基于多模态影像学的轻度脑外伤损伤机制及预后评估的个体差异研究

Mild traumatic brain injury (mTBI) is a prevalent public healthcare concern worldwide. Due to the heterogeneous and complex nature of injury pathophysiology arising from individual variations, the inconsistent findings in the literature has become a bottleneck of the injury mechanism investigation for clinical detection and outcome prediction. On the basis of previous research，this project will focus on individual-based investigation of mTBI and its outcome prediction by combining positron emission tomography (PET), diffusion tensor imaging (DTI), resting state functional magnetic resonance imaging (rs-fMRI), and serum blood biomarker techniques to elucidate the pathophysiological underpinning of mTBI. We will first determine the dopamine level of the injured patients by using PET in conjunction with patients’ neurocognitive evaluation to determine the influencing factor of individual difference. This step will provide a theoretical framework of dopaminergic pathway as an influencing factor that contributes to individual difference. To further elucidate the contribution of brain networks to patients’ outcome variation among individuals, we will determine brain white matter (WM) lesion load as well as the systematic density (participation coefficient) in functional network hub analysis. Furthermore, we will develop a dynamic evolution model by longitudinal comparing brain recovery and compensation (brain plasticity) from acute to chronic stages to further determine the individual difference. Finally, by combining the serum protein biomarker levels with imaging parameters in correlates with patients’ outcome, we will establish an analytical framework and physiological interpretation model for mTBI diagnosis and prognosis at individual level.

轻度脑外伤已成为神经精神系统疾病的高危风险因素，但因其损伤程度及临床表现的个体差异性导致前期研究结论不一致，已成为困扰损伤机制研究的瓶颈问题。本项目在前期研究基础上，将研究聚焦于轻度脑外伤损伤机制及预后的个体差异评估的关键技术研发，联合应用PET、弥散张量及功能静息态等多模态成像技术，以血内生物标记物变化为辅助生理解释。在个体差异的影响因素评估方面，借助PET影像采集患者伤后多巴胺水平，并结合个体应对创伤性事件的认知策略评估，形成损伤个体差异影响因素的理论建模；在个体差异的分析技术方面，研发基于损伤负担的白质纤维定量分析及基于系统密度（参与系数）的功能网络hub方法；在个体差异的结论解释方面，通过对比患者在急性期及慢性恢复期不同时点的脑损伤及代偿研究结果，建立损伤机制的动态演化模型，并联合血内生物标记物特征，建构基于个体差异的轻度脑外伤损伤及预后发生发展变化的分析方法框架及生理解释模型。

轻度脑外伤已成为神经精神系统疾病的高危风险因素，但因其损伤程度及临床表现的个体差异性导致前期研究结论不一致，已成为困扰损伤机制研究的瓶颈问题。本项目在前期研究基础上，联合应用PET、弥散张量及功能静息态等多模态成像技术，以血内生物标记物变化为辅助生理解释，将研究聚焦于轻度脑外伤损伤机制及预后的个体差异评估。本项目纳入了60名轻度脑外伤患者，52名健康被试。在个体差异的影响因素评估方面，借助PET影像采集患者伤后葡萄糖代谢水平，并结合个体伤后症状、应对创伤性事件的认知策略评估，形成损伤个体差异影响因素的理论建模；在个体差异的结论解释方面，通过对比患者在急性期及慢性恢复期不同时点的脑损伤及代偿研究结果，建立损伤机制的动态演化模型，并联合血内生物标记物特征，建构基于个体差异的轻度脑外伤损伤及预后发生发展变化的分析方法框架及生理解释模型。