Abnormal cerebral microstructures revealed by diffusion kurtosis imaging in amyotrophic lateral sclerosis

Abstract

Background: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease in which cerebral structural impairment is a consistent feature.

Purpose: To investigate cerebral microstructural changes in ALS using diffusion kurtosis imaging (DKI) for the first time.

Study type: Prospective.

Subjects: Eighteen ALS patients and 20 healthy controls.

Field strength/sequence: DKI images were obtained by a spin-echo echo-planar imaging sequence on a 3T MRI scanner, with three b-values (0, 1000, and 2000 s/mm² ) and 64 diffusion encoding directions.

Assessment: The revised ALS Functional Rating Scale (ALSFRS-R) was administered to assess disease severity, and the symptom duration and disease progression rate were also recorded. Voxel-based analysis was applied to examine the alteration of DKI metrics (ie, mean kurtosis metrics [MK], axial kurtosis [AK], and radial kurtosis [RK]) and the conventional diffusion metrics (ie, fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity).

Statistical tests: Student's t-test, chi-square test, and Pearson correlation analysis.

Results: ALS patients showed MK reductions in gray matter areas, including the bilateral precentral gyrus, bilateral paracentral lobule, and left anterior cingulate gyrus; they also showed decreased MK values in white matter (WM) in the bilateral precentral gyrus, bilateral corona radiata, bilateral middle corpus callosum, left occipital lobe, and right superior parietal lobule. The spatial distribution of the regions with reduced RK was similar to those with decreased MK. No significant AK difference was found between groups. The correlation analysis revealed significant associations between DKI metrics and clinical assessments such as ALSFRS-R score and disease duration. Additionally, several WM regions showed between-group differences in conventional diffusion metrics; but the spatial extent was smaller than that with reduced DKI metrics.

Data conclusion: The reduction in DKI metrics indicates decreased microstructural complexity in ALS, involving both motor-related areas and extramotor regions. DKI metrics can serve as potential biomarkers for assessing disease severity.

Level of evidence: 2 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2020;51:554-562.

Keywords: amyotrophic lateral sclerosis; diffusion tensor imaging; gray matter; motor pathways; white matter.