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European Radiology
Published in: European Radiology 7/2017

Open Access 01-07-2017 | Contrast Media

Penetration and distribution of gadolinium-based contrast agents into the cerebrospinal fluid in healthy rats: a potential pathway of entry into the brain tissue

Authors: Gregor Jost, Thomas Frenzel, Jessica Lohrke, Diana Constanze Lenhard, Shinji Naganawa, Hubertus Pietsch

Published in: European Radiology | Issue 7/2017

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Abstract

Objective

Signal hyperintensity on unenhanced MRI in certain brain regions has been reported after multiple administrations of some, but not all, gadolinium-based contrast agents (GBCAs). One potential initial pathway of GBCA entry into the brain, infiltration from blood into the cerebrospinal fluid (CSF), was systematically evaluated in this preclinical study.

Methods

GBCA infiltration and distribution in the CSF were investigated in healthy rats using repeated fluid-attenuated MRI up to 4 h after high-dose (1.8 mmol/kg) administration of six marketed and one experimental GBCA. Additionally, gadolinium measurements in CSF, blood and brain tissue samples (after 24 h) were performed using inductively coupled plasma mass spectrometry.

Results

Enhanced MRI signals in the CSF spaces with similar distribution kinetics were observed for all GBCAs. No substantial differences in the gadolinium concentrations among the marketed GBCAs were found in the CSF, blood or brain tissue. After 4.5 h, the concentration in the CSF was clearly higher than in blood but was almost completely cleared and lower than the brain tissue concentration after 24 h.

Conclusions

In contrast to the brain signal hyperintensities, no differences in penetration and distribution into the CSF of healthy rats exist among the marketed GBCAs.

Key Points

• Gadolinium-based contrast agents can cross the blood-CSF barrier.
• Fluid-attenuated MRI shows GBCA distribution with CSF flow.
• GBCA structure and physicochemical properties do not impact CSF penetration and distribution.
• GBCA clearance from CSF was almost complete within 24 h in rats.
• CSF is a potential pathway of GBCA entry into the brain.
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Metadata
Title
Penetration and distribution of gadolinium-based contrast agents into the cerebrospinal fluid in healthy rats: a potential pathway of entry into the brain tissue
Authors
Gregor Jost
Thomas Frenzel
Jessica Lohrke
Diana Constanze Lenhard
Shinji Naganawa
Hubertus Pietsch
Publication date
01-07-2017
Publisher
Springer Berlin Heidelberg
Published in
European Radiology / Issue 7/2017
Print ISSN: 0938-7994
Electronic ISSN: 1432-1084
DOI
https://doi.org/10.1007/s00330-016-4654-2

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