Structural And Functional Brain Impairments In Hepatic Patients With Cirrhosis And Minimal Hepatic Encephalopathy Studied By MR

Objective:This study is designed to investigate structural and functional brain abnormalities in hepatic cirrhosis(HC) and hepatic patients with minimal hepatic encephalopathy(MHE) and evaluate the potential of structural imaging and resting-state functional MR imaging(rs-f MRI) for detecting structural and functional brain changes of MHE. Methods:In this study, we performed structural and functional MRI and longitudinal analyses.1. Thirty patients with chronic hepatic cirrhosis(simple HC group), 32 hepatic patients with MHE(MHE group) and 34 age-,gender- and graduated-matched normal subjects(NC group) were recruited in our study, who performed neuropsychological tests, high resolution 3D T1-weighted anatomical imaging obtained using a magnetization-prepared rapid gradient echo sequence and resting-state f MRI scanning. Brain 3D T1-weighted anatomical images and functional MRI data analyses were progressed by combining voxel-based morphometry(VBM) with regional homogeneity(Re Ho) software. Ony-way ANOVA and two sample t-test were performed to determine the inter-group difference in brain gray matter volume, Re Ho values and neuropsychological test scores. Correlation analyses were explored to detect the relationships between Re Ho values in patients and gray matter volume, neuropsychological test scores.2. Fifteen HBV-related cirrhotic patients without overt hepatic encephalopathy were followed with repeated neuropsychological tests, quantitative assessment of hepatic function and structural MRI acquisitions by the same scanner, the same parameters and the same standards of hepatic function and cognition ability at baseline and again 2 years later. Gray matter volumes were longitudinally progressed and compared between the two times using VBM analysis applied A DARTEL algorithm and SPM 8 package(Statistical Parametric Mapping 8).Paired t-tests were also calculated comparing neuropsychological test scores and hepatic functional scores between the first and second data. The regions showing significant longitudinal difference were extracted as regions of interest calculated using Easy-Volume software, the correlation analyses were performed to measure the relationship between gray matter volume of these regions of each patient and first scores of liver function. Results:1. Compared with the NC group, HC patients showed decreased gray matter volume in putamen and cerebellum,and aggravated in the impaired extent and regions of brain gray matter volume alterations with the episodes of MHE, but increased bilateral thalami volume and decreased volume in medial frontal gyrus were especially exhibited in MHE group. Significantly decreased bilateral thalami Re Ho was mainly exhibited in simple HC group. Especially, MHE group exhibited significantly decreased Re Ho in bilateral brian supplemental motor area, anterior cingulate cortex and superior frontal gyrus, with the extent of impaired neuropsychological test scores lower than simple HC and NC groups(all P<0.05). Positive correlation was significantly exhibited between Re Ho values and volume changes in bilateral thalami in 62 HC patients(r=0.34, P=0.007). Positive correlation of gray matter volume changes between bilateral thalami volume and medial frontal gyrus was also showed in MHE group( r=0.45, P=0.01). Moreover, the Re Ho values in bilateral supplemental motor area, anterior cingulate cortex and superior frontal gyrus negatively correlated with the times of number connection test(r=-0.529、-0.414、-0.45,all P <0.05) and positively correlated with the scores of digit-symbol test in MHE group(r=0.562、0.483、0.459,all P<0.05).2. At the 2-year follow-up, significantly decreased of gray matter volumes was detected in bilateral rectal gyrus/orbital gyrus, whereas increased significantly in bilateral precentral gyrus, with improved obviously in first scores of(P<0.05), and decreased(P<0.05) from baseline in digit-symbol test scores of HC patients by maintenance therapy, but showed an increasing trend in the times of number connection test(P=0.087). No correlation was found for the brain matter volume changes of 2 groups with first liver functional scores in HC patients(all P>0.05). Conclusion:1. Our study combining brain structure with function MR could provide a more reliable objective basis for the mechanisms, clinical noninvasive estimation and early diagnosis of MHE. Brain volume and Re Ho impairments were found in thalamus, caudate, frontal lobe and anterior cingulate gyrus, which could be MR imaging characteristics of structural and functional cerebral abnormalities in MHE patients.2. There were significantly longitudinal brain gray matter volumetric changes in bilateral prefrontal lobe and precentral gyrus of HC patients with disease progression, which may be associated with cognitive and neuropsychiatric impairment of MHE patients.