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Eur Radiol. 2017 Jul;27(7):2877-2885. doi: 10.1007/s00330-016-4654-2. Epub 2016 Nov 10.

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

Author information

1
MR and CT Contrast Media Research, Bayer Pharma AG, Muellerstrasse 178, 13353, Berlin, Germany. gregor.jost@bayer.com.
2
MR and CT Contrast Media Research, Bayer Pharma AG, Muellerstrasse 178, 13353, Berlin, Germany.
3
Institute of Vegetative Physiology, Charité, Berlin, Germany.
4
Department of Radiology, Nagoya University Graduate School of Medicine, Nagoya, Japan.

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.

KEYWORDS:

Brain; Cerebrospinal fluid; Contrast media; Gadolinium; Magnetic resonance imaging

PMID:
27832312
PMCID:
PMC5486780
DOI:
10.1007/s00330-016-4654-2
[Indexed for MEDLINE]
Free PMC Article

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