Unraveling the heterogeneous pathological substrates of relapse-onset multiple sclerosis: a multiparametric voxel-wise 3 T MRI study

Abstract

Background: In multiple sclerosis (MS), pathological processes affecting brain gray (GM) and white matter (WM) are heterogeneous.

Objective: To apply a multimodal MRI approach to investigate the regional distribution of the different pathological processes occurring in the brain WM and GM of relapse-onset MS patients.

Methods: Fifty-seven MS patients (forty-two relapsing remitting [RR], fifteen secondary progressive [SP]) and forty-seven age- and sex-matched healthy controls (HC) underwent a multimodal 3 T MRI acquisition. Between-group voxel-wise differences of brain WM and GM volumes, magnetization transfer ratio (MTR), T₁-weighted(w)/T₂w ratio, intracellular volume fraction (ICV_f), and quantitative susceptibility mapping (QSM) maps were investigated.

Results: Compared to HC, RRMS showed significant WM, deep GM and cortical atrophy, significantly lower MTR and T₁w/T₂w ratio of periventricular and infratentorial WM, deep GM and several cortical areas, lower ICV_f in supratentorial and cerebellar WM and in some cortical areas, and lower QSM values in bilateral periventricular WM (p < 0.001). Compared to RRMS, SPMS patients showed significant deep GM and widespread cortical atrophy, significantly lower MTR of periventricular WM, deep GM and cerebellum, lower T₁w/T₂w ratio of fronto-temporal WM regions, lower ICV_f of some fronto-tempo-occipital WM and cortical areas. They also had increased QSM and T₁w/T₂w ratio in the pallidum, bilaterally (p < 0.001).

Conclusion: A periventricular pattern of demyelination and widespread GM and WM neuro-axonal loss are detectable in RRMS and are more severe in SPMS. Higher T₁w/T₂w ratio and QSM in the pallidum, possibly reflecting iron accumulation and neurodegeneration, may represent a relevant MRI marker to differentiate SPMS from RRMS.

Keywords: Atrophy; Intracellular volume fraction; MRI; Magnetization transfer ratio; Multiple sclerosis; Quantitative susceptibility mapping; T1-weighted/T2-weighted ratio.