Multimodal Magnetic Resonance Imaging Study On Cirrhotic Patients With Minimal Hepatic Encephalopathy

Chapter Ⅰ Brain functional alterations in patients with hepatitis B cirrhosis with minimal hepatic encephalopathy:a resting state magnetic resonance imaging studyChapter Ⅰ 1.1 Brain Functional Abnormalities in Patients with Minimal Hepatic Encephalopathy by using Regional Homogeneity and Functional ConnectivityBackground and aims:Previous studies on brain functional activities in patients with minimal hepatic encephalopathy(MHE)have mostly used single analysis methods.The results obtained are relatively one-sided,and the pathogenesis of the MHE is very complicated.At present,the mechanism of neuropsychological injuries in patients with MHE is still unclear.We aimed to investigate the altered patterns of regional synchronization and functional connections in hepatitis B virus-related cirrhosis patients with and without MHE using both regional homogeneity(ReHo)and region of interest(ROI)-based functional connectivity(FC)computational methodsMaterial and Methods:Data of magnetic resonance imaging scans were collected from 30 cirrhotic patients with MHE,32 cirrhotic patients without MHE(NMHE)and 64 age-/gender-/education level-matched controls.Several regions showing differences in ReHo after analysis of covariance(ANCOVA)were defined as ROIs for FC analysis.Next,post hoc t-tests were applied to calculate the group differences in ReHo and FC(p<0.05)Correlations between clinical variables and the altered ReHo and FC were then assessed in patient groups.Results:Across three groups,significant ReHo differences were found in nine ROI regions mainly within the visual network(VN),dorsal attention network(DAN),somatomotor network(SMN),fronto parietal control(FPC)network and thalamus.Compared with healthy controls(HC),the MHE group exhibited abnormal FC mainly between the right calcarine(CAL.R)and middle frontal gyrus(MFG.L)/right thalamus.The MHE patients showed increased FC between the MFG.L and CAL.R compared to NMHE patients Disease duration of MHE patients was positively correlated with increased mean ReHo values in the right fusiform gyrus(FFG);psychometric hepatic encephalopathy score(PHES)test scores were negatively correlated with increased FC between MFG.L and CAL.R and positively correlated with reduced FC between the CAL.R and THA.R.For NMHE patients,the mean ReHo values in the right frontal pole were positively correlated with disease duration and positively correlated with the PHES scoresConclusion:Our results exhibited that the functional brain modifications in patients with and without MHE are characterized by compound alterations in local coherence and functional connections in the VN,SMN,DAN,FPC networks and thalamus by using a combination of ReHo and ROI-based FC analysis.These functional imaging changes are correlated with disease duration/PHES.This study helped us gain a better understanding of the features of brain network modifications in cirrhosisChapter Ⅰ 1.2 Brain Functional Network Study of Patients with Minimal Hepatic EncephalopathyBackground and objectives:Previous imaging studies have shown brain functional connectivity abnormalities in certain brain regions of patients with minimal hepatic encephalopathy(MHE).However,there is currently no research on the brain function topology of patients with MHE.We aimed to explore the changes in the brain topological properties of in patients with hepatitis B cirrhosis with MHE by applying graph theoretical analysis,and the correlations between the abnormal functional topological properties and clinical variable.Materials and Methods:We collected the resting state brain functional magnetic resonance images from 30 patients with hepatitis B cirrhosis with MHE(MHE),32 patients with hepatitis B cirrhosis without(NMHE),and 64 normal healthy people who were matched with the age,education years,and gender of the two patient groups.The imaging data was post-processed by the DPABI and Gretna software.In order to construct the cerebral function network,the brain was first divided into 90 regions of interest,and then the Pearson correlation coefficient of the average time series was calculated for any two brain regions to obtain the correlation matrix.Next,within a certain range of sparsity,the matrix transformed into a binary matrix,and finally obtained global and local topology parameters of the brain functional networks.The significant differences between groups of global and local topological parameters were evaluated using ANCOVA(Analysis of covariance).Finally,we assessed the relationship between brain functional networks topological characteristics and cirrhotic patients’neuropsychological test scores and disease duration.Result:The whole brain functional network of patients with hepatitis B cirrhosis showed a"small world" topology structure.Compared with the NMHE group,the global efficiency of patients with MHE significantly increased;the global network efficiency was significantly reduced in patients with MHE compared with the normal control group.The shortest path length was significantly reduced in patients with MHE compared with the NMHE group;the shortest path length was significantly increased in NMHE patients compared with the control group.Correlation analysis showed that the neuropsychological test scores of patients with MHE were signmficantly correlated with global parameters(such as shortest path length and global efficiency)(false discovery rate correction,p<0.05).Conclusion:The brain function network of the two groups of patients with cirrhosis showed a "small world" network topology,but its network topology