Characterization of white matter alterations using diffusion kurtosis imaging in patients with amyotrophic lateral sclerosis.

BACKGROUND: To evaluate the degeneration of the corticospinal tract (CST) and corpus callosum (CC) in patients with motor neuron disease and upper motor neuron (UMN) dysfunction using diffusion kurtosis imaging (DKI). METHODS: Twenty-seven patients and 33 healthy controls underwent magnetic resonance imaging along with clinical and neuropsychological testing. Tractography of diffusion tensor images was performed to extract tracts of the bilateral CST and CC. Group mean differences both across the entire averaged tract and along each tract were assessed, including correlations between diffusion metrics and clinical measures. Tract-based spatial statistics (TBSS) was performed to evaluate the spatial distribution of whole-brain microstructural abnormalities in patients. RESULTS: In comparison to controls, patients had significantly higher mean and radial diffusivity and lower fractional anisotropy (FA), kurtosis anisotropy, mean kurtosis (MK), and radial kurtosis (RK) in the CST and CC (p < .017). Along-the-tract analysis revealed changes concentrated in the posterior limb of the internal capsule, corona radiata, and primary motor cortex (false-discovery rate p < .05). FA of the left CST correlated with disease progression rate, whereas MK of the bilateral CST correlated with UMN burden (p < .01). TBSS results corroborated along-tract analysis findings and additionally revealed reduced RK and MK in the fornix, where diffusion tensor imaging (DTI) changes were absent. CONCLUSION: DKI abnormalities in the CST and CC are present in patients with UMN dysfunction, potentially revealing complementary information to DTI regarding the pathology and microstructural alterations occurring in such patients. DKI shows promise as a potential in vivo biomarker for cerebral degeneration in amyotrophic lateral sclerosis.

Motor cortex functional connectivity is associated with underlying neurochemistry in ALS.

OBJECTIVE: To identify structural and neurochemical properties that underlie functional connectivity impairments of the primary motor cortex (PMC) and how these relate to clinical findings in amyotrophic lateral sclerosis (ALS). METHODS: 52 patients with ALS and 52 healthy controls, matched for age and sex, were enrolled from 5 centres across Canada for the Canadian ALS Neuroimaging Consortium study. Resting-state functional MRI, diffusion tensor imaging and magnetic resonance spectroscopy data were acquired. Functional connectivity maps, diffusion metrics and neurometabolite ratios were obtained from the analyses of the acquired multimodal data. A clinical assessment of foot tapping (frequency) was performed to examine upper motor neuron function in all participants. RESULTS: Compared with healthy controls, the primary motor cortex in ALS showed reduced functional connectivity with sensory (T=5.21), frontal (T=3.70), temporal (T=3.80), putaminal (T=4.03) and adjacent motor (T=4.60) regions. In the primary motor cortex, N-acetyl aspartate (NAA, a neuronal marker) ratios and diffusion metrics (mean, axial and radial diffusivity, fractional anisotropy (FA)) were altered. Within the ALS cohort, foot tapping frequency correlated with NAA (r=0.347) and white matter FA (r=0.537). NAA levels showed associations with disturbed functional connectivity of the motor cortex. CONCLUSION: In vivo neurochemistry may represent an effective imaging marker of impaired motor cortex functional connectivity in ALS.