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Bonacchi R, De Meo E. Editorial for "Longitudinal Evolution of the Brain Microstructure in Cirrhotic Patients on Diffusion Kurtosis Imaging". J Magn Reson Imaging 2025; 61:2321-2322. [PMID: 39487817 DOI: 10.1002/jmri.29655] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2024] [Accepted: 09/27/2024] [Indexed: 11/04/2024] Open
Affiliation(s)
| | - Ermelinda De Meo
- Queen Square Multiple Sclerosis Centre, Department of Neuroinflammation, UCL Queen Square Institute of Neurology, Faculty of Brain Sciences, University College London, London, UK
- Department of Neurofarba, University of Florence, Florence, Italy
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Chen YY, Lu ZN, Zhang Q, Zhang YN, Ma WT, Zhang X, Zhang XD, Ni HY, Cheng Y. Longitudinal Evolution of the Brain Microstructure in Cirrhotic Patients on Diffusion Kurtosis Imaging. J Magn Reson Imaging 2025; 61:2310-2320. [PMID: 39485115 DOI: 10.1002/jmri.29648] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2024] [Revised: 10/10/2024] [Accepted: 10/14/2024] [Indexed: 11/03/2024] Open
Abstract
BACKGROUND Although improvement of cognitive function after liver transplantation has been demonstrated in several neuropsychological studies, there is limited research on longitudinal changes in the cirrhotic patients' brain structure before and after transplantation. PURPOSE To investigate longitudinal changes of brain microstructure in cirrhotic patients using diffusion kurtosis imaging (DKI). STUDY TYPE Prospective. SUBJECTS A total of 153 cirrhosis patients, comprising 60 hepatic encephalopathy (HE) patients (16 females/44 males) and 93 no-HE patients (35 females/58 males), along with 93 healthy controls (HCs) (53 females/40 males) were enrolled. Subsequently, 58 recipients completed 1-month postoperative follow-up, 29 patients completed 1-, 3-months, and 17 patients completed 1-, 3-, 6-month follow-up. SEQUENCE Spin-echo single-shot echo-planar sequence using a 3.0 T scanner. ASSESSMENT Diffusion kurtosis estimator software was used to estimate the DKI parameter maps by a MR imaging physicist (Y.-Y.C. with 12 years of experience). STATISTICAL TESTS The diffusion metrics (eg, radial kurtosis [RK], mean kurtosis, fractional anisotropy, mean diffusivity) of the patients before transplantation were compared with those of the HCs using voxel-wise analysis of variance (ANOVA), along with t tests for post hoc analysis. Linear mixed-effects models were applied to the longitudinal data. We imposed a cluster level Family Wise Error (FWE) correction rate of PFWE = 0.05 with voxel-wise cutoff of P = 0.001 together with a cluster-size cutoff of N ≥ 56, and generated smoothness estimates from the preprocessed data using the mixed-model autocorrelation function. RESULTS The RK metrics of the patients decreased significantly in the anterior cingulate cortex (HE/no-HE < HC, ANOVA-F = 21.91). After transplantation, the RK of the pallidum showed a continuous upward trend (time effect T = 11.26); whereas the RK of the right postcentral gyrus showed a continuous downward trend (time effect T = -9.56). In addition, the RK in superior longitudinal fasciculus showed new-onset decrease after transplantation. DATA CONCLUSION Longitudinal changes in DKI metrics reveal the course of brain microstructural changes before and after transplantation in cirrhotic patients, potentially associated with cognitive alterations after surgery. LEVEL OF EVIDENCE 1 TECHNICAL EFFICACY: Stage 4.
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Affiliation(s)
- Yuan-Yuan Chen
- Tianjin International Joint Research Center for Neural Engineering, Academy of Medical Engineering and Translational Medicine, Tianjin University, Tianjin, China
| | - Zi-Ning Lu
- State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China
- Department of Radiology, Tianjin Institutes of Health Science, Tianjin, China
| | - Qi Zhang
- Department of Radiology, Tianjin First Central Hospital, Tianjin, China
| | - Yi-Ning Zhang
- Department of Radiology, Tianjin First Central Hospital, Tianjin, China
| | - Wen-Ting Ma
- Department of Radiology, Tianjin First Central Hospital, Tianjin, China
| | - XiaoDi Zhang
- Department of Radiology, Tianjin First Central Hospital, Tianjin, China
| | - Xiao-Dong Zhang
- Department of Radiology, Tianjin First Central Hospital, Tianjin, China
| | - Hong-Yan Ni
- Department of Radiology, Tianjin First Central Hospital, Tianjin, China
| | - Yue Cheng
- Department of Radiology, Tianjin First Central Hospital, Tianjin, China
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Cai LM, Zeng JY, Huang HW, Tang Y, Li D, Li JQ, Chen HJ. Quantitative susceptibility mapping reveals brain iron accumulation in minimal hepatic encephalopathy: associations with neurocognitive changes. Metab Brain Dis 2024; 40:22. [PMID: 39565400 DOI: 10.1007/s11011-024-01440-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/03/2024] [Accepted: 10/20/2024] [Indexed: 11/21/2024]
Abstract
Brain iron deposition is correlated with minimal hepatic encephalopathy (MHE). This study aimed to investigate the pattern of altered iron distribution, using quantitative susceptibility mapping (QSM), and to clarify the relationship between iron deposition and neurocognitive changes in MHE. We enrolled 32 cirrhotic patients without MHE (NHE), 21 cirrhotic patients with MHE, and 24 healthy controls, and used the Psychometric Hepatic Encephalopathy Score (PHES) to assess neurocognitive function. All participants underwent magnetic resonance scans with a gradient-echo sequence reconstructing for QSM. We performed voxel-wise and region-of-interest (ROI)-wise analyses to investigate the QSM difference across three groups and to examine the relationship between susceptibility value and PHES. MHE patients exhibited increased susceptibility value in widespread brain areas (family-wise error (FWE)-corrected P < 0.05), which was located mainly in cognition-related regions (such as the prefrontal lobe, precuneus, inferior parietal lobule, insula, thalamus, and superior longitudinal fasciculus), sensorimotor regions (such as the precentral/postcentral gyrus, superior parietal lobule, and posterior corona radiata), visual regions (such as the occipital cortex and posterior thalamic radiation), and auditory regions (such as the temporal lobe). NHE patients also followed a trend of increasing susceptibility in the scattered brain regions, but which did not reach statistical significance (FWE-corrected P > 0.05). We observed negative correlations between cirrhotic patients' PHES and regional susceptibility values (FWE-corrected P < 0.05). Brain iron accumulation (measured using QSM) contributes to cognitive impairments in MHE patients. QSM could provide new insights into the pathogenesis of MHE and facilitate monitoring disease development.
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Affiliation(s)
- Li-Min Cai
- Department of Stomatology, Fujian Medical University Union Hospital, Fuzhou, 350001, China
| | - Jing-Yi Zeng
- Department of Radiology, Fujian Medical University Union Hospital, Fuzhou, 350001, China
| | - Hui-Wei Huang
- Department of Radiology, Fujian Medical University Union Hospital, Fuzhou, 350001, China
| | - Ying Tang
- Shanghai Key Laboratory of Magnetic Resonance, School of Physics and Electronic Science, East China Normal University, Shanghai, 200062, China
| | - Dan Li
- Department of Gastroenterology, Fujian Medical University Union Hospital, Fuzhou, 350001, China.
| | - Jian-Qi Li
- Shanghai Key Laboratory of Magnetic Resonance, School of Physics and Electronic Science, East China Normal University, Shanghai, 200062, China.
| | - Hua-Jun Chen
- Department of Radiology, Fujian Medical University Union Hospital, Fuzhou, 350001, China.
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Roy A, Trigun SK. The restoration of hippocampal nerve de-myelination by methylcobalamin relates with the enzymatic regulation of homocysteine level in a rat model of moderate grade hepatic encephalopathy. J Biochem Mol Toxicol 2024; 38:e23695. [PMID: 38511258 DOI: 10.1002/jbt.23695] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2023] [Revised: 02/08/2024] [Accepted: 03/12/2024] [Indexed: 03/22/2024]
Abstract
This article describes how methylcobalamin (MeCbl) restores nerve myelination in a moderate- grade hepatic encephalopathy (MoHE) model of ammonia neurotoxicity. The comparative profiles of myelin basic protein (MBP), homocysteine (Hcy) and methionine synthase (MS: a MeCbl- dependent enzyme) activity versus nerve myelination status were studied in the hippocampus of the control, the MoHE (developed by administering 100 mg/kg bw thioacetamide i.p. for 10 days) and the MoHE rats treated with MeCbl (500 µg/kg BW i.p.) for 7 days. Compared to those of control rats, the hippocampal CA1 and CA3 regions of the MoHE rats showed significantly lower myelinated areas and MBP immunostaining. This coincided with the deranged myelin layering in TEM images, decreased MBP protein and its transcript levels in hippocampus of MoHE rats. However, all these parameters recovered to normal levels after MeCbl treatment. MeCbl is a cofactor of MS that catalyzes the conversion of Hcy to methionine as a feeder step of methylation reactions. We observed significantly increased serum and hippocampal Hcy levels in MoHE rats, however, these levels were restored to control values with a concordant activation of MS due to MeCbl treatment. A significant recovery in neurobehavioral impairments in the MoHE rats due to MeCbl treatment was also observed. These findings suggest that MoHE pathogenesis is associated with deranged nerve myelination in the hippocampus and that MeCbl treatment is able to restore it mainly by activating MS, a MeCbl-dependent Hcy-metabolizing enzyme.
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Affiliation(s)
- Anima Roy
- Biochemistry Section, Department of Zoology, Institute of Science, Banaras Hindu University, Varanasi, India
| | - Surendra Kumar Trigun
- Biochemistry Section, Department of Zoology, Institute of Science, Banaras Hindu University, Varanasi, India
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Dong QY, Lin JH, Wu Y, Cao YB, Zhou MX, Chen HJ. White matter microstructural disruption in minimal hepatic encephalopathy: a neurite orientation dispersion and density imaging (NODDI) study. Neuroradiology 2023; 65:1589-1604. [PMID: 37486421 DOI: 10.1007/s00234-023-03201-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2023] [Accepted: 07/11/2023] [Indexed: 07/25/2023]
Abstract
PURPOSE To evaluate the ability of neurite orientation dispersion and density imaging (NODDI) for detecting white matter (WM) microstructural abnormalities in minimal hepatic encephalopathy (MHE). METHODS Diffusion-weighted images, enabling the estimation of NODDI and diffusion tensor imaging (DTI) parameters, were acquired from 20 healthy controls (HC), 22 cirrhotic patients without MHE (NHE), and 15 cirrhotic patients with MHE. Tract-based spatial statistics were used to determine differences in DTI (including fractional anisotropy [FA] and mean/axial/radial diffusivity [MD/AD/RD]) and NODDI parameters (including neurite density index [NDI], orientation dispersion index [ODI], and isotropic volume fraction [ISO]). Voxel-wise analyses of correlations between diffusion parameters and neurocognitive performance determined by Psychometric Hepatic Encephalopathy Score (PHES) were completed. RESULTS MHE patients had extensive NDI reduction and rare ODI reduction, primarily involving the genu and body of corpus callosum and the bilateral frontal lobe, corona radiata, external capsule, anterior limb of internal capsule, temporal lobe, posterior thalamic radiation, and brainstem. The extent of NDI and ODI reduction expanded from NHE to MHE. In both MHE and NHE groups, the extent of NDI change was quite larger than that of FA change. No significant intergroup difference in ISO/MD/AD/RD was observed. Tissue specificity afforded by NODDI revealed the underpinning of FA reduction in MHE. The NDI in left frontal lobe was significantly correlated with PHES. CONCLUSION MHE is characterized by diffuse WM microstructural impairment (especially neurite density reduction). NODDI can improve the detection of WM microstructural impairments in MHE and provides more precise information about MHE-related pathology than DTI.
