Abstract
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.
Highlights
Diffusion tensor imaging (DTI) allows analysis of the structural connectivity in neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS; Bede and Hardiman, 2014; Agosta et al, 2015; Kassubek and Müller, 2016), Alzheimer’s disease (Teipel et al, 2014), and Parkinsonism (Cochrane and Ebmeier, 2013; Meijer et al, 2013)
The extensive application to the study of ALS has undoubtedly improved the understanding of disease pathophysiology and is likely to have a role in the identification of potential biomarkers of disease progression (Agosta et al, 2010)
In order to avoid an unequal weighting in the statistical analysis for the subjects with five or more scans compared to subjects with lower scan numbers, whole brainbased spatial statistics (WBSS) results were limited to a maximum of two scans from each subject
Summary
Diffusion tensor imaging (DTI) allows analysis of the structural connectivity in neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS; Bede and Hardiman, 2014; Agosta et al, 2015; Kassubek and Müller, 2016), Alzheimer’s disease (Teipel et al, 2014), and Parkinsonism (Cochrane and Ebmeier, 2013; Meijer et al, 2013). The use of DTI has substantially improved the understanding of the in vivo cerebral and spinal neuropathology of the neurodegenerative disorder ALS (Turner, 2011; Turner et al, 2011, 2012; Filippi et al, 2015) as a rapidly progressive neurodegenerative disease with a well-defined neuroanatomical propagation pattern (Braak et al, 2013; Brettschneider et al, 2013; Jucker and Walker, 2013). The recently introduced neuropathological staging system in ALS (Braak et al, 2013; Brettschneider et al, 2013, 2015) has already been transferred to a DTI-based in vivo imaging concept, indicating that ALS may disseminate in regional patterns (Kassubek et al, 2014; Müller et al, 2016). The initially affected CNS tract structure is the corticospinal tract (CST), as the correlate of histopathological ALS-stage 1 (Kassubek et al, 2014; Müller et al, 2016)
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