| Objective:Using the MRS to evaluate the metabolite changes in posterior cingulated cortex and left basal ganglia in patients with liver cirrhosis before and after liver transplantation(LT),and whether the metabolite ratio has relationship with venous ammonia,liver function and neuropsychologicalCNP)tests;Using the MTI to evaluate the MTR changes before and after LT,and whether the metabolite ratio has relationship with venous ammonia,liver function,MRS,GPI and NP tests;to evaluate the cognitive control difference after LT using functional MRI(fMRI)and explore the possible neurologic mechanism.Materials and methods:22 controls and 37 patients diagnosed as liver cirrhosis clinically and radiologically and listed for LT were included in the study.All subjects performed three kinds of neuropsychology tests,that is,number-connection test type A(NCT-A),digital symbol test(DST),and symbol digital test(SDT)before MR examinations.MRS data in cingulate cortex and basal ganglia were acquired by point-resolved echo spin spectroscopy sequence of single voxel 1-hydrogen MRS. The software automatically completed metabolite content measurement,giving the ratio of all metabolites using Cr as a reference,including NAA/Cr,Cho/Cr,mIns/Cr, Glx/Cr.The examination were repeated at 1month and 3month after LT in 18/37 patients.Another 12 patients were also complete the examinations at 1year after LT. All subjects performed axial T1WI,T2WI,MTI with and without MTC.Signal intensities of putamen and globus pallidus were measured on T1WI to compute GPI. In MTI,ROIs were placed on the white matter of parietal lobe,frontal lobe,caudate head,putamen,globus pallidus,thalamus,and occipital lobe.MTR of all ROIs were calculated according to the equation.12 postoperative(1mon)patients,14 cirrhotic patients and 14 healthy volunteers were enrolled in fMRI using modified Stroop task in Chinese character.Image analysis was performed using statistical parameter mapping 5.One-sample t test was used for word-reading and color-naming task in patients and controls,and two-sample t test was also used for inter-group analysis of word-reading and color-naming task in pre and postoperative patients with hepatic cirrhosis and controls.After fMRI examinations were over,behavior tests of Stroop interference were performed for all subjects.Overall reaction time and error numbers were recorded,respectively.Results:1.①Decreased Cho/Cr(t=5.96,P=0.000;t=3.64,P=0.000;), mlns/Cr(t=8.62,P=0.000;t=3.07,P=0.000;),and increased Glx/Cr(r=-4.72,P=0.000; t=-4.58,P=0.000;)in cingulate cortex and basal ganglia were detected in the patients with hepatic cirrhosis;NAA/Cr(t=-5.42,P=0.000)were increased in cingulated cortex.②mIns/Cr of cingulate cortex correlated negatively with Glx/Cr(r=-0.47, P=0.003)and positively with Cho/Cr(r=0.421,P=0.009)which indicate that metabolites of cingulate cortex can better imply the relationship between the coefficients.③The metabolites of both area of interests(ROIs)had no correlation with venous ammonia and Child-Pugh score.④Compared with the scores before LT, the patients had better performance in three NP tests at 1mon and 3mon after LT;and the NP tests were normalized at 3mon after LT.⑤The liver function of cirrhotic patients were in the normal range at 1mon after LT.Cho/Cr and Glx/Cr of both ROIs were normalized at 1mon after LT with the normalization of mIns/Cr at 3mon.⑥mIns/Cr of cingulate cortex correlated significantly with NCT-A(r=-0.743,P=0.000), DST(r=0.59,P=0.000)and SDT(r=0.615,P=0.000),implying that it was a sensitive marker to predict the brain changes of cirrhotic patients before and after LT.⑦Compared with controls,the metabolites of cingulated cortex and basal ganglia were maintained in the normal range at lyear after LT which indicate that the normalization of MRS can be continued once they were improved.2.①Compared with controls,MTR of patients with liver cirrhosis was significantly decreased in all 7 ROIs(P＜0.001)and GPI was increased(t=-6.40, P=0.000).