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Wang Y, Yang L, Shang Y, Huang Y, Ju C, Zheng H, Zhao W, Liu J. Identifying Minimal Hepatic Encephalopathy: A New Perspective from Magnetic Resonance Imaging. J Magn Reson Imaging 2025; 61:11-24. [PMID: 38149764 DOI: 10.1002/jmri.29179] [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: 11/23/2023] [Accepted: 11/27/2023] [Indexed: 12/28/2023] Open
Abstract
Type C hepatic encephalopathy (HE) is a condition characterized by brain dysfunction caused by liver insufficiency and/or portal-systemic blood shunting, which manifests as a broad spectrum of neurological or psychiatric abnormalities, ranging from minimal HE (MHE), detectable only by neuropsychological or neurophysiological assessment, to coma. Though MHE is the subclinical phase of HE, it is highly prevalent in cirrhotic patients and strongly associated with poor quality of life, high risk of overt HE, and mortality. It is, therefore, critical to identify MHE at the earliest and timely intervene, thereby minimizing the subsequent complications and costs. However, proper and sensitive diagnosis of MHE is hampered by its unnoticeable symptoms and the absence of standard diagnostic criteria. A variety of neuropsychological or neurophysiological tests have been performed to diagnose MHE. However, these tests are nonspecific and susceptible to multiple factors (eg, aging, education), thereby limiting their application in clinical practice. Thus, developing an objective, effective, and noninvasive method is imperative to help detect MHE. Magnetic resonance imaging (MRI), a noninvasive technique which can produce many objective biomarkers by different imaging sequences (eg, Magnetic resonance spectroscopy, DWI, rs-MRI, and arterial spin labeling), has recently shown the ability to screen MHE from NHE (non-HE) patients accurately. As advanced MRI techniques continue to emerge, more minor changes in the brain could be captured, providing new means for early diagnosis and quantitative assessment of MHE. In addition, the advancement of artificial intelligence in medical imaging also presents the potential to mine more effective diagnostic biomarkers and further improves the predictive efficiency of MHE. Taken together, advanced MRI techniques may provide a new perspective for us to identify MHE in the future. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.
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Affiliation(s)
- Yisong Wang
- Department of Radiology, The Second Xiangya Hospital of Central South University, Changsha, China
| | - Longtao Yang
- Department of Radiology, The Second Xiangya Hospital of Central South University, Changsha, China
| | - Youlan Shang
- Department of Radiology, The Second Xiangya Hospital of Central South University, Changsha, China
| | - Yijie Huang
- Department of Radiology, The Second Xiangya Hospital of Central South University, Changsha, China
| | - Chao Ju
- Department of Radiology, The Second Affiliated Hospital of Xinjiang Medical University, Urumqi, China
| | - Hairong Zheng
- Paul C. Lauterbur Research Center for Biomedical Imaging, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China
| | - Wei Zhao
- Department of Radiology, The Second Xiangya Hospital of Central South University, Changsha, China
- Paul C. Lauterbur Research Center for Biomedical Imaging, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China
- Clinical Research Center for Medical Imaging in Hunan Province, Changsha, China
| | - Jun Liu
- Department of Radiology, The Second Xiangya Hospital of Central South University, Changsha, China
- Clinical Research Center for Medical Imaging in Hunan Province, Changsha, China
- Department of Radiology Quality Control Center in Hunan Province, Changsha, China
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Mao Z, Gao ZX, Ji T, Huan S, Yin GP, Chen L. Bidirectional two-sample mendelian randomization analysis identifies causal associations of MRI-based cortical thickness and surface area relation to NAFLD. Lipids Health Dis 2024; 23:58. [PMID: 38395962 PMCID: PMC10885469 DOI: 10.1186/s12944-024-02043-x] [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: 12/08/2023] [Accepted: 02/05/2024] [Indexed: 02/25/2024] Open
Abstract
BACKGROUND Non-alcoholic fatty liver disease (NAFLD) patients have exhibited extra-hepatic neurological changes, but the causes and mechanisms remain unclear. This study investigates the causal effect of NAFLD on cortical structure through bidirectional two-sample Mendelian randomization analysis. METHODS Genetic data from 778,614 European individuals across four NAFLD studies were used to determine genetically predicted NAFLD. Abdominal MRI scans from 32,860 UK Biobank participants were utilized to evaluate genetically predicted liver fat and volume. Data from the ENIGMA Consortium, comprising 51,665 patients, were used to evaluate the associations between genetic susceptibility, NAFLD risk, liver fat, liver volume, and alterations in cortical thickness (TH) and surface area (SA). Inverse-variance weighted (IVW) estimation, Cochran Q, and MR-Egger were employed to assess heterogeneity and pleiotropy. RESULTS Overall, NAFLD did not significantly affect cortical SA or TH. However, potential associations were noted under global weighting, relating heightened NAFLD risk to reduced parahippocampal SA and decreased cortical TH in the caudal middle frontal, cuneus, lingual, and parstriangularis regions. Liver fat and volume also influenced the cortical structure of certain regions, although no Bonferroni-adjusted p-values reached significance. Two-step MR analysis revealed that liver fat, AST, and LDL levels mediated the impact of NAFLD on cortical structure. Multivariable MR analysis suggested that the impact of NAFLD on the cortical TH of lingual and parstriangularis was independent of BMI, obesity, hyperlipidemia, and diabetes. CONCLUSION This study provides evidence that NAFLD causally influences the cortical structure of the brain, suggesting the existence of a liver-brain axis in the development of NAFLD.
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Affiliation(s)
- Zun Mao
- Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing, 210023, P. R. China
| | - Zhi-Xiang Gao
- Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing, 210023, P. R. China
| | - Tong Ji
- Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing, 210023, P. R. China
| | - Sheng Huan
- Department of Anesthesiology and Perioperative Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, 210000, P. R. China
| | - Guo-Ping Yin
- Department of Anesthesiology, Nanjing Second Hospital, Nanjing, 210000, P. R. China.
| | - Long Chen
- Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Sciences, Nanjing Normal University, Nanjing, 210023, P. R. China.
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Mai Z, Mao H. Causal effects of nonalcoholic fatty liver disease on cerebral cortical structure: a Mendelian randomization analysis. Front Endocrinol (Lausanne) 2023; 14:1276576. [PMID: 38027213 PMCID: PMC10646496 DOI: 10.3389/fendo.2023.1276576] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/12/2023] [Accepted: 10/13/2023] [Indexed: 12/01/2023] Open
Abstract
Background Previous studies have highlighted changes in the cerebral cortical structure and cognitive function among nonalcoholic fatty liver disease (NAFLD) patients. However, the impact of NAFLD on cerebral cortical structure and specific affected brain regions remains unclear. Therefore, we aimed to explore the potential causal relationship between NAFLD and cerebral cortical structure. Methods We conducted a Mendelian randomization (MR) study using genetic predictors of alanine aminotransferase (ALT), NAFLD, and percent liver fat (PLF) and combined them with genome-wide association study (GWAS) summary statistics from the ENIGMA Consortium. Several methods were used to assess the effect of NAFLD on full cortex and specific brain regions, along with sensitivity analyses. Results At the global level, PLF nominally decreased SA of full cortex; at the functional level, ALT presented a nominal association with reduced SA of parahippocampal gyrus, TH of pars opercularis, TH of pars orbitalis, and TH of pericalcarine cortex. Besides, NAFLD presented a nominal association with reduced SA of parahippocampal gyrus, TH of pars opercularis, TH of pars triangularis and TH of pericalcarine cortex, but increased TH of entorhinal cortex, lateral orbitofrontal cortex and temporal pole. Furthermore, PLF presented a nominal association with reduced SA of parahippocampal gyrus, TH of pars opercularis, TH of cuneus and lingual gyrus, but increased TH of entorhinal cortex. Conclusion NAFLD is suggestively associated with atrophy in specific functional regions of the human brain.
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Affiliation(s)
- Zhiliang Mai
- Department of Digestive Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, China
- Department of Anatomy, Guangdong Medical University, Zhanjiang, China
| | - Hua Mao
- Department of Digestive Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, China
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Qin B, Liang S, Tang S, Liang H, Zhang Y, Liang Z. Altered Spontaneous Brain Activity in Cirrhotic Patients with Minimal Hepatic Encephalopathy: A Meta-Analysis of Resting-State Functional Imaging. Brain Sci 2023; 13:960. [PMID: 37371438 DOI: 10.3390/brainsci13060960] [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: 05/21/2023] [Revised: 06/13/2023] [Accepted: 06/15/2023] [Indexed: 06/29/2023] Open
Abstract
(1) Background: Minimal hepatic encephalopathy (MHE) is an important complication of decompensated cirrhosis. Previous studies have demonstrated spontaneous brain activity alterations in cirrhotic patients with MHE. However, the reported results are inconsistent, which has limited our understanding of the potential neural mechanisms. Thus, we conducted a quantitative meta-analysis of resting-state functional imaging studies to identify the regional activity alterations consistently involved in MHE. (2) Methods: We searched six databases to include resting-state functional imaging studies and compared spontaneous brain activity patterns between MHE patients and healthy controls (HCs), and between cirrhotic patients without minimal hepatic encephalopathy (NMHE) and HCs. Then, a separate whole-brain voxel-wise meta-analysis between MHE or NMHE patients and HCs was conducted using seed-based d mapping with permutation of subject images. We further conducted the conjunction analysis to assess the distinct regional activity alterations between MHE and NMHE patients as compared to HCs. (3) Results: Thirteen studies with twenty datasets were included in this meta-analysis. Compared with HCs, MHE patients showed decreased spontaneous brain activity in the left superior frontal gyrus, left median cingulate/paracingulate gyri, and right precuneus. Compared with NMHE patients, MHE patients indicated decreased spontaneous brain activity in the left superior frontal gyrus, left median cingulate/paracingulate gyri, and right precuneus. (4) Conclusions: MHE is associated with spontaneous brain activity alterations involving the left superior frontal gyrus and median cingulate/paracingulate gyri, which may implicate primarily in spatial working memory and emotional disorders. These findings may contribute to a better understanding of the potential neural mechanisms, and guide further research.