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Affiliation(s)
- Qiu-Yi Dong
- Department of Radiology, Fujian Medical University Union Hospital, Fuzhou, 350001, China
| | - Jia-Hui Lin
- Department of Radiology, Fujian Medical University Union Hospital, Fuzhou, 350001, China
| | - Ye Wu
- School of Computer Science and Engineering, Nanjing University of Science and Technology, Nanjing, 210094, China
| | - Yun-Bin Cao
- Department of Radiology, Fujian Medical University Union Hospital, Fuzhou, 350001, China
| | - Min-Xiong Zhou
- College of Medical Imaging, Shang Hai University of Medicine & Health Sciences, Shanghai, 201318, China
| | - Hua-Jun Chen
- Department of Radiology, Fujian Medical University Union Hospital, Fuzhou, 350001, China.
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Cheng Y, Zhang XD, Chen C, He LF, Li FF, Lu ZN, Man WQ, Zhao YJ, Chang ZX, Wu Y, Shen W, Fan LZ, Xu JH. Dynamic evolution of brain structural patterns in liver transplantation recipients: a longitudinal study based on 3D convolutional neuronal network model. Eur Radiol 2023; 33:6134-6144. [PMID: 37014408 DOI: 10.1007/s00330-023-09604-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2022] [Revised: 02/19/2023] [Accepted: 02/24/2023] [Indexed: 04/05/2023]
Abstract
OBJECTIVES To evaluate the dynamic evolution process of overall brain health in liver transplantation (LT) recipients, we employed a deep learning-based neuroanatomic biomarker to measure longitudinal changes of brain structural patterns before and 1, 3, and 6 months after surgery. METHODS Because of the ability to capture patterns across all voxels from a brain scan, the brain age prediction method was adopted. We constructed a 3D-CNN model through T1-weighted MRI of 3609 healthy individuals from 8 public datasets and further applied it to a local dataset of 60 LT recipients and 134 controls. The predicted age difference (PAD) was calculated to estimate brain changes before and after LT, and the network occlusion sensitivity analysis was used to determine the importance of each network in age prediction. RESULTS The PAD of patients with cirrhosis increased markedly at baseline (+ 5.74 years) and continued to increase within one month after LT (+ 9.18 years). After that, the brain age began to decrease gradually, but it was still higher than the chronological age. The PAD values of the OHE subgroup were higher than those of the no-OHE, and the discrepancy was more obvious at 1-month post-LT. High-level cognition-related networks were more important in predicting the brain age of patients with cirrhosis at baseline, while the importance of primary sensory networks increased temporarily within 6-month post-LT. CONCLUSIONS The brain structural patterns of LT recipients showed inverted U-shaped dynamic change in the early stage after transplantation, and the change in primary sensory networks may be the main contributor. KEY POINTS • The recipients' brain structural pattern showed an inverted U-shaped dynamic change after LT. • The patients' brain aging aggravated within 1 month after surgery, and the subset of patients with a history of OHE was particularly affected. • The change of primary sensory networks is the main contributor to the change in brain structural patterns.
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Affiliation(s)
- Yue Cheng
- Department of Radiology, Tianjin First Central Hospital, Tianjin, China
- College of Intelligence and Computing, Tianjin Key Laboratory of Cognitive Computing and Application, Tianjin University, Tianjin, China
| | - Xiao-Dong Zhang
- Department of Radiology, Tianjin First Central Hospital, Tianjin, China
- College of Intelligence and Computing, Tianjin Key Laboratory of Cognitive Computing and Application, Tianjin University, Tianjin, China
| | - Cheng Chen
- College of Intelligence and Computing, Tianjin Key Laboratory of Cognitive Computing and Application, Tianjin University, Tianjin, China
- Brainnetome Center, Institute of Automation, Chinese Academy of Sciences, Beijing, China
| | - Ling-Fei He
- College of Intelligence and Computing, Tianjin Key Laboratory of Cognitive Computing and Application, Tianjin University, Tianjin, China
- Brainnetome Center, Institute of Automation, Chinese Academy of Sciences, Beijing, China
| | - Fang-Fei Li
- Department of Radiology, Tianjin First Central Hospital, Tianjin, China
| | - Zi-Ning Lu
- Department of Radiology, Tianjin First Central Hospital, Tianjin, China
| | - Wei-Qi Man
- Department of Radiology, Tianjin First Central Hospital, Tianjin, China
| | - Yu-Jiao Zhao
- Department of Radiology, Tianjin First Central Hospital, Tianjin, China
| | | | - Ying Wu
- School of Statistics and Data Science, Key Laboratory for Medical Data Analysis and Statistical Research of Tianjin, Nankai University, Tianjin, China
| | - Wen Shen
- Department of Radiology, Tianjin First Central Hospital, Tianjin, China
| | - Ling-Zhong Fan
- Brainnetome Center, Institute of Automation, Chinese Academy of Sciences, Beijing, China
| | - Jun-Hai Xu
- College of Intelligence and Computing, Tianjin Key Laboratory of Cognitive Computing and Application, Tianjin University, Tianjin, China.
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Zhu L, Zhang W, Chen L, Ren Y, Cao Y, Sun T, Sun B, Liu J, Wang J, Zheng C. Brain Gray Matter Alterations in Hepatic Encephalopathy: A Voxel-Based Meta-Analysis of Whole-Brain Studies. Front Hum Neurosci 2022; 16:838666. [PMID: 35517986 PMCID: PMC9062230 DOI: 10.3389/fnhum.2022.838666] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2021] [Accepted: 02/28/2022] [Indexed: 12/03/2022] Open
Abstract
Background Previous studies on voxel-based morphometry (VBM) have found that there were gray matter alterations in patients with hepatic encephalopathy (HE). However, the reported results were inconsistent and lack a quantitative review. Therefore, this study aims for a quantitative meta-analysis of VBM analysis on patients with HE. Methods The studies in our meta-analysis were collected from Pubmed, Web of Science, and Embase, which were published from January 1947 to October 2021. The seed-based d mapping (SDM) method was applied to quantitatively estimate the regional gray matter abnormalities in patients with HE. A meta-regression analysis was applied to evaluate the relationship between plasma ammonia and gray matter alteration. Results There were nine studies, with sixteen datasets consisting of 333 participants with HE and 429 healthy controls. The pooled and subgroup meta-analyses showed an increase in gray matter volume (GMV) in the bilateral thalamus and the calcarine fissure but a decrease in the GMV in the bilateral insula, the basal ganglia, the anterior cingulate gyrus, and the cerebellum. The meta-regression showed that plasma ammonia was positively associated with the GMV in the left thalamus but was negatively associated with the GMV in the cerebellum and the bilateral striatum. Conclusion Gray matter volume in patients with HE largely varied and could be affected by plasma ammonia. The findings of this study could help us to better understand the pathophysiology of cognitive dysfunction in patients with HE.
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Affiliation(s)
- Licheng Zhu
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Weihua Zhang
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Lei Chen
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yanqiao Ren
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yanyan Cao
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Tao Sun
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Bo Sun
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jia Liu
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China
| | - Jing Wang
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China
| | - Chuansheng Zheng
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Hubei Province Key Laboratory of Molecular Imaging, Wuhan, China
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Jiang Y, Gao Q, Liu Y, Gao B, Che Y, Lin L, Jiang J, Chang P, Song Q, Wang W, Wang N, Miao Y. Reduced White Matter Integrity in Patients With End-Stage and Non-end-Stage Chronic Kidney Disease: A Tract-Based Spatial Statistics Study. Front Hum Neurosci 2021; 15:774236. [PMID: 34955791 PMCID: PMC8709581 DOI: 10.3389/fnhum.2021.774236] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2021] [Accepted: 11/12/2021] [Indexed: 11/13/2022] Open
Abstract
Background and Purpose: Reduced white matter (WM) integrity has been implicated in chronic kidney disease (CKD), especially in end-stage renal disease (ESRD). However, whether the differences in WM abnormalities exist in ESRD and non-end-stage CKD (NES-CKD) remains unclear. Hence, this study aimed to investigate the WM microstructural changes between the two stages using diffusion tensor imaging (DTI) and explore the related influencing factors. Methods: Diffusion tensor imaging’ images were prospectively acquired from 18 patients with ESRD, 22 patients with NES-CKD, and 19 healthy controls (HCs). Tract-based spatial statistics (TBSS) was performed to assess the voxel-wise differences in WM abnormalities among the three groups. The relationships between DTI parameters and biochemical data were also analyzed. Results: Compared with NES-CKDs, FA value was significantly decreased, and AD value increased in ESRDs mainly in brain regions of bilateral anterior thalamic radiation (ATR), the genu and body of corpus callosum (CC), bilateral anterior corona radiata, superior corona radiata, and superior longitudinal fasciculus. Besides, extensive and symmetrical deep WM damages were observed in patients with ESRD, accompanied by increased MD and RD values. Multiple regression analysis revealed that uric acid and serum phosphorus level can be used as independent predictors of WM microstructural abnormalities in clusters with statistical differences in DTI parameters between ESRD and NES-CKD groups. Conclusion: In the progression of CKD, patients with ESRD have more severe WM microstructural abnormalities than NES-CKDs, and this progressive deterioration may be related to uric acid and phosphate levels.
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Affiliation(s)
- Yuhan Jiang
- Department of Radiology, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Qiuyi Gao
- Department of Nephrology, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Yangyingqiu Liu
- Department of Radiology, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Bingbing Gao
- Department of Radiology, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Yiwei Che
- Department of Radiology, The Third People's Hospital of Dalian, Dalian, China
| | | | - Jian Jiang
- Department of Radiology, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Peipei Chang
- Department of Radiology, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Qingwei Song
- Department of Radiology, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Weiwei Wang
- Department of Radiology, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Nan Wang
- Department of Nephrology, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Yanwei Miao
- Department of Radiology, The First Affiliated Hospital of Dalian Medical University, Dalian, China
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Kuang Y, Wu X, Lai H, Wang Z, Lei Q, Zhong W, Yang Y, Deng C, Zhou Z. Abnormal corpus callosum induced by overt hepatic encephalopathy impairs interhemispheric functional coordination in cirrhosis patients. ANNALS OF TRANSLATIONAL MEDICINE 2021; 9:1579. [PMID: 34790785 PMCID: PMC8576733 DOI: 10.21037/atm-21-5109] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/19/2021] [Accepted: 10/21/2021] [Indexed: 11/06/2022]
Abstract
Background Although overt hepatic encephalopathy (OHE) patients were shown to have bilaterally symmetrical structural and functional abnormalities in the whole brain, few studies have focused on the bilateral cerebral hemisphere commissural fibers and measured functional coordination between bilateral hemispheres. This study aimed to investigate the structural changes of the corpus callosum (CC) and interhemispheric functional coordination in patients with OHE and to test the hypothesis that abnormal CC induced by OHE impairs interhemispheric functional coordination in cirrhosis patients. Methods The microstructural integrity and the volumes of each subregion of the CC were analyzed by diffusion tensor imaging (DTI) and three-dimensional T1-weighted imaging. Voxel-mirrored homotopic connectivity (VMHC) was derived from resting-state functional magnetic resonance imaging (MRI). Results Compared with the healthy controls (HCs) and patients without hepatic encephalopathy (noHE), the OHE group showed decreased volumes in all subregions of the CC. In OHE patients, the decreased fractional anisotropy (FA) of CC-5 correlated with decreased VMHC in the middle occipital gyrus (MOG) and precuneus. The value of FA in CC-5 and the volumes of CC-3, CC-4, and CC-5 showed correlations with neuropsychological performance in patients with OHE. Conclusions These findings suggest that impairment of interhemispheric white matter pathways may disturb the functional connectivity associated with coordination and neurocognitive performance.
