目的：(1)探讨肝硬化患者皮层下结构的体积改变；(2)探讨肝硬化患者灰质体积减小与氧化应激损伤的相关性；(3)探讨肝硬化患者局灶性脑白质高信号(WMH)与神经认知功能的相关性。 方法：(1)招募肝硬化患者30例及年龄、性别匹配的健康对照24例。所有受试者接受神经心理学测验、血液生化检查及头部磁共振(MRI)扫描。采用Freesurfer软件分析受试者皮层下结构的体积。在肝硬化组，提取异常的皮层下结构的体积，分析其与临床指标及认知功能的相关性；分析苍白球体积与苍白球指数(PI)的相关性。(2)招募肝硬化患者34例及年龄、性别匹配的健康对照27例。所有受试者接受血液生化检查以及头部MRI扫描。采用基于体素的形态学分析(VBM)比较肝硬化患者与健康对照标准化灰质总体积(gGMV)。比较肝硬化患者与健康对照外周血中的抗氧剂谷胱甘肽(GSH)以及氧化应激标志物丙二醛(MDA)的浓度。在肝硬化组，采用偏相关分析标准化gGMV与血清MDA浓度的相关性。(3)招募肝硬化患者38例，所有病例均排除脑血管疾病危险因素。受试者接受神经心理学测验、血液生化检查以及头部MRI扫描。根据FLAIR图像评估受试者局灶性WMH严重程度，并据此对受试者进行分组(Fazekas量表评分0～1分为WMH无或轻度组，Fazekas量表评分≥2分为WMH中重度组)。比较两组间年龄、性别、肝功能Child-Pugh分级、神经心理学测验评分及轻微型肝性脑病(MHE)发生率的差异；采用Spearman等级相关分析肝硬化患者局灶性WMH严重程度与神经认知功能的相关性；采用多因素Logistic回归分析肝硬化患者中重度局灶性WMH的危险因素。 结果：(1)与健康对照者相比，肝硬化患者双侧壳核、杏仁核、伏隔核体积缩小，双侧苍白球体积增大(P≤0.001)；并且，其左侧壳核及杏仁核体积与数字连接测验A(NCT-A)评分呈负相关(r=-0.410, P=0.034；r=-0.439,P=0.022),双侧苍白球体积与PI呈正相关(r=0.889, P＜0.001；产0.900，P＜0.001)。(2)与健康对照相比，肝硬化患者标准化gGMV减小(P=0.042)，外周血中抗氧化剂GSH水平降低(P＜0.001)，氧化应激标志物MDA水平升高(P＜0.001)。在肝硬化组，血清MDA的水平与标准化gGMV呈负相关(r=-0.378，P=0.036)。(3)与无或轻度WMH组相比，中重度组患者年龄更大(P=0.005)，MHE的发生率更高(P=0.001)，神经认知功能明显减退(P＜0.001)。 Spearman等级相关显示：肝硬化患者局灶性WMH严重程度与NCT-A评分呈正相关(r=0.617，P＜0.001)，与DST评分呈负相关(r=-0.695,P＜0.001)。多因素Logistic回归分析表明：年龄(P=0.025)、 MHE(p=0.007)是肝硬化患者发生中重度局灶性WMH的危险因素。 结论：(1)肝硬化患者存在多个皮层下结构体积异常，其神经认知功能损害可能与左侧壳核以及杏仁核体积缩小有关，锰沉积可能引起双侧苍白球体积增大。(2)肝硬化患者血清MDA水平升高与其脑灰质体积减小有关，提示氧化性损伤可能与肝硬化患者脑灰质丢失有关。(3)肝硬化患者局灶性WMH的严重程度与其神经认知功能损害有明显的相关性，肝硬化患者的局灶性WMH对诊断MHE具有重要提示价值。 图8幅，表9个，参考文献127篇。 关键词：肝硬化；磁共振；皮层下体积；苍白球指数；灰质体积；氧化应激；丙二醛；谷胱甘肽；脑白质高信号；轻微型肝性脑病 分类号：R445

 Objective: (1) To investigate changing volumes of subcortical regions in patients with cirrhosis. (2) To assess the relationship between oxidative damage and grey matter volume (GMV) loss in patients with cirrhosis. (3) To explore the relationship between focal white matter hyperintensity (WMH) and neurocognitive performance in patients with cirrhosis. Methods: (1) Thirty patients with cirrhosis and 24 age- and sex-matched healthy controls were enrolled prospectively. All subjects underwent psychometric tests, blood biochemical determinations and cerebral magnetic resonance imaging (MRI). Volumes of subcortical regions were automatically analyzed by the Freesurfer. In the patient group, the relationships between abnormal subcortical volumes and clinical index and neurocognitive performance were investigated. The relationships between globus pallidus volumes and pallidal index (PI) were examined as well. (2) Thirty-four patients with cirrhosis and 27 age-and sex-matched healthy controls were enrolled prospectively. All subjects underwent cerebral MRI, and voxel-based morphometry (VBM) was performed to assess normalized global GMV. Whole blood glutathione (GSH) and serum malondialdehyde (MDA) levels were determined in all subjects. In the patient group, correlation analysis was used to investigate the relationship between normalized global GMV and serum MDA levels. (3) Thirty-eight patients with cirrhosis without risk factors of cerebrovascular disease were enrolled prospectively. All patients underwent psychometric tests, blood biochemical determinations and cerebral MRI. Fluid