Brain Glymphatic/Lymphatic Imaging by MRI and PET

Since glymphatic was proposed and meningeal lymphatic was discovered, MRI andeven PET were introduced to investigate brain parenchymal interstitial fluid (ISF),cerebrospinal fluid (CSF), and lymphatic outflow in rodents and humans. Previousfindings by ex vivo fluorescent microscopic, and in vivo two-photon imaging in rodentswere reproduced using intrathecal contrast (gadobutrol and the similar)-enhanced MRIin rodents and further in humans. On dynamic MRI of meningeal lymphatics, in contrastto rodents, humans use mainly dorsal meningeal lymphatic pathways of ISF-CSFlymphaticefflux. In mice, ISF-CSF exchange was examined thoroughly using an intracisterninjection of fluorescent tracers during sleep, aging, and neurodegenerationyielding many details. CSF to lymphatic efflux is across arachnoid barrier cells over thedorsal dura in rodents and in humans. Meningeal lymphatic efflux to cervical lymphnodes and systemic circulation is also well delineated especially in humans onintrathecal contrast MRI. Sleep- or anesthesia-related changes of glymphatic-lymphaticflow and the coupling of ISF-CSF-lymphatic drainage are major confounders ininterpreting brain glymphatic/lymphatic outflow in rodents. PET imaging in humansshould be interpreted based on human anatomy and physiology, different in someaspects, using MRI recently. Based on the summary in this review, we propose noninvasiveand longer-term intrathecal SPECT/PET or MRI studies to unravel the roles of brain glymphatic/lymphatic in diseases.