the internal capsule (ICp), and bilateral corona radiata (CR).

Fifty individuals (34 females) with relapsing-remitting MS, n=39, secondary-progressive MS, n=8, and primary-progressive MS, n=3, were examined. Age at evaluation: 42±9.07 years (mean±SD). Disease duration: 10 (7–16.5) years (median (Q1–Q3)). EDSS score: 1.25 (0–3.13). Twenty-six took the PST (score 57 (49.3–72)). The MI of NAWM (average of CC, CP, MCP, ICp and CR) was 5.27±0.31. A negative correlation was observed between the EDSS and the MI of NAWM (r= −0.60, p<0.0001). The PST was positively associated with the MI of the CC (r= 0.55, p=0.003).

The reduction of myelin density in NAWM is associated with deteriorated physical disability and cognitive impairment in MS.