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Affiliation(s)
- Yangying Kuang
- Department of Radiology, Chengdu Women's and Children's Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Xiaojia Wu
- Department of Radiology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Hua Lai
- Department of Radiology, Chengdu Women's and Children's Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Zhigang Wang
- Department of Radiology, Chengdu Women's and Children's Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Qiang Lei
- Department of Radiology, Chengdu Women's and Children's Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Weijia Zhong
- Department of Radiology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Ya Yang
- Department of Radiology, Chengdu Women's and Children's Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Chen Deng
- Department of Radiology, Chengdu Women's and Children's Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Zhiming Zhou
- Department of Radiology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
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Luo S, Zhou ZM, Guo DJ, Li CM, Liu H, Wu XJ, Liang S, Zhao XY, Chen T, Sun D, Shi XL, Zhong WJ, Zhang W. Radiomics-based classification models for HBV-related cirrhotic patients with covert hepatic encephalopathy. Brain Behav 2021; 11:e01970. [PMID: 33236529 PMCID: PMC7882152 DOI: 10.1002/brb3.1970] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/07/2020] [Revised: 11/03/2020] [Accepted: 11/04/2020] [Indexed: 11/16/2022] Open
Abstract
INTRODUCTION The significant abnormalities of precuneus (PC), which are associated with brain dysfunction, have been identified in cirrhotic patients with covert hepatic encephalopathy (CHE). The present study aimed to apply radiomics analysis to identify the significant radiomic features in PC and their subregions, combine with clinical risk factors, then build and evaluate the classification models for CHE diagnosis. METHODS 106 HBV-related cirrhotic patients (54 had current CHE and 52 had non-CHE) underwent the three-dimensional T1-weighted imaging. For each participant, PC and their subregions were segmented and extracted a large number of radiomic features and then identified the features with significant discriminative power as the radiomics signature. The logistic regression analysis was employed to develop and evaluate the classification models, which are constructed using the radiomics signature and clinical risk factors. RESULTS The classification model (R-C model) achieved best diagnostic performance, which incorporated radiomics signature (4 radiomic features from right PC), venous blood ammonia, and the Child-Pugh stage. And the area under the receiver operating characteristic curve values (AUC), sensitivity, specificity, and accuracy values were 0.926, 1.000, 0.765, and 0.848, in the testing set. Application of the radiomics nomogram in the testing set still showed a good predictive accuracy. CONCLUSIONS This study presented the radiomic features of the right PC, as a potential image marker of CHE. The radiomics nomogram that incorporates the radiomics signature and clinical risk factors may facilitate the individualized prediction of CHE.
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Affiliation(s)
- Sha Luo
- Department of Radiology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Zhi-Ming Zhou
- Department of Radiology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Da-Jing Guo
- Department of Radiology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Chuan-Ming Li
- Department of Radiology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Huan Liu
- GE Healthcare Life Sciences, Shanghai, China
| | - Xiao-Jia Wu
- Department of Radiology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Shuang Liang
- Department of Radiology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Xiao-Yan Zhao
- Department of Radiology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Ting Chen
- Department of Radiology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Dong Sun
- Department of Radiology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Xin-Lin Shi
- Department of Radiology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Wei-Jia Zhong
- Department of Radiology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Wei Zhang
- Department of Radiology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
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Characterization of brain microstructural abnormalities in cirrhotic patients without overt hepatic encephalopathy using diffusion kurtosis imaging. Brain Imaging Behav 2021; 14:627-638. [PMID: 31538276 PMCID: PMC7160080 DOI: 10.1007/s11682-019-00141-4] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Cirrhosis is a major public health concern. However, little is known about the neurobiological mechanisms underlying brain microstructure alterations in cirrhotic patients. The purpose of this prospective study was to investigate brain microstructural alterations in cirrhosis with or without minimal hepatic encephalopathy (MHE) and their relationship with patients’ neurocognitive performance and disease duration using voxel-based analysis of diffusion kurtosis imaging (DKI). DKI data were acquired from 30 cirrhotic patients with MHE, 31 patients without MHE (NMHE) and 59 healthy controls. All DKI-derived parametric maps were compared across the three groups to investigate their group differences. Correlation analyses were further performed to assess relationships between altered imaging parameters and clinical data. Voxel-based analysis of DKI data results showed that MHE/NMHE patients had increased radial diffusivity, axial diffusivity (AD) and mean diffusivity in addition to decreased axial kurtosis (AK) and fractional anisotropy of kurtosis in several regions. Compared to controls, these regions were primarily the cingulum, temporal and frontal cortices. The DKI metrics (i.e., AK and AD) were correlated with clinical variables in the two patient groups. In conclusion, DKI is useful for detecting brain microstructural abnormalities in MHE and NMHE patients. Abnormal DKI parameters suggest alterations in brain microstructural complexity in cirrhotic patients, which may contribute to the neurobiological basis of neurocognitive impairment. These results may provide additional information on the pathophysiology of cirrhosis.
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Chen LH, Shi JY, Zou TX, Zhang L, Gou Y, Lin Y, Chen HJ. Disturbance of thalamic metabolism and its association with regional neural dysfunction and cognitive impairment in minimal hepatic encephalopathy. Eur J Radiol 2020; 131:109252. [PMID: 32949859 DOI: 10.1016/j.ejrad.2020.109252] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2020] [Revised: 06/12/2020] [Accepted: 08/10/2020] [Indexed: 12/20/2022]
Abstract
PURPOSE To conduct the first investigation on thalamic metabolic alterations in minimal hepatic encephalopathy (MHE) and elucidate their association with intrinsic neural activity change and cognitive dysfunction. METHODS Thirty-eight cirrhotic patients [18 with MHE, 20 without MHE (NHE)] and 21 healthy controls (HC) were included, all of whom underwent 1H-magnetic resonance spectroscopy, resting-state functional magnetic resonance imaging (fMRI), as well as cognitive assessment based on the Psychometric Hepatic Encephalopathy Score (PHES). Metabolite ratios in the thalamus were measured, including N-acetyl aspartate (NAA)/creatine (Cr), glutamate plus glutamine (Glx)/Cr, choline (Cho)/Cr, and myo-inositol (mI)/Cr. Intrinsic neural activity was evaluated based on frequency-specific amplitude of low-frequency fluctuations (ALFF) using fMRI signals. RESULTS MHE patients showed an increase in Glx/Cr and a decrease in Cho/Cr and mI/Cr, compared with HC. These changes were aggravated from NHE to MHE. Cho/Cr and mI/Cr were positively correlated with regional ALFF derived from the frequency-specific band (0.01-0.027 Hz) and PHES. Receiver operating characteristic curve analysis showed that Cho/Cr and mI/Cr measurements exhibited moderate discrimination ability between NHE and MHE. CONCLUSION Our findings provide evidence that MHE is associated with disturbed metabolism in the thalamus, which may contribute to the altered neural activity and underlie the mechanisms of cognitive impairments. MRS measurements in the thalamus could serve as the potential biomarker for diagnosing MHE among cirrhotic patients.
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Affiliation(s)
- Li-Hong Chen
- Department of Radiology, Fujian Medical University Union Hospital, Fuzhou, 350001, China
| | - Jia-Yan Shi
- Department of Radiology, Fujian Medical University Union Hospital, Fuzhou, 350001, China
| | - Tian-Xiu Zou
- Department of Radiology, Fujian Medical University Union Hospital, Fuzhou, 350001, China
| | - Ling Zhang
- Department of Radiology, Fujian Medical University Union Hospital, Fuzhou, 350001, China; Department of Radiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China
| | - Yaoping Gou
- Fujian Provincial Key Laboratory of Plasma and Magnetic Resonance, Department of Electronic Science, Xiamen University, Xiamen, 361005, China
| | - Yanqin Lin
- Fujian Provincial Key Laboratory of Plasma and Magnetic Resonance, Department of Electronic Science, Xiamen University, Xiamen, 361005, China.
| | - Hua-Jun Chen
- Department of Radiology, Fujian Medical University Union Hospital, Fuzhou, 350001, China.
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Benear SL, Ngo CT, Olson IR. Dissecting the Fornix in Basic Memory Processes and Neuropsychiatric Disease: A Review. Brain Connect 2020; 10:331-354. [PMID: 32567331 DOI: 10.1089/brain.2020.0749] [Citation(s) in RCA: 44] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
Background: The fornix is the primary axonal tract of the hippocampus, connecting it to modulatory subcortical structures. This review reveals that fornix damage causes cognitive deficits that closely mirror those resulting from hippocampal lesions. Methods: We reviewed the literature on the fornix, spanning non-human animal lesion research, clinical case studies of human patients with fornix damage, as well as diffusion-weighted imaging (DWI) work that evaluates fornix microstructure in vivo. Results: The fornix is essential for memory formation because it serves as the conduit for theta rhythms and acetylcholine, as well as providing mnemonic representations to deep brain structures that guide motivated behavior, such as when and where to eat. In rodents and non-human primates, fornix lesions lead to deficits in conditioning, reversal learning, and navigation. In humans, damage to the fornix manifests as anterograde amnesia. DWI research reveals that the fornix plays a key role in mild cognitive impairment and Alzheimer's Disease, and can potentially predict conversion from the former to the latter. Emerging DWI findings link perturbations in this structure to schizophrenia, mood disorders, and eating disorders. Cutting-edge research has investigated how deep brain stimulation of the fornix can potentially attenuate memory loss, control epileptic seizures, and even improve mood. Conclusions: The fornix is essential to a fully functioning memory system and is implicated in nearly all neurological functions that rely on the hippocampus. Future research needs to use optimized DWI methods to study the fornix in vivo, which we discuss, given the difficult nature of fornix reconstruction. Impact Statement The fornix is a white matter tract that connects the hippocampus to several subcortical brain regions and is pivotal for episodic memory functioning. Functionally, the fornix transmits essential neurotransmitters, as well as theta rhythms, to the hippocampus. In addition, it is the conduit by which memories guide decisions. The fornix is biomedically important because lesions to this tract result in irreversible anterograde amnesia. Research using in vivo imaging methods has linked fornix pathology to cognitive aging, mild cognitive impairment, psychosis, epilepsy, and, importantly, Alzheimer's Disease.
