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

Abstract

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.

Surface-based Analyses of Diffusional Kurtosis Imaging in Amyotrophic Lateral Sclerosis: Relationship with Onset Subtypes

“…The same trend emerged in previous studies of ALS that focused on the deep WM. 32,33 In the WM, increased RD and decreased RK have been correlated with demyelination and axonal loss in animal experiments, 58,59 and thus, our observations regarding the subcortical WM are in line with findings from postmortem studies of ALS. 20,56,60,61 We note, however, that DTI and DKI reflect the combined effects of multifaceted pathologies, some of which may act in opposite directions.…”

“…26,27 In addition, the community has not yet reached consensus on the appropriate model for GM. 25,28,29 Recent reports [30][31][32][33] have shown that DKI provides complementary information to DTI in terms of the ALS-related changes in both GM and WM. So far, DKI studies of the GM in ALS have adopted either ROI-based analyses 31 or voxel-based analyses with volumetric smoothing.…”