Sticks or no sticks? White matter microstructure in multiple sclerosis from high-b scaling

Motivation: Representing axons as impermeable sticks is a cornerstone of white matter modeling, e.g. for the Standard Model and related models. However, the validity of this framework in pathology remains unknown. Goal(s): Validate the modeling assumption of axons as impermeable sticks in multiple sclerosis white matter. Approach: We analyze the functional form of the orientationally-averaged signal as a function of b-value up to b=10,000 s/mm2. Results: We find that normal-appearing white matter, T1 black-holes, and T1-hypointense lesions show distinct deviations from the healthy tissue power-law b-1/2 signal scaling. Simulations reveal these deviations may be specific markers for microglia inflammation and unmyelinated leaky axons. Impact: We assess the validity of the modeling assumption of water diffusion along impermeable axons in multiple sclerosis tissue. Pathological processes such as microglial inflammation or demyelination show different behaviors in this experimental regime, highlighting the potential for an imaging biomarker.