Validation of MRI biomarker of white matter degeneration for ALS clinical trials: One small step

Amyotrophic lateral sclerosis (ALS) is a progressive, paralytic disorder characterized by degeneration of motor neurons in the brain and spinal cord.1 It is part of the ALS–frontotemporal dementia spectrum of disorders that dismantle systematically the behavioral-executive-motor neuronal supernetwork. Measures of strength or function have served as primary outcome measures for most ALS treatment trials.2 Advanced neuroimaging techniques offer the potential to aid in diagnosing ALS and monitoring disease progression. Diffusion tensor imaging (DTI), a robust MRI tool for in vivo analysis of white matter (WM) neuronal tracts, has been applied successfully to study ALS in cross-sectional and longitudinal single-center cohort studies.3–6 Regional reduction of DTI metrics such as fractional anisotropy (FA) has been used as a marker for axonal degeneration and myelin degradation.3,4

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