Quantitative assessment of flow between cerebrospinal and interstitial fluid compartments in humans
Abstract
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.
Article Details
Journal Info
Proceedings of the National Academy of Sciences
National Academy of Sciences
Authors (21)
Anders Wåhlin
Department of Applied Physics and Electronics, Umeå University
Sofia Behndig
Department of Diagnostics and Intervention, Biomedical Engineering and Radiation Physics, Umeå University
Johan Eriksson De Ryst
Department of Clinical Science, Neurosciences, Umeå University
Viktor Vigren Näslund
Department of Diagnostics and Intervention, Biomedical Engineering and Radiation Physics, Umeå University
Daniel Dahlgren Lindström
Department of Diagnostics and Intervention, Biomedical Engineering and Radiation Physics, Umeå University
Jan Axelsson
Department of Diagnostics and Intervention, Biomedical Engineering and Radiation Physics, Umeå University
Cecilia Björnfot
Department of Diagnostics and Intervention, Biomedical Engineering and Radiation Physics, Umeå University
Mikael Bylund
Department of Diagnostics and Intervention, Biomedical Engineering and Radiation Physics, Umeå University
Anders Garpebring
Department of Diagnostics and Intervention, Biomedical Engineering and Radiation Physics, Umeå University
Petter Holmlund
Department of Applied Physics and Electronics, Umeå University
Afroditi Lalou
Department of Diagnostics and Intervention, Biomedical Engineering and Radiation Physics, Umeå University
Klara Mogensen
Department of Diagnostics and Intervention, Biomedical Engineering and Radiation Physics, Umeå University
Daniel P. G. Nilsson
Department of Physics, Umeå University
Sara Qvarlander
Department of Diagnostics and Intervention, Biomedical Engineering and Radiation Physics, Umeå University
Pontus Söderström
Department of Applied Physics and Electronics, Umeå University
Tomas Vikner
Department of Diagnostics and Intervention, Biomedical Engineering and Radiation Physics, Umeå University
Krister Wiklund
Department of Physics, Umeå University
Magnus Andersson
Department of Physics, Umeå University
Katrine Riklund
Umeå Center for Functional Brain Imaging, Umeå University
Jan Malm
Department of Clinical Science, Neurosciences, Umeå University
Anders Eklund
Department of Diagnostics and Intervention, Biomedical Engineering and Radiation Physics, Umeå University