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APOE ε4 is risk for cognitive decline even in normal aging, but its effect on the whole-brain functional connectivity (FC) among time in young adults remain elusive. This study aimed to validate the time-by-APOE ε4 interaction on brain FC of this specific population. Longitudinal changes in neuropsychological assessments and resting-state functional magnetic resonance imaging in 26 ε4 carriers and 26 matched non-ε4 carriers were measured for about 3 years. Whole-brain FC was calculated, and a full factorial design was used to compare the difference among groups. Two-sample t test was used for post-hoc analysis. Pearson's correlation analysis was conducted to investigate the relationships between FC and cognitive tests. Of 26 specially appointed ROIs, left superior temporal gyrus (TG) was most sensitive to the effect of time-by-gene interaction. Specifically, the alteration of FC was distributed between the left TG and right TG with GRF correction (voxel-P < 0.001, cluster-P < 0.05), and decreased in ε4 carriers while increased in non-ε4. The main effect of gene showed ε4 carriers has lower FC between left TG and right middle frontal gyrus as compared with non-ε4 both at baseline and follow-up study; ε4 carriers has lower FC between left TG and right supramarginal as compared with non-ε4 at baseline, but no difference in follow-up study. The time-by-APOE ε4 interaction on brain FC was demonstrated at a young age, and left TG was the earliest affected brain regions. The young adult ε4 carriers experience decreased FC among time in the absence overt clinical symptoms., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Previous studies have found abnormal structural and functional brain alterations in breast cancer survivors undergoing chemotherapy. However, the network-level brain changes following chemotherapy remain unknown. The purpose of this study was to investigate the dynamic changes of large-scale within- and between-network functional connectivity in chemotherapy-treated breast cancer patients., Methods: Seventeen breast cancer patients were evaluated with resting state functional MRI (rs-fMRI), neuropsychological tests and blood examination before postoperative chemotherapy (t0), one week after completing chemotherapy (t1) and six months after completing chemotherapy (t2). Nineteen age- and education level-matched healthy controls (HC) were also recruited. Independent components analysis (ICA) was performed to assess network component using rs-fMRI data. The functional network changes were then correlated with cognitive assessment scores and blood biochemical indexes., Results: One-way repeated measures ANOVA revealed significantly changed within-network functional connectivity in the anterior and posterior default mode network (ADMN and PDMN), left and right frontoparietal network (LFPN and RFPN), visual network and self-referential network. Post-hoc test showed that decreased within-network functional connectivity in ADMN, PDMN, LFPN, RFPN, SRN and central network one week after chemotherapy and increased six months after chemotherapy (all P < 0.05). As for the between-network functional connectivity, the PDMN- sensorimotor network connectivity showed the same tendency. Most of these within- and between-network functional connectivity changes were negatively associated with blood biochemical indexes and cognitive assessment scores (all P < 0.05)., Conclusions: These results indicated that chemotherapy may induce widespread abnormalities in resting state networks, which may serve as a potential biomarker of chemotherapy related cognitive impairment, providing insights for further functional recovery treatment.

Background: FK506 binding protein 5 (FKBP5) rs1360780 polymorphism has been identified as a molecular genetic marker associated with the dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis. The impact of FKBP5 rs1360780 on the large-scale brain network connectivity in healthy adults is still unknown., Methods: 479 healthy volunteers (age: 20-80years) completed MRI scans, neuropsychological assessments and blood analysis.All subjects were divided into CC, CT and TT genotypes. Within and between network connectivities (10 sub-networks) were calculated using resting state functional MRI (rs-fMRI) data. The genetic effects and gene-gender/age interaction on large-scale network connectivity were explored., Results: Compared with CC and CT groups, TT group showed increased intra-connectivity in default mode network (DMN) and increased inter-connectivity mainly distributed among the network of DMN, salience network (SAN), dorsal attention network (DAN), ventral attention network (VAN), subcortical network (SUB), and visual network (VIS). Gene-by-gender and gene-by-age interaction were found in inter-connectivity of DAN to VIS and DMN to FPN, respectively. The altered connectivities correlated with anxiety status test score., Limitations: Plasma adrenocorticotropic hormone (ACTH) or cortisol were not measured,or else, we could estimate the hypothalamic-pituitary-adrenal (HPA) axis activity which may strengthen our results., Conclusions: FKBP5 rs1360780 modulates the large-scale brain network connectivity in healthy adults. TT carriers showed the increased intra- and inter-connectivities mainly distributed among the network of DMN, SAN, DAN, VAN, SUB and VIS., Competing Interests: Declaration of Competing Interest We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of, the manuscript entitled. All authors declare that they have no competing interests., (Copyright © 2020. Published by Elsevier B.V.)

Background: Functional dyspepsia (FD) subtypes may differ in terms of pathophysiology, but the underlying mechanisms remain poorly understood., Purpose: To explore spontaneous brain activity in two main FD subtypes, namely epigastric pain syndrome (EPS) and postprandial distress syndrome (PDS), using the amplitude of low-frequency fluctuation (ALFF)., Material and Methods: Thirty-one FD patients (18 EPS and 13 PDS) and 22 matched healthy controls (HC) underwent resting-state functional MRI scanning. Spontaneous brain activity was evaluated by measuring the ALFF and then compared among the EPS, PDS, and HC groups with ANOVA test. Pearson correlation analysis was performed between the ALFF values and clinical indices., Results: Compared to healthy controls, both EPS and PDS patients had increased ALFF in the bilateral precentral/postcentral gyri, insula, and thalami. Furthermore, only the EPS patients displayed increased ALFF in the right middle and inferior frontal gyri, and only the PDS patients showed increased ALFF in the left posterior cingulate cortex (PCC). The ALFF values in the left thalamus were positively correlated with the sleep disturbance in EPS patients, and the ALFF values in the right precentral/postcentral gyri showed a positive correlation with the symptom score in PDS patients., Conclusion: EPS and PDS had similarities of higher spontaneous brain activity in the primary motor/sensory areas and homeostatic-afferent network regions, and differences in the prefrontal region and PCC, providing evidence to suggest the similarity and diversity of pathophysiology in FD subtypes.

The Chinese Imaging Genetics (CHIMGEN) study establishes the largest Chinese neuroimaging genetics cohort and aims to identify genetic and environmental factors and their interactions that are associated with neuroimaging and behavioral phenotypes. This study prospectively collected genomic, neuroimaging, environmental, and behavioral data from more than 7000 healthy Chinese Han participants aged 18-30 years. As a pioneer of large-sample neuroimaging genetics cohorts of non-Caucasian populations, this cohort can provide new insights into ethnic differences in genetic-neuroimaging associations by being compared with Caucasian cohorts. In addition to micro-environmental measurements, this study also collects hundreds of quantitative macro-environmental measurements from remote sensing and national survey databases based on the locations of each participant from birth to present, which will facilitate discoveries of new environmental factors associated with neuroimaging phenotypes. With lifespan environmental measurements, this study can also provide insights on the macro-environmental exposures that affect the human brain as well as their timing and mechanisms of action.

Chemotherapy related cognitive impairments are common in breast cancer patients undergoing chemotherapy. These cognitive dysfunctions are mainly attributable to chemotherapy related brain structural and functional alterations. Multimodality magnetic resonance imaging (MRI) can reveal brain gray matter volume loss, white matter microstructural disruption, reduced gray matter density, impaired cerebral blood flow and brain structural and functional connection networks at both local and global levels. This review outlines the potential applications of multimodality MR imaging techniques in chemotherapy induced cognitive deficit in breast cancer survivors and provides future research perspective in this field.