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Affiliation(s)
- Bin Qin
- Department of Neurology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China
| | - Shuolin Liang
- Department of Neurology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China
| | - Shiting Tang
- Department of Neurology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China
| | - Huo Liang
- Department of Neurology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China
| | - Yunli Zhang
- Department of Neurology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China
| | - Zhijian Liang
- Department of Neurology, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China
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Ji J, Liu YY, Wu GW, Hu YL, Liang CH, Wang XD. Changes in dynamic and static brain fluctuation distinguish minimal hepatic encephalopathy and cirrhosis patients and predict the severity of liver damage. Front Neurosci 2023; 17:1077808. [PMID: 37056312 PMCID: PMC10086246 DOI: 10.3389/fnins.2023.1077808] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2022] [Accepted: 03/13/2023] [Indexed: 03/30/2023] Open
Abstract
PurposeMinimal hepatic encephalopathy (MHE) is characterized by mild neuropsychological and neurophysiological alterations that are not detectable by routine clinical examination. Abnormal brain activity (in terms of the amplitude of low-frequency fluctuation (ALFF) has been observed in MHE patients. However, little is known concerning temporal dynamics of intrinsic brain activity. The present study aimed to investigate the abnormal dynamics of brain activity (dynamic ALFF; dALFF) and static measures [static ALFF; (sALFF)] in MHE patients and to strive for a reliable imaging neuromarkers for distinguishing MHE patients from cirrhosis patients. In addition, the present study also investigated whether intrinsic brain activity predicted the severity of liver damage.MethodsThirty-four cirrhosis patients with MHE, 28 cirrhosis patients without MHE, and 33 age-, sex-, and education-matched healthy controls (HCs) underwent resting-state magnetic resonance imaging (rs-fMRI). dALFF was estimated by combining the ALFF method with the sliding-window method, in which temporal variability was quantized over the whole-scan timepoints and then compared among the three groups. Additionally, dALFF, sALFF and both two features were utilized as classification features in a support vector machine (SVM) to distinguish MHE patients from cirrhosis patients. The severity of liver damage was reflected by the Child–Pugh score. dALFF, sALFF and both two features were used to predict Child–Pugh scores in MHE patients using a general linear model.ResultsCompared with HCs, MHE patients showed significantly increased dALFF in the left inferior occipital gyrus, right middle occipital gyrus, and right insula; increased dALFF was also observed in the right posterior lobe of the cerebellum (CPL) and right thalamus. Compared with HCs, noMHE patients exhibited decreased dALFF in the right precuneus. In contrast, compared with noMHE patients, MHE patients showed increased dALFF in the right precuneus, right superior frontal gyrus, and right superior occipital gyrus. Furthermore, the increased dALFF values in the left precuneus were positively associated with poor digit-symbol test (DST) scores (r = 0.356, p = 0.038); however, dALFF in the right inferior temporal gyrus (ITG) was negatively associated with the number connection test–A (NCT-A) scores (r = -0.784, p = 0.000). A significant positive correlation was found between dALFF in the left inferior occipital gyrus (IOG) and high blood ammonia levels (r = 0.424, p = 0.012). Notably, dALFF values yielded a higher classification accuracy than sALFF values in distinguishing MHE patients from cirrhosis patients. Importantly, the dALFF values predicted the Child–Pugh score (r = 0.140, p = 0.030), whereas sALFF values did not in the current dataset. Combining two features had high accuracy in classification in distinguishing MHE patients from cirrhotic patients and yielded prediction in the severity of liver damage.ConclusionThese findings suggest that combining dALFF and sALFF features is a useful neuromarkers for distinguishing MHE patients from cirrhosis patients and highlights the important role of dALFF feature in predicting the severity of liver damage in MHE.
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Affiliation(s)
- Jiang Ji
- Department of Radiology, General Hospital of Ningxia Medical University, Yinchuan, China
- Department of Radiology, The First Affiliated Hospital of Xinxiang Medical College, Xinxiang, China
| | - Yi-yang Liu
- Department of Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Guo-Wei Wu
- Chinese Institute for Brain Research, Beijing, China
| | - Yan-Long Hu
- Department of Radiology, The First Affiliated Hospital of Xinxiang Medical College, Xinxiang, China
| | - Chang-Hua Liang
- Department of Radiology, The First Affiliated Hospital of Xinxiang Medical College, Xinxiang, China
- *Correspondence: Chang-Hua Liang,
| | - Xiao-dong Wang
- Department of Radiology, General Hospital of Ningxia Medical University, Yinchuan, China
- Xiao-dong Wang,
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Guo JR, Shi JY, Dong QY, Cao YB, Li D, Chen HJ. Altered dynamic spontaneous neural activity in minimal hepatic encephalopathy. Front Neurol 2022; 13:963551. [PMID: 36061995 PMCID: PMC9439282 DOI: 10.3389/fneur.2022.963551] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2022] [Accepted: 07/27/2022] [Indexed: 11/29/2022] Open
Abstract
Background and aims: Abnormal regional neural activity has been identified by the analysis of the static amplitude of low-frequency fluctuation (ALFF) in the setting of minimal hepatic encephalopathy (MHE). Brain activity is highly dynamic. This work sought to evaluate the temporal variability of ALFF to reveal MHE-related alterations in the dynamics of spontaneous neural activity. Methods A total of 29 healthy controls and 49 patients with cirrhosis [including 20 patients with MHE and 29 patients without MHE (NHE)] who underwent resting-state functional magnetic resonance imaging and Psychometric Hepatic Encephalopathy Score (PHES) examination were enrolled in this investigation. Utilizing a sliding-window approach, we calculated the dynamic ALFF (dALFF) variability to reflect the temporal dynamics of regional neural activity. An analysis of the correlation between dALFF variability and PHES was performed, and receiver operating characteristic (ROC) curve analysis to determine the potential of the dALFF variability index in identifying MHE was completed. Results The dALFF variability in the bilateral precuneus/posterior cingulate gyrus and left middle frontal gyrus progressively decreased from NHE to MHE group. In cirrhotic patients, the value of dALFF variability in the bilateral precuneus/posterior cingulate gyrus was positively correlated with their neurocognitive performance (r = 0.383 and P = 0.007). The index of dALFF variability in the bilateral precuneus/posterior cingulate gyrus could be used to distinguish NHE and MHE patients, with moderate power (area under the ROC curve = 0.712 and P = 0.012). Conclusion Our findings highlight the existence of aberrant dynamic brain function in MHE, which could underlie the neural basis of cognitive impairments and could be associated with the development of the disease. Analyzing dALFF could facilitate new biomarker identification for MHE.
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Affiliation(s)
- Jie-Ru Guo
- Department of Gastroenterology, Fujian Medical University Union Hospital, Fuzhou, China
| | - Jia-Yan Shi
- Department of Radiology, Fujian Medical University Union Hospital, Fuzhou, China
| | - Qiu-Yi Dong
- Department of Radiology, Fujian Medical University Union Hospital, Fuzhou, China
| | - Yun-Bin Cao
- Department of Radiology, Fujian Medical University Union Hospital, Fuzhou, China
| | - Dan Li
- Department of Gastroenterology, Fujian Medical University Union Hospital, Fuzhou, China
- Dan Li
| | - Hua-Jun Chen
- Department of Radiology, Fujian Medical University Union Hospital, Fuzhou, China
- *Correspondence: Hua-Jun Chen
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Cai LM, Shi JY, Dong QY, Wei J, Chen HJ. Aberrant stability of brain functional architecture in cirrhotic patients with minimal hepatic encephalopathy. Brain Imaging Behav 2022; 16:2258-2267. [PMID: 35729463 DOI: 10.1007/s11682-022-00696-9] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/03/2022] [Indexed: 01/22/2024]
Abstract
To investigate the stability changes of brain functional architecture and the relationship between stability change and cognitive impairment in cirrhotic patients. Fifty-one cirrhotic patients (21 with minimal hepatic encephalopathy (MHE) and 30 without MHE (NHE)) and 29 healthy controls (HCs) underwent resting-state functional magnetic resonance imaging and neurocognitive assessment using the Psychometric Hepatic Encephalopathy Score (PHES). Voxel-wise functional connectivity density (FCD) was calculated as the sum of connectivity strength between one voxel and others within the entire brain. The sliding window correlation approach was subsequently utilized to calculate the FCD dynamics over time. Functional stability (FS) is measured as the concordance of dynamic FCD. From HCs to the NHE and MHE groups, a stepwise reduction of FS was found in the right supramarginal gyrus (RSMG), right middle cingulate cortex, left superior frontal gyrus, and bilateral posterior cingulate cortex (BPCC), whereas a progressive increment of FS was observed in the left middle occipital gyrus (LMOG) and right temporal pole (RTP). The mean FS values in RSMG/LMOG/RTP (r = 0.470 and P = 0.001; r = -0.458 and P = 0.001; and r = -0.384 and P = 0.005, respectively) showed a correlation with PHES in cirrhotic patients. The FS index in RSMG/LMOG/BPCC/RTP showed moderate discrimination potential between the NHE and MHE groups. Changes in FS may be linked to neuropathological bias of cognitive impairment in cirrhotic patients and could serve as potential biomarkers for MHE diagnosis and monitoring the progression of hepatic encephalopathy.
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Affiliation(s)
- Li-Min Cai
- 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
| | - Qiu-Yi Dong
- Department of Radiology, Fujian Medical University Union Hospital, Fuzhou, 350001, China
| | - Jin Wei
- 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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Cheng Y, Zhang G, Zhang X, Li Y, Li J, Zhou J, Huang L, Xie S, Shen W. Identification of minimal hepatic encephalopathy based on dynamic functional connectivity. Brain Imaging Behav 2021; 15:2637-2645. [PMID: 33755921 DOI: 10.1007/s11682-021-00468-x] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/02/2021] [Indexed: 12/26/2022]
Abstract
To investigate whether dynamic functional connectivity (DFC) metrics can better identify minimal hepatic encephalopathy (MHE) patients from cirrhotic patients without any hepatic encephalopathy (noHE) and healthy controls (HCs). Resting-state functional MRI data were acquired from 62 patients with cirrhosis (MHE, n = 30; noHE, n = 32) and 41 HCs. We used the sliding time window approach and functional connectivity analysis to extract the time-varying properties of brain connectivity. Three DFC characteristics (i.e., strength, stability, and variability) were calculated. For comparison, we also calculated the static functional connectivity (SFC). A linear support vector machine was used to differentiate MHE patients from noHE and HCs using DFC and SFC metrics as classification features. The leave-one-out cross-validation method was used to estimate the classification performance. The strength of DFC (DFC-Dstrength) achieved the best accuracy (MHE vs. noHE, 72.5%; MHE vs. HCs, 84%; and noHE vs. HCs, 88%) compared to the other dynamic features. Compared to static features, the classification accuracies of the DFC-Dstrength feature were improved by 10.5%, 8%, and 14% for MHE vs. noHE, MHE vs. HC, and noHE vs. HCs, respectively. Based on the DFC-Dstrength, seven nodes were identified as the most discriminant features to classify MHE from noHE, including left inferior parietal lobule, left supramarginal gyrus, left calcarine, left superior frontal gyrus, left cerebellum, right postcentral gyrus, and right insula. In summary, DFC characteristics have a higher classification accuracy in identifying MHE from cirrhosis patients. Our findings suggest the usefulness of DFC in capturing neural processes and identifying disease-related biomarkers important for MHE identification.
