Brain Function And Structural Changes In End-stage Renal Disease Maintenance Hemodialysis Patients Based On Multimodal Magnetic Resonance Imaging

Objective: To investigate the changes of brain local neuronal spontaneous activity in maintenance hemodialysis patients with end-stage renal disease(ESRD)using resting-state functional magnetic resonance imaging(rs-f MRI)with amplitude of low frequency fluctuation(ALFF)algorithm.Materials and methods: Thirty-two ESRD patients who received maintenance hemodialysis treatment in the Department of Nephrology and Kidney Transplantation of The Affiliated Hospital of Qingdao University from August 2018 to July 2020 were collected,and 45 healthy volunteers matched in age and sex were recruited from the local community as the control group.T2-FLAIR,3D T1 WI high-resolution anatomical images and rs-f MRI images of all subjects were collected using a GE 3T MRI scanner,and Data Processing Assistant for Resting-State f MRI(DPARSF)software based on MATLAB platform was used for data processing to calculate the mean ALFF(m ALFF)values of the whole brain of the two groups of subjects.Various blood biochemical indicators including serum creatinine,urea,hemoglobin,serum potassium,serum sodium and serum calcium were measured in ESRD group within 24 hours after hemodialysis and before brain MRI scan.Two-sample T-test was used for comparison between groups,and Pearson correlation analysis was used to explore the correlation between ALFF value changes and clinical and laboratory indicators.Results: Compared with healthy controls,ESRD patients had decreased m ALFF in bilateral precuneus(Pcu),posterior cingulate cortex(PCC),superior frontal gyrus,middle frontal gyrus and inferior frontal gyrus(Gaussian random field correction with voxel-level threshold P<0.001 and cluster-level threshold P<0.01,two-tailed).There was no significant correlation between the changed value in ESRD patients clinical and biochemical indicators(P>0.05).Conclusions: ESRD patients with maintenance hemodialysis have decreased spontaneous brain activity,and mainly affected default mode network(DMN)of the brain,especially in the PCC/Pcu and prefrontal cortex,which may be the potential neuropathological mechanism mediating their cognitive impairment.Objective: Using both ROI-and seed-based FC analyses of resting-state functional magnetic resonance imaging(rs-f MRI)to examine the abnormalities in interactions within and between DMN subsystems,and to determine the impaired pattern of DMN in maintenance hemodialysis patients with end-stage renal disease(ESRD).We also attempted to determine the associations between these FC changes and the clinical and laboratory variables in patients with ESRD.Materials and methods: All subjects and data in the included study were the same as those in Part I.The rs-f MRI data were preprocessed by the Data Processing Assistant for Resting-State f MRI(DPARSF)software based on MATLAB platform.In the ROI-based FC analysis,11 brain regions that constitute the three subsystems of DMN were selected to define ROI,which are respectively the core hub subsystem [consisting of the PCC and anterior medial prefrontal cortex(a MPFC)],the dorsal medial prefrontal cortex(d MPFC)subsystem [consisting of the dorsal MPFC(d MPFC),temporal parietal junction(TPJ),lateral temporal cortex(LTC),and temporal pole(Temp P)],and the medial temporal lobe(MTL)subsystem [including the ventral MPFC(v MPFC),posterior inferior parietal lobule(p IPL),retrosplenial cortex(Rsp),parahippocampal cortex(PHC),and hippocampal formation(HF)].The functional connectivity between the ROI and ROI pairs of the two groups was calculated.In the seed-based FC analysis,PCC,a MPFC,d MPFC and v MPFC were selected as seed to calculate the functional connectivity between each seed and other voxels in the whole brain of the two groups.Two-sample t-test was used for inter-group comparison,and Pearson correlation analysis was used to explore the correlation between FC changes and clinical and laboratory indicators.Results:(1)Results of ROI-based FC analysis: compared with the healthy controls(HCs),in the d MPFC subsystem,ESRD patients exhibited significantly reduced connectivity in the d MPFC-TPJ ROI pair.In the MTL subsystem,significantly reduced connectivity was found in the p IPL-Rsp and p IPL-PHC ROI pair.Moreover,the ESRD patients exhibited significantly hypoconnectivity between the DMN hubs and two subsystems(PCC-a MPFC,PCC-p IPL,PCCRsp,a MPFC-d MPFC,a MPFC-TPJ,a MPFC-Rsp)(NBS correction,P<0.05).