The gut-brain axis in end-stage renal disease (ESRD) is attracting more and more attention. However, the mechanism of gut-brain axis based cognitive disorders in ESRD patients remains unclear. The purpose of this study was to investigate the linkages between the gut microbiota, inflammatory cytokines, brain default mode network (DMN) and cognitive function in ESRD patients. Methods: This prospective study enrolled 28 ESRD patients (13 males and 15 females, mean age of 44 ± 14 years) and 19 healthy controls (HCs) (12 males and 7 females, mean age of 44 ± 10 years). All subjects underwent stool microbiota analysis, blood inflammatory cytokines examination, brain MRI scans and cognitive assessments. Resting state functional MRI (rs-fMRI) data were used to construct DMN and graph theory was applied to characterize network topological properties. Two samples t-test was applied for the comparisons between ESRD and HCs. Correlation analysis and mediation analysis were conducted among factors with significant group differences. Results: ESRD patients displayed gut microbiota alterations, increased systemic inflammation and worse cognitive performance compared to HCs (all p < 0.05). Graph analysis revealed disrupted DMN topological organization, aberrant nodal centralities and functional connectivities (FCs) in ESRD patients relative to HCs (all p < 0.05, FDR corrected). Significant correlations were found between gut microbiota, inflammatory cytokines, DMN network measures and cognitive assessments. Mediation analysis found that gut microbiota alteration impaired DMN connectivity by increasing systemic inflammation. Conclusion: The present study first revealed gut microbiota alterations, systemic inflammation, DMN dissociation and cognitive dysfunction in ESRD patients simultaneously and further illuminated their inner relationship., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Alzheimer's disease (AD) is a progressive neurodegenerative disease that develops insidiously and causes dementia finally. There are also clinical complications in advanced dementia, such as eating problems, infections, which will lead to the decline of patients' life quality, and the rising cost of care for AD to our society. AD will be important public health challenge. Early detection of AD may be a key issue to prevent, delay, and stop the disease. Gut microbiome and neuroinflammation are closely related with nervous system diseases, although the specific mechanism is not clear. This review introduces the relationship between neuroinflammation, gut microbiome, and AD.

Neuroinflammation has an important influence in pathogenesis of acute hepatic encephalopathy (AHE). 11 C-PK11195 and 18 F-DPA-714 targeted to translocator protein (TSPO) have potential application in positron emission tomography (PET) as a molecular probe of neuroinflammation. The aim of this study was to compare these two radiotracers and their effectiveness in detecting neuroinflammation for the imaging of AHE rat models. Furthermore, using the new radiotracer 18 F-DPA-714, we analyzed the effectiveness of therapeutic treatment for neuroinflammation in AHE. First, we performed a comparative study of 11 C-PK1195 and 18 F-DPA-714 PET to image neuroinflammation in AHE rats induced by thioacetamide. Twenty-four rats were divided into either control group (n = 12) or AHE group (n = 12). Next, each group was subdivided depending on the radiotracer used during PET imaging (n = 6). Radiotracer uptake values encompassing the whole brain were compared. Lastly, we used the optimized tracer to monitor anti-neuroinflammation effects in AHE-induced rats. Forty-six rats were divided into four groups: [normal saline (NS) group (n = 13), minocycline (MINO) group (n = 11), dexamethasone (DEXA) group (n = 11), MINO+DEXA group (n = 11)]. 18 F-DPA-714 PET was performed and the uptake values were calculated. The rotarod test, biochemical indices, and histopathological examinations were quantitatively measured and compared. AHE rats showed reduced motor ability, elevated ammonia levels, and higher liver function indices (all P < 0.05) with unchanged inflammatory factors (all P > 0.05), compared to control group. Both 11 C-PK11195 and 18 F-DPA-714 PET can detect neuroinflammation of AHE rats. Behavioral studies showed that MINO and/or DEXA improved the motor ability in AHE rats (P < 0.05); however, no differences were found for liver function or inflammatory markers among the four groups (all P > 0.05). The average uptake values of whole brain and multiple brain areas in the MINO+DEXA group were lower compared to all other groups (all P < 0.05), which was demonstrated by CD11b stains of microglia. Our results show that both 11 C-PK11195 and 18 F-DPA-714 PET can detect neuroinflammation in AHE-induced rat models. Additionally, the combined use of minocycline and dexamethasone can effectively inhibit neuroinflammation in AHE-induced rats, which can be sensitively monitored by 18 F-DPA-714 PET.

Hepatic encephalopathy (HE), as a complication of cirrhosis, is a serious brain disease, which may lead to death. Accurate diagnosis of HE and its intermediate stage, i.e., minimal HE (MHE), is very important for possibly early diagnosis and treatment. Brain connectivity network, as a simple representation of brain interaction, has been widely used for the brain disease (e.g., HE and MHE) analysis. However, those studies mainly focus on finding disease-related abnormal connectivity between brain regions, although a large number of studies have indicated that some brain diseases are usually related to local structure of brain connectivity network (i.e., subnetwork), rather than solely on some single brain regions or connectivities. Also, mining such disease-related subnetwork is a challenging task because of the complexity of brain network. To address this problem, we proposed a novel frequent-subnetwork-based method to mine disease-related subnetworks for MHE classification. Specifically, we first mine frequent subnetworks from both groups, i.e., MHE patients and non-HE (NHE) patients, respectively. Then we used the graph-kernel based method to select the most discriminative subnetworks for subsequent classification. We evaluate our proposed method on a MHE dataset with 77 cirrhosis patients, including 38 MHE patients and 39 NHE patients. The results demonstrate that our proposed method can not only obtain the improved classification performance in comparison with state-of-the-art network-based methods, but also identify disease-related subnetworks which can help us better understand the pathology of the brain diseases.

Background and Objectives: Cognition in ESRD may be improved by kidney transplantation, but mechanisms are unclear. We explored patterns of resting-state networks with resting-state functional magnetic resonance imaging among patients with ESRD before and after kidney transplantation., Design, Setting, Participants, & Measurements: Thirty-seven patients with ESRD scheduled for kidney transplantation and 22 age-, sex-, and education-matched healthy subjects underwent resting-state functional magnetic resonance imaging. Patients were imaged before and 1 and 6 months after kidney transplantation. Functional connectivity of seven resting-state subnetworks was evaluated: default mode network, dorsal attention network, central executive network, self-referential network, sensorimotor network, visual network, and auditory network. Mixed effects models tested associations of ESRD, kidney transplantation, and neuropsychological measurements with functional connectivity., Results: Compared with controls, pretransplant patients showed abnormal functional connectivity in six subnetworks. Compared with pretransplant patients, increased functional connectivity was observed in the default mode network, the dorsal attention network, the central executive network, the sensorimotor network, the auditory network, and the visual network 1 and 6 months after kidney transplantation ( P =0.01). Six months after kidney transplantation, no significant difference in functional connectivity was observed for the dorsal attention network, the central executive network, the auditory network, or the visual network between patients and controls. Default mode network and sensorimotor network remained significantly different from those in controls when assessed 6 months after kidney transplantation. A relationship between functional connectivity and neuropsychological measurements was found in specific brain regions of some brain networks., Conclusions: The recovery patterns of resting-state subnetworks vary after kidney transplantation. The dorsal attention network, the central executive network, the auditory network, and the visual network recovered to normal levels, whereas the default mode network and the sensorimotor network did not recover completely 6 months after kidney transplantation. Neural resting-state functional connectivity was lower among patients with ESRD compared with control subjects, but it significantly improved with kidney transplantation. Resting-state subnetworks exhibited variable recovery, in some cases to levels that were no longer significantly different from those of normal controls., (Copyright © 2018 by the American Society of Nephrology.)

Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder resulting from a dysregulation of the brain-gut axis. However, its exact neural substrate still remains unclear. This study investigated the changes of intrinsic whole brain functional connectivity pattern in IBS using functional connectivity density (FCD). We acquired resting-state functional magnetic resonance imaging (rs-fMRI) data from thirty-two IBS patients and thirty-two healthy controls. Functional connectivity density, a data-driven algorithm, was used to compute the long-range and short-range FCD values for each voxel in the brain of each subject, implying the amount of distant and local functional connections of cortical hubs. The FCD maps were compared between IBS patients and healthy controls. Pearson correlations analysis was also performed between abnormal FCD values and clinical/psychometric scores in patients. Compared to healthy controls, IBS patients showed concurrently decreased long- and short-range FCD in bilateral anterior midcingulate cortices (aMCC) and inferior parietal lobules (IPL), and decreased long-range FCD in right anterior insula, and decreased short-range FCD in bilateral prefrontal cortices, subgenual anterior cingulate cortices and caudates. IBS patients also had concurrently increased long- and short-range FCD mainly in primary sensorimotor cortices, as well as increased long-range FCD in right supplementary motor area and increased short-range FCD in occipital lobe. In addition, some regions with altered FCD showed abnormal functional connectivity in brain regions involved in pain matrix of IBS patients. Furthermore, the abnormal FCD values in right anterior insula and left caudate showed significant correlation with severity of symptoms and disease duration of IBS patients respectively. In conclusion, patients with IBS have widely disrupted FCD, which decreased in brain regions involved in homeostatic afferent network, emotional arouse, and cognitive regulation, while increased in regions associated with sensorimotor modulation. And the observed functional connectivity alterations unveiled complicated working patterns of pain matrix in IBS patients. This study may provide us with new insight into the underlying brain network topology of IBS.

In this study, we seek to explore alterations of coupling between functional connectivity density (FCD) and amplitude of low frequency fluctuation (ALFF) in systemic lupus erythematosus patients without overt neuropsychiatric symptoms (non-NPSLE) by using resting-state functional MR imaging. This study was approved by the institutional ethical review board, and all participants signed written informed consent prior to the study. Twenty six non-NPSLE patients and 35 matched healthy controls underwent resting-state functional MR imaging. The correlation analysis between FCD and ALFF was conducted to assess the imaging coupling. Pearson correlation analysis was performed to correlate imaging variables to clinical and neuropsychological data in non-NPSLE patients. According to the consistent alteration of FCD and ALFF, region of interests were identified including the right inferior temporal gyrus, bilateral hippocampus-parahippocampus (H-PH), left posterior cingulate cortex, superior parietal gyrus, postcentral gyrus, and bilateral precuneus. Across-voxel correlation analysis showed decreased coupling strengths in some brain regions. Correlations between FCD, ALFF, and coupling strength in H-PH and C3/C4/MoCA were found. The imaging coupling between FCD and ALFF was decreased in non-NPSLE patients, indicating brain function alteration in non-NPSLE patients, especially the abnormal coupling between FCD and ALFF of the hippocampus-parahippocampus might be an imaging biomarker of brain dysfunction in non-NPSLE patients.

Recent studies showed many cirrhosis patients may have diabetes mellitus (DM), however, the effect of DM on brain in cirrhotic patients is unclear. This study included 34 cirrhosis patients (17 with DM, 17 without DM) and 17 age-, sex-matched healthy controls. MRI examination and neuropsychological tests were performed. Fractional amplitude of low-frequency fluctuation (fALFF) and voxel-based morphometry algorithms were used to obtain fALFF values and gray matter volume, which were compared and correlated with clinical variables. In cirrhosis patients with and without DM, fALFF values were decreased in the left postcentral gyrus, right precentral gyrus, left supramarginal gyrus, bilateral lingual gyri and occipital lobe, while increased in the left orbital frontal gyrus. Gray matter volume was decreased in bilateral caudates and putamen, while increased in bilateral thalami. Compared with non-DM cirrhosis patients, DM cirrhosis patients showed decreased fALFF values in bilateral caudates and decreased gray matter volume in bilateral thalami. The blood glucose levels of cirrhosis patients showed negative correlations with fALFF values in bilateral caudates and gray matter volume in bilateral thalami. In conclusion, DM aggravates brain damage in cirrhosis patients. Thus, it is important to pay more attention to the management of DM in cirrhotic patients.

In this study, we used resting-state functional magnetic resonance imaging to explore the genetic effects of amyloid precursor protein (APP) or presenilins mutation and apolipoprotein E (APOE) ε4 on the default-mode network (DMN) in cognitively intact young adults (24.1 ± 2.5 years). Both the APP or presenilin-1/2 group and the APOE ε4 group had significantly lower DMN functional connectivity (FC) in the some brain regions like precuneus/middle cingulate cortices (PCu/MCC) than controls (AlphaSim corrected, P < 0.05). Only a lower FC tendency was demonstrated (control < APOE ε4 < APP or presenilin-1/2 group). Moreover, lower FC in PCu/MCC is correlated with some neuropsychological assessments such as similarity test in APOE ε4 group. These findings indicate that DMN FC alteration in APP or presenilin-1/2 or APOE ε4 subjects is prior to the occurrence of neurological alterations and clinical symptoms, and DMN FC might be a valuable biomarker to detect genetic risk in the preclinical stage.

This resting-state functional magnetic resonance imaging (rs-fMRI) study investigated intrinsic brain abnormalities in irritable bowel syndrome (IBS) and effect of anxiety and depression. Thirty IBS patients and 31 matched healthy controls underwent rs-fMRI scanning. Regional brain activity was evaluated by measuring the amplitude of low-frequency fluctuation (ALFF) and compared between IBS patients and healthy controls with a two-sample t-test. Areas with abnormal ALFF were further used as seeds in subsequent inter-regional functional connectivity (FC) analysis. Statistical analyses were also performed by including anxiety and depression as covariates to evaluate their effect. Compared to healthy controls, IBS patients showed decreased ALFF in several core default mode network regions (medial prefrontal cortex [MPFC], posterior cingulate cortex [PCC], bilateral inferior parietal cortices [IPC]), and in middle frontal cortex, right orbital part of the superior frontal gyrus (ORBsup), dorsal anterior cingulate cortex (dACC), and ventral anterior cingulated cortex (vACC), while they showed increased ALFF in bilateral posterior insula and cuneus. In addition, IBS patients revealed decreased inter-regional positive FC between MPFC and right ORBsup, between vACC and PCC, as well as decreased negative FC between MPFC and left posterior insula, while they showed increased negative FC between MPFC and cuneus. The inclusion of anxiety and depression as covariates abolished ALFF differences in dACC and vACC, but none of the FC differences., In Conclusion: IBS patients had disturbed intrinsic brain function. High levels of anxiety and depression in IBS patients could account for their decreased intrinsic brain activity in regions (the ACC) involved in affective processing.

Diabetes mellitus is a common metabolic disease which is associated with increasing risk for multiple cognitive declines. Alterations in brain functional connectivity are believed to be the mechanisms underlying the cognitive function impairments. During the past decade, resting-state functional magnetic resonance imaging (rs-fMRI) has been developed as a major tool to study brain functional connectivity in vivo. This paper briefly reviews the diabetes-associated cognitive impairment, analysis algorithms and clinical applications of rs-fMRI. We also provide future perspectives of rs-fMRI in diabetes.

We used arterial-spin labeling (ASL) MR imaging, a non-invasive technique to evaluate cerebral blood flow (CBF) changes in patients with end-stage renal disease (ESRD) undergoing peritoneal dialysis (PD) and hemodialysis (HD), and nondialysis ESRD patients compared with healthy cohort. Ninety seven ESRD patients including 32 PD patients (20 male, 12 female; mean age 33 ± 8 years), 33 HD patients (22 male, 11 female; mean age 33 ± 8 years) and 32 nondialysis patients (20 male, 12 female; mean age 35 ± 7 years) and 31 age- and gender-matched healthy controls (20 male, 11 female; mean age 32 ± 8 years) were included in this study. All subjects underwent ASL MR imaging, neuropsychologic tests, and ESRD patients underwent laboratory testing. CBF values were compared among PD, HD, nondialysis patients and control groups. Correlation analysis and multiple regression analysis were performed to investigate the association between CBF values and hemoglobin, neuropsychologic test results, serum creatinine, urea levels, disease duration, and dialysis duration. Elevated CBFs of whole brain region, gray matter, and white matter were found in all ESRD patient groups compared with healthy controls (all P < 0.001). However, compared with non-dialysis ESRD patients, both PD and HD patients had widespread regional CBF decline mainly in bilateral frontal and anterior cingulate cortices. There were no differences for CBF between PD and HD patient groups. Negative correlations were observed between mean CBFs of whole brain region, gray matter, and white matter and the hemoglobin level in all ESRD patients. Multiple linear regression showed elevated CBF of multiple brain areas correlated with some neuropsychological tests in ESRD patients (all P < 0.001, AlphaSim corrected), but the association was not present or shrank after adjusting hemoglobin level. This study found that mean CBF was predominantly increased in patients with ESRD, which correlated with their hemoglobin level and neurocognitive disorders. There were no differences of CBF change and cognitive function between PD and HD ESRD patients with long-term treatment. The degree of anemia may be a predominant risk factor for cognitive impairment in these ESRD patients.