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Affiliation(s)
- Yue Cheng
- Department of Radiology, Tianjin First Center Hospital, Tianjin, 300192, China
| | - Gaoyan Zhang
- College of Intelligence and Computing, Tianjin Key Laboratory of Cognitive Computing and Application, Tianjin University, Tianjin, 300072, China.
| | - Xiaodong Zhang
- Department of Radiology, Tianjin First Center Hospital, Tianjin, 300192, China
| | - Yuexuan Li
- College of Intelligence and Computing, Tianjin Key Laboratory of Cognitive Computing and Application, Tianjin University, Tianjin, 300072, China
| | - Jingli Li
- Department of Radiology, Tianjin First Center Hospital, Tianjin, 300192, China
| | - Jiamin Zhou
- Department of Radiology, Tianjin First Center Hospital, Tianjin, 300192, China
| | - Lixiang Huang
- Department of Radiology, Tianjin First Center Hospital, Tianjin, 300192, China
| | - Shuangshuang Xie
- Department of Radiology, Tianjin First Center Hospital, Tianjin, 300192, China
| | - Wen Shen
- Department of Radiology, Tianjin First Center Hospital, Tianjin, 300192, China
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Cao Y, Wu B, Chen T, Diao W, Jia Z. Altered intrinsic brain activity in patients with hepatic encephalopathy. J Neurosci Res 2021; 99:1337-1353. [PMID: 33583085 DOI: 10.1002/jnr.24788] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2020] [Revised: 01/04/2021] [Accepted: 01/10/2021] [Indexed: 02/05/2023]
Abstract
Neuropsychiatric deficits are common in patients with liver cirrhosis (LC), especially in those with hepatic encephalopathy (HE). Previous studies reveal abnormalities in brain activity underlying the neuropsychiatric deficits in LC patients; however, the results are inconsistent. We conducted a meta-analysis of resting-state functional magnetic resonance imaging studies using anisotropic effect-size signed differential mapping software on LC patients to characterize the most consistent regional activity alterations, and to evaluate the potential effect of liver transplantation (LT) on brain function. Meta-regression analyses were performed to explore the relationship between brain alterations and clinical variables. Compared with healthy controls, the typical patterns of increased regional activity in the fronto-striato-cerebellar network and decreased activity in the visuo-sensorimotor network and cingulate gyrus were identified in LC patients, which remained significant in the subgroup meta-analyses of minimal HE (MHE) and overt HE (OHE) patients. Functional deficits in the default mode network (DMN) were found in OHE patients compared with MHE patients. Ammonia level positively correlated with brain activity in the right middle temporal gyrus, and the completion time of number connection test A negatively correlated with brain activity in the left anterior cingulate gyrus. In addition, patients showed increased activity in the visuo-sensorimotor network and precuneus after LT. Our study suggests that alterations in the fronto-striato-cerebellar and visuo-sensorimotor networks may be the potential pathophysiological mechanisms underlying HE, and deficits in the DMN may indicate the progression of HE. LT may improve brain function in the visuo-sensorimotor network. This study has registered in the PROSPERO (CRD42020212758).
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Affiliation(s)
- Yuan Cao
- Department of Nuclear Medicine, West China Hospital of Sichuan University, Chengdu, P.R. China.,Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital of Sichuan University, Chengdu, P.R. China
| | - Baolin Wu
- Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital of Sichuan University, Chengdu, P.R. China
| | - Taolin Chen
- Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital of Sichuan University, Chengdu, P.R. China
| | - Wei Diao
- Department of Nuclear Medicine, West China Hospital of Sichuan University, Chengdu, P.R. China.,Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital of Sichuan University, Chengdu, P.R. China
| | - Zhiyun Jia
- Department of Nuclear Medicine, West China Hospital of Sichuan University, Chengdu, P.R. China.,Huaxi MR Research Center (HMRRC), Department of Radiology, West China Hospital of Sichuan University, Chengdu, P.R. China
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Lan F, Lin G, Cao G, Li Z, Ma D, Liu F, Duan M, Fu H, Xiao W, Qi Z, Wang T. Altered Intrinsic Brain Activity and Functional Connectivity Before and After Knee Arthroplasty in the Elderly: A Resting-State fMRI Study. Front Neurol 2020; 11:556028. [PMID: 33133006 PMCID: PMC7550714 DOI: 10.3389/fneur.2020.556028] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2020] [Accepted: 08/18/2020] [Indexed: 12/03/2022] Open
Abstract
Objective: This study aimed to investigate the brain functional alterations with resting-state functional magnetic resonance imaging (rs-fMRI) in older patients with knee osteoarthritis (KOA) before and after total knee arthroplasty (TKA) and to assess the causal relationship of the brain function and neuropsychological changes. Methods: We performed rs-fMRI to investigate brain function of 23 patients aged ≥65 with KOA and 23 healthy matched controls. Of the KOA patients, 15 completed postoperative rs-fMRI examinations. Analyzes of the amplitude of low-frequency fluctuation (ALFF) and functional connectivity (FC) were used to estimate differences in brain functional parameters between KOA patients, postoperative patients, and the controls. The relationship between changes of pre- and post-surgical status in ALFF and neuropsychological test results was analyzed. Results: Compared with the controls, all patients with KOA exhibited decreased ALFF in the default mode network (bilateral angular gyrus, precuneus gyrus, medial superior frontal gyrus) and increased ALFF in the bilateral amygdala and cerebellum posterior lobe before surgery (P < 0.001). Altered ALFF persisted in the same brain regions 1 week postoperatively. The decreased ALFF in the left precuneus gyrus and middle temporal gyrus was found after surgery when compared with preoperative data (P < 0.01). Preoperatively, the KOA patients exhibited increased FC between the left precuneus gyrus and the right supplementary motor area compared to the controls (P < 0.001), but this connectivity became no significant difference after TKA. The left Cerebelum_9 was found to have decreased FC with the right precuneus gyrus postoperatively (P < 0.001) although this was not significantly different before surgery. The significantly altered ALFF values were not correlated with changes in cognitive assessment scores. Conclusion: In older patients with end-stage KOA, functional alterations in important brain regions were detected with the persistence and further changes observed at an early stage after knee replacement. Our data further our understanding of brain functional abnormalities and cognitive impairment in older patients following knee replacement, which may provide therapeutic targets for preventive/treatment strategy to be developed. Trial registration: Clinical Trial Registration: http://www.chictr.org.cn/index.aspx, ChiCTR1800016437; Registered June 1, 2018.
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Affiliation(s)
- Fei Lan
- Department of Anesthesiology, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Disorders, Beijing Institute for Brain Disorders, Beijing, China
| | - Guanwen Lin
- Department of Anesthesiology, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Disorders, Beijing Institute for Brain Disorders, Beijing, China.,Department of Anesthesiology, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou, China
| | - Guanglei Cao
- Department of Orthopedics, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Zheng Li
- Department of Orthopedics, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Daqing Ma
- Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Anaesthesia Research of the Section of Anaesthetics, Pain Medicine and Intensive Care, Chelsea and Westminster Hospital, London, United Kingdom
| | - Fangyan Liu
- Department of Anesthesiology, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Disorders, Beijing Institute for Brain Disorders, Beijing, China
| | - Mei Duan
- Department of Anesthesiology, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Disorders, Beijing Institute for Brain Disorders, Beijing, China
| | - Huiqun Fu
- Department of Anesthesiology, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Disorders, Beijing Institute for Brain Disorders, Beijing, China
| | - Wei Xiao
- Department of Anesthesiology, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Disorders, Beijing Institute for Brain Disorders, Beijing, China
| | - Zhigang Qi
- Department of Radiology, Xuanwu Hospital, Capital Medical University, Beijing, China
| | - Tianlong Wang
- Department of Anesthesiology, Xuanwu Hospital, Capital Medical University, National Clinical Research Center for Geriatric Disorders, Beijing Institute for Brain Disorders, Beijing, China
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11
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Zhou GP, Shi XY, Wei HL, Qu LJ, Yu YS, Zhou QQ, Yin X, Zhang H, Tao YJ. Disrupted Intraregional Brain Activity and Functional Connectivity in Unilateral Acute Tinnitus Patients With Hearing Loss. Front Neurosci 2019; 13:1010. [PMID: 31607851 PMCID: PMC6761222 DOI: 10.3389/fnins.2019.01010] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2019] [Accepted: 09/05/2019] [Indexed: 12/19/2022] Open
Abstract
Purpose The present study combined fractional amplitude of low-frequency fluctuations (fALFF), regional homogeneity (ReHo), and functional connectivity (FC) to explore brain functional abnormalities in acute tinnitus patients (AT) with hearing loss. Methods We recruited twenty-eight AT patients and 31 healthy controls (HCs) and ran resting-state functional magnetic resonance imaging (fMRI) scans. fALFF, ReHo, and FC were conducted and compared between AT patients and HCs. After that, we calculated correlation analyses among abnormal fALFF, ReHo, FC, and clinical data in AT patients. Results Compared with HCs, AT showed increased fALFF values in the right inferior temporal gyrus (ITG). In contrast, significantly decreased ReHo values were observed in the cerebellar vermis, the right calcarine cortex, the right precuneus, the right supramarginal gyrus (SMG), and the right middle frontal gyrus (MFG). Based on the differences in the fALFF and ReHo maps, the latter of which we defined as region-of-interest (ROI) for FC analysis, the right ITG exhibited increased connectivity with the right precentral gyrus. In addition, the right MFG demonstrated decreased connectivity with both the bilateral anterior cingulate cortex (ACC) and the left precentral gyrus. Conclusion By combining ReHo, fALFF, and FC analyses, our work indicated that AT with hearing loss had abnormal intraregional neural activity and disrupted connectivity in several brain regions which mainly involving the non-auditory area, and these regions are major components of default mode network (DMN), attention network, visual network, and executive control network. These findings will help us enhance the understanding of the neuroimaging mechanism in tinnitus populations. Moreover, these abnormalities remind us that we should focus on the early stages of this hearing disease.
