Brain Glymphatic/Lymphatic Imaging by MRI and PET

Abstract

Since glymphatic was proposed and meningeal lymphatic was discovered, MRI and even PET were introduced to investigate brain parenchymal interstitial fluid (ISF), cerebrospinal fluid (CSF), and lymphatic outflow in rodents and humans. Previous findings by ex vivo fluorescent microscopic, and in vivo two-photon imaging in rodents were reproduced using intrathecal contrast (gadobutrol and the similar)-enhanced MRI in rodents and further in humans. On dynamic MRI of meningeal lymphatics, in contrast to rodents, humans use mainly dorsal meningeal lymphatic pathways of ISF-CSF-lymphatic efflux. In mice, ISF-CSF exchange was examined thoroughly using an intra-cistern injection of fluorescent tracers during sleep, aging, and neurodegeneration yielding many details. CSF to lymphatic efflux is across arachnoid barrier cells over the dorsal dura in rodents and in humans. Meningeal lymphatic efflux to cervical lymph nodes and systemic circulation is also well-delineated especially in humans onintrathecal contrast MRI. Sleep-or anesthesia-related changes of glymphatic-lymphatic flow and the coupling of ISF-CSF-lymphatic drainage are major confounders ininterpreting brain glymphatic/lymphatic outflow in rodents. PET imaging in humans should be interpreted based on human anatomy and physiology, different in some aspects, using MRI recently. Based on the summary in this review, we propose non-invasive and longer-term intrathecal SPECT/PET or MRI studies to unravel the roles of brain glymphatic/lymphatic in diseases.

Repetitive transcranial magnetic stimulation increases the brain’s drainage efficiency in a mouse model of Alzheimer’s disease

“…Collectively, these findings provide novel mechanistic insights of rTMS for the treatment of early stage AD via improved clearance of Aβ deposits through brain glymphatic system and meningeal lymphatics. Our findings also suggest that improvement of CSF clearance efficiency, which can be measured by clinically available imaging techniques [ 4 , 33 , 39 ], may serve as a prognostic biomarker for the effectiveness of rTMS in AD patients.…”

“…Together with our findings that rTMS treatment prevented the cognitive decline in 5xFAD mice, we hypothesize that the still limited accumulation of toxic Aβ, neuroinflammation and neuronal damage at early stage of AD may allow for better therapeutic effect of rTMS. It is also worth noting that the clearance efficiency of the glymphatic/meningeal lymphatic systems can now be measured by clinically available imaging techniques like intrathecal injection of Gadobutrol-based contrast tracer in combination with dynamic contrast enhanced magnetic resonance imaging techniques [ 4 , 33 , 39 ], therefore could serve as the prognostic marker of the disease and the effectiveness of rTMS treatment. Further exploration of the mechanistic targets of rTMS is warranted for its therapeutic potential for patients with AD and other neuropsychiatric disorders.…”

Fluids and flows in brain cancer and neurological disorders

“…The CSF flow clears large proteins such as Aβ and Tau to the perivenous space through a dilution process with IF, finally removing them from the brain. These flows also clear through the meningeal lymphatics, found surrounding the brain, and into cervical lymph nodes (Eide et al, 2018;D. S. Lee et al, 2020).…”

A functional role of meningeal lymphatics in sex difference of stress susceptibility in mice

“…We would like to point out that the drainage function of the meningeal lymphatics can be assessed by clinically available imaging techniques, such as magnetic resonance imaging (MRI) and computed tomography (CT) 26,32,88,89 . It will therefore be worth examining in the future whether abnormalities in the meningeal lymphatics can serve as a novel biomarker for early diagnosis and prediction for the effectiveness of depression treatment in the clinics.…”