Mapping of CSF transport using high spatiotemporal resolution dynamic contrast‐enhanced MRI in mice: Effect of anesthesia. Issue 6 (11th January 2021)

• Record Type: Journal Article
• Authors: Stanton, Evan Hunter; Persson, Niklas Daniel Åke; Gomolka, Ryszard Stefan; Lilius, Tuomas; Sigurðsson, Björn; Lee, Hedok; Xavier, Anna Lenice Ribeiro; Benveniste, Helene; Nedergaard, Maiken; Mori, Yuki
• Is Part Of: Magnetic resonance in medicine. Volume 85:Issue 6(2021)
• Page Start: 3326
• Page End: 3342
• Publication Date: 2021-01-11
• Subjects: cerebrospinal fluid flow -- dynamic contrast‐enhanced magnetic resonance imaging -- fluid dynamics -- free precession sequence -- glymphatic system; Nuclear magnetic resonance -- Periodicals; Electron paramagnetic resonance -- Periodicals; 616.07548
• DOI: 10.1002/mrm.28645
• Languages: English
• ISSNs: 0740-3194

Abstract

Abstract : 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 mm 3 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.