Objectives: To noninvasively assess global cerebral blood flow (CBF), oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO2) in young adults with end-stage renal disease (ESRD)., Methods: Thirty-six patients and 38 healthy volunteers were included and took part in MR examinations, blood and neuropsychological tests. CBF and OEF were measured by phase-contrast and T2-relaxation-under-spin-tagging MRI techniques, respectively. CMRO2 was computed from CBF, OEF and hematocrit according to Fick's principle. Correlations were performed between MR measurements, blood biochemistry measurements and neuropsychological test scores., Results: Compared with controls, ESRD patients had elevated CBF (72.9 ± 12.5 vs. 63.8 ± 8.5 ml min(-1) 100 g(-1), P < 0.001), elevated OEF (47.2 ± 10.2 vs. 35.8 ± 5.4 %, P < 0.001), but unaffected CMRO2 (199.5 ± 36.4 vs. 193.8 ± 28.6 μmol O2 min(-1) 100 g(-1), P = 0.879). Hematocrit negatively correlated with CBF (r = -0.640, P < 0.001) and OEF (r = -0.701, P < 0.001), but not with CMRO2. Altered neuropsychological test scores of ESRD patients were associated with OEF and CBF, but not with CMRO2. There were weak relationships between eGFR and hematocrit (r = 0.308, P = 0.068) or CBF (r = 0.318, P = 0.059)., Conclusion: Our findings suggested that anaemic young adults with ESRD may afford higher CBF and OEF to maintain a normal CMRO2. Despite this compensatory process, however, cognitive function was still impaired and its severity was correlated with their CBF and OEF abnormality., Key Points: • Anaemic young adults with ESRD may afford higher CBF and OEF. • Anaemic young adults with ESRD maintain a normal CMRO 2 . • Cognitive function was still impaired in young ESRD adults. • The severity of cognitive dysfunction correlated with CBF and OEF changes.

Cerebral hyperperfusion, anemia and hypertension are common in patients with end-stage renal disease (ESRD). Young ESRD adults might afford a better hemodynamic tolerance; however, their cerebral vascular disorders are often overlooked. This phase-contrast MRI study investigated relationships between cerebral blood flow (CBF), anemia and hypertension in young adults undergoing hemodialysis (HD). Blood flows, velocities, and cross-sectional areas of bilateral internal carotid arteries and vertebral arteries were quantified on phase maps in 33 patients and 27 healthy controls. Cerebral oxygen delivery (COD) and vascular resistance were (CVR) were computed based on CBF, hemoglobin and mean arterial pressure (MAP). We found strong correlations among hemoglobin, MAP and CBF. Hemoglobin rather than MAP was directly related to CBF. COD was negatively related to MAP, while CVR was positively related to hemoglobin. The cross-sectional areas of arteries were increased which were directly associated with hemoglobin rather than MAP. HD patients were of elevated CBF, decreased COD and unchanged CVR. Although elevated CBF compensated anemia-induced hypoxia, COD of these patients was still lower. Anemia directly contributed to elevated CBF and hypertension affected CBF through anemia. Unaffected CVR of young patients probably indicated that they could maintain basic functions of cerebral circulation under multiple risk factors.

Purpose: To investigate structural and functional alterations of the default mode network (DMN) in the brain after renal transplantation in patients with end-stage renal disease by using diffusion-tensor imaging and resting-state functional MR imaging., Materials and Methods: This prospective study was approved by the local medical research ethics committee, and written informed consent was obtained. Twenty-one patients with end-stage renal disease (15 men, six women; mean age ± standard deviation, 32 years ± 9.5) who were scheduled to undergo renal transplantation and 21 healthy control subjects (15 men, six women; mean age, 31 years ± 6.5) were included. Diffusion-tensor imaging and resting-state functional MR imaging were performed in all subjects. Patients were imaged both before and 1 month after renal transplantation. Structural (mean diffusivity, fractional anisotropy, path length, and number of tracts derived from diffusion-tensor imaging tractography) and functional (temporal correlation coefficient derived from resting-state functional MR imaging) connectivity of the DMN were quantitatively compared with two-sample t tests or paired t tests. Intergroup correlation analysis was performed to compare structural or functional indexes and results of neuropsychological or blood biochemistry tests., Results: Mean diffusivity was decreased in the fiber bundles connecting the posterior cingulate cortex and the precuneus to the bilateral inferior parietal lobules in patients after renal transplantation compared with that in patients before transplantation (P < .05). Temporal correlation coefficients for patients after renal transplantation nearly reached the levels of those for control subjects (all, P > .05). The change in mean diffusivity of the fiber bundles connecting the posterior cingulate cortex and the precuneus to the right inferior parietal lobule positively correlated with the change in hematocrit levels (r = 0.522, P = .015), the change in temporal correlation coefficients between the posterior cingulate cortex or precuneus and left or right inferior parietal lobules correlated with changes in number connection test type A scores (r = -0.549, P = .010) and digit symbol test scores (r = 0.533, P = .013)., Conclusion: Functional connectivity changes in the DMN, which were associated with improved hematocrit levels and cognitive function, may recover earlier than structural connectivity changes do 1 month after renal transplantation., (© RSNA, 2015.)

Hepatic encephalopathy (HE) is a common complication after implantation of a transjugular intrahepatic portosystemic shunt (TIPS). Neuroimaging offers a variety of techniques for non-invasive evaluation of alterations in metabolism, as well as structural and functional changes of the brain in patients after TIPS implantation. In this article, we review the epidemiology and pathophysiology of post-TIPS HE. The potential of neuroimaging including positron emission tomography and multimodality magnetic resonance imaging to investigate the pathophysiology of post-TIPS HE is presented. We also give a perspective on the role of neuroimaging in this field.

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., Competing Interests: UJS is a consultant for and/or receives research support from Bayer, Bracco, GE Healthcare, Medrad, and Siemens Healthcare. All other authors had no conflict of interest to declare.

To investigate alterations of functional connectivity density (FCD) in patients with end-stage renal disease (ESRD) by using resting-state functional magnetic resonance imaging (rs-fMRI). Medical research ethics committee approval from Jinling hospital and written informed consent from each subject were obtained. Forty six patients with ESRD, consisting of 21 patients minimal nephrotic encephalopathy (MNE) and 25 non-nephro-encephalopathy (non-NE), as well as 23 healthy controls underwent rs-fMRI. Neuropsychological tests were performed in all subjects, while laboratory tests were performed in ESRD patients. A voxel-wise whole brain functional connectivity analysis was used to generate long- and short-range FCD maps. The maps among MNE, non-NE, and healthy controls groups were compared by using one-way analysis of variance tests. A multiple regression analysis was performed to evaluate the correlations between FCD and the variables of neuropsychological or laboratory tests. Compared with healthy controls, non-NE showed decreased long-range FCD mainly in parietal lobe. Moreover, MNE showed further decreased long-range FCD in bilateral middle prefrontal cortex (MPFC), anterior cingulate cortex (ACC) and right superior frontal gyrus. Meanwhile, non-NE showed decreased short-range FCD mainly in frontal cortex, and further reduction in bilateral ACC and right superior parietal gyrus in MNE. In addition, patients with ESRD mainly exhibited increased long-range FCD in left temporal lobe and caudate; and increased short-range FCD in bilateral orbitofrontal cortex and temporal gyri (P < 0.05, AlphaSim corrected). The number connection test type A score, serum creatinine, urea, and dialysis duration showed negative correlation with FCD in some brain regions, while the digital symbol test scores positively correlated with short-range FCD in left inferior parietal lobule (all P < 0.05, AlphaSim corrected). The prominent long- and short-range FCD reduction was found mainly in default mode network (DMN) and bilateral frontal and parietal lobes, while the progressively decreased long- and short-range FCD in ACC/MPFC and the long-range FCD in left superior frontal gyrus from non-NE to MNE was associated with cognition dysfunction in ESRD patients.

