Longitudinal Diffusion Tensor Imaging-Based Assessment of Tract Alterations: An Application to Amyotrophic Lateral Sclerosis

Objective: The potential of magnetic resonance imaging (MRI) as a technical biomarker for cerebral microstructural alterations in neurodegenerative diseases is under investigation. In this study, a framework for the longitudinal analysis of diffusion tensor imaging (DTI)-based mapping was applied to the assessment of predefined white matter tracts in amyotrophic lateral sclerosis (ALS), as an example for a rapid progressive neurodegenerative disease. Methods: DTI was performed every 3 months in six patients with ALS (mean (M) = 7.7; range 3 to 15 scans) and in six controls (M = 3; range 2-5 scans) with the identical scanning protocol, resulting in a total of 65 longitudinal DTI datasets. Fractional anisotropy (FA), mean diffusivity (MD), axonal diffusivity (AD), radial diffusivity (RD), and the ratio AD/RD were studied to analyze alterations within the corticospinal tract (CST) which is a prominently affected tract structure in ALS and the tract correlating with Braak's neuropathological stage 1. A correlation analysis was performed between progression rates based on DTI metrics and the revised ALS functional rating scale (ALS-FRS-R). Results: Patients with ALS showed an FA and AD/RD decline along the CST, while DTI metrics of controls did not change in longitudinal DTI scans. The FA and AD/RD decrease progression correlated significantly with ALS-FRS-R decrease progression. Conclusion: On the basis of the longitudinal assessment, DTI-based metrics can be considered as a possible noninvasive follow-up marker for disease progression in neurodegeneration. This finding was demonstrated here for ALS as a fast progressing neurodegenerative disease.