Characterizing white matter lesions in multiple sclerosis with time-dependent diffusion MRI reveals the signature of axonal beading

We observe diffusivity time-dependence along white matter axons in normal-appearing white matter (NAWM) and lesions in 5 relapse remitting multiple sclerosis (MS) patients. The long-time diffusivity along axons is higher in MS lesion than that in NAWM due to persistent demyelination and axonal loss, consistent with previous studies. Further, the axial diffusivity time-dependence is weaker in MS lesions than in NAWM, probably caused by beading due to increased mitochondria in astrocytes/axons in MS lesions. we propose the axial diffusivity time-dependence as a potential specific biomarker for beading, to monitor the progression and treatment response of MS.