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Affiliation(s)
- Gang-Ping Zhou
- Department of Radiology, The Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing, China
| | - Xin-Yi Shi
- Department of ENT, The Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing, China
| | - Heng-Le Wei
- Department of Radiology, The Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing, China
| | - Li-Jie Qu
- Department of Radiology, The Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing, China
| | - Yu-Sheng Yu
- Department of Radiology, The Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing, China
| | - Qing-Qing Zhou
- Department of Radiology, The Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing, China
| | - Xindao Yin
- Department of Radiology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Hong Zhang
- Department of Radiology, The Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing, China
| | - Yue-Jin Tao
- Department of ENT, The Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing, China
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12
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Abstract
The review considers modern ideas about the clinic and pathogenesis of minimal hepatic encephalopathy (MHE). It is discussed the present of cognitive impairment in this category of patients. The data of functional MRI are analyzed, and these results allow taking a fresh look at the origin of clinical disorders in this condition. The importance of cerebral connections disruption is emphasized. It is focused on the fact that in the functioning of the central nervous system the spontaneous activity of the brain has a significant importance. Separately is analyzed "the resting state". It is concluded that MHE, despite its minimal manifestations, is a clinically significant condition requiring attention of a specialists. With that, it is often not diagnosed on time in clinical practice, which could lead to more severe damage of the cerebral functions. As evidenced by the data obtained at the present time, quite extensive changes in the neuronal activity are underlid of the cognitive deficit.
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Affiliation(s)
- I V Damulin
- I.M. First Moscow State Medical University, Ministry of Health of Russia, Moscow, Russia.,A.S Loginov Moscow clinical scientific center of the Moscow healthcare Department, Moscow, Russia
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13
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Zöllner HJ, Butz M, Jördens M, Füllenbach ND, Häussinger D, Schmitt B, Wittsack HJ, Schnitzler A. Chemical exchange saturation transfer imaging in hepatic encephalopathy. NEUROIMAGE-CLINICAL 2019; 22:101743. [PMID: 30856541 PMCID: PMC6411782 DOI: 10.1016/j.nicl.2019.101743] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/12/2018] [Revised: 02/04/2019] [Accepted: 03/02/2019] [Indexed: 01/08/2023]
Abstract
Hepatic encephalopathy (HE) is a common complication in liver cirrhosis and associated with an invasion of ammonia into the brain through the blood-brain barrier. Resulting higher ammonia concentrations in the brain are suggested to lead to a dose-dependent gradual increase of HE severity and an associated impairment of brain function. Amide proton transfer-weighted (APTw) chemical exchange saturation transfer (CEST) imaging has been found to be sensitive to ammonia concentration. The aim of this work was to study APTw CEST imaging in patients with HE and to investigate the relationship between disease severity, critical flicker frequency (CFF), psychometric test scores, blood ammonia, and APTw signals in different brain regions. Whole-brain APTw CEST images were acquired in 34 participants (14 controls, 20 patients (10 minimal HE, 10 manifest HE)) on a 3 T clinical MRI system accompanied by T1 mapping and structural images. T1 normalized magnetization transfer ratio asymmetry analysis was performed around 3 ppm after B0 and B1 correction to create APTw images. All APTw images were spatially normalized into a cohort space to allow direct comparison. APTw images in 6 brain regions (cerebellum, occipital cortex, putamen, thalamus, caudate, white matter) were tested for group differences as well as the link to CFF, psychometric test scores, and blood ammonia. A decrease in APTw intensities was found in the cerebellum and the occipital cortex of manifest HE patients. In addition, APTw intensities in the cerebellum correlated positively with several psychometric scores, such as the fine motor performance scores MLS1 for hand steadiness / tremor (r = 0.466; p = .044) and WRT2 for motor reaction time (r = 0.523; p = .022). Moreover, a negative correlation between APTw intensities and blood ammonia was found for the cerebellum (r = −0.615; p = .007) and the occipital cortex (r = −0.478; p = .045). An increase of APTw intensities was observed in the putamen of patients with minimal HE and correlated negatively with the CFF (r = −0.423; p = .013). Our findings demonstrate that HE is associated with regional differential alterations in APTw signals. These variations are most likely a consequence of hyperammonemia or hepatocerebral degeneration processes, and develop in parallel with disease severity.
Ammonia is suggested to play a key role in the emergence of HE. Increase of ammonia in HE patients might be studied with APTw CEST. HE leads to regionally decreasing APTw CEST signal. APTw CEST correlates with blood ammonia levels and psychometric test scores. APTw CEST is possibly linked to hyperammonemia or hepatocerebral degeneration.
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Affiliation(s)
- Helge Jörn Zöllner
- Institute of Clinical Neuroscience and Medical Psychology, Medical Faculty, Heinrich Heine University Düsseldorf, Germany; Department of Diagnostic and Interventional Radiology, Medical Faculty, Heinrich Heine University Düsseldorf, Germany.
| | - Markus Butz
- Institute of Clinical Neuroscience and Medical Psychology, Medical Faculty, Heinrich Heine University Düsseldorf, Germany
| | - Markus Jördens
- Department of Gastroenterology, Hepatology and Infectiology, Medical Faculty, Heinrich Heine University Düsseldorf, Germany
| | - Nur-Deniz Füllenbach
- Department of Gastroenterology, Hepatology and Infectiology, Medical Faculty, Heinrich Heine University Düsseldorf, Germany
| | - Dieter Häussinger
- Department of Gastroenterology, Hepatology and Infectiology, Medical Faculty, Heinrich Heine University Düsseldorf, Germany
| | - Benjamin Schmitt
- Siemens Ltd. Australia, Healthcare Sector, 160 Herring Road, Macquarie Park, NSW 2113,Australia
| | - Hans-Jörg Wittsack
- Department of Diagnostic and Interventional Radiology, Medical Faculty, Heinrich Heine University Düsseldorf, Germany
| | - Alfons Schnitzler
- Institute of Clinical Neuroscience and Medical Psychology, Medical Faculty, Heinrich Heine University Düsseldorf, Germany
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14
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Zhang G, Cheng Y, Shen W, Liu B, Huang L, Xie S. The short-term effect of liver transplantation on the low-frequency fluctuation of brain activity in cirrhotic patients with and without overt hepatic encephalopathy. Brain Imaging Behav 2018; 11:1849-1861. [PMID: 27917450 DOI: 10.1007/s11682-016-9659-6] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
Previous neuropsychological studies have demonstrated that liver transplantation (LT) is an effective method for improving the cognitive function of cirrhotic patients. However, the neural basis underlying the effects of LT is still unclear. Neuroimaging studies investigating changes in brain structures or functional networks mainly focus on patients without overt hepatic encephalopathy (HE). In this study, we recruited patients with and without overt HE and studied alterations in resting-state brain activity by quantizing the amplitude of low-frequency fluctuation (ALFF) before and 1 month after LT to study the short-term effect of LT in each group. Neuropsychological analyses indicated significant improvement of cognitive function in both groups. ALFF analysis showed that the brain activity in regions regulating motor function, vision, attention, and working memory were restored in both groups, reflecting the neuroplasticity of the brain. However, some persistent impairments and new-onset impairments in other regions related to these cognitive functions were observed in each group. Between-group comparison showed that although cognitive performance improved in both groups, the specific neural basis of LT in each group was different. The significant correlations of altered brain activity in regions showing LT and group effect with altered performance in neuropsychological and biochemical tests suggest a possible neuroimaging marker for the monitoring of short-term recovery of HE and the difference in individual recovery of cognitive performance. The findings in the present study help us further understand the neural effect of LT in patients with and without overt HE.
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Affiliation(s)
- Gaoyan Zhang
- School of Computer Science and Technology, Tianjin Key Laboratory of Cognitive Computing and Application, Tianjin University, Tianjin, 300350, People's Republic of China
| | - Yue Cheng
- Department of Radiology, Tianjin First Central Hospital, Fukang Road No. 24, Nankai District, Tianjin, 300192, People's Republic of China.
| | - Wen Shen
- Department of Radiology, Tianjin First Central Hospital, Fukang Road No. 24, Nankai District, Tianjin, 300192, People's Republic of China
| | - Baolin Liu
- School of Computer Science and Technology, Tianjin Key Laboratory of Cognitive Computing and Application, Tianjin University, Tianjin, 300350, People's Republic of China.,State Key Laboratory of Intelligent Technology and Systems, National Laboratory for Information Science and Technology, Tsinghua University, Beijing, 100084, People's Republic of China
| | - Lixiang Huang
- Department of Radiology, Tianjin First Central Hospital, Fukang Road No. 24, Nankai District, Tianjin, 300192, People's Republic of China
| | - Shuangshuang Xie
- Department of Radiology, Tianjin First Central Hospital, Fukang Road No. 24, Nankai District, Tianjin, 300192, People's Republic of China
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15
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Sun Q, Fan W, Ye J, Han P. Abnormal Regional Homogeneity and Functional Connectivity of Baseline Brain Activity in Hepatitis B Virus-Related Cirrhosis With and Without Minimal Hepatic Encephalopathy. Front Hum Neurosci 2018; 12:245. [PMID: 29988437 PMCID: PMC6024159 DOI: 10.3389/fnhum.2018.00245] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2017] [Accepted: 05/29/2018] [Indexed: 12/16/2022] Open
Abstract
Background and Aims: Abnormalities in neural activity have been reported in cirrhosis with minimal hepatic encephalopathy (MHE). However, little is known about the neurophysiological mechanisms in this disorder. We aimed to investigate the altered patterns of regional synchronization and functional connections in hepatitis B virus-related cirrhosis (HBV-RC) patients with and without MHE using both regional homogeneity (ReHo) and region of interest (ROI)-based functional connectivity (FC) computational methods. Methods: Data of magnetic resonance imaging scans were collected from 30 HBV-RC patients with MHE, 32 HBV-RC patients without MHE (NMHE) and 64 well-matched controls. Several regions showing differences in ReHo after one-way analysis of variance (ANOVA) were defined as ROIs for FC analysis. Next, post hoc t-tests were applied to calculate the group differences in ReHo and FC (false discovery rate (FDR) correction, p < 0.05). Correlations between clinical variables and the altered ReHo and FC were then assessed in patient groups. Results: Across three groups, significant ReHo differences were found in nine ROI regions mainly within the visual network (VN), dorsal attention network (DAN), somatomotor network (SMN), fronto parietal control (FPC) network and thalamus. Compared with healthy controls (HC), the MHE group exhibited abnormal FC mainly between the right calcarine (CAL.R) and middle frontal gyrus (MFG.L)/right thalamus. The MHE patients showed increased FC between the MFG.L and CAL.R compared to NMHE patients. Disease duration of MHE patients was positively correlated with increased mean ReHo values in the right fusiform gyrus (FFG); psychometric hepatic encephalopathy score (PHES) test scores were negatively correlated with increased FC between MFG.L and CAL.R and positively correlated with reduced FC between the CAL.R and THA.R. For NMHE patients, the mean ReHo values in the right frontal pole were positively correlated with disease duration and positively correlated with the PHES scores. Conclusion: Our results exhibited that the functional brain modifications in patients with and without MHE are characterized by compound alterations in local coherence and functional connections in the VN, SMN, DAN, FPC networks and thalamus by using a combination of ReHo and ROI-based FC analysis. These functional imaging changes are correlated with disease duration/PHES. This study helped us gain a better understanding of the features of brain network modifications in cirrhosis.