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Affiliation(s)
- Susan L Benear
- Department of Psychology, Temple University, Philadelphia, Pennsylvania, USA
| | - Chi T Ngo
- Center for Lifespan Psychology, Max Planck Institute for Human Development, Berlin, Germany
| | - Ingrid R Olson
- Department of Psychology, Temple University, Philadelphia, Pennsylvania, USA
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14
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Impaired brain glucose metabolism in cirrhosis without overt hepatic encephalopathy: a retrospective 18F-FDG PET/CT study. Neuroreport 2020; 30:776-782. [PMID: 31261240 PMCID: PMC6635050 DOI: 10.1097/wnr.0000000000001284] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
OBJECTIVES There are subclinical neurologic deficits in cirrhotic patients without overt hepatic encephalopathy. We aimed to use F-fluorodeoxyglucose PET/computed tomography to explore the impaired brain glucose metabolism of subclinical hepatic encephalopathy in cirrhosis. METHODS Thirty-seven patients with hepatitis B virus-related cirrhosis without overt hepatic encephalopathy and 49 controls were enrolled in the study. The patients' Model for End-Stage Liver Disease scores were calculated. All participants underwent resting state F-fluorodeoxyglucose PET/computed tomography. Between-group comparisons of brain PET/computed tomography data were conducted with two-sample t-tests and multivariate tests with Statistical Parametric Mapping 8 software. RESULTS Most of the patients (30/37) had a Model for End-Stage Liver Disease score of less than 20. The patients and controls did not significantly differ in baseline characteristics, such as sex, age, plasma glucose level, smoking history or BMI, but they did significantly differ in blood uric acid level and serum levels of bilirubin, albumin, total protein, alkaline phosphatase, alanine aminotransferase and aspartate aminotransferase (P < 0.0001). Relative to brain glucose metabolism in the controls, that in the patients involved both hyper- and hypometabolic regions (P < 0.001). The relative hypometabolic regions included the parietal, occipital and limbic lobes, and the hypermetabolic regions included the hippocampus, parahippocampal gyri, right basal ganglia and circumventricular organs. CONCLUSION Patients with cirrhosis have characteristic patterns of brain glycometabolic impairment. F-fluorodeoxyglucose PET/computed tomography may serve as a preclinical biomarker for brain damage in cirrhosis.
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15
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Reduced Cortical Complexity in Cirrhotic Patients with Minimal Hepatic Encephalopathy. Neural Plast 2020; 2020:7364649. [PMID: 32256557 PMCID: PMC7104259 DOI: 10.1155/2020/7364649] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2019] [Revised: 01/28/2020] [Accepted: 02/12/2020] [Indexed: 01/09/2023] Open
Abstract
Purpose Gray matter volume loss, regional cortical thinning, and local gyrification index alteration have been documented in minimal hepatic encephalopathy (MHE). Fractal dimension (FD), another morphological parameter, has been widely used to describe structural complexity alterations in neurological or psychiatric disease. Here, we conducted the first study to investigate FD alterations in MHE. Methods and Materials We performed high-resolution structural magnetic resonance imaging on cirrhotic patients with MHE (n = 20) and healthy controls (n = 21). We evaluated their cognitive performance using the psychometric hepatic encephalopathy score (PHES). The regional FD value was calculated by Computational Anatomy Toolbox (CAT12) and compared between groups. We further estimated the association between patients' cognitive performance and FD values. Results MHE patients presented significantly decreased FD values in the left precuneus, left supramarginal gyrus, right caudal anterior cingulate cortex, right isthmus cingulate cortex, right insula, bilateral pericalcarine cortex, and bilateral paracentral cortex compared to normal controls. In addition, the FD values in the right isthmus cingulate cortex and right insula were shown to be positively correlated with patients' cognitive performance. Conclusion Aberrant cortical complexity is an additional characteristic of MHE, and FD analysis may provide novel insight into the neurobiological basis of cognitive dysfunction in MHE.
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16
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Zhang XD, Zhao LR, Zhou JM, Su YY, Ke J, Cheng Y, Li JL, Shen W. Altered hippocampal functional connectivity in primary Sjögren syndrome: a resting-state fMRI study. Lupus 2020; 29:446-454. [PMID: 32075510 DOI: 10.1177/0961203320908936] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Structural and metabolic abnormalities in the hippocampus have been associated with the pathophysiological mechanism of central nervous system involvement in primary Sjögren syndrome (pSS). Nevertheless, how hippocampal function is altered in pSS remains unknown. The purpose of our study is to investigate the alterations in hippocampal functional connectivity (FC) in pSS by using resting-state functional magnetic resonance imaging (rs-fMRI). Thirty-eight patients with pSS and 38 age- and education level-matched healthy controls (HCs) underwent magnetic resonance imaging examination. Prior to each MRI examination, neuropsychological tests were performed. Left and right hippocampal FCs were analyzed by using seed-based whole-brain correlation and compared between pSS and HCs. Spearman correlation analysis was performed between the z-value of hippocampal FC in brain regions with significant difference between the two groups and neuropsychological tests/clinical data in pSS. Compared with the controls, the patients with pSS showed decreased hippocampal FC between the left hippocampus and the right inferior occipital gray (IOG)/inferior temporal gray (ITG), as well as between the right hippocampus and right IOG/middle occipital gray (MOG), left MOG, and left middle temporal gray. In addition, increased hippocampal FCs were detected between the left hippocampus and left putamen, as well as between the right hippocampus and right cerebellum posterior lobe. Moreover, the visual reproduction score positively correlated with the FC between right hippocampus and right IOG/MOG. The white matter hyperintensity score negatively correlated with the FC between left hippocampus and right IOG/ITG. In conclusion, patients with pSS suffered decreased hippocampal FC mainly sited in the occipital and temporal cortex with right hippocampal laterality. Altered hippocampal FC might be a potential biomarker in detecting brain function changes and guiding neuroprotection in pSS.
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Affiliation(s)
- X-D Zhang
- Department of Radiology, Tianjin First Central Hospital, Tianjin, China
| | - L-R Zhao
- Department of Rheumatology, Tianjin First Central Hospital, Tianjin, China
| | - J-M Zhou
- Department of Radiology, Tianjin First Central Hospital, Tianjin, China
- Department of Radiology, Tianjin First Central Clinical Hospital, Tianjin Medical University, Tianjin, China
| | - Y-Y Su
- Department of Radiology, First Affiliated Hospital, Soochow University, Suzhou, China
| | - J Ke
- Department of Radiology, First Affiliated Hospital, Soochow University, Suzhou, China
| | - Y Cheng
- Department of Radiology, Tianjin First Central Hospital, Tianjin, China
| | - J-L Li
- Department of Radiology, Tianjin First Central Hospital, Tianjin, China
- Department of Radiology, Tianjin First Central Clinical Hospital, Tianjin Medical University, Tianjin, China
| | - W Shen
- Department of Radiology, Tianjin First Central Hospital, Tianjin, China
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17
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Chen QF, Zou TX, Yang ZT, Chen HJ. Identification of patients with and without minimal hepatic encephalopathy based on gray matter volumetry using a support vector machine learning algorithm. Sci Rep 2020; 10:2490. [PMID: 32051514 PMCID: PMC7016173 DOI: 10.1038/s41598-020-59433-1] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2019] [Accepted: 01/29/2020] [Indexed: 12/13/2022] Open
Abstract
Minimal hepatic encephalopathy (MHE) is characterized by diffuse abnormalities in cerebral structure, such as reduced cortical thickness and altered brain parenchymal volume. This study tested the potential of gray matter (GM) volumetry to differentiate between cirrhotic patients with and without MHE using a support vector machine (SVM) learning method. High-resolution, T1-weighted magnetic resonance images were acquired from 24 cirrhotic patients with MHE and 29 cirrhotic patients without MHE (NHE). Voxel-based morphometry was conducted to evaluate the GM volume (GMV) for each subject. An SVM classifier was employed to explore the ability of the GMV measurement to diagnose MHE, and the leave-one-out cross-validation method was used to assess classification accuracy. The SVM algorithm based on GM volumetry achieved a classification accuracy of 83.02%, with a sensitivity of 83.33% and a specificity of 82.76%. The majority of the most discriminative GMVs were located in the bilateral frontal lobe, bilateral lentiform nucleus, bilateral thalamus, bilateral sensorimotor areas, bilateral visual regions, bilateral temporal lobe, bilateral cerebellum, left inferior parietal lobe, and right precuneus/posterior cingulate gyrus. Our results suggest that SVM analysis based on GM volumetry has the potential to help diagnose MHE in cirrhotic patients.
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Affiliation(s)
- Qiu-Feng Chen
- College of Computer and Information Sciences, Fujian Agriculture and Forestry University, Fuzhou, 350002, China
| | - Tian-Xiu Zou
- Department of Radiology, Fujian Medical University Union Hospital, Fuzhou, 350001, China
| | - Zhe-Ting Yang
- Department of Radiology, Fujian Medical University Union Hospital, Fuzhou, 350001, China
| | - Hua-Jun Chen
- Department of Radiology, Fujian Medical University Union Hospital, Fuzhou, 350001, China.
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18
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Ye M, Guo Z, Li Z, Lin X, Li J, Jiang G, Teng Y, Qiu Y, Han L, Lv X. Aberrant inter-hemispheric coordination characterizes the progression of minimal hepatic encephalopathy in patients with HBV-related cirrhosis. NEUROIMAGE-CLINICAL 2020; 25:102175. [PMID: 31954985 PMCID: PMC6965735 DOI: 10.1016/j.nicl.2020.102175] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/11/2019] [Revised: 11/26/2019] [Accepted: 01/10/2020] [Indexed: 12/19/2022]
Abstract
Patients with hepatitis B virus (HBV)-related cirrhosis (HBV-RC) and minimal hepatic encephalopathy (MHE) exhibit alterations in homotopic inter-hemispheric functional connectivity (FC) and corpus callosum (CC) degeneration. However, the progression of inter-hemispheric dysconnectivity in cirrhotic patients from no MHE (NMHE) to MHE and its association with the progression of diseased-related cognitive impairment remain uncharacterized. We hypothesized that inter-hemispheric dysconnectivity exists in NMHE patients and further deteriorates at the MHE stage, which is associated with performance measured by psychometric hepatic encephalopathy scores (PHES) that can characterize cirrhotic patients with NMHE and MHE. Using inter-hemispheric homotopic FC and CC (and its subfields) volumetric measurements in 31 patients with HBV-RC (17 with NMHE and 14 with MHE) and 37 healthy controls, we verified that MHE patients had significant attenuated inter-hemispheric homotopic FC in the bilateral cuneus, post-central gyrus, inferior parietal lobule, and superior temporal gyms, as well as CC degeneration in total CC, CC2, CC3, and CC4 (each comparison had a corrected P < 0.05). In contrast, NMHE patients had relatively less severe inter-hemispheric homotopic FC and no CC degeneration. In addition, the degeneration of the CC and inter-hemispheric homotopic functional disconnections correlated with poor PHES performances in all cirrhotic patients (NMHE and MHE). Furthermore, impairment of inter-hemispheric homotopic FC partially mediated the association between CC degeneration and worse PHES performance. Notably, a combination of inter-hemispheric homotopic FC and CC volumes had higher discriminative values according to the area under the curve (AUC) score (AUC = 0.908, P < 0.001) to classify patients into MHE or NMHE groups when compared with either alone. Our findings shed light on the progression of inter-hemispheric dysconnectivity in relation to the progression of disease-related cognitive impairment in patients with HBV-RC.
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Affiliation(s)
- Min Ye
- Department of Geriatrics, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, China; Department of Geriatrics, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China
| | - Zheng Guo
- Department of Oncology, The First Affiliated Hospital of Ganzhou Medical University, Ganzhou, Guangdong, China
| | - Zhipeng Li
- Department of Medical Imaging, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, China
| | - Xiaoshan Lin
- Department of Radiology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong, China
| | - Jing Li
- Department of Medical Imaging, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, China
| | - Guihua Jiang
- Department of Medical Imaging, Guangdong No. 2 Provincial People's Hospital, Guangzhou, Guangdong, China
| | - Yun Teng
- Department of Radiology, Lianjiang people' hospital, Zhanjiang, Guangdong, China
| | - Yingwei Qiu
- Department of Radiology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong, China.
| | - Lujun Han
- Department of Medical Imaging, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, China.
| | - Xiaofei Lv
- Department of Medical Imaging, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, China
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Xu XY, Ding HG, Li WG, Jia JD, Wei L, Duan ZP, Liu YL, Ling-Hu EQ, Zhuang H, Hepatology CSO, Association CM. Chinese guidelines on management of hepatic encephalopathy in cirrhosis. World J Gastroenterol 2019; 25:5403-5422. [PMID: 31576089 PMCID: PMC6767982 DOI: 10.3748/wjg.v25.i36.5403] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2019] [Revised: 06/07/2019] [Accepted: 08/24/2019] [Indexed: 02/06/2023] Open
Abstract
The Chinese Society of Hepatology developed the current guidelines on the management of hepatic encephalopathy in cirrhosis based on the published evidence and the panelists' consensus. The guidelines provided recommendations for the diagnosis and management of hepatic encephalopathy (HE) including minimal hepatic encephalopathy (MHE) and overt hepatic encephalopathy, emphasizing the importance on screening MHE in patients with end-stage liver diseases. The guidelines emphasized that early identification and timely treatment are the key to improve the prognosis of HE. The principles of treatment include prompt removal of the cause, recovery of acute neuropsychiatric abnormalities to baseline status, primary prevention, and secondary prevention as soon as possible.
