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Clinical application of intrathecal gadobutrol for assessment of cerebrospinal fluid tracer clearance to blood
Per K. Eide, … , Markus Herberg Hovd, Geir Ringstad
Per K. Eide, … , Markus Herberg Hovd, Geir Ringstad
Published April 6, 2021
Citation Information: JCI Insight. 2021;6(9):e147063. https://doi.org/10.1172/jci.insight.147063.
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Clinical Medicine Neuroscience

Clinical application of intrathecal gadobutrol for assessment of cerebrospinal fluid tracer clearance to blood

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Abstract

BACKGROUND Methodology for estimation of cerebrospinal fluid (CSF) tracer clearance could have wide clinical application in predicting excretion of intrathecal drugs and metabolic solutes from brain metabolism and for diagnostic workup of CSF disturbances.METHODS The MRI contrast agent gadobutrol (Gadovist) was used as a CSF tracer and injected into the lumbar CSF. Gadobutrol is contained outside blood vessels of the CNS and is eliminated along extravascular pathways, analogous to many CNS metabolites and intrathecal drugs. Tracer enrichment was verified and assessed in CSF by MRI at the level of the cisterna magna in parallel with obtaining blood samples through 48 hours.RESULTS In a reference patient cohort (n = 29), both enrichment within CSF and blood coincided in time. Blood concentration profiles of gadobutrol through 48 hours varied between patients diagnosed with CSF leakage (n = 4), idiopathic normal pressure hydrocephalus dementia (n = 7), pineal cysts (n = 8), and idiopathic intracranial hypertension (n = 4).CONCLUSION Assessment of CSF tracer clearance is clinically feasible and may provide a way to predict extravascular clearance of intrathecal drugs and endogenous metabolites from the CNS. The peak concentration in blood (at about 10 hours) was preceded by far peak tracer enhancement at MRI in extracranial lymphatic structures (at about 24 hours), as shown in previous studies, indicating a major role of the spinal canal in CSF clearance capacity.FUNDING The work was supported by the Department of Neurosurgery, Oslo University Hospital; the Norwegian Institute for Air Research; and the University of Oslo.

Authors

Per K. Eide, Espen Mariussen, Hilde Uggerud, Are H. Pripp, Aslan Lashkarivand, Bjørnar Hassel, Hege Christensen, Markus Herberg Hovd, Geir Ringstad

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Figure 5

Study design.

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Study design.
A standardized protocol was followed in all study particip...
A standardized protocol was followed in all study participants. T1-weighted MRI scanning was performed before the intrathecal (Ith) MRI contrast agent injection (Pre), and thereafter standardized T1-weighted MRI sequences were obtained at defined time points at 1, 2–2.5, 4–5, 5–6.5, 22–26, and 46–54 hours. Blood samples for whole blood concentration estimation of MRI contrast agent were obtained in conjunction with each of the MRI acquisitions. Illustration: Øystein Horgmo, University of Oslo.

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