肝硬化患者肝移植前后脑代谢改变的MR波谱研究

Cerebral metabolic changes in cirrhotic patients before and after liver transplantation： a MR spectroscopy study

目的 采用1H-MRS定量分析肝硬化患者肝移植前后脑代谢的变化.方法 选取37例肝硬化患者（患者组）和22名健康志愿者（对照组）进行神经心理学测试及点分辨自旋回波波谱序列（PRESS）MRS,并于肝移植术后1、3个月对18例患者进行随访,测量数字连线试验（NCT-A）、数字符号试验（DST）、符号数字试验（SDT）等神经心理学各指标及后扣带回、左侧基底节MRS各代谢物的含量.采用独立样本t检验比较对照组和患者组术前的神经心理学、MRS各参数;利用方差分析统计肝移植前后神经心理学测试、MRS的变化;用Pearson相关性检验分析各时间点扣带回和左侧基底节MRS各指标与神经心理学测试之间的相关性.结果 （1）移植术前患者组与对照组比较,后扣带回N-乙酰天冬氨酸（NAA）/肌酸（Cr）、胆碱（Cho）/Cr、肌醇（mI）/Cr、谷氨酸复合物（Glx）/Cr分别为1.96±0.21和1.73±0.12、0.65±0.12和0.83±0.09、0.41±0.14和0.72±0.11、2.37±0.38和1.92±0.32,两组差异有统计学意义（t值分别为-5.42、5.96、8.62、-4.72,P值均＜0.01）;基底节Cho/Cr、mI/Cr、Glx/Cr分别为0.63±0.16和0.77±0.10、0.38±0.17和0.53±0.21、1. 70±0.36和1.29±0.30,两组差异有统计学意义（t值分别为3.64、3.07、-4.58,P值均＜0.01）;（2）患者组的NCT-A测试时间[（5 8.17±19.12）s]明显长于对照组[（37.68±8.02）s],差异有统计学意义（t=4.14,P＜0.01）;而DST[（36.67±9.91）分]及SDT[（31.67±9.49）分]成绩明显低于对照组[（55.36±9.27）、（50.73±8.34）分],差异有统计学意义（t值分别为4.60、4.65,P值均＜0.01）.移植术后1个月患者组NCT-A、DST、SDT分别为（53.06±12.71）s、（41.89±8.17）、（37.44±7.68）分,术后3个月分别为（35.72 ±5.20）s、（54.39±5.69）分、（49.39±5.65）分,与术前比较差异有统计学意义（F值分别为33.554、85.772、83.061,P值均＜0.01）.（3）术后1个月患者组后扣带回NAA/Cr、Cho/Cr、mI/Cr、Glx/Cr分别为1.79±0.19、0.90士0.14、0.39±0.15、1.86士0.32,术后3个月分别为1.66±0.18、0.92±0.08、0.71±0.10、1.75±0.25,与术前比较差异有统计学意义（F值分别为12.658、38.178、75.186、19.420,P值均＜0.01）.术后1个月患者组基底节Cho/Cr、mI/Cr、Glx/Cr分别为0.81±0.08、0.47 ±0.25、1.30 ±0.20,术后3个月分别为0.80 ±0.09、0.61±0.27、1.23±0.25,与术前比较差异有统计学意义（F值分别为9.447、8.027、17.952,P值均＜0.01）.（4）术前扣带回的mI/Cr与NCT-A及DST、SDT之间具有相关性（r值分别为0.743、0.597、0.615,P值均＜0.01）.结论 肝硬化患者脑代谢异常是可逆性的,后扣带回mI/Cr可作为监测肝移植后脑代谢恢复状况的指标.

Objective To quantitatively evaluate the metabolic changes in posterior cingulated cortex and left basal ganglia in patients with liver cirrhosis before and after liver Transplantation （LT）.Methods A total of 22 controls and 37 cirrhotic patients listed for LT were enrolled in the study. Brain MRS （PRESS sequence） and neuropsychological （NP） tests were performed in all subjects. Eighteen patients were followed up at 1 month and 3 month after LT. The NP parameters including number connection test-A （ NCT-A）, digital symbol test （DST） and symbol digital test （SDT） were measured. MRS metabolic contents were measured automatically at posterior cingulate cortex （PCC） and left basal ganglia （LBG）.Independent t-test was used to compare the parameters of NP test and MRS metabolites between the 2 groups. The changes of the parameters before and after LT were compared using analysis of variance.Pearson correlation test was also used to analysis the relationship between NP test parameters and MRS metabolites. Results （ 1 ） Before LT, significant difference of metabolites was found in the PCC between the two groups [ NAA/Cr（1.96 ±0.21, 1.73 ±0. 12）, Cho/Cr（0. 65 ±0. 12,0. 83 ±0.09）, mI/Cr （0.41 ±0.14,0.72±0.11）, Glx/Cr（2. 37 ±0. 38,1. 92 ±0. 32） （t= -5.42,5.96,8.62,-4.72,P＜0.01）].And statistical significance also were found in LBG between the 2 groups [ Cho/Cr （0. 63 ± 0. 16,0. 77 ±0. 10）, mI/Cr（0.38 ±0. 17,0.53 ±0.21）, GIx/Cr（1.70 ±0.36,1.29 ±0.30）, （t =3.64,3.07,-4.58 ,P ＜ 0. 01 ）]. （2）Compared with controls, the patients before LT had longer NCT-A reaction time [ （58. 17 ±19. 12） s,（37.68 ±8.02） s,t =4. 14,P＜0.01], lower scores of DST （36.67 ±9.91,55.36 ±9.27,t = 4.60,P＜0.01） and SDT （31.67 ±9.49,50.73 ±8.34,t = 4.652,P＜0.01） before LT. All the scores of NP tests changed significantly at 1 and 3 month after LT compared with those before LT[ NCT-A （53.06±12.71） s,（35.72 ±5.20） s,F =33.554,P ＜0.01 ], DST（41.89 ±8. 17,54.39 ±5.69,F =85.772,P＜0.01）,SDT（37.44±7.68,49.39±5.65,F=83.061,P＜0.01）]. （3） In the 18 patients who were followed, Cho/Cr [ PCC （0. 90 ± 0. 14,0. 92 ± 0. 08, F = 38. 178, P ＜ 0. 01 ）; LBG （0. 81 ± 0. 08,0. 80 ±0.09,F =9.447,P ＜0.01）] and Glx/Cr [ PCC（1.86 ±0.32,1.75 ±0.25,F = 19.420, P ＜0. 01 ）; LBG（ 1.30 ±0. 20,1.23 ±0. 25 ,F = 17. 952,P ＜0. 01 ） ] recovered at 1 month after LT, while the mI/Cr [PCC （0.39±0.15,0.71 ±0. 10,F =75. 186,P＜0.01） ;LBG （0.47 ±0.25,0.61 ±0.27,F =8. 027, P ＜ 0. 01 ） ] recovered at 3 month after LT. （4）mI/Cr of cingulate cortex correlated significantly with NCT-A, DST and SDT （r= -0.743, 0.597, 0.615, P＜0.01 ） before LT. Conclusion Cerebral metabolic changes in patients with liver cirrhosis is reversible and MRS of the posterior cingulate cortex is a helpful method in following up the changes after LT. mI/Cr is a useful indicator to predict the brain changes of cirrhotic patients before and after LT.