Abstract
BACKGROUND: Brain structural alterations have been implicated in the pathophysiology of minimal hepatic encephalopathy (MHE). This study aimed to investigate cortical microstructural abnormalities and their correlation with cognitive impairment in MHE using neurite orientation dispersion and density imaging (NODDI) and voxel-wise gray matter-based spatial statistics (GBSS). METHODS: The NODDI model was fit to multi-shell diffusion-weighted magnetic resonance imaging (dMRI) acquisitions obtained from 35 healthy controls (HC), 41 cirrhotic patients without MHE (NHE), and 21 cirrhotic patients with MHE. The metrics of NODDI, including neurite density index (NDI) and orientation dispersion index (ODI), were compared among groups using GBSS. The relationships between NODDI-derived parameters and neurocognitive performance, measured by the Psychometric Hepatic Encephalopathy Score (PHES), were assessed in the cirrhotic patients. RESULTS: The MHE group showed decreased NDI in several cortical regions, primarily including the default mode network (DMN)-related regions, left insula, left middle frontal gyrus, bilateral lateral temporal cortex, and the sensorimotor, visual, and auditory cortices [family-wise error (FWE)-corrected P<0.05]. The regions with decreased NDI in the MHE group were more extensive than those in the NHE group. There was no significant difference in ODI across the three groups (FWE-corrected P>0.05). Reduced NDI in the right parahippocampal gyrus and lingual gyrus correlated with PHES in the cirrhotic patients (FWE-corrected P<0.05). CONCLUSIONS: This study provides evidence for the microstructural modulation of cortical neurites in MHE and contributes to our understanding of the latent biological basis of MHE-related cognitive impairments.