TY  - JOUR
AU  - van Osch, Matthias J P
AU  - Wåhlin, Anders
AU  - Scheyhing, Paul
AU  - Mossige, Ingrid
AU  - Hirschler, Lydiane
AU  - Eklund, Anders
AU  - Mogensen, Klara
AU  - Gomolka, Ryszard
AU  - Radbruch, Alexander
AU  - Qvarlander, Sara
AU  - Decker, Andreas
AU  - Nedergaard, Maiken
AU  - Mori, Yuki
AU  - Eide, Per Kristian
AU  - Deike-Hofmann, Katerina
AU  - Ringstad, Geir
TI  - Human brain clearance imaging: Pathways taken by magnetic resonance imaging contrast agents after administration in cerebrospinal fluid and blood.
JO  - NMR in biomedicine
VL  - 37
IS  - 9
SN  - 0952-3480
CY  - New York, NY
PB  - Wiley
M1  - DZNE-2024-00951
SP  - e5159
PY  - 2024
AB  - 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.
KW  - Humans
KW  - Contrast Media: pharmacokinetics
KW  - Magnetic Resonance Imaging
KW  - Brain: diagnostic imaging
KW  - Brain: metabolism
KW  - Metabolic Clearance Rate
KW  - Animals
KW  - Cerebrospinal Fluid: metabolism
KW  - Cerebrospinal Fluid: diagnostic imaging
KW  - brain clearance (Other)
KW  - cerebrospinal fluid (Other)
KW  - glymphatics (Other)
KW  - intrathecal injection (Other)
KW  - intravenous injection (Other)
KW  - Contrast Media (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:38634301
DO  - DOI:10.1002/nbm.5159
UR  - https://pub.dzne.de/record/271079
ER  -