To investigate the effect of hemodialysis (HD) on cognitive dysfunction in patients with end-stage renal disease (ESRD) using resting-state functional MR imaging (rs-fMRI) with regional homogeneity (ReHo) and functional connectivity algorithms. The rs-fMRI data were acquired in 58 ESRD patients (HD patients, n = 32, 22 male and 10 female, mean age 36.5 ± 9.6 years; non-HD ESRD patients, n = 26, 16 male and 10 female, mean years of 35.6 ± 8.2) and 32 healthy controls (22 male and 10 female, mean years of 32.7 ± 8.8). A battery of neuropsychological and blood laboratory tests were prescribed. The Kendall's coefficient of concordance (KCC) was used to measure ReHo for each subject. The ReHo maps were compared by using ANOVA tests among HD, non-HD, and healthy control groups. Regions showing ReHo differences between HD and non-HD patients were defined as seeds for further functional connectivity analysis. A multiple regression analysis was performed to evaluate the relationships between ReHo index and neuropsychological tests, serum creatinine and urea levels, disease and dialysis duration. Compared with healthy controls, both HD patients and non-HD patients showed decreased ReHo in the multiple areas of bilateral frontal, parietal and temporal lobes. Compared with the non-HD, HD patients showed decreased ReHo mainly in default mode network (DMN) including bilateral precuneus, posterior cingulate cortex, inferior parietal lobe, right postcentral gyrus, bilateral superior temporal gyri, right supramarginal gyrus and right angular gyrus. Some reduced ReHo brain regions correlated with some neuropsychological tests, serum creatinine and urea levels, and dialysis duration. Brain regions with ReHo reduction showed increased region-to-region functional network in HD patients compared with non-HD patients. Widespreadly decreased ReHo values were found in both HD and non-HD patients. Lower ReHo values mainly in the DMN correlated with cognition impairments were observed in HD patients compared with non-HD patients, while increased functional connectivity was found between these brain regions. HD might have an adverse effect on the cognitive function in ESRD patients.

Purpose: To longitudinally evaluate long- and short-range functional connectivity density (FCD) alteration in cirrhotic patients one month after liver transplantation (LT) and their correlation with cognitive changes by using resting-state functional magnetic resonance imaging (rs-fMRI)., Methods: Twenty seven candidates awaiting LT and 24 age-, gender-, and education-matched healthy controls (HCs) were studied. All 27 patients and HCs performed rs-fMRI examinations. Of 27 cirrhotic patients, 13 patients received LT underwent the repeated rs-fMRI examinations one month after LT. Laboratory and psychometric tests were carried out. The long- and short-range FCD maps derived from degree centrality calculation were compared. Correlations between FCD alteration and laboratory/psychometric changes were evaluated as well., Results: In cirrhotic patients, most of the brain areas with altered long- and short-range FCD could reverse one month after LT, which was accompanied with cognitive and liver functional improvement. The reduced long-range FCD in right posterior cingulate cortex (PCC) and Left middle frontal gyrus (MFG), and reduced short-range FCD in right precuneus (PCu) persisted in the early period after LT. In addition, one month after LT, the post-LT group showed reduced long-range FCD in right rectus gyrus (REC) and left medial prefrontal cortex (MPFC), and reduced short-range FCD in left middle temporal gyrus (MTG), when compared with the pre-LT group. We found Δdigital symbol test (ΔDST) score positively correlated with long-range ΔFCD in right precentral gyrus (preCG) (r = 0.72, P < 0.01) and right supplementary motor area (SMA) (r = 0.59, P < 0.05)., Conclusion: LT results in favorable effect on cognitive function in cirrhotic patient, which can be reflected by FCD alteration. However, persistence of PCC/PCu functional connectivity disturbance one month after LT indicates complete cognitive function restoration may need a longer time., (Copyright © 2015. Published by Elsevier B.V.)

To investigate the short-term brain activity changes in cirrhotic patients with Liver transplantation (LT) using resting-state functional MRI (fMRI) with regional homogeneity (ReHo) method. Twenty-six cirrhotic patients as transplant candidates and 26 healthy controls were included in this study. The assessment was repeated for a sub-group of 12 patients 1 month after LT. ReHo values were calculated to evaluate spontaneous brain activity and whole brain voxel-wise analysis was carried to detect differences between groups. Correlation analyses were performed to explore the relationship between the change of ReHo with the change of clinical indexes pre- and post-LT. Compared to pre-LT, ReHo values increased in the bilateral inferior frontal gyrus (IFG), right inferior parietal lobule (IPL), right supplementary motor area (SMA), right STG and left middle frontal gyrus (MFG) in patients post-LT. Compared to controls, ReHo values of post-LT patients decreased in the right precuneus, right SMA and increased in bilateral temporal pole, left caudate, left MFG, and right STG. The changes of ReHo in the right SMA, STG and IFG were correlated with change of digit symbol test (DST) scores (P < 0.05 uncorrected). This study found that, at 1 month after LT, spontaneous brain activity of most brain regions with decreased ReHo in pre-LT was substantially improved and nearly normalized, while spontaneous brain activity of some brain regions with increased ReHo in pre-LT continuously increased. ReHo may provide information on the neural mechanisms of LT' effects on brain function.

Background: Susceptibility-weighted imaging (SWI) has been used to detect micro-bleeds and iron deposits in the brain. However, no reports have been published on the application of SWI in studying iron changes in the brain of cirrhotic patients., Purpose: To compare the susceptibility of different brain structures in cirrhotic patients with that in healthy controls and to evaluate susceptibility as a potential biomarker and correlate the measured susceptibility and cadaveric brain iron concentration for a variety of brain structures., Material and Methods: Forty-three cirrhotic patients (27 men, 16 women; mean age, 50 ± 9 years) and 34 age- and sex-matched healthy controls (22 men, 12 women; mean age, 47 ± 7 years) were included in this retrospective study. Susceptibility was measured in the frontal white matter, basal ganglia, midbrain, and dentate nucleus and compared with results gathered from two postmortem brain studies. Correlation between susceptibility and clinical biomarkers and neuropsychiatric tests scores was calculated., Results: In cirrhotic patients, the susceptibility of left frontal white matter, bilateral caudate head, and right substantia nigra was higher than that in healthy controls (P < 0.05). There was a positive correlation between susceptibility and iron concentration from one postmortem brain study (r = 0.835, P = 0.01) in eight deep grey matter structures and another in five brain structures (r = 0.900, P = 0.03). The susceptibility of right caudate head (r = 0.402) and left caudate head (r = 0.408) correlated with neuropsychological test scores (both P < 0.05)., Conclusion: Abnormal iron deposits occur in cirrhotic patients and abnormal susceptibility of some brain regions appears to reflect neurocognitive changes., (© The Foundation Acta Radiologica 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.)

Neurological or psychiatric abnormalities associated with hepatic encephalopathy (HE) range from subclinical findings to coma. HE is commonly accompanied with the accumulation of toxic substances in bloodstream. The toxicity effect of hyperammonemia on astrocyte, such as the alteration in neurotransmission, oxidative stress, astrocyte swelling, is considered as an important factor in the pathogenesis of HE. Besides, neuroinflammation has captured more attention in the process of HE, but the mechanism of neuroinflammation leading to HE remains unclear. Molecular imaging techniques such as positron emission tomography (PET) and magnetic resonance imaging (MRI) targeting activated microglia and/ or other mediators appear to be promising noninvasive approaches to assess HE. This review focuses on novel imaging and therapy strategies of neuroinflammation in HE.