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Affiliation(s)
- Qing Sun
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Wenliang Fan
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jin Ye
- Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Ping Han
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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16
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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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17
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Zhang G, Cheng Y, Shen W, Liu B, Huang L, Xie S. Brain Regional Homogeneity Changes in Cirrhotic Patients with or without Hepatic Encephalopathy Revealed by Multi-Frequency Bands Analysis Based on Resting-State Functional MRI. Korean J Radiol 2018; 19:452-462. [PMID: 29713223 PMCID: PMC5904472 DOI: 10.3348/kjr.2018.19.3.452] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2017] [Accepted: 11/23/2017] [Indexed: 01/07/2023] Open
Abstract
Objective To investigate brain regional homogeneity (ReHo) changes of multiple sub-frequency bands in cirrhotic patients with or without hepatic encephalopathy using resting-state functional MRI. Materials and Methods This study recruited 46 cirrhotic patients without clinical hepatic encephalopathy (noHE), 38 cirrhotic patients with clinical hepatic encephalopathy (HE), and 37 healthy volunteers. ReHo differences were analyzed in slow-5 (0.010−0.027 Hz), slow-4 (0.027−0.073 Hz), and slow-3 (0.073−0.198 Hz) bands. Routine analysis of (0.010−0.080 Hz) band was used as a benchmark. Associations of abnormal ReHo values in each frequency band with neuropsychological scores and blood ammonia level were analyzed. Pattern classification analyses were conducted to determine whether ReHo differences in each band could differentiate the three groups of subjects (patients with or without hepatic encephalopathy and healthy controls). Results Compared to routine analysis, more differences between HE and noHE were observed in slow-5 and slow-4 bands (p < 0.005, cluster > 12, overall corrected p < 0.05). Sub-frequency band analysis also showed that ReHo abnormalities were frequency-dependent (overall corrected p < 0.05). In addition, ReHo abnormalities in each sub-band were correlated with blood ammonia level and neuropsychological scores, especially in the left inferior parietal lobe (overall corrected p < 0.05 for all frequency bands). Pattern classification analysis demonstrated that ReHo differences in lower slow-5 and slow-4 bands (both p < 0.05) and higher slow-3 band could differentiate the three groups (p < 0.05). Compared to routine analysis, ReHo features in slow-4 band obtained better classification accuracy (89%). Conclusion Cirrhotic patients showed frequency-dependent changes in ReHo. Sub-frequency band analysis is important for understanding HE and clinical monitoring.
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Affiliation(s)
- Gaoyan Zhang
- Tianjin Key Laboratory of Cognitive Computing and Application, School of Computer Science and Technology, Tianjin University, Tianjin 300350, 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
| | - Baolin Liu
- Tianjin Key Laboratory of Cognitive Computing and Application, School of Computer Science and Technology, Tianjin University, Tianjin 300350, China.,State Key Laboratory of Intelligent Technology and Systems, National Laboratory for Information Science and Technology, Tsinghua University, Beijing 100084, China
| | - Lixiang Huang
- Department of Radiology, Tianjin First Central Hospital, Tianjin 300192, China
| | - Shuangshuang Xie
- Department of Radiology, Tianjin First Central Hospital, Tianjin 300192, China
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18
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Altered Spontaneous Brain Activity in Children with Early Tourette Syndrome: a Resting-state fMRI Study. Sci Rep 2017; 7:4808. [PMID: 28684794 PMCID: PMC5500479 DOI: 10.1038/s41598-017-04148-z] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2016] [Accepted: 05/16/2017] [Indexed: 12/05/2022] Open
Abstract
Tourette syndrome (TS) is a childhood-onset chronic disorder characterized by the presence of multiple motor and vocal tics. This study investigated the alterations of spontaneous brain activities in children with TS by resting-state functional magnetic resonance imaging (rs-fMRI). We obtained rs-fMRI scans from 21 drug-naïve and pure TS children and 29 demographically matched healthy children. The amplitude of low-frequency fluctuation (ALFF), fractional ALFF (fALFF) and regional homogeneity (ReHo) of rs-fMRI data were calculated to measure spontaneous brain activity. We found significant alterations of ALFF or fALFF in vision-related structures including the calcarine sulcus, the cuneus, the fusiform gyrus, and the left insula in TS children. Decreased ReHo was found in the right cerebellum. Further analysis showed that the ReHo value of the right cerebellum was positively correlated with TS duration. Our study provides empirical evidence for abnormal spontaneous neuronal activity in TS patients, which may implicate the neurophysiological mechanism in TS children. Moreover, the right cerebellum can be potentially used as a biomarker for the pathophysiology of early TS in children.
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Zhong WJ, Zhou ZM, Zhao JN, Wu W, Guo DJ. Abnormal spontaneous brain activity in minimal hepatic encephalopathy: resting-state fMRI study. Diagn Interv Radiol 2017; 22:196-200. [PMID: 26742646 DOI: 10.5152/dir.2015.15208] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
PURPOSE We aimed to assess the abnormality of baseline spontaneous brain activity in minimal hepatic encephalopathy (MHE) by amplitude of low frequency fluctuation (ALFF) and fraction ALFF (fALFF). METHODS A total of 14 MHE patients and 14 healthy controls were included in our study. Both ALFF and fALFF of functional magnetic resonance imaging were calculated for statistical analysis. RESULTS Compared with healthy controls, patients with MHE had significantly decreased ALFF in the bilateral medial prefrontal cortex (MPFC), left superior frontal gyrus, right precentral gyrus, left opercular part of inferior frontal gyrus, left gyrus rectus, bilateral precuneus, and the posterior lobe of right cerebellum; and they had significantly decreased fALFF in the bilateral MPFC, right middle frontal gyrus, right superior temporal gyrus, and the posterior lobe of left cerebellum. CONCLUSION ALFF and fALFF changes in many brain regions demonstrate abnormality of the spontaneous neuronal activity in MHE. Especially the impairment of right precuneus and left MPFC may play a critical role in manifestation of MHE. Changes of ALFF and fALFF in the precuneus and the MPFC can be used as a potential marker for MHE.
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Affiliation(s)
- Wei-Jia Zhong
- Department of Radiology, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
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20
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Cheng Y, Huang LX, Zhang L, Ma M, Xie SS, Ji Q, Zhang XD, Zhang GY, Zhang XN, Ni HY, Shen W. Longitudinal Intrinsic Brain Activity Changes in Cirrhotic Patients before and One Month after Liver Transplantation. Korean J Radiol 2017; 18:370-377. [PMID: 28246517 PMCID: PMC5313525 DOI: 10.3348/kjr.2017.18.2.370] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2016] [Accepted: 10/08/2016] [Indexed: 01/27/2023] Open
Abstract
Objective To evaluate the spontaneous brain activity alterations in liver transplantation (LT) recipients using resting-state functional MRI. Materials and Methods Twenty cirrhotic patients as transplant candidates and 25 healthy controls (HCs) were included in this study. All patients repeated the MRI study one month after LT. Amplitude of low-frequency fluctuation (ALFF) values were compared between cirrhotic patients (both pre- and post-LT) and HCs as well as between the pre- and post-LT groups. The relationship between ALFF changes and venous blood ammonia levels and neuropsychological tests were investigated using Pearson's correlation analysis. Results In the cirrhotic patients, decreased ALFF in the vision-related regions (left lingual gyrus and calcarine), sensorimotor-related regions (left postcentral gyrus and middle cingulate cortex), and the default-mode network (bilateral precuneus and left inferior parietal lobule) were restored, and the increased ALFF in the temporal and frontal lobe improved in the early period after LT. The ALFF decreases persisted in the right supplementary motor area, inferior parietal lobule, and calcarine. The ALFF changes in the right precuneus were negatively correlated with changes in number connection test-A scores (r = 0.507, p < 0.05). Conclusion LT improved spontaneous brain activity and the results for associated cognition tests. However, decreased ALFF in some areas persisted, and new-onset abnormal ALFF were possible, indicating that complete cognitive function recovery may need more time.