②MTR and GPI of all the locations had no correlation with venous ammonia and Child-Pugh score.③1mon after LT,MTR of parental lobe(t=2.824, P=0.008),frontal lobe(t=2.361,P=0.024),caudate head(t=2.238,P=0.032)and globus pallidus(t=2.726,P=0.010)was significantly increased in cirrhotic patients compared with those before LT;MTR of all the ROIs were increased 3mon after LT but only the putamen(31.64±1.26),thalamus(35.16±1.23)and occipital lobe (37.26±2.18)were in the normal range.④The improvement of GPI was progressive and did not normalized at 3mon after LT.⑤There is no correlation between MTR, GPI and NP tests before and 1mon,3mon after LT.⑥MTR of frontal lobe,globus pallidus and occipital lobe had correlation with Cho/Cr and mIns/Cr in basal ganglia before LT(P＜0.05);mIns/Cr in basal ganglia had correlation with parental lobe, frontal lobe,caudate head and occipital lobe in patients 1mon after LT(P＜0.05).The correlation disappeared at 3mon after LT.⑦All the ROIs of MTR and GPI were improved at lyear after LT and had no difference with those in controls.3.①All of the three groups performed faster incongruous word-reading task than incongruous color-naming task(t=-12.447,P＜0.001;t=-5.62,P＜0.001;t=-8.188, P＜0.001);the reaction time of incongruous word-reading in postoperative patients was shorter than the preoperative patients(t=2.34,P＜0.05)and had no difference with the controls(t=1.001,P＞0.1),while the reaction time of incongruous color-naming task in postoperative patients had no difference with the preoperative patients(t=0.037, P＞0.5).All groups had similar errors for performing both tasks(t=-7.089,P＜0.001; t=-3.78,P＜0.001;t=-9.031,P＞0.05;);the postoperative patients had less errors in word-reading than those in the preoperative patients(t=3.03,P＜0.05)and had no difference with the controls(t=0.8,P＞0.1),while postoperative patients performed the similar errors in color-naming compare with the preoperative patients(t=0.05,P＞0.5).②The postoperative patients had more brain areas activated in incongruous color-naming task than incongruous word-reading task,including bilateral middle frontal lobe,bilateral inferior frontal lobe,bilateral medial frontal lobe,right posterior cingulate cortex,parental lobe and basal ganglia.③Compared with the preoperative patients,the postoperative group had more activation in frontal lobe,cingulated cortex,parental lobe and basal ganglia,when performing both tasks especially incongruous color-naming task.④While compared with the controls,the frontal lobe, cingulated cortex,inferior parental lobe and temporal lobe were activated less in postoperative group when performing both tasks.Conclusion:①The cirrhotic patients had typical MRS changes in the PCC and basal ganglia,which demonstrated as the decrease of mIns/Cr and Cho/Cr,and the increase of Glx/Cr.There was correlation between mIns/Cr of the PCC and neuropsychology test,which indicated PCC could be a sensitive index to exam the metabolic changes in cirrhotics.②The metabolic changes in the brain of cirrhotics could be reversible.The normalization of Cho/Cr and Glx/Cr occurred at 1mon after LT,while mIns/Cr occurred at 3mon.③The cirrhotic patients had universally decreased MTR combined with GPI of the basal ganglia elevation implying minimal brain edema.④The reversible changes of MTR supported the hypothesis of brain edema,because MTR increased rapidly at 1mon after LT,and some part of the brain parenchyma normalized at 3mon after LT.⑤GPI improved slowly and progressively and normalized at lyear after LT.⑥The correlation between mIns/Cr of the basal ganglia and MTR was found,which indicate that hyperammonia was the main reason of HE and other factors may also participate in the pathogenesis.⑦The cognitive function of cirrhotic patients was partially improved in both behavioral test and fMRI which was paralyzed with the brain metabolic changes.
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