attribute parameters changed significantly,and some abnormal topological parameter values were significantly correlated with the patient neuropsychological test scores.It suggests that changes in brain function network topology may be one of potential neural mechanisms leading to neurocognitive dysfunction of MHEChapter Ⅱ Brain microstructure study in patients with hepatitis B cirrhosis with minimal hepatic encephalopathy based on magnetic resonance diffusion imagingChapter Ⅱ 2.1 Brain microstructural study of patients with hepatitis B cirrhosis with minimal hepatic encephalopathy by voxel-based analysis of diffusion kurtosis imagingObjectives:To study the brain microstructural changes of patients with hepatitis B cirrhosis secondary to minimal hepatic encephalopathy using voxel-based analysis of diffusion kurtosis imaging(DKI)data,and the relationship between these abnormal changes and patient neural recognition as well as disease durationMaterials and Methods:Thirty patients with cirrhosis secondary to minimal hepatic encephalopathy(MHE),thirty-one patients without minimal hepatic encephalopathy(NMHE)and fifty-nine healthy subjects were scanned for DKI.Data preprocessing of DKI raw images is followed by a variety of DKI parameter maps,including fractional anisotropy、radial diffusivity、axial diffusivity(AD)、mean diffusivity、mean kurtosis、axial kurtosis(AK),and kurtosis fractional anisotropy.Voxel-based analysis was performed on the parameter maps of three groups to detect abnormal brain gray and white matter with significant differenceResults:Compared with health controls,MHE/NMHE patients had increased radial diffusivity,AD and mean diffusivity and decreased mean kurtosis,AK and fractional anisotropy of kurtosis in many regions mainly involving the cingulum,temporal and frontal cortices in comparison with controls.The DKI metrics(i.e.,AK and AD)in several brain regions were correlated with neuropsychological test score or/and disease duration in the two patient groups.Conclusion:Patients with MHE have brain microstructural changes before clinical symptoms appear,including abnormal gray matter structure,impaired white matter fiber integrity and complexity.DKI parameter values(i.e.,axial kurtosis and axial diffusivity)in some brain regions of MHE patients were correlated with disease duration,indicating that the brain microstructural changes are progressive as the disease progresses.This study provides a new perspective for understanding the neuropathological mechanisms of patients with MHE.Chapter Ⅱ 2.2 Brain white matter network changes in patients with minimal hepatic encephalopathy by graph theory analysisBackground and objectives:More and more studies have suggested that minimal hepatic encephalopathy(MBE)may affect the white matter structure of the brain.However,no study has explored the changes of the topological properties of the white matter network in patients with cirrhosis with MHE at the level of the white matter network.Therefore,the changes of the topological characteristics of the white matter structure connection network in this disease are still unclear.Therefore,the aim of this study is to construct the white matter structure network in hepatitis B cirrhotic patients with or without MHE.The changes of the white matter network attributes and topological characteristics in patients with MHE are studied by graph theory analysisMaterials and Methods:30 patients with hepatitis B cirrhosis with MHE,31 patients without MHE and 59 healthy subjects were collected in this study.The PANDA software was used to preprocess the diffusion tensor imaging data,and the cerebral white matter fiber was subjected to deterministic fiber tracking.The Anatomical Automatic Labeling(AAL)template was applied to divide the brain into 90 brain regions,and then the brain white matter network was constructed using graph theory analysis.We analyzed the group differences of white matter network topological parameters of the three groups.Finally,the correlation analysis was used to evaluate the relationship between topographic parameters with statistical differences and psychometric hepatic encephalopathy score(PHES)and disease duration of cirrhotic patientsResult:There were significant differences in the global and local topological parameters of white matter network between patients with or without minimal hepatic encephalopathy Compared with the control group,the brain network of the two cirrhosis groups exhibited a significant decrease in the network local efficiency and increased shortest characteristic path length,which indicated that the white matter network of cirrhosis patients shifted to the random network.For the local topological parameters,compared with healthy controls,the brain regions with reduced nodal degree centrality,nodal efficiency and shortest characteristic path length were mainly located in frontal-parietal network,default network,subcortical regions(such as pallidus and putamen)in patients with MHE,and the local parameters of these brain regions were related to PHES performances and disease duration of cirrhotic patientsConclusion:This study reveals that the white matter structure network of patients with MHE is a small world network topology structure from the level of brain network,but its topological characteristic parameters have significant abnormal changes,mainly involving the frontal-parietal network,default network and subcortical regions(such as pallidus and putamen).It suggests that the white matter structure network has been affected in MHE patients before clinical symptoms appear.This study provides some help for understanding the neuropathological mechanism of MHE.