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Affiliation(s)
- Xiao-Yuan Xu
- Department of Infectious Diseases, Peking University First Hospital, Beijing 100034, China
| | - Hui-Guo Ding
- Hepatology and Digestion Center, Beijing You-An Hospital, Capital Medical University, Beijing 100069, China
| | - Wen-Gang Li
- Department of Liver Oncology, Cancer Radiation Therapy Center, Fifth Medical Center, PLA General Hospital, Beijing 100039, China
| | - Ji-Dong Jia
- Hepatology Center, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China
| | - Lai Wei
- Hepatobiliary and Pancreatic Department, Beijing Tsinghua Changgeng Hospital, Beijing 102218, China
| | - Zhong-Ping Duan
- Artificial Liver Center, Beijing You-An Hospital, Capital Medical University, Beijing 100069, China
| | - Yu-Lan Liu
- Department of Gastroenterology, Peking University People's Hospital, Beijing 100044, China
| | - En-Qiang Ling-Hu
- Department of Gastroenterology, First Medical Center, PLA General Hospital, Beijing 100853, China
| | - Hui Zhuang
- Department of Pathogenic Biology, Peking University Health Science Center, Beijing 100191, China
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Sato T, Endo K, Kakisaka K, Suzuki Y, Kooka Y, Sawara K, Ito K, Sasaki M, Takikawa Y. Decreased Mean Kurtosis in the Putamen is a Diagnostic Feature of Minimal Hepatic Encephalopathy in Patients with Cirrhosis. Intern Med 2019; 58:1217-1224. [PMID: 30626839 PMCID: PMC6543222 DOI: 10.2169/internalmedicine.2116-18] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/02/2023] Open
Abstract
Objective To prevent the development of overt hepatic encephalopathy, the early intervention for minimal hepatic encephalopathy (MHE) based on an accurate diagnosis is essential. This study investigated whether or not magnetic resonance diffusion kurtosis imaging (DKI) and diffusion tensor imaging (DTI) could detect brain microstructure abnormalities in MHE. The aim was to confirm whether or not brain microstructure abnormalities detected by magnetic resonance (MR) imaging could be used for the diagnosis of MHE. Methods Thirty-two subjects were prospectively examined with a 3-T MR scanner. Tract-based spatial statistics and region of interest analyses of diffusion imaging were performed to compare the mean kurtosis (MK), fractional anisotropy (FA), and mean diffusivity (MD) values between patients with and without minimal hepatic encephalopathy. The diagnostic performance for the detection of MHE was assessed with a receiver operating characteristic analysis. Results Ten subjects were diagnosed with MHE by neuropsychological testing. After the exclusion of unsuitable subjects, we analyzed 9 subjects with MHE and 14 without MHE. The patients with MHE had a reduced MK in the widespread white matter. We also found significant decreases in the MK in the caudate nucleus, putamen, globus pallidus, and/or thalamus in the subjects with MHE. The MK in the putamen showed the best diagnostic performance for differentiating the subjects with MHE from those without MHE (cut-off value, 0.74; sensitivity, 0.89; specificity, 0.86). Conclusion DKI detects changes in the cerebral white matter and basal ganglia regions of patients with MHE more sensitively than DTI. The MK values in the putamen can be a useful marker for diagnosing MHE from cirrhotic patients without MHE.
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Affiliation(s)
- Takuro Sato
- Division of Hepatology, Department of Internal Medicine, Iwate Medical University, Japan
| | - Kei Endo
- Division of Hepatology, Department of Internal Medicine, Iwate Medical University, Japan
| | - Keisuke Kakisaka
- Division of Hepatology, Department of Internal Medicine, Iwate Medical University, Japan
| | - Yuji Suzuki
- Division of Hepatology, Department of Internal Medicine, Iwate Medical University, Japan
| | - Yohei Kooka
- Division of Hepatology, Department of Internal Medicine, Iwate Medical University, Japan
| | - Kei Sawara
- Division of Hepatology, Department of Internal Medicine, Iwate Medical University, Japan
| | - Kenji Ito
- Division of Ultrahigh Field MRI, Institute for Biomedical Sciences, Iwate Medical University, Japan
| | - Makoto Sasaki
- Division of Ultrahigh Field MRI, Institute for Biomedical Sciences, Iwate Medical University, Japan
| | - Yasuhiro Takikawa
- Division of Hepatology, Department of Internal Medicine, Iwate Medical University, Japan
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21
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Wang M, Cui J, Liu Y, Zhou Y, Wang H, Wang Y, Zhu Y, Nguchu BA, Qiu B, Wang X, Yu Y. Structural and functional abnormalities of vision-related brain regions in cirrhotic patients: a MRI study. Neuroradiology 2019; 61:695-702. [PMID: 30949745 PMCID: PMC6511351 DOI: 10.1007/s00234-019-02199-9] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2018] [Accepted: 03/12/2019] [Indexed: 12/20/2022]
Abstract
Purpose Previous studies have focused on global cerebral alterations observed in cirrhosis. However, little was known about the specific abnormalities of vision-related brain regions in cirrhotic patients. In this study, we sought to explore neurological alterations of vision-related regions by measuring brain resting-state network connectivity, based on the structural investigation in cirrhotic patients without clinical sign of hepatic encephalopathy (HE). Methods Structural and functional magnetic resonance image (MRI) data were collected from 20 hepatitis B virus (HBV)-related cirrhotic patients without clinical sign of HE and from 20 healthy controls (HC). Voxel-based morphometric (VBM) analysis and brain functional network analysis were performed to detect abnormalities in cerebral structure and function. Results Cirrhotic patients showed regions with the most significant gray matter reduction primarily in vision-related brain regions, including the bilateral lingual gyri, left putamen, right fusiform gyrus, and right calcarine gyrus, and other significant gray matter reductions were distributed in bilateral hippocampus. Based on structural investigation focused on vision-related regions, brain functional network analysis revealed decreased functional connectivity between brain functional networks within vision-related regions (primary visual network (PVN), higher visual network (HVN), visuospatial network (VSN)) in the patient group compared with HC group. Conclusion These results indicate that structural and functional impairment were evident in the vision-related brain regions in cirrhotic patients without clinical sign of hepatic encephalopathy. The physiopathology and clinical relevance of these changes could not be ascertained from the present study, which provided a basis for further evolution of the disease.
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Affiliation(s)
- Mingquan Wang
- Department of Radiology, The First Affiliated Hospital of AnHui Medical University, Hefei, 230022, Anhui, China
| | - Jin Cui
- Centers for Biomedical Engineering, University of Science and Technology of China, Hefei, Anhui, China
| | - Yanpeng Liu
- Centers for Biomedical Engineering, University of Science and Technology of China, Hefei, Anhui, China
| | - Yawen Zhou
- Centers for Biomedical Engineering, University of Science and Technology of China, Hefei, Anhui, China
| | - Huijuan Wang
- Centers for Biomedical Engineering, University of Science and Technology of China, Hefei, Anhui, China
| | - Yanming Wang
- Centers for Biomedical Engineering, University of Science and Technology of China, Hefei, Anhui, China
| | - Yuying Zhu
- Centers for Biomedical Engineering, University of Science and Technology of China, Hefei, Anhui, China
| | | | - Bensheng Qiu
- Centers for Biomedical Engineering, University of Science and Technology of China, Hefei, Anhui, China
| | - Xiaoxiao Wang
- Centers for Biomedical Engineering, University of Science and Technology of China, Hefei, Anhui, China
| | - Yongqiang Yu
- Department of Radiology, The First Affiliated Hospital of AnHui Medical University, Hefei, 230022, Anhui, China.
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Li JL, Jiang H, Zhang XD, Huang LX, Xie SS, Zhang L, Cheng Y, Shen W. Microstructural brain abnormalities correlate with neurocognitive dysfunction in minimal hepatic encephalopathy: a diffusion kurtosis imaging study. Neuroradiology 2019; 61:685-694. [PMID: 30918990 DOI: 10.1007/s00234-019-02201-4] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2019] [Accepted: 03/12/2019] [Indexed: 12/19/2022]
Abstract
PURPOSE To investigate the diffusion kurtosis imaging (DKI) in early minimal hepatic encephalopathy (MHE) diagnosis and evaluate the correlations between changes in DKI metrics and cognitive performance. METHODS We enrolled 116 cirrhosis patients, divided into non-HE (n = 61) and MHE (n = 55), and 46 normal controls (NCs). All patients underwent cognitive testing before magnetic resonance imaging. DKI metrics were calculated through whole-brain voxel-based analysis (VBA) and differences between the groups were assessed. Pearson correlation between the DKI metrics and cognitive performance was analysed. The receiver operating characteristic (ROC) curve was used to analyse the diagnostic efficiency of DKI metrics for MHE. RESULTS MHE patients had significantly altered DKI metrics in a wide range of regions; lower fractional anisotropy (FA) and higher mean diffusivity (MD) are mainly located in the corpus callosum, left temporal white matter (WM), and right medial frontal WM. Furthermore, significantly altered kurtosis metrics included lower mean kurtosis (MK) in the corpus callosum and left thalamus, lower radial kurtosis (RK) in the corpus callosum, and lower axial kurtosis (AK) in the right anterior thalamic radiation. Alterations in axial diffusivity (AD), radial diffusivity (RD), and MD were closely correlated with cognitive scores. The ROC curves indicated AD in the forceps minor had the highest predictive performance for MHE in the cirrhosis patients (area under curve = 0.801, sensitivity = 77.05%, specificity = 74.55%). CONCLUSIONS Altered DKI metrics indicate brain microstructure abnormalities in MHE patients, some of which may be used as neuroimaging markers for early MHE diagnosis.
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Affiliation(s)
- Jing-Li Li
- Department of Radiology, Tianjin First Central Hospital, Tianjin, 300192, China
| | - Heng Jiang
- Department of Oncology, Western Theater Command Air Force Hospital of PLA, Chengdu, 610021, China
| | - Xiao-Dong Zhang
- Department of Radiology, Tianjin First Central Hospital, Tianjin, 300192, China
| | - Li-Xiang Huang
- Department of Radiology, Tianjin First Central Hospital, Tianjin, 300192, China
| | - Shuang-Shuang Xie
- Department of Radiology, Tianjin First Central Hospital, Tianjin, 300192, China
| | - Li Zhang
- Department of Transplantation Surgery, Tianjin First Central Hospital, Tianjin, 300192, China
| | - Yue Cheng
- Department of Radiology, Tianjin First Central Hospital, Tianjin, 300192, China.
| | - Wen Shen
- Department of Radiology, Tianjin First Central Hospital, Tianjin, 300192, China.
