结合脑连接与生物标记物分析的轻度脑外伤损伤机制及针刺干预验证

Mild traumatic brain injury (mTBI), the morbidity rate as high as 1%, is not considered as “mild”, which can induce sever and long-lasting emotion and cognitive impairments. More attentions have been paid to the clinical challenge problems about the accurate diagnosis and prognosis evaluation of mTBI. On the basis of preliminary study, the current project focuses on the model of brain injury of mTBI by combining neuroimaging and blood biomarkers. By employing multi-time points tracking in a longitude study, we aim to design the research from the main mTBI characteristics including the time-varying injury pattern, coherences of brain functional and structural changes, as well as the individual differences in injury severity and outcomes. The overarching focus of this proposal is to develop the following key techniques including the brain connectivity properties methods, biomarker based quantitative analysis as well as clinical targeting verification through acupuncture therapy. Firstly, to handle the low sensitivity of CT technique, we develop the brain connectivity analysis and coherence of brain function and structural methods to explore the characteristics of time-varying and coexisting relations between brain structural and function injuries by using MRI. Secondly, this project aims to collect neuroimaging and blood biomarker datasets and develop machine learning method to predict neuropsychological outcomes in individual patients, which can address the limitation of subjective bias by post concussion symptom. Finally, this project employs acupuncture intervention treatment to verify the application of the injury model based on the concept of “Theranostics”, which can address the issue of clinical verification and feedback improvements in the developed methods.

发病率高达1%的轻度脑外伤并非“轻度”，可诱发持续的情绪及认知功能障碍，围绕其准确诊断与预后评估研究一度成为医学界的挑战性问题。本项目在前期研究基础上，聚焦于影像学与血液生物标记物联合表征的轻度脑外伤损伤机制模型建构，突破其损伤的动态时变性、结构功能共变性、个体差异性的研究方法瓶颈，围绕脑连接模型建构、血液生物标记物定量分析、针刺治疗靶向验证一条主线展开研究。首先，区别于以往CT技术灵敏度低的问题，采用多时点动态跟踪磁共振成像技术，研发脑网络属性表征与结构功能耦合共变方法，构建损伤机制动态模型；其次，区别于以往脑外伤后遗症评价的主观偏倚性问题，引入多维血液生物标记物客观指标，并研发基于个体差异的模式识别预后分类方法，实现损伤机制模型的定量分析；最后，区别以往研究缺乏治疗干预验证的问题，以针刺治疗为干预手段，实现“诊断治疗学”为核心的影像学和血液生物标记物联合表征的损伤机制模型的有效性验证。

发病率高达1%的轻度脑外伤并非“轻度”，可诱发持续的情绪及认知功能障碍，围绕其准确诊断与预后评估研究一度成为医学界的挑战性问题。本项目聚焦于本项目聚焦于建构磁共振成像的轻度脑外伤损伤机制模型，通过多时点跟踪实验，以损伤的动态时变性、个体差异性、结构功能共变性为切入点，围绕脑连接计算方法、血液生物标记物联合评估、针刺治疗验证等关键科学问题展开研究。首先，突破动态时变性与结构功能共变性研究瓶颈，研发脑网络属性表征与结构功能耦合共变方法，构建了胼胝体亚分区结构纤维辐射功能连接度及尾状核功能亚分区网络损伤机制模型；其次，联合影像学与血液炎症因子生物标记物客观指标，探讨了轻度脑外伤炎症因子与认知障碍存在的相关调节关系，并研发基于个体损伤差异的影像与血液标记物特征的轻度脑外伤预后评估方法，实现对损伤机制模型的定量分析；接着，围绕轻度脑外伤损伤的性别差异问题，分别从形态皮层厚度、功能脑网络连接模式及脑血流代谢水平差异等不同维度探讨了性别差异的损伤机制；最后，在揭示轻度脑外伤头痛涉及疼痛重要核团与缺省模式脑网络认知偏向调节异常的基础上，以针刺治疗为干预手段，进一步探讨了针刺相对于安慰剂存在认知为导向的偏侧性调节干预机制。项目执行期内在Journal of Neurology Neurosurgery and Psychiatry (SCI IF: 8.2), Journal of Neurotrauma（SCI IF：5.002）等SCI检索国际期刊发表论文共12篇，国际会议论文12篇，授权国家发明专利1项,获批软件著作权3项；项目负责人入选三秦人才学者计划。研究成果得到发表在Nature Reviews Neuroscience，Neuroscience & Biobehavioral Reviews等论文的正面引用。项目负责人，作为副主编著有《针灸影像学》学术专著一部；参编英文专著两部，联合领域专家出版专刊2部。项目执行期内培养博硕士共8名，2名研究人员晋升副高职称；项目负责人作为主要发起人，协助推动了中国针灸学会脑科学产学研创新联盟的成立，担任副理事长及副秘书长，有效促进学科的发展与进步。课题组还与美国哈佛大学，佛罗里达大学，香港大学建立了长期的互访人员培养计划。