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@ARTICLE{vanOsch:271079,
author = {van Osch, Matthias J P and Wåhlin, Anders and Scheyhing,
Paul and Mossige, Ingrid and Hirschler, Lydiane and Eklund,
Anders and Mogensen, Klara and Gomolka, Ryszard and
Radbruch, Alexander and Qvarlander, Sara and Decker, Andreas
and Nedergaard, Maiken and Mori, Yuki and Eide, Per Kristian
and Deike-Hofmann, Katerina and Ringstad, Geir},
title = {{H}uman brain clearance imaging: {P}athways taken by
magnetic resonance imaging contrast agents after
administration in cerebrospinal fluid and blood.},
journal = {NMR in biomedicine},
volume = {37},
number = {9},
issn = {0952-3480},
address = {New York, NY},
publisher = {Wiley},
reportid = {DZNE-2024-00951},
pages = {e5159},
year = {2024},
abstract = {Over the last decade, it has become evident that
cerebrospinal fluid (CSF) plays a pivotal role in brain
solute clearance through perivascular pathways and
interactions between the brain and meningeal lymphatic
vessels. Whereas most of this fundamental knowledge was
gained from rodent models, human brain clearance imaging has
provided important insights into the human system and
highlighted the existence of important interspecies
differences. Current gold standard techniques for human
brain clearance imaging involve the injection of
gadolinium-based contrast agents and monitoring their
distribution and clearance over a period from a few hours up
to 2 days. With both intrathecal and intravenous injections
being used, which each have their own specific routes of
distribution and thus clearance of contrast agent, a clear
understanding of the kinetics associated with both
approaches, and especially the differences between them, is
needed to properly interpret the results. Because it is
known that intrathecally injected contrast agent reaches the
blood, albeit in small concentrations, and that similarly
some of the intravenously injected agent can be detected in
CSF, both pathways are connected and will, in theory, reach
the same compartments. However, because of clear differences
in relative enhancement patterns, both injection approaches
will result in varying sensitivities for assessment of
different subparts of the brain clearance system. In this
opinion review article, the 'EU Joint Programme -
Neurodegenerative Disease Research (JPND)' consortium on
human brain clearance imaging provides an overview of
contrast agent pharmacokinetics in vivo following
intrathecal and intravenous injections and what typical
concentrations and concentration-time curves should be
expected. This can be the basis for optimizing and
interpreting contrast-enhanced MRI for brain clearance
imaging. Furthermore, this can shed light on how molecules
may exchange between blood, brain, and CSF.},
subtyp = {Review Article},
keywords = {Humans / Contrast Media: pharmacokinetics / Magnetic
Resonance Imaging / Brain: diagnostic imaging / Brain:
metabolism / Metabolic Clearance Rate / Animals /
Cerebrospinal Fluid: metabolism / Cerebrospinal Fluid:
diagnostic imaging / brain clearance (Other) / cerebrospinal
fluid (Other) / glymphatics (Other) / intrathecal injection
(Other) / intravenous injection (Other) / Contrast Media
(NLM Chemicals)},
cin = {AG Radbruch},
ddc = {610},
cid = {I:(DE-2719)5000075},
pnm = {353 - Clinical and Health Care Research (POF4-353)},
pid = {G:(DE-HGF)POF4-353},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:38634301},
doi = {10.1002/nbm.5159},
url = {https://pub.dzne.de/record/271079},
}