A Pilot MRI Study Of Resting-state Brain Function And Cerebral Blood Flow In Non-NPSLE Patients

Part I:A Pilot MRI Study of resting-state Brain Function in non-NPSLE patientsObjective:In this study,we sought to explore alterations of brain gray matter volume and regional brain activity in systemic lupus erythematosus patients without overt neuropsychiatric symptoms(non-NPSLE)by using voxel based morphometry(VBM)and blood oxygenation level dependent functional magnetic resonance imaging(BOLD-f MRI)technologies.Then we also assessed the correlations between the mean VBM and ReHo of multiple abnormal brain areas and some clinical indexes,in order to detect biological markers and to further understand the brain damage mechanism of NPSLE.Material and Methods:Thirty-one patients with non-NPSLE and thirty-one sex,age,and education levels matched health controls were enrolled in the experiment.We also recorded some clinical indexes of non-NPSLE patients such as C3,C4,serum creatinine and systemic lupus erythematosus disease activity index(SLEDAI).All subjects underwent conventional MRI,and then the three-dimensional T1 BRAVO structural and BOLD-fMRI functional examinations were performed in patients with normal conventional MRI findings.Data processing and statistical analysis were performed by using CAT12 and DPARSF software packages.Translation or rotation parameters of all subjects were less than 2 mm translation or less than 2°angular rotation in any axis,so we recruited 24 patients with non-NPSLE and 28 health controls.Two sample t-test was used to compare the VBM and ReHo differences between non-NPSLE and healty control groups,respectively.Furthermore,we also analysised the correlation between the mean VBM and ReHo of multiple abnormal brain areas and some clinical indexes.Results:1.Compared to the controls,the non-NPSLE group showed significantly decreased VBM in multiple areas including the left supplementary motor area,right fusiform gyrus,right middle cingulate cortex,left middle temporal gyrus,left insula lobe,right inferior orbital gyrus,left parahippocampal gyrus,left calcarine gyrus,left angular gyrus,left cerebellum,right precentral gyrus;while this group showed no significant brain regions with increased VBM.Moreover,the negative correlation between the mean VBM in the right fusiform gyrus,right middle cingulate cortex and C4 were found(r=-0.429,P<0.05;r=-0.492,P<0.05).2.Compared to the controls,the non-NPSLE group showed significantly decreased ReHo in multiple areas including the left superior medial gyrus,left anterior cingulate cortex,left middle orbital gyrus,left inferior orbital gyrus;while the ReHo was significantly increased in the right calcarine gyrus,left middle occipital gyrus,left superior occipital gyrus,left hippocampus,left superior parietal lobule.We also found the serum creatinine level was positively correlated with the mean ReHo in the right calcarine gyrus,left superior occipital gyrus(r=0.525,P<0.05;r=0.419,P<0.05).Conclusion:1.The systemic lupus erythematosus patients without overt neuropsychiatric symptoms(non-NPSLE)showed the alterations of brain gray matter volume and regional brain activity,and the abnormalities of brain structure and brain function may be independent;2.The mean VBM in the right fusiform gyrus and right middle cingulate cortex were related to the disease activity of SLE,which helped to elucidate the underlying brain injury mechanism of SLE;while the mean ReHo in the right calcarine gyrus,left superior occipital gyrus may be considered to be a predictor of disease progression and an available marker for lupus nephritis.Part II:Cerebral Blood Flow measurements in non-NPSLE patients using 3D Arterial Spin Labeling:a Pilot StudyObjective:Based on the results of Part I,changes in brain function were mainly located in the frontal lobe in non-NPSLE patients,but no obvious abnormal functional changes were found in the posterior cingulate cortex and precuneus,which were the critical brain regions of the default network.We selected the bilateral frontal lobes,posterior cingulate cortex,and precuneus as regions of interesting(ROI),to investigate whether the cerebral blood flow had changed in non-NPSLE patients.Moreover,we aimed to study the effects of different post label delay on the resulting CBF maps such as PLD=1.5s,PLD=2.5s and to explore the proper PLD for SLE.Material and Methods:In this study,we enrolled 24 non-NPSLE and 24 sex,age,and education levels matched health controls who were included in the Part I.All subjects underwent axial three-dimensional T1 BRAVO and three-dimensional ASL with different post label delay such as PLD=1.5s,PLD=2.5s.We imported 3D-ASL raw data into the post-processing workstation GE AW 4.6,then fused the brain anatomy images with cerebral blood flow maps,and selected ROI at the bilateral frontal lobes,posterior cingulate cortex and precuneus on the fusion image,recorded the average CBF value of each ROI.Differences of CBF with multiple ROIs between non-NPSLE and healty control groups were assessed by using two-sample T test.Paired-sample T test was performed in non-NPSLE patients with bilateral cerebral symmetry position ROIs and with PLD=1.5s and PLD=2.5s.Results:1.The mean CBF of the non-NPSLE group in the bilateral frontal lobes,posterior cingulate cortex and precuneus were significantly lower than the health controls(all P<0.05).The mean CBF of the left frontal lobe was significantly lower than the opposite side(P<0.05)in the non-NPSLE patients.However,there were no statistical difference between bilateral posterior cingulate cortex and precuneus(P>0.05).2.Compared with PLD=1.5s,the non-NPSLE patients showed significantly higher mean CBF of the bilateral frontal lobes,posterior cingulate cortex and precuneus with PLD=2.5s(P<0.05).While,there were no statistical difference between PLD=1.5s and PLD=2.5s in the health controls(P>0.05).Conclusion:1.The patients with systemic lupus erythematosus without overt neuropsychiatric symptoms(non-NPSLE)had occurred cerebral blood flow abnormalities in some specific brain regions,in which the frontal lobe was more sensitive to change in CBF,and may be a potential predictor of cognitive changes,so this study provided an evidence for the early intervention of the SLE.2.Multiple PLDs could help to provide more informations in the diagnosis of non-NPSLE patients.When relatively short PLD was applied,perfusion abnormalities could be observed in the early period,whereas long PLD led to more accurate quantitative information of collateral circulation.