Diffusion tensor imaging in multiple sclerosis at different final outcomes

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Inflammatory demyelination and axonal degeneration are mainstays of multiple sclerosis (MS) pathology. Contemporary MS therapeutic agents suppress inflammation and associated demyelination. Particularly during progressive phases an additional rationale is to provide protection and even trophic stimulus for demyelinated and degenerating axons.1
However, a patient's degree of demyelination and axonal degeneration can only be roughly estimated based on clinical symptoms, neurochemical analyzes, or standard clinical MRI. Magnetic resonance diffusion tensor imaging (DTI) may provide more information on MS pathology than T1‐ and T2‐weighted MRI alone. For example, a decrease in fractional anisotropy (FA) has repeatedly been reported in MS,2 although this finding appears not to be consistent.4 This may depend on the specific anatomical site5 or may be due to progressive or reversible changes over time.2 The decreased FA was confirmed as a global measure and found both in regions of NAWM and in local lesional areas.7 The commonly used DTI metrics, fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) are all derived from the DTI eigenvalues (λ1, λ2, and λ3). Radial diffusivity ((λ2+λ3)/2) is influenced by the status of the myelin layer, while AD (λ1) is associated with axonal changes. Indeed, decreased AD has been seen in the normal‐appearing white matter in the early stages of MS, while an increase in AD was observed in later stages of MS.8 The available data thus suggest that the RD metric can be useful for estimating myelin loss, while the AD metric seems to depend on the stage of the disease.8 These parameters have not been studied in relation to lifelong final clinical outcomes.
In this study of patients with a prolonged history of MS characterized by survival into old age, DTI measures were evaluated as disease biomarkers, in particular RD as a potential marker of demyelination and AD as a potential marker of axonal degeneration. As in several other previously published studies,2 this study focuses on the corpus callosum (CC) as a representative area of disease progress. The CC is a densely packed fiber structure and the largest fiber tract connecting the cerebral hemispheres. Due to its highly uniform and dense fiber structure, the CC presents a high level of diffusion anisotropy and orientational coherence, with a high inherent FA. Thus confounding factors, like crossing fibers, tend to be negligible, which increases the overall likelihood of detecting minute disease‐related changes in diffusion as well.

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