TY - JOUR

T1 - Mapping of CSF transport using high spatiotemporal resolution dynamic contrast-enhanced MRI in mice

T2 - Effect of anesthesia

AU - Stanton, Evan Hunter

AU - Persson, Niklas Daniel Åke

AU - Gomolka, Ryszard Stefan

AU - Lilius, Tuomas

AU - Sigurðsson, Björn

AU - Lee, Hedok

AU - Xavier, Anna Lenice Ribeiro

AU - Benveniste, Helene

AU - Nedergaard, Maiken

AU - Mori, Yuki

PY - 2021

Y1 - 2021

N2 - 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.

AB - 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.

KW - cerebrospinal fluid flow

KW - dynamic contrast-enhanced magnetic resonance imaging

KW - fluid dynamics

KW - free precession sequence

KW - glymphatic system

U2 - 10.1002/mrm.28645

DO - 10.1002/mrm.28645

M3 - Journal article

C2 - 33426699

AN - SCOPUS:85099079435

VL - 85

SP - 3326

EP - 3342

JO - Magnetic Resonance in Medicine

JF - Magnetic Resonance in Medicine

SN - 0740-3194

IS - 6

ER -