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23
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Zheng W, Zhu WW, Feng ZC, Liang Q, Rong PF, Li LF, Liao YJ, Wang W. Increased serum malondialdehyde levels are associated with grey matter volume loss in patients with non-alcoholic cirrhosis. Quant Imaging Med Surg 2019; 9:230-237. [PMID: 30976547 DOI: 10.21037/qims.2018.12.12] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Background Grey matter volume (GMV) loss has been observed in patients with non-alcoholic cirrhosis, but the underlying mechanisms are unknown. Oxidative stress (OS) is a recognized feature and systemic phenomenon of cirrhosis. However, little is known about whether OS is associated with GMV loss in cirrhosis. This study aimed to assess the relationship between oxidative damage and GMV loss in patients with non-alcoholic cirrhosis. Methods Thirty-four patients with non-alcoholic cirrhosis and 27 age- and sex-matched healthy controls were enrolled in this prospective study. All subjects underwent brain magnetic resonance imaging (MRI), and voxel-based morphometry (VBM) was performed to assess normalized global GMV. As an OS marker, serum malondialdehyde (MDA) levels were determined in all subjects. In the patient group, a correlation analysis was used to investigate the relationship between serum MDA levels and normalized global GMV. Results Compared with healthy controls, cirrhotic patients displayed a significant decrease in normalized global GMV and a significant increase in serum MDA levels. In the patient group, serum MDA levels were negatively correlated with normalized global GMV adjusted for age, sex and Child-Pugh class. Conclusions Increased serum MDA levels were associated with GMV loss in patients with non-alcoholic cirrhosis, suggesting that oxidative damage may be involved in GMV loss observed in cirrhotic patients.
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Affiliation(s)
- Wei Zheng
- Department of Radiology, The Third Xiangya Hospital, Central South University, Changsha 410013, China
| | - Wen-Wei Zhu
- Department of Radiology, The Third Xiangya Hospital, Central South University, Changsha 410013, China
| | - Zhi-Chao Feng
- Department of Radiology, The Third Xiangya Hospital, Central South University, Changsha 410013, China
| | - Qi Liang
- Department of Radiology, The Third Xiangya Hospital, Central South University, Changsha 410013, China
| | - Peng-Fei Rong
- Department of Radiology, The Third Xiangya Hospital, Central South University, Changsha 410013, China
| | - Li-Feng Li
- Department of Radiology, The Third Xiangya Hospital, Central South University, Changsha 410013, China
| | - Yun-Jie Liao
- Department of Radiology, The Third Xiangya Hospital, Central South University, Changsha 410013, China
| | - Wei Wang
- Department of Radiology, The Third Xiangya Hospital, Central South University, Changsha 410013, China
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Zhang XD, Zhang LJ. Multimodal MR imaging in hepatic encephalopathy: state of the art. Metab Brain Dis 2018; 33:661-671. [PMID: 29374342 DOI: 10.1007/s11011-018-0191-9] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/03/2017] [Accepted: 01/17/2018] [Indexed: 02/07/2023]
Abstract
Hepatic encephalopathy (HE) is a neurological or neuropsychological complication due to liver failure or portosystemic shunting. The clinical manifestation is highly variable, which can exhibit mild cognitive or motor impairment initially, or gradually progress to a coma, even death, without treatment. Neuroimaging plays a critical role in uncovering the neural mechanism of HE. In particular, multimodality MR imaging is able to assess both structural and functional derangements of the brain with HE in focal or neural network perspectives. In recent years, there has been rapid development in novel MR technologies and applications to investigate the pathophysiological mechanism of HE. Therefore, it is necessary to update the latest MR findings regarding HE by use of multimodality MRI to refine and deepen our understanding of the neural traits in HE. Herein, this review highlights the latest MR imaging findings in HE to refresh our understanding of MRI application in HE.
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Affiliation(s)
- Xiao Dong Zhang
- Department of Radiology, Tianjin First Central Hospital, Clinical School of Tianjin Medical University, Tianjin, 300192, People's Republic of China
| | - Long Jiang Zhang
- Department of Medical Imaging, Jinling Hospital, Medical School of Nanjing University, No. 305 Zhongshan East Road, Nanjing, 210002, Jiangsu Province, People's Republic of China.
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25
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Brain Microstructural Abnormalities in Patients With Cirrhosis Without Overt Hepatic Encephalopathy: A Voxel-Based Diffusion Kurtosis Imaging Study. AJR Am J Roentgenol 2017; 209:1128-1135. [PMID: 28813200 DOI: 10.2214/ajr.17.17827] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
OBJECTIVE This study aimed to investigate whole-brain microstructural abnormalities and their correlation with cognitive impairment in patients with cirrhosis using diffusion kurtosis imaging (DKI). SUBJECTS AND METHODS Eighteen patients with cirrhosis and 17 healthy control subjects underwent DKI. Cognition was measured using psychometric hepatic encephalopathy (HE) scores. Whole-brain voxel-based analyses were performed to investigate between-group differences in DKI-derived parameters, including mean kurtosis, axial kurtosis, and radial kurtosis. RESULTS Compared with control subjects, the patients with cirrhosis had lower psychometric HE scores, indicating cognitive impairments. The patients with cirrhosis had significantly lower global mean kurtosis, axial kurtosis, and radial kurtosis in gray matter (GM) and white matter (WM). Voxel-based analyses showed that patients with cirrhosis had decreased mean kurtosis, axial kurtosis, and radial kurtosis in diffuse GM regions (particularly in the cingulate cortex, precuneus, insular cortex, frontal areas, basal ganglia, hippocampus and parahippocampal gyrus, supramarginal gyrus and angular gyrus, postcentral and precentral gyrus, and cerebellum) and WM regions (particularly in the corpus callosum, internal capsule, frontal regions, parietal regions, occipital regions, and cerebellum). The DKI metrics were positively correlated with psychometric HE score among patients. CONCLUSION Lower DKI parameters suggest decreased brain microstructural complexity in patients with cirrhosis, which may contribute to the neurobiologic basis of cognitive impairment.
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Diabetes Mellitus is Associated with More Severe Brain Spontaneous Activity Impairment and Gray Matter Loss in Patients with Cirrhosis. Sci Rep 2017; 7:7775. [PMID: 28798299 PMCID: PMC5552886 DOI: 10.1038/s41598-017-08075-x] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2017] [Accepted: 07/06/2017] [Indexed: 11/25/2022] Open
Abstract
Recent studies showed many cirrhosis patients may have diabetes mellitus (DM), however, the effect of DM on brain in cirrhotic patients is unclear. This study included 34 cirrhosis patients (17 with DM, 17 without DM) and 17 age-, sex-matched healthy controls. MRI examination and neuropsychological tests were performed. Fractional amplitude of low-frequency fluctuation (fALFF) and voxel-based morphometry algorithms were used to obtain fALFF values and gray matter volume, which were compared and correlated with clinical variables. In cirrhosis patients with and without DM, fALFF values were decreased in the left postcentral gyrus, right precentral gyrus, left supramarginal gyrus, bilateral lingual gyri and occipital lobe, while increased in the left orbital frontal gyrus. Gray matter volume was decreased in bilateral caudates and putamen, while increased in bilateral thalami. Compared with non-DM cirrhosis patients, DM cirrhosis patients showed decreased fALFF values in bilateral caudates and decreased gray matter volume in bilateral thalami. The blood glucose levels of cirrhosis patients showed negative correlations with fALFF values in bilateral caudates and gray matter volume in bilateral thalami. In conclusion, DM aggravates brain damage in cirrhosis patients. Thus, it is important to pay more attention to the management of DM in cirrhotic patients.
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Nardone R, De Blasi P, Höller Y, Brigo F, Golaszewski S, Frey VN, Orioli A, Trinka E. Intracortical inhibitory and excitatory circuits in subjects with minimal hepatic encephalopathy: a TMS study. Metab Brain Dis 2016; 31:1065-70. [PMID: 27255390 DOI: 10.1007/s11011-016-9848-4] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2016] [Accepted: 05/25/2016] [Indexed: 01/31/2023]
Abstract
Minimal hepatic encephalopathy (MHE) is the earliest form of hepatic encephalopathy (HE) and affects up to 80 % of patients with liver cirrhosis. By definition, MHE is characterized by psychomotor slowing and subtle cognitive deficits, but obvious clinical manifestations are lacking. Given its covert nature, MHE is often underdiagnosed. This study was aimed at detecting neurophysiological changes, as assessed by means of transcranial magnetic stimulation (TMS), involved in the early pathogenesis of the HE. We investigated motor cortex excitability in 15 patients with MHE and in 15 age-matched age-matched cirrhotic patients without MHE; the resting motor threshold, the short-interval intracortical inhibition (SICI) and the intracortical facilitation (ICF) were examined. Paired-pulse TMS revealed significant increased SICI and reduced ICF in the patients with MHE. These findings may reflect abnormalities in intrinsic brain activity and altered organization of functional connectivity networks. In particular, the results suggest a shift in the balance between intracortical inhibitory and excitatory mechanisms towards a net increase of inhibitory neurotransmission. Together with other neurophysiological (in particular EEG) and neuroimaging techniques, TMS may thus provide early markers of cerebral dysfunction in cirrhotic patients with MHE.
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Affiliation(s)
- Raffaele Nardone
- Department of Neurology, Christian Doppler Klinik, Paracelsus Medical University, Salzburg, Austria.
- Department of Neurology, Franz Tappeiner Hospital, Via Rossini, 5, 39012, Merano, BZ, Italy.
| | | | - Yvonne Höller
- Department of Neurology, Christian Doppler Klinik, Paracelsus Medical University, Salzburg, Austria
| | - Francesco Brigo
- Department of Neurology, Franz Tappeiner Hospital, Via Rossini, 5, 39012, Merano, BZ, Italy
- Department of Neurological and Movement Sciences, Section of Clinical Neurology, University of Verona, Verona, Italy
| | - Stefan Golaszewski
- Department of Neurology, Christian Doppler Klinik, Paracelsus Medical University, Salzburg, Austria
| | - Vanessa N Frey
- Department of Neurology, Christian Doppler Klinik, Paracelsus Medical University, Salzburg, Austria
| | - Andrea Orioli
- Department of Neurology, Franz Tappeiner Hospital, Via Rossini, 5, 39012, Merano, BZ, Italy
| | - Eugen Trinka
- Department of Neurology, Christian Doppler Klinik, Paracelsus Medical University, Salzburg, Austria
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Golaszewski S, Langthaler PB, Schwenker K, Florea C, Christova M, Brigo F, Trinka E, Nardone R. Abnormal cortical synaptic plasticity in minimal hepatic encephalopathy. Brain Res Bull 2016; 125:200-4. [DOI: 10.1016/j.brainresbull.2016.07.011] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2016] [Revised: 07/23/2016] [Accepted: 07/25/2016] [Indexed: 12/13/2022]
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Oeltzschner G, Butz M, Wickrath F, Wittsack HJ, Schnitzler A. Covert hepatic encephalopathy: elevated total glutathione and absence of brain water content changes. Metab Brain Dis 2016; 31:517-27. [PMID: 26563124 DOI: 10.1007/s11011-015-9760-3] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/22/2015] [Accepted: 11/06/2015] [Indexed: 01/20/2023]
Abstract
Recent pathophysiological models suggest that oxidative stress and hyperammonemia lead to a mild brain oedema in hepatic encephalopathy (HE). Glutathione (GSx) is a major cellular antioxidant and known to be involved in the interception of both. The aim of this work was to study total glutathione levels in covert HE (minimal HE and HE grade 1) and to investigate their relationship with local brain water content, levels of glutamine (Gln), myo-inositol (mI), neurotransmitter levels, critical flicker frequency (CFF), and blood ammonia. Proton magnetic resonance spectroscopy ((1)H MRS) data were analysed from visual and sensorimotor cortices of thirty patients with covert HE and 16 age-matched healthy controls. Total glutathione levels (GSx/Cr) were quantified with respect to creatine. Furthermore, quantitative MRI brain water content measures were evaluated. Data were tested for links with the CFF and blood ammonia. GSx/Cr was elevated in the visual (mHE) and sensorimotor (mHE, HE 1) MRS volumes and correlated with blood ammonia levels (both P < 0.001). It was further linked to Gln/Cr and mI/Cr (P < 0.01 in visual, P < 0.001 in sensorimotor) and to GABA/Cr (P < 0.01 in visual). Visual GSx/Cr correlated with brain water content in the thalamus, nucleus caudatus, and visual cortex (P < 0.01). Brain water measures did neither show group effects nor correlations with CFF or blood ammonia. Elevated total glutathione levels in covert HE (< HE 2) correlate with blood ammonia and may be a regional-specific reaction to hyperammonemia and oxidative stress. Brain water content is locally linked to visual glutathione levels, but appears not to be associated with changes of clinical parameters. This might suggest that cerebral oedema is only marginally responsible for the symptoms of covert HE.
