Mapping of CSF transport using high spatiotemporal resolution dynamic contrast-enhanced MRI in mice: Effect of anesthesia

Evan Hunter Stanton, Niklas Daniel Åke Persson, Ryszard Stefan Gomolka, Tuomas Lilius, Björn Sigurðsson, Hedok Lee, Anna Lenice Ribeiro Xavier, Helene Benveniste, Maiken Nedergaard, Yuki Mori

Research output: Contribution to journalArticleScientificpeer-review


Purpose Dynamic contrast-enhanced MRI (DCE-MRI) represents the only available approach for glymphatic cerebrospinal fluid (CSF) flow 3D mapping in the brain of living animals and humans. The purpose of this study was to develop a novel DCE-MRI protocol for mapping of the glymphatic system transport with improved spatiotemporal resolution, and to validate the new protocol by comparing the transport in mice anesthetized with either isoflurane or ketamine/xylazine. Methods The contrast agent, gadobutrol, was administered into the CSF of the cisterna magna and its transport visualized continuously on a 9.4T preclinical scanner using 3D fast-imaging with a steady-state free-precession sequence (3D-FISP), which has a spatial resolution of 0.001 mm3 and a temporal resolution of 30 s. The MR signals were measured dynamically for 60 min in multiple volumes of interest covering the entire CSF space and brain parenchyma. Results The results confirm earlier findings that glymphatic CSF influx is higher under ketamine/xylazine than with isoflurane anesthesia. This was extended to account for new details about the distinct CSF efflux pathways under the two anesthetic regimens. Dynamic contrast MR shows that CSF clearance occurs mainly along the vagus nerve near the jugular vein under isoflurane and via the olfactory bulb under ketamine/xylazine. Conclusion The improved spatial and temporal sampling rates afforded by 3D-FISP shed new light on the pharmacological modulation of CSF efflux paths. The present observations may have the potential to set a new standard for future experimental DCE-MRI studies of the glymphatic system.
Original languageEnglish
JournalMagnetic Resonance in Medicine
Issue number6
Pages (from-to)3326-3342
Number of pages17
Publication statusPublished - 2021
MoE publication typeA1 Journal article-refereed

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