(2)Results of seed-based FC analysis: Compared with HCs,ESRD patients exhibited significantly decreased PCC-seeded FC with the bilateral a MPFC and Pcu.For the a MPFC seed,only the bilateral PCC showed significantly decreased FC in patients with ESRD compared with HCs.For the d MPFC seed,the bilateral a MPFC showed significantly decreased FC in patients with ESRD compared with HCs(Gaussian random field correction with voxel-level threshold P<0.001 and cluster-level threshold P<0.01,two-tailed).For the v MPFC seed,no brain regions were found significant differences between the two groups.(3)Results of correlation analysis: For ESRD patients,FC values between the a MPFC and PCC extracted from the seed-based analysis were positively correlated with the creatinine level(r=0.426,P=0.015)and urea level(r=0.475,P=0.006).Conclusions: Different subsystems of the DMN have inconsistent degrees of impairment in ESRD patients with maintenance hemodialysis.The cortical hubs(PCC and a MPFC)are preferentially disrupted,and other subsystems may develop progressive impairment to a certain degree as the disease develops.Objective: To investigate the structural connectivity of the entire cerebral cortex in maintenance hemodialysis patients with end-stage renal disease(ESRD)using fiber connectivity density(FiCD)mapping based on diffusion tensor imaging(DTI).Materials and methods: Twenty-five ESRD patients who underwent maintenance hemodialysis treatment in the Department of Nephrology and Kidney Transplantation,Affiliated Hospital of Qingdao University,and 20 healthy volunteers matched in age and sex from January 2019 to January 2020 were included for this study.T2-FLAIR,3D T1 WI high-resolution anatomical images and DTI images of all subjects were collected using a GE 3T MRI scanner.The cognitive function of all subjects was assessed with mini-mental State Examination(MMSE)after brain MRI scan.Various blood biochemical indicators including serum creatinine,urea,hemoglobin,hematocrit,cholesterol,triglyceride,serum potassium,serum sodium,serum calcium and parathyroid hormone(PTH)were measured in ESRD group.Between-group differences were compared at vertex level.using the General Linear Model.Two-sample T-test was used to compare the mean global FiCD values and neuropsychiatric scale scores between the two groups,and Pearson correlation analysis was used to explore the correlation between FiCD changes and clinical and laboratory indicators.Results:(1)The MMSE score(P<0.001)and mean global FiCD value was significantly deceased in ESRD patients compared with HCs(P<0.05).(2)The vertexwise intergroup comparison showed the FiCD values of the bilateral dorsolateral prefrontal cortex[(DLPFC),including the bilateral middle and inferior frontal gyrus],inferior parietal,lateral middle temporal,and right middle occipital cortex were significantly decreased in ESRD patients,whereas some regions in the bilateral DLPFC(including the bilateral middle and right inferior frontal gyrus),lateral temporal(including the bilateral superior and right middle temporal gyrus),and left middle occipital cortex of the ESRD group showed significantly increased FiCD values compared to those of HCs(P<0.01 with Monte Carlo correction).(3)Correlation analysis results show that,for ESRD patients,the increased FiCD values in the right middle frontal gyrus were negatively correlated with serum creatinine(r=-0.580,P=0.007)and urea levels(r=-0.646,P=0.002).The increased FiCD values in the left middle frontal gyrus were negatively correlated with dialysis duration(r=-0.531,P=0.016)and PTH levels(r=-0.569,P=0.009).There were no significant correlations between FiCD values and other clinical variables(P>0.05).Conclusions: ESRD patients with maintenance hemodialysis had extensive cortical structural connectivity impairment.There may be a compensation mechanism of cortical structural recombination that plays a role in the way the brain adapts to maintain optimal network function in ESRD patients.In addition,serum creatinine,urea and PTH levels may be risk factors for brain structural network decompensation in ESRD patients.