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Affiliation(s)
- Georg Oeltzschner
- Institute of Clinical Neuroscience and Medical Psychology, Medical Faculty, Heinrich-Heine-University Düsseldorf, Universitätsstr. 1, D-40225, Düsseldorf, Germany.
- Department of Diagnostic and Interventional Radiology, Medical Faculty, Heinrich-Heine-University Düsseldorf, D-40225, Düsseldorf, Germany.
| | - Markus Butz
- Institute of Clinical Neuroscience and Medical Psychology, Medical Faculty, Heinrich-Heine-University Düsseldorf, Universitätsstr. 1, D-40225, Düsseldorf, Germany
| | - Frithjof Wickrath
- Department of Diagnostic and Interventional Radiology, Medical Faculty, Heinrich-Heine-University Düsseldorf, D-40225, Düsseldorf, Germany
| | - Hans-Jörg Wittsack
- Department of Diagnostic and Interventional Radiology, Medical Faculty, Heinrich-Heine-University Düsseldorf, D-40225, Düsseldorf, Germany
| | - Alfons Schnitzler
- Institute of Clinical Neuroscience and Medical Psychology, Medical Faculty, Heinrich-Heine-University Düsseldorf, Universitätsstr. 1, D-40225, Düsseldorf, Germany
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30
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Nardone R, Taylor AC, Höller Y, Brigo F, Lochner P, Trinka E. Minimal hepatic encephalopathy: A review. Neurosci Res 2016; 111:1-12. [PMID: 27153746 DOI: 10.1016/j.neures.2016.04.009] [Citation(s) in RCA: 50] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2016] [Revised: 04/02/2016] [Accepted: 04/23/2016] [Indexed: 02/07/2023]
Abstract
Minimal hepatic encephalopathy (MHE) is the earliest form of hepatic encephalopathy and can affect up to 80% of patients with liver cirrhosis. By definition, MHE is characterized by cognitive function impairment in the domains of attention, vigilance and integrative function, but obvious clinical manifestation are lacking. MHE has been shown to affect daily functioning, quality of life, driving and overall mortality. The diagnosis can be achieved through neuropsychological testing, recently developed computerized psychometric tests, such as the critical flicker frequency and the inhibitory control tests, as well as neurophysiological procedures. Event related potentials can reveal subtle changes in patients with normal neuropsychological performances. Spectral analysis of electroencephalography (EEG) and quantitative analysis of sleep EEG provide early markers of cerebral dysfunction in cirrhotic patients with MHE. Neuroimaging, in particular MRI, also increasingly reveals diffuse abnormalities in intrinsic brain activity and altered organization of functional connectivity networks. Medical treatment for MHE to date has been focused on reducing serum ammonia levels and includes non-absorbable disaccharides, probiotics or rifaximin. Liver transplantation may not reverse the cognitive deficits associated with MHE. We performed here an updated review on epidemiology, burden and quality of life, neuropsychological testing, neuroimaging, neurophysiology and therapy in subjects with MHE.
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Affiliation(s)
- Raffaele Nardone
- Department of Neurology, Christian Doppler Klinik and Centre for Cognitive Neuroscience, Paracelsus Medical University, Salzburg, Austria; Department of Neurology, Franz Tappeiner Hospital, Italy.
| | - Alexandra C Taylor
- Department of Neurology, Christian Doppler Klinik and Centre for Cognitive Neuroscience, Paracelsus Medical University, Salzburg, Austria
| | - Yvonne Höller
- Department of Neurology, Christian Doppler Klinik and Centre for Cognitive Neuroscience, Paracelsus Medical University, Salzburg, Austria
| | - Francesco Brigo
- Department of Neurology, Franz Tappeiner Hospital, Italy; Department of Neurological and Movement Sciences, Section of Clinical Neurology, University of Verona, Italy
| | - Piergiorgio Lochner
- Department of Neurology, Saarland University Medical Center, Homburg, Germany
| | - Eugen Trinka
- Department of Neurology, Christian Doppler Klinik and Centre for Cognitive Neuroscience, Paracelsus Medical University, Salzburg, Austria
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Chen HJ, Jiang LF, Sun T, Liu J, Chen QF, Shi HB. Resting-state functional connectivity abnormalities correlate with psychometric hepatic encephalopathy score in cirrhosis. Eur J Radiol 2015; 84:2287-95. [PMID: 26321490 DOI: 10.1016/j.ejrad.2015.08.005] [Citation(s) in RCA: 42] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2015] [Revised: 07/31/2015] [Accepted: 08/12/2015] [Indexed: 12/11/2022]
Abstract
BACKGROUND & AIMS Neurocognitive impairment is a common complication of cirrhosis and regarded as the important characteristic for early stage of hepatic encephalopathy (HE). This study aimed to investigate the changes in brain network centrality of functional connectivity among cirrhotic patients and uncover the mechanisms about early HE. METHODS Twenty-four cirrhotic patients without overt HE and 21 healthy controls were enrolled and underwent resting-state fMRI and Psychometric Hepatic Encephalopathy Score (PHES) tests. Whole-brain functional network was constructed by measuring the temporal correlations of every pairs of brain gray matter voxels; and then voxel-wise degree centrality (DC), an index reflecting importance of a node in functional integration, was calculated and compared between two groups. A seed-based resting-state functional connectivity (RSFC) analysis was further performed to investigate abnormal functional connectivity pattern of those regions with changed DC. RESULTS Compared with controls, the cirrhotic patients had worse performances in all neurocognitive tests and lower PHES score. Meanwhile, patients showed decreased DC in bilateral medial prefrontal gyrus and anterior cingulate cortex, left middle frontal gyrus, and bilateral thalamus; while increased DC in right middle occipital gyrus and parahippocampal gyrus/inferior temporal gyrus. The seed-based RSFC analyses revealed that the relevant functional networks, such as default-mode and attention networks, visual network, and thalamo-cortical circuits, were disturbed in cirrhotic patients. The DC changes were correlated with PHES score in patient group. CONCLUSIONS Our findings further confirm brain network disorganization in cirrhotic patients with neurocognitive impairments and may provide a new perspective for understanding HE-related mechanisms.
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Affiliation(s)
- Hua-Jun Chen
- Department of Radiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
| | - Long-Feng Jiang
- Department of Infectious Diseases, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China
| | - Tao Sun
- Department of Radiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China
| | - Jun Liu
- Department of Radiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China
| | - Qiu-Feng Chen
- School of Information Science and Engineering, Central South University, Changsha 410083, China
| | - Hai-Bin Shi
- Department of Radiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
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Wu X, Lv XF, Zhang YL, Wu HW, Cai PQ, Qiu YW, Zhang XL, Jiang GH. Cortical signature of patients with HBV-related cirrhosis without overt hepatic encephalopathy: a morphometric analysis. Front Neuroanat 2015; 9:82. [PMID: 26106307 PMCID: PMC4458689 DOI: 10.3389/fnana.2015.00082] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2015] [Accepted: 05/26/2015] [Indexed: 12/21/2022] Open
Abstract
Previous studies have shown that patients with hepatitis B virus-related cirrhosis (HBV-RC) without overt hepatic encephalopathy (OHE) are associated with a varying degree of cognitive dysfunction. Several resting-state functional magnetic resonance imaging (fMRI) studies have been conducted to explore the neural correlates of such cognitive deficits, whereas little effort has been made to investigate the cortical integrity in cirrhotic patients without OHE. Here, using cortical thickness, surface area and local gyrification index (lGI), this study performed a comprehensive analysis on the cortical morphometry of patients with HBV-RC without OHE (HBV-RC-NOHE) vs. matched healthy controls. Compared with healthy controls, we found significantly increased cortical thickness in the bilateral lingual and parahippocampal gyrus, right posterior cingulate cortex, precuneus, peri-calcarine sulcus and fusiform gyrus in patient with HBV-RC-NOHE, which may closely relate to be the low-grade brain edema. Cortical gyrification analysis showed significantly increased lGI in the left superior and inferior parietal cortex as well as lateral occipital cortex, which was speculated to be associated with disruptions in white matter connectivity and sub-optimal intra-cortical organization. In addition, the mean cortical thickness/lGI of the regions with structural abnormalities was shown to be negatively correlated with psychometric hepatic encephalopathy score (PHES) of the patients with HBV-RC-NOHE. These morphological changes may serve as potential markers for the preclinical diagnosis and progression of HBV-RC-NOHE.
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Affiliation(s)
- Xiu Wu
- Key Laboratory for NeuroInformation of Ministry of Education, School of Life Science and Technology, University of Electronic Science and Technology of China Chengdu, China ; Department of Medical Imaging, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine Guangzhou, China
| | - Xiao-Fei Lv
- Department of Medical Imaging, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine Guangzhou, China
| | - Yu-Ling Zhang
- Key Laboratory for NeuroInformation of Ministry of Education, School of Life Science and Technology, University of Electronic Science and Technology of China Chengdu, China
| | - Hua-Wang Wu
- Key Laboratory for NeuroInformation of Ministry of Education, School of Life Science and Technology, University of Electronic Science and Technology of China Chengdu, China ; Department of Medical imaging, Guangzhou Brain Hospital, The Affiliated Hospital of Guangzhou Medical University Guangzhou, China
| | - Pei-Qiang Cai
- Department of Medical Imaging, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine Guangzhou, China
| | - Ying-Wei Qiu
- Department of Medical Imaging, Guangdong No. 2 Provincial People's Hospital Guangzhou, China
| | - Xue-Lin Zhang
- Medical Imaging Centre, Nanfang Hospital, Southern Medial University Guangzhou, China
| | - Gui-Hua Jiang
- Department of Medical Imaging, Guangdong No. 2 Provincial People's Hospital Guangzhou, China
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Lv XF, Liu K, Qiu YW, Cai PQ, Li J, Jiang GH, Deng YJ, Zhang XL, Wu PH, Xie CM, Wen G. Anomalous gray matter structural networks in patients with hepatitis B virus-related cirrhosis without overt hepatic encephalopathy. PLoS One 2015; 10:e0119339. [PMID: 25786256 PMCID: PMC4364769 DOI: 10.1371/journal.pone.0119339] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2014] [Accepted: 01/13/2015] [Indexed: 01/15/2023] Open
Abstract
Background and Purpose Increasing evidence suggests that cirrhosis may affect the connectivity among different brain regions in patients before overt hepatic encephalopathy (OHE) occurs. However, there has been no study investigating the structural reorganization of these altered connections at the network level. The primary focus of this study was to investigate the abnormal topological organization of the structural network in patients with hepatitis B virus-related cirrhosis (HBV-RC) without OHE using structural MRI. Methods Using graph theoretical analysis, we compared the global and regional topological properties of gray matter structural networks between 28 patients with HBV-RC without OHE and 30 age-, sex- and education-matched healthy controls. The structural correlation networks were constructed for the two groups based on measures of gray matter volume. Results The brain network of the HBV-RC group exhibited a significant decrease in the clustering coefficient and reduced small-worldness at the global level across a range of network densities. Regionally, brain areas with altered nodal degree/betweenness centrality were observed predominantly in association cortices (frontal and temporal regions) (p < 0.05, uncorrected), including a significantly decreased nodal degree in the inferior temporal gyrus (p < 0.001, uncorrected). Furthermore, the HBV-RC group exhibited a loss of association hubs and the emergence of an increased number of non-association hubs compared with the healthy controls. Conclusion The results of this large-scale gray matter structural network study suggest reduced topological organization efficiency in patients with HBV-RC without OHE. Our findings provide new insight concerning the mechanisms of neurobiological reorganization in the HBV-RC brain from a network perspective.