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Affiliation(s)
- Yue Cheng
- Department of Radiology, Tianjin First Central Hospital, Tianjin 300192, China
| | - Li-Xiang Huang
- Department of Radiology, Tianjin First Central Hospital, Tianjin 300192, China
| | - Li Zhang
- Department of Transplantation Surgery, Tianjin First Central Hospital, Tianjin 300192, China
| | - Ming Ma
- Department of Transplantation Surgery, Tianjin First Central Hospital, Tianjin 300192, China
| | - Shuang-Shuang Xie
- Department of Radiology, Tianjin First Central Hospital, Tianjin 300192, China
| | - Qian Ji
- Department of Radiology, Tianjin First Central Hospital, Tianjin 300192, China
| | - Xiao-Dong Zhang
- Department of Radiology, Tianjin First Central Hospital, Tianjin 300192, China
| | - Gao-Yan Zhang
- School of Computer Science and Technology, Tianjin Key Laboratory of Cognitive Computing and Application, Tianjin University, Tianjin 300072, China
| | - Xue-Ning Zhang
- Department of Radiology, The Second Hospital of Tianjin Medical University, Tianjin 300211, China
| | - Hong-Yan Ni
- 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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Chen HJ, Zhang L, Jiang LF, Chen QF, Li J, Shi HB. Identifying minimal hepatic encephalopathy in cirrhotic patients by measuring spontaneous brain activity. Metab Brain Dis 2016; 31:761-9. [PMID: 26886109 DOI: 10.1007/s11011-016-9799-9] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/04/2015] [Accepted: 01/26/2016] [Indexed: 12/11/2022]
Abstract
It has been demonstrated that minimal hepatic encephalopathy (MHE) is associated with aberrant regional intrinsic brain activity in cirrhotic patients. However, few studies have investigated whether altered intrinsic brain activity can be used as a biomarker of MHE among cirrhotic patients. In this study, 36 cirrhotic patients (with MHE, n = 16; without MHE [NHE], n = 20) underwent resting-state functional magnetic resonance imaging (fMRI). Spontaneous brain activity was measured by examining the amplitude of low-frequency fluctuations (ALFF) in the fMRI signal. MHE was diagnosed based on the Psychometric Hepatic Encephalopathy Score (PHES). A two-sample t-test was used to determine the regions of interest (ROIs) in which ALFF differed significantly between the two groups; then, ALFF values within ROIs were selected as classification features. A linear discriminative analysis was used to differentiate MHE patients from NHE patients. The leave-one-out cross-validation method was used to estimate the performance of the classifier. The classification analysis was 80.6 % accurate (81.3 % sensitivity and 80.0 % specificity) in terms of distinguishing between the two groups. Six ROIs were identified as the most discriminative features, including the bilateral medial frontal cortex/anterior cingulate cortex, posterior cingulate cortex/precuneus, left precentral and postcentral gyrus, right lingual gyrus, middle frontal gyrus, and inferior/superior parietal lobule. The ALFF values within ROIs were correlated with PHES in cirrhotic patients. Our findings suggest that altered regional brain spontaneous activity is a useful biomarker for MHE detection among cirrhotic patients.
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Affiliation(s)
- Hua-Jun Chen
- Department of Radiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.
| | - Ling Zhang
- 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
| | - Qiu-Feng Chen
- School of Information Science and Engineering, Central South University, Changsha, 410083, China
| | - Jun Li
- Department of Infectious Diseases, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.
| | - Hai-Bin Shi
- Department of Radiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.
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Aberrant Resting-State Functional Connectivity Density in Patients with Hepatitis B Virus-Related Cirrhosis. BIOMED RESEARCH INTERNATIONAL 2016; 2016:4168512. [PMID: 27403426 PMCID: PMC4923523 DOI: 10.1155/2016/4168512] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/19/2016] [Accepted: 05/18/2016] [Indexed: 12/14/2022]
Abstract
There is increasing evidence that cirrhosis may affect functional connectivity among various brain regions in patients prior to onset of overt hepatic encephalopathy (HE). However, most investigators have focused mainly on alterations in functional connectivity strengths, and the changes in functional connectivity density (FCD) are largely unknown. Here, we investigated alterations in resting-state FCD in patients with hepatitis B virus-related cirrhosis (HBV-RC) without overt HE. Totally, 31 patients with HBV-RC without overt HE and 30 age- and sex-matched healthy controls underwent resting-state functional MRI examinations. FCD mapping was employed to compute local and global FCD maps. Then, short-range and long-range FCD values were calculated and voxel-based comparisons were performed between the two groups. The HBV-RC group showed significant decreases in FCD, including decreased short-range FCDs in the bilateral middle cingulum gyrus/precuneus, the bilateral cuneus, and the left lingual gyrus/inferior occipital gyrus and decreased long-range FCD in the bilateral cuneus/precuneus. In addition, the decreased long-range FCD in the bilateral cuneus/precuneus in the HBV-RC group was related to performance on the psychometric hepatic encephalopathy score (PHES) test. These findings suggest aberrant functional connectivity density in cirrhotic patients prior to overt HE onset, which may provide better insight into understanding the pathophysiological mechanisms underlying the cirrhotic-related cognitive impairment.
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Chen QF, Chen HJ, Liu J, Sun T, Shen QT. Machine Learning Classification of Cirrhotic Patients with and without Minimal Hepatic Encephalopathy Based on Regional Homogeneity of Intrinsic Brain Activity. PLoS One 2016; 11:e0151263. [PMID: 26978777 PMCID: PMC4792397 DOI: 10.1371/journal.pone.0151263] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2015] [Accepted: 02/12/2016] [Indexed: 12/15/2022] Open
Abstract
Machine learning-based approaches play an important role in examining functional magnetic resonance imaging (fMRI) data in a multivariate manner and extracting features predictive of group membership. This study was performed to assess the potential for measuring brain intrinsic activity to identify minimal hepatic encephalopathy (MHE) in cirrhotic patients, using the support vector machine (SVM) method. Resting-state fMRI data were acquired in 16 cirrhotic patients with MHE and 19 cirrhotic patients without MHE. The regional homogeneity (ReHo) method was used to investigate the local synchrony of intrinsic brain activity. Psychometric Hepatic Encephalopathy Score (PHES) was used to define MHE condition. SVM-classifier was then applied using leave-one-out cross-validation, to determine the discriminative ReHo-map for MHE. The discrimination map highlights a set of regions, including the prefrontal cortex, anterior cingulate cortex, anterior insular cortex, inferior parietal lobule, precentral and postcentral gyri, superior and medial temporal cortices, and middle and inferior occipital gyri. The optimized discriminative model showed total accuracy of 82.9% and sensitivity of 81.3%. Our results suggested that a combination of the SVM approach and brain intrinsic activity measurement could be helpful for detection of MHE in cirrhotic patients.
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Affiliation(s)
- Qiu-Feng Chen
- School of Information Science and Engineering, Central South University, Changsha 410083, China
- * E-mail: (QFC); (HJC)
| | - Hua-Jun Chen
- Department of Radiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China
- * E-mail: (QFC); (HJC)
| | - Jun Liu
- Department of Radiology, 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
| | - Qun-Tai Shen
- School of Information Science and Engineering, Central South University, Changsha 410083, China
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Su YY, Liang X, Schoepf UJ, Varga-Szemes A, West HC, Qi R, Kong X, Chen HJ, Lu GM, Zhang LJ. APOE Polymorphism Affects Brain Default Mode Network in Healthy Young Adults: A STROBE Article. Medicine (Baltimore) 2015; 94:e1734. [PMID: 26717353 PMCID: PMC5291594 DOI: 10.1097/md.0000000000001734] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
To investigate the effect of apolipoprotein E (APOE) gene polymorphism on the resting-state brain function, structure, and blood flow in healthy adults younger than 35 years, using multimodality magnetic resonance (MR) imaging.Seventy-six healthy adults (34 men, 23.7 ± 2.8 y; 31 APOE ε4/ε3 carriers, 31 ε3/ε3 carriers, and 14 ε2/ε3 carriers) were included. For resting-state functional MRI data, default mode network (DMN) and amplitude of low-frequency fluctuation maps were extracted and analyzed. Voxel-based morphometry, diffusion tensor imaging from structural imaging, and cerebral blood flow based on arterial spin labeling MR imaging were also analyzed. Correlation analysis was performed between the above mentioned brain parameters and neuropsychological tests.There were no differences in neuropsychological performances, amplitude of low-frequency fluctuation, gray/white matter volumes, fractional anisotropy, mean diffusivity, or whole brain cerebral blood flow among the 3 groups. As for DMN, the ε4/ε3 group showed increased functional connectivities (FCs) in the left medial prefrontal cortex and bilateral posterior cingulate cortices/precuneus compared with the ε3/ε3 group, and increased FCs in the left medial prefrontal cortex and right temporal lobe compared with the ε2/ε3 group (P < 0.05, Alphasim corrected). No differences of DMN FCs were found between the ε2/ε3 and ε3/ε3 groups. FCs in the right temporal lobe positively correlated with the performances of vocabulary learning, delayed recall, and graph recall in all participants (P < 0.05).APOE ε4 carriers exhibited significantly increased DMN FCs when compared with ε3 and ε2 carriers. The ε4 affects DMN FCs before brain structure and blood flow in cognitively intact young patients, suggesting DMN FC may serve as a potential biomarker for the detection of early manifestations of genetic effect.
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Affiliation(s)
- Yun Yan Su
- From the Department of Medical Imaging, Jinling Hospital, Medical School of Nanjing University, Nangjing, Jiangsu Province, China (YYS, XL, RQ, XK, HJC, GML, LJZ); and Division of Cardiovascular Imaging, Medical University of South Carolina, Ashley River Tower, Charleston, South Carolina (UJS, AV-S, HCW)
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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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Alonso J, Córdoba J, Rovira A. Brain magnetic resonance in hepatic encephalopathy. Semin Ultrasound CT MR 2014; 35:136-52. [PMID: 24745889 DOI: 10.1053/j.sult.2013.09.008] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
The term hepatic encephalopathy (HE) covers a wide spectrum of neuropsychiatric abnormalities caused by portal-systemic shunting. The diagnosis requires demonstration of liver dysfunction or portal-systemic shunts and exclusion of other neurologic disorders. Most patients with this condition have liver dysfunction caused by cirrhosis, but it also occurs in patients with acute liver failure and less commonly, in patients with portal-systemic shunts that are not associated with hepatocellular disease. Various magnetic resonance (MR) techniques have improved our knowledge about the pathophysiology of HE. Proton MR spectroscopy and T1-weighted imaging can detect and quantify accumulations of brain products that are normally metabolized or eliminated such as glutamine and manganese. Other MR techniques such as T2-weighted and diffusion-weighted imaging can identify white matter abnormalities resulting from disturbances in cell volume homeostasis secondary to brain hyperammonemia. Partial or complete recovery of these abnormalities has been observed with normalization of liver function or after successful liver transplantation. MR studies have undoubtedly improved our understanding of the mechanisms involved in the pathogenesis of HE, and some findings can be considered biomarkers for monitoring the effects of therapeutic measures focused on correcting this condition.
