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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2026,5,5]]},"abstract":"<jats:p>\n                    According to glymphatic system theory, cerebrospinal fluid (CSF) perfuses the brain\u2019s interstitial space to support waste clearance, but the magnitude of this flow and the outflow pathway of interstitial fluid (ISF) in humans remain uncertain. To achieve flow quantification, we applied a compartment-model approach applied in conjunction with serial quantitative MRI data acquired after intrathecal gadolinium administration. Using the method, we estimated CSF-to-ISF inflow to 45 \u00b1 20 mL\/h, in patients with suspected idiopathic normal pressure hydrocephalus. Tissue-specific contributions were 34 \u00b1 14 mL\/h in cortical gray matter, 11\u00b16 mL\/h in white matter, and 0.4 \u00b1 0.3 mL\/h in subcortical gray matter, suggesting that CSF perfusion occurs primarily in superficial regions near the subarachnoid space. A lack of correlation between inflow and total craniospinal system outflow (r = 0.03,\n                    <jats:italic toggle=\"yes\">P<\/jats:italic>\n                    = 0.91) suggested that ISF recirculates back into CSF rather than exiting the craniospinal system via a separate route. Independent experiments in healthy older individuals using intravenous gadolinium administration supported ISF-to-CSF recirculation, where contrast material that presumably crossed the blood\u2013brain barrier subsequently appeared in the subarachnoid space, allowing ISF-to-CSF flow quantification. These findings provide a quantitative framework for studying brain clearance in humans and support subarachnoid space recirculation as an important efflux route.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2526239123","type":"journal-article","created":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T17:37:36Z","timestamp":1777484256000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":4,"title":["Quantitative assessment of flow between cerebrospinal and interstitial fluid compartments in humans"],"prefix":"10.1073","volume":"123","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6784-1945","authenticated-orcid":false,"given":"Anders","family":"W\u00e5hlin","sequence":"first","affiliation":[{"name":"Department of Applied Physics and Electronics, Ume\u00e5 University","place":["Ume\u00e5, Sweden"]},{"name":"Department of Diagnostics and Intervention, Biomedical Engineering and Radiation Physics, Ume\u00e5 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