Advancing insights into in vivo meningeal lymphatic vessels with stereoscopic wide-field photoacoustic microscopy

Fei Yang; Zhiyang Wang; Wenbin Shi; Miao Wang; Rui Ma; Wuyu Zhang; Xipeng Li; Erqi Wang; Wenjie Xie; Zhan Zhang; Qi Shen; Feifan Zhou; Sihua Yang

doi:10.1038/s41377-024-01450-0

Advancing insights into in vivo meningeal lymphatic vessels with stereoscopic wide-field photoacoustic microscopy

Light Sci Appl. 2024 Apr 25;13(1):96. doi: 10.1038/s41377-024-01450-0.

Authors

Fei Yang^#^{1

2}, Zhiyang Wang^#^{1

2}, Wenbin Shi^{1

2}, Miao Wang³, Rui Ma^{1

2}, Wuyu Zhang^{1

2}, Xipeng Li^{1

2}, Erqi Wang^{1

2}, Wenjie Xie^{1

2}, Zhan Zhang^{4

5}, Qi Shen^{6

7}, Feifan Zhou⁸, Sihua Yang^{9

10

11}

Affiliations

¹ MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, South China Normal University, Guangzhou, 510631, China.
² Guangdong Provincial Key Laboratory of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou, 510631, China.
³ Key Laboratory of Biomedical Engineering of Hainan Province, School of Biomedical Engineering, Hainan University, Haikou, 570100, China.
⁴ Department of Neurology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, China.
⁵ Guangdong Province Key Laboratory of Brain Function and Disease, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510120, China.
⁶ MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, South China Normal University, Guangzhou, 510631, China. shenqi@scnu.edu.cn.
⁷ Guangdong Provincial Key Laboratory of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou, 510631, China. shenqi@scnu.edu.cn.
⁸ Key Laboratory of Biomedical Engineering of Hainan Province, School of Biomedical Engineering, Hainan University, Haikou, 570100, China. zhouff@hainanu.edu.cn.
⁹ MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, South China Normal University, Guangzhou, 510631, China. yangsh@scnu.edu.cn.
¹⁰ Guangdong Provincial Key Laboratory of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou, 510631, China. yangsh@scnu.edu.cn.
¹¹ Guangdong Basic Research Center of Excellence for Structure and Fundamental Interactions of Matter, South China Normal University, Guangzhou, 510006, China. yangsh@scnu.edu.cn.

^# Contributed equally.

Abstract

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.

Abstract

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