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Affiliation(s)
- Juli Alonso
- Departament de Radiologia, Unitat de Ressonància Magnètica (IDI), Hospital Vall d'Hebron, Vall d'Hebron Institut of Research (VHIR), Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, Spain
| | - Juan Córdoba
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Barcelona, Spain; Departament de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain; Servei de Medicina Interna-Hepatologia, Hospital Vall d'Hebron, Vall d'Hebron Institut of Research (VHIR), Barcelona, Spain
| | - Alex Rovira
- Departament de Radiologia, Unitat de Ressonància Magnètica (IDI), Hospital Vall d'Hebron, Vall d'Hebron Institut of Research (VHIR), Barcelona, Spain; Departament de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain.
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Aberrant spontaneous brain activity in chronic tinnitus patients revealed by resting-state functional MRI. NEUROIMAGE-CLINICAL 2014; 6:222-8. [PMID: 25379434 PMCID: PMC4215464 DOI: 10.1016/j.nicl.2014.09.011] [Citation(s) in RCA: 61] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/23/2014] [Revised: 09/12/2014] [Accepted: 09/13/2014] [Indexed: 11/24/2022]
Abstract
OBJECTIVE The neural mechanisms that give rise to the phantom sound of tinnitus are poorly understood. This study aims to investigate whether aberrant spontaneous brain activity exists in chronic tinnitus patients using resting-state functional magnetic resonance imaging (fMRI) technique. MATERIALS AND METHODS A total of 31 patients with chronic tinnitus patients and 32 healthy age-, sex-, and education-matched healthy controls were prospectively examined. Both groups had normal hearing thresholds. We calculated the amplitude of low-frequency fluctuations (ALFFs) of fMRI signals to measure spontaneous neuronal activity and detect the relationship between fMRI information and clinical data of tinnitus. RESULTS Compared with healthy controls, we observed significant increased ALFF within several selected regions including the right middle temporal gyrus (MTG), right superior frontal gyrus (SFG), and right angular gyrus; decreased ALFF was detected in the left cuneus, right middle occipital gyrus and bilateral thalamus. Moreover, tinnitus distress correlated positively with increased ALFF in right MTG and right SFG; tinnitus duration correlated positively with higher ALFF values in right SFG. CONCLUSIONS The present study confirms that chronic tinnitus patients have aberrant ALFF in many brain regions, which is associated with specific clinical tinnitus characteristics. ALFF disturbance in specific brain regions might be used to identify the neuro-pathophysiological mechanisms in chronic tinnitus patients.
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Zhang LJ, Wu S, Ren J, Lu GM. Resting-state functional magnetic resonance imaging in hepatic encephalopathy: current status and perspectives. Metab Brain Dis 2014; 29:569-82. [PMID: 24562590 DOI: 10.1007/s11011-014-9504-9] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2013] [Accepted: 02/06/2014] [Indexed: 02/06/2023]
Abstract
Hepatic encephalopathy (HE) is a neuropsychiatric syndrome which develops in patients with severe liver diseases and/or portal-systemic shunting. Minimal HE, the earliest manifestation of HE, has drawn increasing attention in the last decade. Minimal HE is associated with a series of brain functional changes, such as attention, working memory, and so on. Blood oxygen level dependent (BOLD) functional MRI (fMRI), especially resting-state fMRI has been used to explore the brain functional changes of HE, yielding important insights for understanding pathophysiological mechanisms and functional reorganization of HE. This paper briefly reviews the principles of BOLD fMRI, potential applications of resting-state fMRI with advanced post-processing algorithms such as regional homogeneity, amplitude of low frequency fluctuation, functional connectivity and future research perspective in this field.
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Affiliation(s)
- Long Jiang Zhang
- Department of Medical Imaging, Jinling Hospital, Medical School of Nanjing University, 305 Zhongshan East Road, Xuanwu District, Nangjing, Jiangsu Province, China, 210002,
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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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30
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Cui Y, Jiao Y, Chen YC, Wang K, Gao B, Wen S, Ju S, Teng GJ. Altered spontaneous brain activity in type 2 diabetes: a resting-state functional MRI study. Diabetes 2014; 63:749-60. [PMID: 24353185 DOI: 10.2337/db13-0519] [Citation(s) in RCA: 156] [Impact Index Per Article: 14.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Previous research has shown that type 2 diabetes mellitus (T2DM) is associated with an increased risk of cognitive impairment. Patients with impaired cognition often show decreased spontaneous brain activity on resting-state functional magnetic resonance imaging (rs-fMRI). This study used rs-fMRI to investigate changes in spontaneous brain activity among patients with T2DM and to determine the relationship of these changes with cognitive impairment. T2DM patients (n = 29) and age-, sex-, and education-matched healthy control subjects (n = 27) were included in this study. Amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo) values were calculated to represent spontaneous brain activity. Brain volume and cognition were also evaluated among these participants. Compared with healthy control subjects, patients with T2DM had significantly decreased ALFF and ReHo values in the occipital lobe and postcentral gyrus. Patients performed worse on several cognitive tests; this impaired cognitive performance was correlated with decreased activity in the cuneus and lingual gyrus in the occipital lobe. Brain volume did not differ between the two groups. The abnormalities of spontaneous brain activity reflected by ALFF and ReHo measurements in the absence of structural changes in T2DM patients may provide insights into the neurological pathophysiology underlying diabetes-associated cognitive decline.
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Affiliation(s)
- Ying Cui
- Jiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, Medical School of Southeast University, Nanjing, China
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Xu J, Rees G, Yin X, Song C, Han Y, Ge H, Pang Z, Xu W, Tang Y, Friston K, Liu S. Spontaneous neuronal activity predicts intersubject variations in executive control of attention. Neuroscience 2014; 263:181-92. [PMID: 24447598 DOI: 10.1016/j.neuroscience.2014.01.020] [Citation(s) in RCA: 42] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2013] [Revised: 01/10/2014] [Accepted: 01/10/2014] [Indexed: 01/27/2023]
Abstract
Executive control of attention regulates our thoughts, emotion and behavior. Individual differences in executive control are associated with task-related differences in brain activity. But it is unknown whether attentional differences depend on endogenous (resting state) brain activity and to what extent regional fluctuations and functional connectivity contribute to individual variations in executive control processing. Here, we explored the potential contribution of intrinsic brain activity to executive control by using resting-state functional magnetic resonance imaging (fMRI). Using the amplitude of low-frequency fluctuations (ALFF) as an index of spontaneous brain activity, we found that ALFF in the right precuneus (PCUN) and the medial part of left superior frontal gyrus (msFC) was significantly correlated with the efficiency of executive control processing. Crucially, the strengths of functional connectivity between the right PCUN/left msFC and distributed brain regions, including the left fusiform gyrus, right inferior frontal gyrus, left superior frontal gyrus and right precentral gyrus, were correlated with individual differences in executive performance. Together, the ALFF and functional connectivity accounted for 67% of the variability in behavioral performance. Moreover, the strength of functional connectivity between specific regions could predict more individual variability in executive control performance than regionally specific fluctuations. In conclusion, our findings suggest that spontaneous brain activity may reflect or underpin executive control of attention. It will provide new insights into the origins of inter-individual variability in human executive control processing.
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Affiliation(s)
- J Xu
- Research Center for Sectional and Imaging Anatomy, Shandong University School of Medicine, Jinan, Shandong, China; UCL Institute of Cognitive Neuroscience, London, United Kingdom; Wellcome Trust Centre for Neuroimaging, University College London (UCL) Institute of Neurology, London, United Kingdom
| | - G Rees
- UCL Institute of Cognitive Neuroscience, London, United Kingdom; Wellcome Trust Centre for Neuroimaging, University College London (UCL) Institute of Neurology, London, United Kingdom
| | - X Yin
- Research Center for Sectional and Imaging Anatomy, Shandong University School of Medicine, Jinan, Shandong, China
| | - C Song
- UCL Institute of Cognitive Neuroscience, London, United Kingdom
| | - Y Han
- Department of Radiology, Affiliated Hospital of Medical College, Qingdao University, Qingdao, Shandong, China
| | - H Ge
- Research Center for Sectional and Imaging Anatomy, Shandong University School of Medicine, Jinan, Shandong, China
| | - Z Pang
- Department of Epidemiology, Qingdao Municipal Central for Disease Control and Prevention, Qingdao, Shandong, China
| | - W Xu
- Department of Radiology, Affiliated Hospital of Medical College, Qingdao University, Qingdao, Shandong, China
| | - Y Tang
- Research Center for Sectional and Imaging Anatomy, Shandong University School of Medicine, Jinan, Shandong, China
| | - K Friston
- Wellcome Trust Centre for Neuroimaging, University College London (UCL) Institute of Neurology, London, United Kingdom
| | - S Liu
- Research Center for Sectional and Imaging Anatomy, Shandong University School of Medicine, Jinan, Shandong, China.
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32
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Altered baseline brain activity in type 2 diabetes: a resting-state fMRI study. Psychoneuroendocrinology 2013; 38:2493-501. [PMID: 23786881 DOI: 10.1016/j.psyneuen.2013.05.012] [Citation(s) in RCA: 109] [Impact Index Per Article: 9.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/19/2013] [Revised: 05/06/2013] [Accepted: 05/20/2013] [Indexed: 01/08/2023]
Abstract
PURPOSE This study aims to investigate whether altered baseline brain activity exists in type 2 diabetes mellitus (T2DM) patients using resting-state functional magnetic resonance imaging (rs-fMRI) and whether abnormal neural activity in the middle temporal gyrus (MTG) is correlated with cognitive function. METHODS T2DM patients (n=28) were compared with nondiabetic age-, sex-, and education-matched control subjects (n=29) using rs-fMRI. We computed the amplitude of low-frequency fluctuations (ALFF) of fMRI signals to measure spontaneous neuronal activity and detect the relationship between rs-fMRI information and clinical data. RESULTS Compared with healthy controls, T2DM patients had significantly decreased ALFF values in the bilateral middle temporal gyrus, left fusiform gyrus, left middle occipital gyrus, right inferior occipital gyrus; and increased ALFF values in both the bilateral cerebellum posterior lobe and right cerebellum culmen. Moreover, we found an inverse correlation between the ALFF values in the MTG and both the HbA1c (r=-0.451, p=0.016) and the score of Trail Making Test-B (r=-0.420, p=0.026) in the patient group. On the other hand, C-peptide level and pancreatic β-cell function had a positive correlation (r=0.429, p=0.023; r=0.453, p=0.016, respectively) with the ALFF value in the middle temporal gyrus. CONCLUSION The present study confirms that T2DM patients have altered ALFF in many brain regions, which is associated with poor neurocognitive performances, severity of consistent hyperglycemic state and impaired β-cell function. ALFF disturbance in MTG may play a central role in cognitive decline associated with T2DM and serve as reference for future clinical diagnosis.
