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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\u2010based contrast agents and monitoring their distribution and clearance over a period from a few hours up to 2\u2009days. 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 \u201cEU Joint Programme \u2013 Neurodegenerative Disease Research (JPND)\u201d 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\u2013time curves should be expected. This can be the basis for optimizing and interpreting contrast\u2010enhanced MRI for brain clearance imaging. Furthermore, this can shed light on how molecules may exchange between blood, brain, and CSF.<\/jats:p>","DOI":"10.1002\/nbm.5159","type":"journal-article","created":{"date-parts":[[2024,4,18]],"date-time":"2024-04-18T04:01:06Z","timestamp":1713412866000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":61,"title":["Human brain clearance imaging: Pathways taken by magnetic resonance imaging contrast agents after administration in cerebrospinal fluid and blood"],"prefix":"10.1002","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7034-8959","authenticated-orcid":false,"given":"Matthias J. P.","family":"van Osch","sequence":"first","affiliation":[{"name":"C. J. 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