不同亚型功能性消化不良杏仁核环路的脑功能及结构磁共振成像研究

Functional dyspepsia (FD), the most common functional gastrointestinal disorder, seriously compromises the quality of life of patients. According to the Rome III criteria, FD is simply classified into two subgroups based on patients’ main clinical performance; however, results from large cohort clinical studies questioned the effectiveness of the current FD diagnosis standard. It is urgent to develop new diagnosis and evaluation methods for FD. FD subgroups have different clinical performances and psychological traits (such as the anxiety). Neuroimaging studies based on the brain-gut axis have revealed that the main abnormalities of FD locate in limbic system regions. Our previous study also found that another type of functional gastrointestinal disorders showed increased activity in amygdala circuit. However, whether amygdala circuit would clarify the mechanism of psychological and emotional abnormalities of FD and whether it could be used as an indicator of FD image subtyping is unclear, which needs further investigation. The current project will examine the changes of amygdala circuit in FD subgroups, by combining the multi-mode magnetic resonance imaging (MRI) e.g., functional connectivity, structural connectivity, and clinical (level of brain-gut peptide) and neuropsychological evaluations. By doing this, this project will help to understand the neuropathology of FD psychological and emotional abnormalities. In addition, based on the amygdala circuit biomarker, we will further perform the image subtyping on FD by using clustering analysis-based pattern recognition, and then compare its effectiveness with the clinical classification, which will help to provide objective imaging evidence for more accurate clinical classification of FD in the future.

功能性消化不良(FD)是临床上最常见的功能性胃肠病，严重影响患者生活质量。现行罗马Ⅲ标准根据临床症状将FD简单分为两型，但大样本临床研究质疑该标准的效能，急需开发新的诊断评估方法。不同亚型FD的临床及精神心理特征(焦虑等)不同。基于脑-肠轴互动的神经影像学研究揭示FD的主要异常位于边缘系统等。申请人前期研究发现其他类型功能性胃肠病杏仁核环路活性增加，但杏仁核环路能否阐明不同亚型FD心理情绪异常的神经病理机制及用作FD影像学分型的指标尚需深入研究。本项目拟采用功能和结构连接等MR分析技术，建立FD杏仁核环路模型，观察不同亚型FD杏仁核环路的差异，并与临床(脑肠肽等)及精神心理量表评估进行相关分析，阐明不同亚型FD心理情绪异常的神经病理机制。基于杏仁核环路指标，拟利用模式识别聚类分析技术对FD进行影像学分型，并与临床分型进行比较分析，评估其效能，为今后FD更精准的临床分型提供客观的影像学依据。

在本项目中，我们使用多种磁共振成像分析方法，对功能性消化不良的神经病理生理机制进行了系统、深入的研究。我们比较了不同亚型功能性消化不良（上腹痛综合征、餐后不适综合征）和正常对照的脑灰质体积和脑功能的改变，发现功能性消化不良患者相比正常对照、以及不同亚型患者之间的脑灰质体积无明显差异，但与正常对照相比，不同亚型功能性消化不良都表现出双侧感觉运动皮层、丘脑、岛叶的脑神经自发活动增强。此外，仅上腹痛综合征亚型表现出前额叶脑神经自发活动的增强，而仅餐后不适综合征亚型表现出后扣带回活动的增强，该研究结果证实不同亚型功能性消化不良的神经病理生理机制存在共同点和不同点，提示脑功能磁共振检查能敏感检测功能性消化不良不同亚型的表现。此外，本项目还发现功能性消化不良患者脑白质功能连接网络出现异常，主要表现为连接额叶、脑岛以及丘脑的四对纤维骨架的白质功能连接减低。功能性消化不良患者杏仁核神经环路存在异常，且与另一种常见的功能性胃肠病-肠易激综合征杏仁核神经环路的改变模式不一致。. 通过国家自然科学基金的资助，项目组已基本完成了项目计划书的内容。目前课题组共发表SCI论著5篇、修回SCI论文1篇，发表中文论著3篇（含中华消化杂志1篇）、中文综述1篇。资助项目执行期间课题组培养肠病研究方向硕士研究生2名，课题组成员获“江苏省青年医学人才”、“江苏省333高层次人才”。