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Xue T, Yuan K, Cheng P, Zhao L, Zhao L, Yu D, Dong T, von Deneen KM, Gong Q, Qin W, Tian J. Alterations of regional spontaneous neuronal activity and corresponding brain circuit changes during resting state in migraine without aura. NMR IN BIOMEDICINE 2013; 26:1051-1058. [PMID: 23348909 DOI: 10.1002/nbm.2917] [Citation(s) in RCA: 87] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/28/2012] [Revised: 12/02/2012] [Accepted: 12/09/2012] [Indexed: 06/01/2023]
Abstract
Although previous resting-state studies have reported abnormal functional cerebral changes in patients with migraine without aura (MwoA), few have focused on alterations in both regional spontaneous neuronal activity and corresponding brain circuits in MwoA patients during rest. Eighteen MwoA patients and 18 age- and gender-matched healthy controls (HC) were recruited in the current study. Baseline cerebral alterations were investigated using amplitude of low-frequency fluctuation (ALFF) and region of interest (ROI)-based functional connectivity (FC) analyses. Compared with HC, MwoA patients showed decreased ALFF values in the left rostral anterior cingulate cortex (rACC) and bilateral prefrontal cortex (PFC) as well as increased ALFF values in the right thalamus. FC analysis also revealed abnormal FCs associated with these ROIs. In addition, ALFF values of the left rACC correlated with duration of disease in MwoA. Our findings could lead to a better understanding of intrinsic functional architecture of baseline brain activity in MwoA, providing both regional and brain circuit spontaneous neuronal activity properties.
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Affiliation(s)
- Ting Xue
- Life Sciences Research Center, School of Life Sciences and Technology, Xidian University, Xi'an, Shaanxi, 710071, China
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Lv XF, Ye M, Han LJ, Zhang XL, Cai PQ, Jiang GH, Qiu YW, Qiu SJ, Wu YP, Liu K, Liu ZY, Wu PH, Xie CM. Abnormal baseline brain activity in patients with HBV-related cirrhosis without overt hepatic encephalopathy revealed by resting-state functional MRI. Metab Brain Dis 2013; 28:485-92. [PMID: 23836055 DOI: 10.1007/s11011-013-9420-4] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2013] [Accepted: 06/26/2013] [Indexed: 12/11/2022]
Abstract
Neurocognitive dysfunction of varying degrees is common in patients with hepatitis B virus-related cirrhosis (HBV-RC) without overt hepatic encephalopathy (OHE). However, the neurobiological mechanisms underlying these dysfunctions are not well understood. We sought to identify changes in the neural activity of patients with HBV-RC without OHE in the resting state by using the amplitude of low-frequency fluctuation (ALFF) method and to determine whether these changes were related to impaired cognition. Resting-state functional MRI data from 30 patients with HBV-RC and 30 healthy controls matched for age, sex, and years of education were compared to determine any differences in the ALFF between the two groups. Cognition was measured with the psychometric hepatic encephalopathy score (PHES), and the relationship between these scores and ALFF variation was assessed. Compared with controls, patients showed widespread lower standardized ALFF (mALFF) values in visual association areas (bilateral lingual gyrus, middle occipital gyrus, and left inferior temporal gyrus), motor-related areas (bilateral precentral gyrus, paracentral lobule, and right postcentral gyrus), and the default mode network (bilateral cuneus/precuneus and inferior parietal lobule). Higher mALFF values were found in the bilateral orbital gyrus/rectal gyrus. In patients, mALFF values were significantly positive correlated with the PHES in the right middle occipital gyrus and bilateral precentral gyrus. Our findings of resting-state abnormalities in patients with HBV-RC without OHE suggest that neurocognitive dysfunction in patients with HBV-RC without OHE may be caused by abnormal neural activity in multiple brain regions.
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Affiliation(s)
- Xiao-Fei Lv
- State Key Laboratory of Oncology in South China
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Mapping metabolic brain activity in three models of hepatic encephalopathy. Int J Hypertens 2013; 2013:390872. [PMID: 23573412 PMCID: PMC3612461 DOI: 10.1155/2013/390872] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2012] [Accepted: 02/19/2013] [Indexed: 11/17/2022] Open
Abstract
Cirrhosis is a common disease in Western countries. Liver failure, hyperammonemia, and portal hypertension are the main factors that contribute to human cirrhosis that frequently leads to a neuropsychiatric disorder known as hepatic encephalopathy (HE). In this study, we examined the differential contribution of these leading factors to the oxidative metabolism of diverse brain limbic system regions frequently involved in memory process by histochemical labelling of cytochrome oxidase (COx). We have analyzed cortical structures such as the infralimbic and prelimbic cotices, subcortical structures such as hippocampus and ventral striatum, at thalamic level like the anterodorsal, anteroventral, and mediodorsal thalamus, and, finally, the hypothalamus, where the mammillary nuclei (medial and lateral) were measured. The severest alteration is found in the model that mimics intoxication by ammonia, followed by the thioacetamide-treated group and the portal hypertension group. No changes were found at the mammillary bodies for any of the experimental groups.
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Qi R, Zhang LJ, Zhong J, Zhang Z, Ni L, Zheng G, Lu GM. Disrupted thalamic resting-state functional connectivity in patients with minimal hepatic encephalopathy. Eur J Radiol 2013; 82:850-6. [PMID: 23332976 DOI: 10.1016/j.ejrad.2012.12.016] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2012] [Revised: 11/29/2012] [Accepted: 12/21/2012] [Indexed: 01/02/2023]
Abstract
BACKGROUND AND PURPOSE Little is known about the role of thalamus in the pathophysiology of minimal hepatic encephalopathy (MHE). The purpose of this study was to investigate whether the thalamic functional connectivity was disrupted in cirrhotic patients with MHE by using resting-state functional magnetic resonance imaging (rs-fMRI). MATERIALS AND METHODS Twenty seven MHE patients and twenty seven age- and gender- matched healthy controls participated in the rs-fMRI scans. The functional connectivity of 11 thalamic nuclei were characterized by using a standard seed-based whole-brain correlation method and compared between MHE patients and healthy controls. Pearson correlation analysis was performed between the thalamic functional connectivity and venous blood ammonia levels/neuropsychological tests scores of patients. RESULTS The ventral anterior nucleus (VAN) and the ventral posterior medial nucleus (VPMN) in each side of thalamus showed abnormal functional connectivities in MHE. Compared with healthy controls, MHE patients demonstrated significant decreased functional connectivity between the right/left VAN and the bilateral putamen/pallidum, inferior frontal gyri, insula, supplementary motor area, right middle frontal gyrus, medial frontal gyrus. In addition, MHE patients showed significantly decreased functional connectivity with the right/left VPMN in the bilateral middle temporal gyri (MTG), temporal lobe, and right superior temporal gyrus. The venous blood ammonia levels of MHE patients negatively correlated with the functional connectivity between the VAN and the insula. Number connecting test scores showed negative correlation with the functional connectivity between the VAN and the insula, and between the VPMN and the MTG. CONCLUSION MHE patients had disrupted thalamic functional connectivity, which mainly located in the bilateral ventral anterior nuclei and ventral posterior medial nuclei. The decreased connectivity between thalamus and many cortices, and basal ganglia indicated reduced integrity of thalamic RSN in MHE.
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Affiliation(s)
- Rongfeng Qi
- Department of Medical Imaging, Jinling Hospital, Clinical School of Medical College, Nanjing University, Nanjing 210002, China
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Dynamic changes of intrinsic brain activity in cirrhotic patients after transjugular intrahepatic portosystemic shunt: a resting-state FMRI study. PLoS One 2012; 7:e46681. [PMID: 23056400 PMCID: PMC3462766 DOI: 10.1371/journal.pone.0046681] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2012] [Accepted: 09/02/2012] [Indexed: 02/06/2023] Open
Abstract
PURPOSE The majority of cirrhotic patients who underwent transjugular intrahepatic portosystemic shunt (TIPS) experienced the first post-TIPS hepatic encephalopathy (HE) episode within the first three months after TIPS insertion. However, so far, little is known about the exact neuro-pathophysiological mechanism of TIPS's effects on brain function. We aimed to investigate the dynamics of brain function alteration of post-TIPS patients using resting-state functional MRI (rs-fMRI). MATERIALS AND METHODS Sixteen cirrhotic patients who were scheduled for TIPS and 16 healthy controls were included in the rs-fMRI scans. Ten patients repeated the MRI study in a median 8-day follow-up interval following TIPS and seven in a median 3-month follow-up. The amplitude of low frequency fluctuation (ALFF), an index reflecting the spontaneous brain activity, was compared between patients before TIPS and healthy controls as well as patients pre- and post-TIPS. RESULTS Compared with healthy controls, patients showed decreased ALFF in frontal and parietal regions and increased ALFF in insula. Patients who underwent the median 8-day follow-up fMRI examinations showed decreased ALFF in posterior cingulate cortex (PCC)/precuneus and increased ALFF in anterior cingulate cortex (ACC). Of 10 patients in this group, 9 had moderate to large increase rate of ALFF value (>20%, mean 49.19%) in ACC, while only one patient with the smallest increase rate of ALFF value (<10%) in ACC, who experienced three episodes of overt HE during the 3-month follow-up. In the median 3-month follow up observation, patients displayed persistently decreased ALFF in PCC, ACC and medial prefrontal cortex (MPFC), while no increased regional ALFF was observed. CONCLUSION TIPS insertion alters cirrhotic patients' ALFF patterns in the resting state, which may imply different short-term and moderate-term effects on cirrhotic patients, i.e., both impairment and compensatory mechanism of brain functions in peri-TIPS and continuous impairment of brain function 3 months following TIPS.
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