attenuated inversion recovery (FLAIR) images were reviewed for focal WMH. Patients were divided into two groups according to the severity of focal WMH. Those with Fazekas score 0～1 were classified as no or mild focal WMH, while those with Fazekas score≥2 were classified as moderate or severe focal WMH. The two groups were compared concerning age, gender, Child-Pugh scale, psychometric test results and the incidence of minimal hepatic encephalopathy (MHE). Spearman rank correlation analysis was conducted to investigate the relationship between the severity of focal WMH and neurocognitive performance. Multivariate logistic regression analysis was performed to identify risk factors for the presence and extent of focal WMH. Results: (1) Compared with healthy controls, patients with cirrhosis displayed decreased bilateral putamen, amygdala and nucleus accumbens volumes and increased bilateral globus pallidus volumes (P≤0.001). In the patient group, the volumes of the left putamen and amygdala negatively correlated with the number connection test-A (NCT-A) score (r=—0.410, P=0.034; r=—0.439, P=0.022), and the volumes of bilateral globus pallidus positively correlated with PI (r=0.889, P<0.001; r=0.900, P< 0.001). (2) Compared with healthy controls, patients with cirrhosis displayed significant decrease in normalized global GMV (P=0.042) and whole blood GSH levels (P<0.001) and a significant increase in serum MDA levels (P<0.001). In the patient group, serum MDA levels were negatively correlated with normalized global GMV adjusted for age, sex and Child-Pugh class (r=—0.378, P=0.036). (3) Compared with patients in no or mild WMH group, patients in moderate or severe WMH group were older (P=0.005) and with higher MHE prevalence (P=0.001) and showed worse results in the psychometric tests (P< 0.001). Correlation analysis revealed a significant positive correlation between the severity of focal WMH and NCT-A (r=0.617, P<0.001) and a significant negative correlation between the severity of focal WMH and DST (r=—0.695, P <0.001). Multivariate logistic regression analysis showed significant relationships between the severity of focal WMH and age (P=0.025) and MHE (P=0.007). Conclusion: (1) Abnormalities of subcortical volumes appeared bilaterally symmetrical in patients with cirrhosis. Decreased left putamen and amygdala volumes might contribute to poor neurocognitive performance, and the Mn deposition might contribute to increased globus pallidus volumes in patients with cirrhosis. (2) Increased serum MDA levels were associated with GMV loss in patients with cirrhosis, suggesting that oxidative damage may be involved in GMV loss observed in patients with cirrhosis. (3) The severity of focal WMH is related to neurocognitive impairment in patients with cirrhosis, and focal WMH indicates the possibility of MHE. 8 figures, 9 tables and 127 references. Keywords: cirrhosis; magnetic resonance imaging; subcortical volume; pallidal index; grey matter volume; glutathione; malondialdehyde; oxidative stress; white matter hyperintensity; minimal hepatic encephalopathy Classification: R445