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Affiliation(s)
- Xiao-Fei Lv
- Imaging and Interventional Radiology, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China
| | - Kai Liu
- Medical Imaging Centre, Nanfang Hospital, Southern Medial University, Guangzhou, People’s Republic of China
| | - Ying-Wei Qiu
- Department of medical imaging, The First Affiliated Hospital of Gannan Medical University, Ganzhou, People's Republic of China
- Department of Medical Imaging, Guangdong No. 2 Provincial People’s Hospital, Guangzhou, People's Republic of China
| | - Pei-Qiang Cai
- Imaging and Interventional Radiology, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China
| | - Jing Li
- Imaging and Interventional Radiology, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China
| | - Gui-Hua Jiang
- Department of Medical Imaging, Guangdong No. 2 Provincial People’s Hospital, Guangzhou, People's Republic of China
| | - Yan-Jia Deng
- Medical Imaging Centre, Nanfang Hospital, Southern Medial University, Guangzhou, People’s Republic of China
| | - Xue-Lin Zhang
- Medical Imaging Centre, Nanfang Hospital, Southern Medial University, Guangzhou, People’s Republic of China
| | - Pei-Hong Wu
- Imaging and Interventional Radiology, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China
| | - Chuan-Miao Xie
- Imaging and Interventional Radiology, Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China
- * E-mail: (CMX); (GW)
| | - Ge Wen
- Medical Imaging Centre, Nanfang Hospital, Southern Medial University, Guangzhou, People’s Republic of China
- * E-mail: (CMX); (GW)
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Chen HJ, Chen R, Yang M, Teng GJ, Herskovits EH. Identification of minimal hepatic encephalopathy in patients with cirrhosis based on white matter imaging and Bayesian data mining. AJNR Am J Neuroradiol 2014; 36:481-7. [PMID: 25500314 DOI: 10.3174/ajnr.a4146] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND AND PURPOSE White matter abnormalities have been demonstrated to play an important role in minimal hepatic encephalopathy. In this study, we aimed to evaluate whether WM diffusion tensor imaging can be used to identify minimal hepatic encephalopathy among patients with cirrhosis. MATERIALS AND METHODS Our study included 65 patients with cirrhosis with covert hepatic encephalopathy (29 with minimal hepatic encephalopathy and 36 without hepatic encephalopathy). Participants underwent DTI, from which we generated mean diffusivity and fractional anisotropy maps. We used a Bayesian machine-learning technique, called Graphical-Model-based Multivariate Analysis, to determine WM regions that characterize group differences. To further test the clinical significance of these potential biomarkers, we performed Cox regression analysis to assess the potential of these WM regions in predicting survival. RESULTS In mean diffusivity or fractional anisotropy maps, 2 spatially distributed WM regions (predominantly located in the bilateral frontal lobes, corpus callosum, and parietal lobes) were consistently identified as differentiating minimal hepatic encephalopathy from no hepatic encephalopathy and yielded 75.4%-81.5% and 83.1%-92.3% classification accuracy, respectively. We were able to follow 55 of 65 patients (median = 18 months), and 15 of these patients eventually died of liver-related causes. Survival analysis indicated that mean diffusivity and fractional anisotropy values in WM regions were predictive of survival, in addition to the Child-Pugh score. CONCLUSIONS Our findings indicate that WM DTI can provide useful biomarkers differentiating minimal hepatic encephalopathy from no hepatic encephalopathy, which would be helpful for minimal hepatic encephalopathy detection and subsequent treatment.
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Affiliation(s)
- H-J Chen
- From the Jiangsu Key Laboratory of Molecular and Functional Imaging (H.-J.C., M.Y., G.-J.T.), Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, China Department of Radiology (H.-J.C.), The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - R Chen
- Department of Diagnostic Radiology and Nuclear Medicine (R.C., E.H.H.), University of Maryland School of Medicine, Baltimore, Maryland
| | - M Yang
- From the Jiangsu Key Laboratory of Molecular and Functional Imaging (H.-J.C., M.Y., G.-J.T.), Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, China
| | - G-J Teng
- From the Jiangsu Key Laboratory of Molecular and Functional Imaging (H.-J.C., M.Y., G.-J.T.), Department of Radiology, Zhongda Hospital, Medical School, Southeast University, Nanjing, China
| | - E H Herskovits
- Department of Diagnostic Radiology and Nuclear Medicine (R.C., E.H.H.), University of Maryland School of Medicine, Baltimore, Maryland
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Kong X, Wen JQ, Qi RF, Luo S, Zhong JH, Chen HJ, Ji GJ, Lu GM, Zhang LJ. Diffuse interstitial brain edema in patients with end-stage renal disease undergoing hemodialysis: a tract-based spatial statistics study. Medicine (Baltimore) 2014; 93:e313. [PMID: 25526483 PMCID: PMC4603090 DOI: 10.1097/md.0000000000000313] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Abstract
To investigate white matter (WM) alterations and their correlation with cognition function in end-stage renal disease (ESRD) patients undergoing hemodialysis (HD) using diffusion tensor imaging (DTI) with tract-based spatial statistics (TBSS) approach. This prospective HIPAA-complaint study was approved by our institutional review board. Eighty HD ESRD patients and 80 sex- and age-matched healthy controls were included. Neuropsychological (NP) tests and laboratory tests, including serum creatinine and urea, were performed. DTI data were processed to obtain fractional anisotropy (FA) and mean diffusivity (MD) maps with TBSS. FA and MD difference between the 2 groups were compared. We also explored the associations of FA values in WM regions of lower FA with ages, NP tests, disease, and dialysis durations, serum creatinine and urea levels of ESRD patients. Compared with controls, HD ESRD patients had lower FA value in the corpus callosum, bilateral corona radiate, posterior thalamic radiation, left superior longitudinal fasciculus, and right cingulum (P<0.05, FWE corrected). Almost all WM regions had increased MD in HD ESRD patients compared with controls (P<0.05, FWE corrected). In some regions with lower FA, FA values showed moderate correlations with ages, NP tests, and serum urea levels. There was no correlation between FA values and HD durations, disease durations, and serum creatinine levels of ESRD patients (all P>0.05). Diffuse interstitial brain edema and moderate WM integrity disruption occurring in HD ESRD patients, which correlated with cognitive dysfunction, and serum urea levels might be a risk factor for these WM changes.
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Affiliation(s)
- Xiang Kong
- From the Department of Medical Imaging (K-X, Q-RF, L-S, C-HJ, L-GM, Z-LJ); National Clinical Research Center of Kidney Diseases, Jinling Hospital, Medical School of Nanjing University, Nanjing, China (W-JQ); Department of Imaging Sciences, University of Rochester School of Medicine and Dentistry, Rochester, NY (Z-JH); and Center for Cognition and Brain Disorders and the Affiliated Hospital, Hangzhou Normal University, Hangzhou, China (J-GJ)
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Zhang R, Liu K, Yang L, Zhou T, Qian S, Li B, Peng Z, Li M, Sang S, Jiang Q, Sun G. Reduced white matter integrity and cognitive deficits in maintenance hemodialysis ESRD patients: a diffusion-tensor study. Eur Radiol 2014; 25:661-8. [PMID: 25326436 DOI: 10.1007/s00330-014-3466-5] [Citation(s) in RCA: 58] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2014] [Revised: 09/10/2014] [Accepted: 10/07/2014] [Indexed: 01/14/2023]
Abstract
OBJECTIVES The purpose of this investigation was to examine the association between cognition disorders and microstructural white matter (WM) changes in maintenance hemodialysis end-stage renal disease (ESRD) patients. METHODS Twenty-six maintenance hemodialysis ESRD patients and 28 healthy controls underwent diffusion tensor imaging (DTI), Mini Mental State Examination (MMSE), Trial Marking Test-A&B (TMT-A&B), and white matter hyperintensity (WMH) assessment. Tract-based spatial statistics (TBSS) analyses was performed to evaluate WM changes in the patients. Relationships between behavioural performances, clinical data, and the DTI index were tested, respectively, by correlation analysis at the voxel level. RESULTS ESRD patients showed significant decreased fractional anisotropy (FA) in 14 WM regions, and increased mean diffusivity (MD) and radial diffusivity (RD) in widespread regions. Significant positive correlations between FA values and MMSE scores were found in the right anterior corona radiata and the left anterior thalamic radiation; significant negative correlations between the TMT-B time consumption and FA values were identified in the bilateral superior longitudinal fasciculus. Positive linear relationships between MD, RD values, and the duration of hemodialysis were found in several WM regions. CONCLUSION Structural damages to radiation and associative fibre tracts, caused by brain oedema and WM demyelination, may account for the cognitive deficits in ESRD patients.
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Affiliation(s)
- Ruijie Zhang
- Department of Medical Imaging, Jinan Military General Hospital, No.25, Shifan Road, Jinan, Shandong Province, China, 250031
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Ding S, Yang J, Liu L, Ye Y, Wang X, Hu J, Chen B, Zhuge Q. Elevated dopamine induces minimal hepatic encephalopathy by activation of astrocytic NADPH oxidase and astrocytic protein tyrosine nitration. Int J Biochem Cell Biol 2014; 55:252-63. [DOI: 10.1016/j.biocel.2014.09.003] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2014] [Revised: 08/14/2014] [Accepted: 09/01/2014] [Indexed: 12/12/2022]
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Zhang XD, Zhang LJ, Wu SY, Lu GM. Multimodality magnetic resonance imaging in hepatic encephalopathy: An update. World J Gastroenterol 2014; 20:11262-11272. [PMID: 25170210 PMCID: PMC4145764 DOI: 10.3748/wjg.v20.i32.11262] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2013] [Revised: 01/29/2014] [Accepted: 05/29/2014] [Indexed: 02/06/2023] Open
Abstract
Hepatic encephalopathy (HE) is a neuropsychiatric complication of cirrhosis or acute liver failure. Currently, HE is regarded as a continuous cognitive impairment ranging from the mildest stage, minimal HE to overt HE. Hyperammonaemia and neuroinflammation are two main underlying factors which contribute to the neurological alterations in HE. Both structural and functional impairments are found in the white mater and grey mater involved in HE. Although the investigations into HE pathophysiological mechanism are enormous, the exact pathophysiological causes underlying HE remain controversial. Multimodality magnetic resonance imaging (MRI) plays an important role in helping to understand the pathological process of HE. This paper reviews the up-to-date multimodality MRI methods and predominant findings in HE patients with a highlight of the increasingly important role of blood oxygen level dependent functional MRI.
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