OBJECTIVE: Diffusion tensor imaging (DTI) is sensitive to white matter tract 
pathology. A core signature involving the corticospinal tracts (CSTs) has been 
identified in amyotrophic lateral sclerosis (ALS). Raised neurofilament light 
chain protein (NfL) in cerebrospinal fluid (CSF) is thought to reflect axonal 
damage in a range of neurological disorders. The relationship between these two 
measures was explored.
METHODS: CSF and serum NfL concentrations and DTI acquired at 3 Tesla on the 
same day were obtained from ALS patients (n = 25 CSF, 40 serum) and healthy, 
age-similar controls (n = 17 CSF, 25 serum). Within-group correlations between 
NfL and DTI measures of microstructural integrity in major white matter tracts 
(CSTs, superior longitudinal fasciculi [SLF], and corpus callosum) were 
performed using tract-based spatial statistics.
RESULTS: NfL levels were higher in patients compared to controls. CSF levels 
correlated with clinical upper motor neuron burden and rate of disease 
progression. Higher NfL levels were significantly associated with lower DTI 
fractional anisotropy and increased radial diffusivity in the CSTs of ALS 
patients, but not in controls.
INTERPRETATION: Elevated CSF and serum NfL is, in part, a result of CST 
degeneration in ALS. This highlights the wider potential for combining 
neurochemical and neuroimaging-based biomarkers in neurological disease.