轻微肝性脑病的氢质子MR波谱研究

目的 应用氢质子MR波谱(~1H-MRS)检测肝硬化患者脑内代谢物改变,评价其异常变化是否能鉴别轻微肝性脑病(MHE),并与临床神经心理测试进行相关性分析.方法 选取54例肝硬化患者(肝硬化组)和13名健康志愿者(正常对照组)完成神经心理测试,包括数字连接试验A(NCT-A)和数码-符号试验(DST),54例肝硬化患者中包括肝性脑病(HE)9例(HE组)、MHE 23例(MHE组)、无HE和MHE者22例(无HE组).所有患者和志愿者均进行常规头颅MR扫描以及枕叶皮质、左侧顶叶白质的~1H-MRS扫描,分别计算各代谢物包括N-乙酰天冬氨酸(NAA)、胆碱化合物(Cho)、肌醇(mI)和谷氨酰胺复合物(Glx)与肌酸(Cr)的比值.正常对照组与肝硬化组的代谢物比值比较采用独立样本t检验,正常对照组和肝硬化各分组间代谢物比值的比较采用单因素方差分析,组间两两比较采用非参数Mann-Whitney U检验,并用Bonferroni法进行校正.~1H-MRS代谢物比值与HE分级、神经心理测试结果、静脉血氨的相关性分析采用Spearman等级相关分析.结果 肝硬化组枕叶皮质和左顶叶白质的代谢物比值NAA/Cr、Cho/Cr/、mI/Cr、Glx/Cr值分别为1.55±0.12、0.48±0.10、0.42±0.14、2.52±0.48和1.73±0.17、0.75±0.16、0.42±0.16、2.75±0.59,其中无HE组为1.53±0.10、0.48±0.09、0.51±0.11、2.20±0.39和1.69±0.15、0.82±0.14、0.53±0.12、2.40±0.40,MHE组为1.58±0.13、0.48±0.08、0.38±0.13、2.62±0.39和1.78±0.18、0.74±0.14、0.38±0.15、2.84±0.58,HE组分别为1.54±0.12、0.50±0.13、0.29±0.07、3.04±0.31和1.70±0.19、0.62±0.16、0.29±0.07、3.37±0.38.正常对照组相应部位代谢物比值分别为1.61±0.06、0.60±0.10、0.63±0.04、2.05±0.11和1.78±0.07、1.01±0.14、0.70±0.07、1.93±0.34.与正常对照组比较,肝硬化组及肝硬化各分组的Cho/Cr、mI/Cr值均降低,Glx/Cr值均升高,差异均有统计学意义(肝硬化组与对照组比较,枕叶皮质:t值分别为3.196、9.394、-6.527,肝硬化各分组与对照组比较,F值分别为5.097、25.896、20.204,P值均＜0.01.左顶叶白质:t值分别为5.592、9.717、-6.681,F值分别为16.435、28.660、21.283,P值均＜0.01＝.枕叶皮质和左顶叶白质的Glx/Cr值在无HE组、MHE组和HE组间的差异均有统计学意义(P值均＜0.0084＝,mI/Cr值在无HE组和MHE组间比较差异也有统计学意义(P＜0.0084＝.Cho/Cr、mI/Cr值与肝硬化患者HE的严重程度成负相关(枕叶皮质Cho/Cr和mI/Cr的r值分别为-0.316和-0.740,P值均＜0.01;左顶叶白质Cho/Cr和mI/Cr的r值分别为-0.620和-0.749,P值均＜0.01＝,Glx/Cr值与其呈正相关(枕叶皮质和左顶叶白质的r值分别为0.709、0.720,P值均＜0.01＝.正常对照组NCT-A值为(49±8)s,DST值为39 ±6,肝硬化组HE、MHE、无HE组患者NCT-A值分别为(134±37)、(83±26)、(64 ±22)s,DST值分别为15±2、25±9、35±8.正常对照组和肝硬化组67例的代谢物比值Cho/Cr、mI/Cr、Clx/Cr的改变与神经心理测试有很好相关性(P＜0.01＝,其中Glx/Cr值与NCT-A为正相关(枕叶皮质r=0.570,左顶叶白质r=0.541),与DST值为负相关(枕叶皮质r=-0.642,左顶叶白质r=-0.632).各代谢物比值与静脉血氨值之间无相关性.结论 ~1H-MRS研究能显示肝硬化患者大脑皮质与白质区代谢物异常改变,以mI/Cr值和Glx/Cr值明显,并且与神经心理测试之间存在相关性,可以作为HE分级的参考,对MHE有提示作用.

