Open this publication in new window or tab >>Umeå University, Faculty of Medicine, Department of Diagnostics and Intervention.
Umeå University, Faculty of Medicine, Department of Diagnostics and Intervention. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
Umeå University, Faculty of Medicine, Department of Diagnostics and Intervention. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
Umeå University, Faculty of Medicine, Department of Diagnostics and Intervention. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
Umeå University, Faculty of Medicine, Department of Diagnostics and Intervention.
Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics.
Umeå University, Faculty of Medicine, Department of Diagnostics and Intervention.
Umeå University, Faculty of Medicine, Department of Diagnostics and Intervention.
Umeå University, Faculty of Science and Technology, Department of Physics.
Umeå University, Faculty of Medicine, Department of Diagnostics and Intervention.
Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics.
Umeå University, Faculty of Medicine, Department of Diagnostics and Intervention. Department of Medical Physics, University of Wisconsin, School of Medicine and Public Health, WI, Madison, United States.
Umeå University, Faculty of Science and Technology, Department of Physics.
Umeå University, Faculty of Science and Technology, Department of Physics. Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR).
Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Diagnostics and Intervention.
Umeå University, Faculty of Medicine, Department of Clinical Sciences, Neurosciences.
Umeå University, Faculty of Medicine, Department of Diagnostics and Intervention. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
Show others...
2026 (English)In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 123, no 18, article id e2526239123Article in journal (Refereed) Published
Abstract [en]
According to glymphatic system theory, cerebrospinal fluid (CSF) perfuses the brain’s 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 ± 20 mL/h, in patients with suspected idiopathic normal pressure hydrocephalus. Tissue-specific contributions were 34 ± 14 mL/h in cortical gray matter, 11±6 mL/h in white matter, and 0.4 ± 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, P = 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–brain 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.
Place, publisher, year, edition, pages
Proceedings of the National Academy of Sciences (PNAS), 2026
Keywords
brain clearance, cerebrospinal fluid, flow, glymphatic system, interstitial fluid
National Category
Neurosciences
Identifiers
urn:nbn:se:umu:diva-253049 (URN)10.1073/pnas.2526239123 (DOI)2-s2.0-105037794560 (Scopus ID)
Funder
Swedish Foundation for Strategic Research, RMX18-0152Swedish Research Council, 2021-00711Swedish Research Council, 2022-04263Swedish Heart Lung Foundation, 20210653
2026-05-112026-05-112026-05-11Bibliographically approved