Abstract
ObjectiveUsing diffusion tensor imaging (DTI), we examined chronic stable MS lesions, peri-lesional white matter (PLWM) and normal appearing white matter (NAWM) in patients with relapsing-remitting multiple sclerosis (RRMS) for evidence of progressive tissue destruction and evaluated whether diffusivity change is associated with conventional MRI parameters and clinical findings.MethodPre- and post-gadolinium T1, T2 and DTI images were acquired from 55 consecutive RRMS patients at baseline and 42.3 ± 9.7 months later. Chronic stable T2 lesions of sufficient size were identified in 43 patients (total of 134 lesions). Diffusivity parameters such as axial diffusivity (AD), radial diffusivity (RD), mean diffusivity (MD) and fractional anisotropy (FA) were compared at baseline and follow-up. MRI was also performed in 20 normal subjects of similar age and gender.ResultsWithin the core of chronic MS lesions the diffusion of water molecules significantly increased over the follow-up period, while in NAWM all diffusivity indices remained stable. Since increase of AD and RD in lesional core was highly concordant, indicating isotropic nature of diffusivity change, and considering potential effect of crossing fibers on directionally-selective indices, only MD, a directionally-independent measure, was used for further analysis. The significant increase of MD in the lesion core during the follow-up period (1.29 ± 0.19 μm2/ms and 1.34 ± 0.20 μm2/ms at baseline and follow-up respectively, P < 0.0001) was independent of age or disease duration, total brain lesion volume or new lesion activity, lesion size or location and baseline tissue damage (T1 hypointensity). Change of MD in the lesion core, however, was associated with progressive brain atrophy (r = 0.47, P = 0.002). A significant gender difference was also observed: the MD change in male patients was almost twice that of female patients (0.030 ± 0.04 μm2/ms and 0.058 ± 0.03 μm2/ms in female and male respectively, P = 0.01). Sub-analysis of lesions with lesion-free surrounding revealed the largest MD increase in the lesion core, while MD progression gradually declined towards PLWM. MD in NAWM remained stable over the follow-up period.ConclusionThe significant increase of isotropic water diffusion in the core of chronic stable MS lesions likely reflects gradual, self-sustained tissue destruction in demyelinated white matter that is more aggressive in males.
Highlights
Multiple sclerosis (MS) is a chronic inflammatory neurodegenerative disease of the central nervous system (CNS)
Within the core of chronic MS lesions the diffusion of water molecules significantly increased and fractional anisotropy (FA) decreased over the follow-up period, while in normal appearing white matter (NAWM) all diffusivity indices remained stable
The current study addresses longitudinal microstructural changes within chronic stable demyelinated MS lesions using diffusion tensor imaging (DTI)
Summary
Multiple sclerosis (MS) is a chronic inflammatory neurodegenerative disease of the central nervous system (CNS). While acute inflammatory demyelination is thought to be a principal cause of axonal transection and subsequent axonal degeneration, other factors including axonal damage of permanently demyelinated axons and slow axonal burning at the lesion edge may contribute to tissue damage, in the progressive phase of the disease. Contrary to the massive, rapid axonal damage that accompanies acute focal inflammation, chronic neurodegeneration is a continuous and slow process (Smith, 2006). In the current study we used diffusion tensor imaging (DTI), a wellestablished and widely used technique for assessing white matter (WM) microstructure, to examine chronic stable MS lesions and peri-lesional white matter (PLWM) in patients with relapsing-remitting MS (RRMS) for evidence of progressive tissue alteration. We evaluated whether diffusivity change is associated with conventional MRI parameters and clinical findings
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