Yang Fei, Wang Zhiyang, Shi Wenbin, Wang Miao, Ma Rui, Zhang Wuyu, Li Xipeng, Wang Erqi, Xie Wenjie, Zhang Zhan, Shen Qi, Zhou Feifan, Yang Sihua
MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, South China Normal University, Guangzhou, 510631, China.
Guangdong Provincial Key Laboratory of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou, 510631, China.
Light Sci Appl. 2024 Apr 25;13(1):96. doi: 10.1038/s41377-024-01450-0.
Meningeal lymphatic vessels (mLVs) play a pivotal role in regulating metabolic waste from cerebrospinal fluid (CSF). However, the current limitations in field of view and resolution of existing imaging techniques impede understanding the stereoscopic morphology and dynamic behavior of mLVs in vivo. Here, we utilized dual-contrast functional photoacoustic microscopy to achieve wide-field intravital imaging of the lymphatic system, including mLVs and glymphatic pathways. The stereoscopic photoacoustic microscopy based on opto-acoustic confocal features has a depth imaging capability of 3.75 mm, facilitating differentiation between mLVs on the meninges and glymphatic pathways within the brain parenchyma. Subsequently, using this imaging technique, we were able to visualize the dynamic drainage of mLVs and identify a peak drainage period occurring around 20-40 min after injection, along with determining the flow direction from CSF to lymph nodes. Inspiringly, in the Alzheimer's disease (AD) mouse model, we observed that AD mice exhibit a ~ 70% reduction in drainage volume of mLVs compared to wild-type mice. With the development of AD, there is be continued decline in mLVs drainage volume. This finding clearly demonstrates that the AD mouse model has impaired CSF drainage. Our study opens up a horizon for understanding the brain's drainage mechanism and dissecting mLVs-associated neurological disorders.
脑膜淋巴管（mLVs）在调节脑脊液（CSF）中的代谢废物方面起着关键作用。然而，现有成像技术在视野和分辨率方面的当前局限性阻碍了对体内mLVs的立体形态和动态行为的理解。在这里，我们利用双对比功能光声显微镜实现了包括mLVs和类淋巴途径在内的淋巴系统的宽视野活体成像。基于光声共聚焦的立体光声显微镜具有3.75毫米的深度成像能力，有助于区分脑膜上的mLVs和脑实质内的类淋巴途径。随后，使用这种成像技术，我们能够可视化mLVs的动态引流，并确定注射后约20 - 40分钟出现的引流高峰期，同时确定从脑脊液到淋巴结的流动方向。令人鼓舞的是，在阿尔茨海默病（AD）小鼠模型中，我们观察到与野生型小鼠相比，AD小鼠的mLVs引流体积减少了约70%。随着AD的发展，mLVs引流体积持续下降。这一发现清楚地表明AD小鼠模型存在脑脊液引流受损的情况。我们的研究为理解大脑的引流机制和剖析与mLVs相关的神经疾病开辟了视野。
