In Vivo Imaging of Lymphatic Drainage of Cerebrospinal Fluid in Mouse

BACKGROUND: Mouse models are commonly used to study central nervous system disorders, in which cerebrospinal fluid (CSF) drainage may be disturbed. However, mouse CSF drainage into lymphatics has not been thoroughly characterized. We aimed to image this using an in vivo approach that combined quantum dot fluorescent nanoparticles with hyperspectral imaging. FINDINGS: Quantum dot 655 was injected into the CSF of the cisterna magna in seven mice and visualized by in vivo hyperspectral imaging at time points 20 and 40 min, 1, 2, and 6 h after injection. In controls (n = 4), quantum dots were applied directly onto intact dura mater covering the cisterna magna. After imaging, lymph nodes in the neck were harvested and processed post-mortem for histological analysis. After injection into the CSF, quantum dot signal was detected in vivo in submandibular lymph nodes of all mice studied as early as 20 min, but not in controls. Post-mortem gross and histological examination of lymph nodes confirmed in vivo observations. CONCLUSIONS: Non-invasive in vivo hyperspectral imaging is a useful tool to study CSF lymphatic drainage and is relevant to understanding this pathway in CNS disease models.