White matter microstructural impairments in amyotrophic lateral sclerosis: A mean apparent propagator MRI study

BACKGROUND: White matter (WM) impairment is a hallmark of amyotrophic lateral sclerosis (ALS). This study evaluated the capacity of mean apparent propagator magnetic resonance imaging (MAP-MRI) for detecting ALS-related WM alterations. METHODS: Diffusion images were obtained from 52 ALS patients and 51 controls. MAP-derived indices [return-to-origin/-axis/-plane probability (RTOP/RTAP/RTPP) and non-Gaussianity (NG)/perpendicular/parallel NG (NG(⊥)/NG(||))] were computed. Measures from diffusion tensor/kurtosis imaging (DTI/DKI) and neurite orientation dispersion and density imaging (NODDI) were also obtained. Voxel-wise analysis (VBA) was performed to determine differences in these parameters. Relationship between MAP parameters and disease severity (assessed by the revised ALS Functional Rating Scale (ALSFRS-R)) was evaluated by Pearson’s correlation analysis in a voxel-wise way. ALS patients were further divided into two subgroups: 29 with limb-only involvement and 23 with both bulbar and limb involvement. Subgroup analysis was then conducted to investigate diffusion parameter differences related to bulbar impairment. RESULTS: The VBA (with threshold of P < 0.05 after family-wise error correction (FWE)) showed that ALS patients had significantly decreased RTOP/RTAP/RTPP and NG/ NG(⊥)/NG(||) in a set of WM areas, including the bilateral precentral gyrus, corona radiata, posterior limb of internal capsule, midbrain, middle corpus callosum, anterior corpus callosum, parahippocampal gyrus, and medulla. MAP-MRI had the capacity to capture WM damage in ALS, which was higher than DTI and similar to DKI/NODDI. RTOP/RTAP/NG/NG(⊥)/NG(||) parameters, especially in the bilateral posterior limb of internal capsule and middle corpus callosum, were significantly correlated with ALSFRS-R (with threshold of FWE-corrected P < 0.05). The VBA (with FWE-corrected P < 0.05) revealed the significant RTAP reduction in subgroup with both bulbar and limb involvement, compared with those with limb-only involvement. CONCLUSIONS: Microstructural impairments in corticospinal tract and corpus callosum represent the consistent characteristic of ALS. MAP-MRI could provide alternative measures depicting ALS-related WM alterations, complementary to the common diffusion imaging methods.