Dynamic Magnetic Resonance Imaging of Human Subarachnoid Space Using Intrathecal Gadolinium Contrast

Summary

Background: Cerebrospinal fluid (CSF) is the liquid that fills the space around the brain and spinal cord. Researchers do not fully understand how CSF flows and drains around the brain. They want to test a tracer (gadobutrol)-a special dye injected into the CSF-to find out if it is safe to use and can help them get clearer pictures of the CSF during magnetic resonance imaging (MRI) scans of the brain. Objective: To test gadobutrol in the CSF during MRI scans of healthy people. Eligibility: Healthy volunteers aged 18 years and older. They must be screened under NIH protocol 89N0045. Design: Participants will check into the clinic for a 3-day stay. They will have a lumbar puncture: An area on their lower back will be numbed. A thin needle will be inserted into the space around the spinal cord. A sample of CSF will be taken for research. Then a low dose of gadobutrol will be injected into the CSF. Participants will have 4 or 5 MRI scans of the brain-30 minutes, 4 hours, 8 hours (this one is optional), 24 hours, and 48 hours after receiving the gadobutrol. For the scan, they will lie on a table that slides into a cylinder. Special padding will be used to hold their head still. The MRI uses magnetic fields to create images of the inside of the body. Blood and urine samples will also be collected at each scan. Participants will return for an additional MRI 1 week after they leave the clinic. They will have 2 follow-up phone calls 4 and 12 weeks after the start of the study.