Patients with end-stage renal disease (ESRD) suffer from a number of complex neurological complications including vascular damage and cognitive dysfunction. It is of great significance to detect the neurological complications and improve the prognosis of ESRD patients. Many new noninvasive MRI techniques have been steadily used for the diagnosis of occult central nervous system complications in ESRD patients. This gives an opportunity to understand the pathophysiological mechanisms of these neurological disorders. This paper is a review that presents the MRI findings of occult brain damage in ESRD patients, outlines the applications of advanced MRI techniques, and introduces a brief perspective in this study field.

To investigate white matter (WM) alterations and their correlation with cognition function in end-stage renal disease (ESRD) patients undergoing hemodialysis (HD) using diffusion tensor imaging (DTI) with tract-based spatial statistics (TBSS) approach. This prospective HIPAA-complaint study was approved by our institutional review board. Eighty HD ESRD patients and 80 sex- and age-matched healthy controls were included. Neuropsychological (NP) tests and laboratory tests, including serum creatinine and urea, were performed. DTI data were processed to obtain fractional anisotropy (FA) and mean diffusivity (MD) maps with TBSS. FA and MD difference between the 2 groups were compared. We also explored the associations of FA values in WM regions of lower FA with ages, NP tests, disease, and dialysis durations, serum creatinine and urea levels of ESRD patients. Compared with controls, HD ESRD patients had lower FA value in the corpus callosum, bilateral corona radiate, posterior thalamic radiation, left superior longitudinal fasciculus, and right cingulum (P<0.05, FWE corrected). Almost all WM regions had increased MD in HD ESRD patients compared with controls (P<0.05, FWE corrected). In some regions with lower FA, FA values showed moderate correlations with ages, NP tests, and serum urea levels. There was no correlation between FA values and HD durations, disease durations, and serum creatinine levels of ESRD patients (all P>0.05). Diffuse interstitial brain edema and moderate WM integrity disruption occurring in HD ESRD patients, which correlated with cognitive dysfunction, and serum urea levels might be a risk factor for these WM changes.

To investigate the contribution of brain default mode network (DMN) in the early diagnosis of the minimal hepatic encephalopathy (MHE), the mildest form of HE from cirrhotic patients by using resting-state functional magnetic resonance imaging (rs-fMRI). This study was approved by the local ethical committee, and a written informed consent was obtained from each participant. A total of 103 cirrhotic patients (34 MHE, 69 non-HE) and 103 matched healthy controls underwent rs-fMRI scanning. The DMN correlation map was acquired by using unbiased seed-based functional connectivity analysis and compared among MHE patients, non-HE patients, and healthy controls with analysis of variance tests. Pearson correlation analysis was performed between the abnormal DMN connectivity and neuropsychological performances. Receiver operator characteristic (ROC) analysis was used to evaluate the contribution of DMN connectivity strength in the differential diagnosis between MHE and non-HE. Compared with the healthy controls, MHE and non-HE patients showed decreased DMN connectivity in medial prefrontal cortex (MPFC), left superior frontal gyrus (SFG), left temporal lobe, and bilateral middle temporal gyri (MTG). The MHE patients showed even more decreased connectivity in MPFC, left SFG, and right MTG when compared with non-HE patients. Pearson correlation analyses revealed that the decreased connectivity strength of some DMN regions correlated with patients' neuropsychological tests scores. Connectivity strength of the MPFC, right MTG, and left SFG could differentiate MHE from non-HE, of which the MPFC had the highest effectiveness (sensitivity = 81.5%, specificity = 70.4%). Cirrhotic patients had gradually reduced DMN functional connectivity from non-HE patients to MHE patients. DMN function, especially the MPFC, might be a useful imaging marker for differentiating MHE from cirrhotic patients.

Purpose: To explore changes in functional connectivity and topological organization of brain functional networks in cirrhotic patients with minimal hepatic encephalopathy (MHE) and non hepatic encephalopathy (nonHE) and their relationship with clinical markers., Materials and Methods: Resting-state functional MR imaging was acquired in 22 MHE, 29 nonHE patients and 33 healthy controls. Functional connectivity networks were obtained by computing temporal correlations between any pairs of 90 cortical and subcortical regions. Graph analysis measures were quantitatively assessed for each subject. One-way analysis of covariance was applied to identify statistical differences of functional connectivity and network parameters among three groups. Correlations between clinical markers, such as Child-Pugh scores, venous blood ammonia level, and number connection test type A (NCT-A)/digit symbol test (DST) scores, and connectivity/graph metrics were calculated., Results: Thirty functional connectivities represented by edges were found to be abnormal (P<0.05, FDR corrected) in cirrhotic patients, in which 16 edges (53.3%) were related with sub-cortical regions. MHE patients showed abnormal small-world attributes in the functional connectivity networks. Cirrhotic patients had significantly reduced nodal degree in 8 cortical regions and increased nodal centrality in 3 cortical regions. Twenty edges were correlated with either NCT-A or DST scores, in which 13 edges were related with sub-cortical regions. No correlation was found between Child-Pugh scores and graph theoretical measures in cirrhotic patients., Conclusion: Disturbances of brain functional connectivity and small world property loss are associated with neurocognitive impairment of cirrhotic patients. Reorganization of brain network occurred during disease progression from nonHE to MHE., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

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.

The changes of whole brain functional connectivity in hemodialysis (HD) patients with end-stage renal disease (ESRD) are still unclear, which may be associated with multiple factors, such as elevated neurotoxins, anemia, and side effects of hemodialysis. Resting-state functional magnetic resonance imaging (rs-fMRI) data of 71 patients (43 males, 28 females; mean age, 33.4 ± 9.4 years) and 43 age- and gender-matched healthy volunteers (29 males, 14 females; mean age, 30.6 ± 8.8 years) were acquired. Neuropsychological tests including number connection test type A (NCT-A), digit symbol test (DST), line-tracing test (LTT), serial-dotting test (SDT), self-rating depression scale (SDS) and self-rating anxiety scale (SAS) were used to evaluate cognitive and psychiatric conditions in all subjects. Blood biochemistry tests including serum creatinine levels, blood urea, hematocrit, and Ca(2+) level were taken in HD patients. Forty-two connections significantly different between HD patients with ESRD and controls were found (all P < 0.05, Bonferroni corrected) and identified as connectivities of interests (COIs), among which 39 connections (92.9%) were markedly decreased in patients. Of the 39 weaker connections, 24 were related to the frontal lobe regions. Widespread weakening of cortical and subcortical network connectivity in ESRD patients was more directly related with neuropsychological impairments and anemia rather than serum creatinine level, blood urea and dialysis duration. In particular, impairments in the medial prefrontal lobe could play an important role in mediating psychological dysfunctions.

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.

