基于多尺度双模态成像技术探究注意缺陷多动障碍中脑类淋巴系统的作用机制

注意缺陷多动障碍（ADHD）是最常见的儿童精神行为发育障碍之一，其发病机制未完全阐明。本课题组前期研究显示ADHD患者脑内存在脑类淋巴系统的重要结构—V-R间隙增宽及脑白质发育不良，提示ADHD可能存在脑类淋巴系统异常。但脑类淋巴系统构成复杂，从μm至cm尺度的结构均参与代谢，目前的检测技术局限难以直接全面了解其代谢全过程。由于脑脊液中代谢废物经脑类淋巴系统排出，可以通过观察其代谢了解脑类淋巴系统。本研究拟采用非选择性双模态对比剂BCN-dual-NPs模拟脑代谢废物，使用双光子荧光显像及定量磁共振成像技术，并结合生物物理模型，以期通过多尺度双模态影像技术实现对ADHD动物模型脑类淋巴系统从微观到宏观的整体动态精准观测，探究ADHD脑类淋巴系统的结构及功能变化，并探讨脑类淋巴系统的影响因素在ADHD中的相关机制，为ADHD发病机制研究提供依据，并为其它精神行为发育障碍疾病提供新的研究思路。

Attention deficit/ hyperactivity disorder (ADHD) is one of the most common pediatric neurodevelopmental disorders, whose pathogenesis still remains unclear. Our previous studies showed that the V-R space, an important structure of the glymphatic system, was enlarged in ADHD patients, accompanied by the development retardation of white matter. The findings indicate that ADHD patients may have an abnormal glymphatic system structure and function. Nonetheless, the histological structures of glymphatic system are very complicated, including the structures rangeing form several μm to 1 cm. The previous imaging technique can hardly observe the full metabolic process of glymphatic system directly. Since the metabolic waste in the cerebrospinal fluid can be cleared away by the glymphatic system, the observation of this process can help us to learn the structure and function of the glymphatic system. In this study, the nonselective dual-modality contrast agent, BCN-dual-NPs, will be invoked to simulate the metabolic waste. Both two-photon florescence imaging and magnetic resonance imaging (MRI) with post-processing by histological MRI will be used to observe the glymphatic system in ADHD mouse model. With the help of such multimodal and multiscale imaging technique, this study aims to evaluate the structural and functional change in the glymphatic system of ADHD from the microscopic to the macroscopic dimensions. Furthermore, the investigation on the alteration of the associated drivers of glymphatic transport in ADHD will be conducted. The main purpose of this study is to provide evidences for further researches of ADHD pathogenesis, as well as to provide new insights into the pathogenic mechanism of the other neurodevelopmental diseases.