A study of proton MR spectroscopy in patients with minimal hepatic encephalopathy

Objective To evaluate changes of regional cerebral metabolism by proton MR spectroscopy (~1H-MRS) in patients with minimal hepatic encephalopathy (MHE) and to correlate these changes with the neuropsychological test. Methods Fifty-four patients with cirrhosis including nine patients with hepatic encephalopathy (HE),23 patients with MHE,22 patients without HE and 13 controls underwent neuropsychological tests and ~1H-MRS scanning. The volumes of interest included occipital gray matter and left parietal white matter regions. Ratio of spectral peak areas of N-acetylaspartate (NAA),choline (Cho),myo-inositol (mI),and glutamine/glutamate (Glx) relative to creatine (Cr) were acquired. Statistical analysis was conducted using independent t test and one-way analysis of variance. The results of different groups were compared by using the nonparametric Mann-Whitney U test with Bonferroni correction. Correlations among the ~1H-MRS ratios, the grade of HE, neuropsychological test and ammonia data were calculated with Spearman correlation test. Results The ratios of NAA/Cr,Cho/Cr,mI/Cr,Glx/Cr of the occipital gray matter and left parietal white matter regions in patients with cirrhosis are 1.55±0.12,0.48±0.10,0.42±0.14,2.52±0.48 and 1.73±0.17,0.75±0.16,0.42±0.16,2.75±0.59respectively,and they are 1.53±0.10,0.48±0.09,0.51±0.11,2.20±0.39 and 1.69±0.15,0.82±0.14,0.53±0.12,2.40±0.40 in patients without HE,1.58±0.13,0.48±0.08,0.38±0.13,2.62±0.39 and 1.78±0.18,0.74±0.14,0.38±0.15,2.84±0.58 in patients with MHE,1.54±0.12,0.50±0.13,0.29±0.07,3.04±0.31 and 1.70±0.19,0.62±0.16,0.29±0.07,3.37±0.38 inpatients with HE.Compared with controls, decreased mI/Cr and Cho/Cr ratios and elevated Glx/Cr ratios were found in patients with cirrhosis (t=3.196,9.394,-6.527,P＜0.01,occipital gray matter. t=5.592,9.717,-6.681,P＜0.01,left parietal white matter＝ and in subgroup of patients without HE, with MHE and HE (F=5.097,25.896,20.204,P＜0.01,occipital gray matter.F=16.435,28.660,21.283,P＜0.01,left parietal white matter).Significant difference in these metabolic alterations was also found among the different groups of cirrhosis especially the ratios of Glx/Cr in occipital gray matter and left parietal white matter (P＜0.0084).The ratios of mI/Cr also significantly altered between patients without HE and with MHE (P＜0.0084).There was a significant negative correlation between the ratios of Cho/Cr,mI/Cr and the grade of HE (P＜0.01＝ and a significant positive correlation between the ratios of Glx/Cr and the grade of HE (r=0.709,P＜0.01,occipital gray matter; r=0.720,P＜0.01,left parietal white matter＝.NCT-A and DST of controls is (49±8) s and 39±6.They are (134±37),(83±26),(64±22) second and 15±2,25±9,35±8 in patients with HE,MHE and without HE respectively.The metabolic alterations of Cho/Cr,mI/Cr,Glx/Cr correlated significantly with neurepsychological tests in all subjects (P＜0.01＝.There was a significant positive and a negative correlation between the ratios of Glx/Cr and the data of NCT-A and DST respectively (r=0.570,-0.642,occipital gray matter; r=0.541,-0.632,left parietal white matter).The metabolic alterations of Glx/Cr had no correlation with ammonia data as well as other metabolic alterations.Conclusions ~1H-MRS study shows cerebral metabolic alterations of gray and white matter in patients with cirrhosis,especially the reduction in mI/Cr ratio and increase in Glx/Cr ratio. These changes correlate well with the neuropsychological tests and may be useful in predicting the presence of MHE.