基于结构与静息态功能MRI神经网络分析对肝性脑病发作后持续性神经认知功能损害的机制研究

Hepatic encephalopathy (HE) is a frequent complication in cirrhotic patients. Recent studies demonstrate the persistence of cognitive impairments even after resolution of HE, such as deficits in learning and control-executive function, which predict higher risk of HE recurrence. However, it remains unknown about mechanisms underlying these cognitive impairments so far. Our primary finding is that patients with previous HE episode develop aberrant brain topological characteristics, which may be associated with the persistent cognitive impairments. Therefore, this study will involve 30 cirrhotic patients with previous HE, 30 cirrhotic patients without previous HE, and 30 age- and sex-matched healthy controls. The cognitive assessments, DTI and resting-state fMRI are administrated to each subject. Brain white-matter structural connection is depicted with DTI data; while functional connectivity is measured by temporal correlation based on resting-state fMRI data. Graph theory-based analyses are performed to characterize global and nodal properties of brain networks, which then are compared across three groups. The correlation analyses are also performed to examine the relationship between altered brain network properties and cognitive impairments. This study will improve our understanding about mechanisms underlying persistent cognitive deficits after HE, which would be useful in identifying potent biomarkers for treatment and secondary prophylaxis of HE.

肝性脑病（HE）是肝硬化常见并发症，及时诊治可使HE临床症状缓解、消失。但最新研究表明HE发作后患者会出现轻微而持续性神经认知功能损害，集中表现为执行控制能力及学习能力下降，并预示HE复发风险，关系到疾病的防治。而目前关于这些认知损害产生的特征性脑神经机制尚未清楚，无法为临床诊治提供有力证据。我们预实验发现HE发作后患者存在脑结构与功能网络拓扑学属性改变，有可能是认知损害的重要机制之一。在预实验及既往对HE患者脑部MRI研究的基础上，本课题以肝硬化患者为对象，基于DTI与静息态fMRI分别构建全脑结构、功能网络，应用图论分析，对比有HE发作史者、无HE发作史者、以及健康者脑网络拓扑学属性，检测全局网络效率的改变并定位相关异常脑区，分析脑网络异常与HE后认知障碍相关性，以从新的视角探寻HE后持续性认知损害的机制，有助于阐明HE演变规律，发掘潜在影像学标志，为HE诊治及预防提供新的理论依据。

研究背景和目的：显性肝性脑病（OHE）如得到及时诊治，患者可进入恢复期；近年来研究表明：恢复期内患者仍会持续存在轻微性认知功能损害（如执行控制和学习能力障碍），可被视为复发性的轻微型肝性脑病（MHE），其是OHE复发的独立风险因素，因此关系到疾病的二级防治。人脑认知功能的重要基础是优化的脑网络拓扑学组织结构，以同时保证高效的功能分割和功能整合能力。该项目研究目的为：应用基于结构与功能MRI的神经网络拓扑学分析对rMHE认知功能损害的机制进行探讨。方法：本研究入组具有OHE发作史肝硬化患者（Prior-OHE）30例、无OHE发作史肝硬化患者（non-Prior-OHE）30例、及健康被试者30例。采用PHES（Psychometric Hepatic Encephalopathy Score）系列量表评估被试者的认知功能水平。利用弥散张量成像成像（DTI）和静息态fMRI数据分别构建全脑结构、功能连接网络。图论方法用于分析脑结构和功能网络的拓扑学属性。利用相关性分析判断脑拓扑学属性改变与认知损害的关联性。结果：Prior-OHE组脑结构网络拓扑学效率属性（global efficiency、local efficiency）降低；而其脑功能网络退化向随机网络改变，总体效率下降，但也存在功能代偿性表现（如nodal efficiency升高）。以上改变从non-Prior-OHE到Prior-OHE呈现递进式发展，并与患者认知功能损害具有显著关联性。结论：全脑网络拓扑学属性改变是rMHE的重要特征，是患者认知损害的神经机制之一，可作为疾病监测和预后判断的潜在影像学标志；上述结果也为肝性脑病的二级诊治提供了新的理论依据。