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

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.

Cortico-efferent tract involvement in primary lateral sclerosis and amyotrophic lateral sclerosis: A two-centre tract of interest-based DTI analysis

“…In addition, disease duration of the 3.0 T PLS sample was significantly higher than the 1.5 T PLS sample. However, although the ALS-associated slope of FA alterations over time has been reported at the individual level ( Baldaranov et al, 2017 ), only a weak correlation could be shown at the group level ( Kassubek et al, 2014 ). Still, the higher disease duration in the 3.0 T PLS patient sample may be responsible for the lower rate of not stageable PLS patients in the 3.0 T PLS patient sample compared to the 1.5 T PLS patient sample (11% for 3.0 T vs 34% for 1.5 T).…”

MRI-Based Mapping of Cerebral Propagation in Amyotrophic Lateral Sclerosis

“…A study with 65 DTI scans from ALS patients and healthy controls with several follow-up measurements ( Baldaranov et al, 2017 ) showed an FA decrease in the CST that correlated with the revised ALS functional rating scale (ALS-FRS-R – Cedarbaum et al, 1999 ). In other studies, both the clinical severity as assessed by the slope of the ALS-FRS-R and the disease duration significantly correlated with the resulting staging scheme ( Kassubek et al, 2014 , 2018b ).…”

Connectome‐Based Propagation Model in Amyotrophic Lateral Sclerosis

“…Brain network analyses have contributed valuable insights into cerebral pathology in vivo and have been extensively applied to various neurodegenerative conditions . With increasing availability of noninvasive imaging data for brain structure, including diffusion tensor imaging (DTI), the research area of network neuroscience is able to extend the focus from cross‐sectional comparison studies toward the longitudinal development of brain disorders . However, the step toward predicting individual disease progression has yet to be unraveled.…”