Purpose: The exact neuro-pathophysiological effect of transjugular intrahepatic portosystemic shunt (TIPS) on brain function remains unclear. The purpose of this study was to investigate the longitudinal brain activity changes in cirrhotic patients with TIPS insertion using resting-state functional MRI (fMRI) with regional homogeneity (ReHo) method., Methods: Fifteen cirrhotic patients without overt hepatic encephalopathy (OHE) planned for TIPS procedure and 15 age- and gender-matched healthy controls were included in this study. Eleven of the 15 patients underwent repeated fMRI examinations at median 7-day following TIPS, 8 patients in median 3-month, and 7 patients in median 1-year follow-up duration, respectively. Regional homogeneity was calculated by the Kendall's coefficient of concordance (KCC) and compared between patients before TIPS and healthy controls with two-sample t test as well as pre-and post-TIPS patients with paired t test. Correlations between the pre- and post-TIPS changes of ReHo and the changes of venous blood ammonia level and number connection test type A (NCT-A)/digit symbol test (DST) scores were calculated by crossing subjects., Results: Compared with healthy controls, 15 cirrhotic patients before TIPS procedure showed decreased ReHo in the bilateral frontal, parietal, temporal and occipital lobes and increased ReHo in the bilateral caudate. Compared with the pre-TIPS patients, 11 post-TIPS patients in the median 7-day follow-up examinations demonstrated decreased ReHo in the medial frontal gyrus (MFG), superior parietal gyrus (SPG), middle/superior temporal gyrus (M/STG), anterior cingulate cortex (ACC), caudate, and increased ReHo in the insula. Eight post-TIPS patients in the median 3-month follow-up examinations showed widespread decreased ReHo in the bilateral frontal and parietal lobes, ACC, caudate, and increased ReHo in the insula and precuneus/cuneus. In the median 1-year follow-up studies, seven post-TIPS patients displayed decreased ReHo in the bilateral frontal and parietal lobes, ACC, supplementary motor area (SMA), posterior cingulate cortex (PCC), and increased ReHo in the caudate and insula (P<0.05, Alphasim corrected). The changes of ReHo values in bilateral IPL, MFG, caudate and SMA were correlated with changes of DST scores during the median 3-month follow-up (all P<0.05)., Conclusion: The TIPS implantation had a persistent effect on brain function in cirrhotic patients including both predominant impairment and compensation mechanisms, with the most significant alterations in the median 3-month period after TIPS. The ReHo analysis may be potentially valuable for uncovering the mechanism of TIPS' effects on brain function., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Minimal hepatic encephalopathy (MHE) is associated with changes in functional connectivity. To investigate the patterns of modular changes of the functional connectivity in the progression of MHE, resting-state functional magnetic resonance imaging was acquired in 24 MHE patients, 31 cirrhotic patients without minimal hepatic encephalopathy (non-HE), and 38 healthy controls. Newman's metric, the modularity Q value, was maximized and compared in three groups. Topological roles with the progression of MHE were illustrated by intra- and intermodular connectivity changes. Results showed that the Q value of MHE patients was significantly lower than that of controls (P < 0.01) rather than that of non-HE patients (P > 0.05), which was correlated with neuropsychological test scores rather than the ammonia level and Child-Pugh score. Less intrasubcortical connections and more isolated subcortical modules were found with the progression of MHE. The non-HE patients had the same numbers of connect nodes as controls and had more hubs compared with MHE patients and healthy controls. Our findings supported that both intra- and intermodular connectivity, especially those related to subcortical regions, were continuously impaired in cirrhotic patients. The adjustments of hubs and connector nodes in non-HE patients could be a compensation for the decreased modularity in their functional connectivity networks.

To investigate the pattern of brain volume changes in patients with end-stage renal disease (ESRD) using voxel-based morphometry (VBM) and correlation with clinical and neuropsychological (NP) tests. Fifty seven ESRD patients with no anatomical abnormalities in conventional magnetic resonance imaging [24 patients with abnormal NP scores, 16 male, 39 ± 12 years; 33 patients with normal NP scores, 23 male, 35 ± 9.7 years] and 22 age- and gender-matched healthy controls (14 male, 36 ± 10.1 years) were recruited in this study. Results from VBM analysis were analyzed with ANOVA test among 3 groups (controls, minimal nephro-encephalopathy group, non-nephro-encephalopathy group). Multiple linear regression analysis was used to investigate the effect of serum urea and creatinine, and dialysis duration on the brain volumes in ESRD patients. Correlation analysis was performed to investigate the association between NP scores with the brain volumes in ESRD patients. Compared with healthy controls, ESRD patients showed diffusely decreased gray matter volume that further decreased in the presence of encephalopathy. Multiple linear regression results showed that serum urea was negatively associated with changes in gray matter volume in many regions, while dialysis duration was negatively associated with some white matter volume changes (All P < 0.05, AlphaSim correction). NP scores correlated with some decreased gray matter volume in ESRD patients (All P < 0.05, AlphaSim correction). No correlation was found between white matter volume and any NP test scores in ESRD patients. This study found predominantly decreased gray matter volume in ESRD patients, which was associated with neurocognitive dysfunction. Serum urea level may be a risk factor for decreased gray matter in ESRD patients.

Purpose: To investigate patterns of whole-brain functional connectivity in patients with minimal hepatic encephalopathy (HE) by using functional magnetic resonance (MR) imaging., Materials and Methods: This study was approved by the local institutional review board and was HIPAA compliant. All participants provided written informed consent. Neuropsychiatric tests including number connection test type A and digit symbol test were used to define minimal HE. Twenty-three patients with minimal HE and 25 age- and sex-matched healthy volunteers were included in this study. Resting-state functional MR imaging was performed by using a 3-T MR imaging unit. Functional connectivities between 90 pairs of cortical and subcortical regions in patients with minimal HE were compared with those in control participants, and significantly different connectivities were chosen as connectivities of interest (COIs). Correlations between neuropsychiatric tests and correlation coefficients of COIs were calculated., Results: Among the 51 COIs that were significantly different in patients with minimal HE from those in control participants, 44 connectivities were weaker in patients with minimal HE. All 22 COIs related to subcortical regions of interest (bilateral putamen, pallidum, and thalamus) were weaker in patients with minimal HE. Of 29 cortical COIs, 22 connectivities were weaker and seven were stronger in patients with minimal HE. Nearly all COIs with significant differences correlated with digital symbol test scores (P<.05, false discovery rate corrected). No correlation was found among blood ammonia level, Child-Pugh scores, or any COIs in patients with minimal HE (P>.05, false discovery rate corrected)., Conclusion: Widespread cortical and subcortical network connectivity changes that correlated with neuropsychologic impairment were found in patients with minimal HE. In particular, impairment in the basal ganglia-thalamocortical circuit could play an important role in mediating neurocognitive dysfunction, especially for psychomotor speed and attention deficits in patients with minimal HE., (© RSNA, 2012)

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.

Purpose: To evaluate the effect of hepatic encephalopathy (HE), hepatic failure, and portosystemic shunt (PS) on the brain volume alteration in cirrhotic patients with MRI voxel-based morphometry (VBM)., Methods: Sixty cirrhotic patients (overt HE [OHE], n = 11; minimal HE [MHE], n = 19; non HE [nHE], n = 30) including 12 with pre- and post-transjugular intrahepatic portosystemic shunt (TIPS) scanning and 40 healthy controls were recruited. Neuropsychological and laboratory tests were performed in all patients. VBM was analyzed with ANOVA test among 4 groups, and t-tests for patients with different hepatic function, PS scores, and TIPS. Multiple linear regression was performed to investigate the effect of venous blood ammonia levels, Child-Pugh scores, and PS on the brain volumes in all patients., Results: Cirrhotic patients exhibited decreased volume in many areas of gray matter (GM), increased volume in thalamus, and increased whiter matter (WM) volume, with the extent of affected brain volume greater in HE patients than nHE patients. Hepatic failure also resulted in decreased GM volume. Patients with high PS scores and TIPS displayed decreased GM and increased WM volume in some regions. Post-TIPS patients displayed increased GM volume in the thalamus. Multiple covariate regression results suggested that Child-Pugh score was a major factor to affect GM volume, while PS mainly affected WM volume., Conclusion: Brain structure abnormalities appeared bilaterally symmetrical in cirrhotic patients, and the impairment was more extensive in HE patients than those without HE. Increased thalamus volume was not associated with HE progression. Hepatic failure and PS altered cirrhotic patients' brain structure.

