TY - JOUR

T1 - Human brain clearance imaging

T2 - Pathways taken by magnetic resonance imaging contrast agents after administration in cerebrospinal fluid and blood

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, Katerina

AU - Ringstad, Geir

N1 - Publisher Copyright: © 2024 The Authors. NMR in Biomedicine published by John Wiley & Sons Ltd.

PY - 2024

Y1 - 2024

N2 - 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.

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 - brain clearance

KW - cerebrospinal fluid

KW - glymphatics

KW - intrathecal injection

KW - intravenous injection

U2 - 10.1002/nbm.5159

DO - 10.1002/nbm.5159

M3 - Review

C2 - 38634301

AN - SCOPUS:85190949684

JO - NMR in Biomedicine

JF - NMR in Biomedicine

SN - 0952-3480

ER -