Background: Little is known about how spontaneous brain activity progresses from non-hepatic encephalopathy (non-HE) to minimal HE (MHE). The purpose of this study was to evaluate the evolution pattern of spontaneous brain activities in cirrhotic patients using resting-state fMRI with a regional homogeneity (ReHo) method., Methodology/principal Findings: Resting-state fMRI data were acquired in 47 cirrhotic patients (minimal HE [MHE], n = 20, and non-HE, n = 27) and 25 age-and sex-matched healthy controls. The Kendall's coefficient of concordance (KCC) was used to measure the regional homogeneity. The regional homogeneity maps were compared with ANOVA tests among MHE, non-HE, and healthy control groups and t-tests between each pair in a voxel-wise way. Correlation analyses were performed to explore the relationships between regional ReHo values and Child-Pugh scores, number connection test type A (NCT-A), digit symbol test (DST) scores, venous blood ammonia levels. Compared with healthy controls, both MHE and non-HE patients showed decreased ReHo in the bilateral frontal, parietal and temporal lobes and increased ReHo in the bilateral caudate. Compared with the non-HE, MHE patients showed decreased ReHo in the bilateral precuneus, cuneus and supplementary motor area (SMA). The NCT-A of cirrhotic patients negatively correlated with ReHo values in the precuneus, cuneus and lingual gyrus. DST scores positively correlated with ReHo values in the cuneus, precuneus and lingual gyrus, and negatively correlated with ReHo values in the bilateral caudate (P<0.05, AlphaSim corrected)., Conclusions/significance: Diffused abnormal homogeneity of baseline brain activity was nonspecific for MHE, and only the progressively decreased ReHo in the SMA and the cuneus, especially for the latter, might be associated with the development of MHE. The ReHo analysis may be potentially valuable for detecting the development from non-HE to MHE.

Background: Recently, increasing numbers of studies have demonstrated that, in humans, a default-mode functional network exists in the resting state. Abnormal default-mode network in various diseases has been reported; however, no report concerning hepatic cirrhosis has been published to date., Purpose: To prospectively explore whether the resting-state network in patients with hepatic cirrhosis is abnormal or not, using functional magnetic resonance imaging (fMRI)., Material and Methods: 14 patients with hepatic cirrhosis (12 male, two female; 45+/-9 years) and 14 age- and gender-matched healthy volunteers (12 male, two female; 42+/-10 years) participated in a blocked-design fMRI study. A modified Stroop task with Chinese characters was used as the target stimulus. Statistical Parametric Mapping 99 software was employed to process the functional data. Individual maps and group data were generated for patients with hepatic cirrhosis and for healthy controls, respectively. Intergroup analysis between patients and healthy controls was also generated using the two-sample t-test model. Cluster analyses were done based on the group data, and an identical P value < or =0.01 with continuously connected voxels of no less than 10 was defined as significant deactivation. After fMRI scanning was complete, behavioral Stroop interference tests were performed on all subjects; reaction time and error number were recorded., Results: Functionally, deactivation of the posterior cingulate cortex (PCC) and precuneus was absent when subjects performed the incongruous word-reading task; deactivation of the PCC, precuneus, and ventral medial prefrontal cortex was increased when they performed the incongruous color-naming task., Conclusion: The functional as well as behavioral data suggest that cirrhotic patients may have an abnormal deactivation mode. The absence of deactivation in the PCC and precuneus may be a sensitive rather than specific marker in patients with hepatic cirrhosis.

Purpose: This study was conducted in order to investigate the topological organization of functional and structural brain networks in diabetic kidney disease (DKD) and its potential clinical relevance. Methods: Two hundred two subjects (62 DKD patients, 60 diabetes mellitus [DM] patients, and 80 healthy controls) underwent laboratory examination, neuropsychological test, and magnetic resonance imaging (MRI). Large-scale functional and structural brain networks were constructed and graph theoretical network analyses were performed. The effect of renal function on brain functional and structural networks in DKD patients was further evaluated. Correlations were performed between network properties and neuropsychological scores and clinical variables. Results: Progressing deteriorated global and local network topology organizations (especially for functional network) were observed for DKD patients compared with control subjects (all p < 0.05, Bonferroni-corrected), with intermediate values for the patients with DM. DKD patients showed normally appearing functional–structural coupling compared with controls, while DM patients manifested functional–structural decoupling (p < 0.05, Bonferroni-corrected). Impaired kidney function markedly affected functional and structural network organization in DKD patients (all p < 0.05). Urea nitrogen correlated with global and local efficiency in the structural networks (r = − 0.551, p < 0.001; r = − 0.476, p < 0.001, respectively). Global and local efficiency in the structural networks and normalized characteristic path length in the functional networks were associated with information processing speed and/or psychomotor speed. Conclusion: DKD patients showed enhanced functional and structural brain network disruption and normally appearing functional–structural coupling compared with DM patients, which correlated with kidney function, renal toxins, and cognitive performance. Key Points: • DKD patients showed markedly disrupted functional and structural brain network efficiency measures compared with DM patients and healthy controls. • Reduced kidney function clearly deteriorated functional and structural brain networks in DKD patients. • DKD patients displayed normally appearing functional–structural coupling compared with DM patients. [ABSTRACT FROM AUTHOR]

Objectives: To assess how the severity of hepatic encephalopathy (HE) affects perfusion and metabolic changes in cirrhotic patients and the association between severity and liver disease and anemia.Methods: The study groups comprised 31 healthy subjects and 33 cirrhotic patients who underwent MR examinations, and blood and neuropsychological tests. Of the cirrhotic patients, 14 were unaffected, and 11 had covert HE (CHE) and 8 overt HE (OHE). Global cerebral blood flow (CBF), oxygen extraction fraction (OEF), and metabolic rate of oxygen (CMRO2) were noninvasively measured by phase-contrast and T2-relaxation-under-spin-tagging MRI. Correlations were performed between MR measurements, hematocrits, ammonia levels, Child-Pugh scores and neuropsychological test scores.Results: Compared with the values in healthy subjects, CBF was higher in unaffected patients, the same in CHE patients and lower in OHE patients, OEF was higher in all patients, and CMRO2 was the same in unaffected and CHE patients and lower in OHE patients. Hematocrit was negatively correlated with CBF and OEF, but not with CMRO2. Ammonia level was negatively correlated with CBF and CMRO2, and Child-Pugh score was negatively correlated with CMRO2.Conclusions: The severity-associated alterations in cirrhotic patients indicate that homeostasis of oxygen delivery and oxidative metabolism in HE is regulated by multiple mechanisms. These physiological alterations appeared to be associated with the degree of anemia, ammonia level, and liver function.Key Points: • CBF, OEF and CMRO2 did not change monotonically with HE progression. • Anemia possibly contributed to CBF and OEF changes in cirrhotic patients. • Liver dysfunction mainly contributed to changes in CMRO2 in cirrhotic patients. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate image quality and diagnostic accuracy for acute infarct detection and radiation dose of 70 kVp whole brain CT perfusion (CTP) and CT angiography (CTA) reconstructed from CTP source data.Methods: Patients were divided into three groups (n = 50 each): group A, 80 kVp, 21 scanning time points; groups B, 70 kVp, 21 scanning time points; group C, 70 kVp, 17 scanning time points. Objective and subjective image quality of CTP and CTA were compared. Diagnostic accuracy for detecting acute infarct and cerebral artery stenosis ≥ 50 % was calculated for CTP and CTA with diffusion weighted imaging and digital subtraction angiography as reference standards. Effective radiation dose was compared.Results: There were no differences in any perfusion parameter value between three groups (P > 0.05). No difference was found in subjective image quality between three groups (P > 0.05). Diagnostic accuracy for detecting acute infarct and vascular stenosis showed no difference between three groups (P > 0.05). Compared with group A, radiation doses of groups B and C were decreased by 28 % and 37 % (both P < 0.001), respectively.Conclusion: Compared with 80 kVp protocol, 70 kVp brain CTP allows comparable vascular and perfusion assessment and lower radiation dose while maintaining high diagnostic accuracy in detecting acute infarct.Key Points: • 70 kVp whole brain CTP can provide diagnostic image quality. • 70 kVp CTP diagnostic accuracy was maintained vs. 80 kVp protocol. • 70 kVp CTP radiation doses were lower than 80 kVp protocol. [ABSTRACT FROM AUTHOR]