Timeline

Start

2026-10-14

Primary completion

2028-03-15

Completion

2028-03-15

Publications

• Background Eide PK, Ringstad G. Cerebrospinal fluid egress to human parasagittal dura and the impact of sleep deprivation. Brain Res. 2021 Dec 1;1772:147669. doi: 10.1016/j.brainres.2021.147669. Epub 2021 Sep 26.
• Background Ringstad G, Eide PK. Safety of Intrathecal Gadolinium-based Contrast Agents and Benefit versus Risk. Radiology. 2021 Apr;299(1):E223-E224. doi: 10.1148/radiol.2021203351. Epub 2021 Feb 16. No abstract available.
• Background Patel M, Atyani A, Salameh JP, McInnes M, Chakraborty S. Safety of Intrathecal Administration of Gadolinium-based Contrast Agents: A Systematic Review and Meta-Analysis. Radiology. 2020 Oct;297(1):75-83. doi: 10.1148/radiol.2020191373. Epub 2020 Jul 28.
• Background Halvorsen M, Edeklev CS, Fraser-Green J, Lovland G, Vatnehol SAS, Gjertsen O, Nedregaard B, Sletteberg R, Ringstad G, Eide PK. Off-label intrathecal use of gadobutrol: safety study and comparison of administration protocols. Neuroradiology. 2021 Jan;63(1):51-61. doi: 10.1007/s00234-020-02519-4. Epub 2020 Aug 15.
• Background Edeklev CS, Halvorsen M, Lovland G, Vatnehol SAS, Gjertsen O, Nedregaard B, Sletteberg R, Ringstad G, Eide PK. Intrathecal Use of Gadobutrol for Glymphatic MR Imaging: Prospective Safety Study of 100 Patients. AJNR Am J Neuroradiol. 2019 Aug;40(8):1257-1264. doi: 10.3174/ajnr.A6136. Epub 2019 Jul 18.
• Background Eide PK, Lashkarivand A, Pripp A, Valnes LM, Hovd MH, Ringstad G, Blennow K, Zetterberg H. Plasma neurodegeneration biomarker concentrations associate with glymphatic and meningeal lymphatic measures in neurological disorders. Nat Commun. 2023 Apr 12;14(1):2084. doi: 10.1038/s41467-023-37685-5.
• Background Okar SV, Dieckhaus H, Beck ES, Gaitan MI, Norato G, Pham DL, Absinta M, Cortese IC, Fletcher A, Jacobson S, Nair G, Reich DS. Highly Sensitive 3-Tesla Real Inversion Recovery MRI Detects Leptomeningeal Contrast Enhancement in Chronic Active Multiple Sclerosis. Invest Radiol. 2024 Mar 1;59(3):243-251. doi: 10.1097/RLI.0000000000001011.
• Background Zhou Y, Cai J, Zhang W, Gong X, Yan S, Zhang K, Luo Z, Sun J, Jiang Q, Lou M. Impairment of the Glymphatic Pathway and Putative Meningeal Lymphatic Vessels in the Aging Human. Ann Neurol. 2020 Mar;87(3):357-369. doi: 10.1002/ana.25670. Epub 2020 Jan 30.
• Background Louveau A, Herz J, Alme MN, Salvador AF, Dong MQ, Viar KE, Herod SG, Knopp J, Setliff JC, Lupi AL, Da Mesquita S, Frost EL, Gaultier A, Harris TH, Cao R, Hu S, Lukens JR, Smirnov I, Overall CC, Oliver G, Kipnis J. CNS lymphatic drainage and neuroinflammation are regulated by meningeal lymphatic vasculature. Nat Neurosci. 2018 Oct;21(10):1380-1391. doi: 10.1038/s41593-018-0227-9. Epub 2018 Sep 17.
• Background Okar SV, Fagiani F, Absinta M, Reich DS. Imaging of brain barrier inflammation and brain fluid drainage in human neurological diseases. Cell Mol Life Sci. 2024 Jan 12;81(1):31. doi: 10.1007/s00018-023-05073-3.
• Background Ringstad G, Eide PK. Cerebrospinal fluid tracer efflux to parasagittal dura in humans. Nat Commun. 2020 Jan 17;11(1):354. doi: 10.1038/s41467-019-14195-x.
• Background Eide PK, Lashkarivand A, Hagen-Kersten AA, Gjertsen O, Nedregaard B, Sletteberg R, Lovland G, Vatnehol SAS, Pripp AH, Valnes LM, Ringstad G. Intrathecal Contrast-Enhanced Magnetic Resonance Imaging of Cerebrospinal Fluid Dynamics and Glymphatic Enhancement in Idiopathic Normal Pressure Hydrocephalus. Front Neurol. 2022 Apr 6;13:857328. doi: 10.3389/fneur.2022.857328. eCollection 2022.
• Background Eide PK, Pripp AH, Ringstad G, Valnes LM. Impaired glymphatic function in idiopathic intracranial hypertension. Brain Commun. 2021 Mar 21;3(2):fcab043. doi: 10.1093/braincomms/fcab043. eCollection 2021.
• Background Eide PK, Mariussen E, Uggerud H, Pripp AH, Lashkarivand A, Hassel B, Christensen H, Hovd MH, Ringstad G. Clinical application of intrathecal gadobutrol for assessment of cerebrospinal fluid tracer clearance to blood. JCI Insight. 2021 May 10;6(9):e147063. doi: 10.1172/jci.insight.147063.
• Background Smyth LCD, Xu D, Okar SV, Dykstra T, Rustenhoven J, Papadopoulos Z, Bhasiin K, Kim MW, Drieu A, Mamuladze T, Blackburn S, Gu X, Gaitan MI, Nair G, Storck SE, Du S, White MA, Bayguinov P, Smirnov I, Dikranian K, Reich DS, Kipnis J. Identification of direct connections between the dura and the brain. Nature. 2024 Mar;627(8002):165-173. doi: 10.1038/s41586-023-06993-7. Epub 2024 Feb 7.
• Background Absinta M, Ha SK, Nair G, Sati P, Luciano NJ, Palisoc M, Louveau A, Zaghloul KA, Pittaluga S, Kipnis J, Reich DS. Human and nonhuman primate meninges harbor lymphatic vessels that can be visualized noninvasively by MRI. Elife. 2017 Oct 3;6:e29738. doi: 10.7554/eLife.29738.
• Background Louveau A, Smirnov I, Keyes TJ, Eccles JD, Rouhani SJ, Peske JD, Derecki NC, Castle D, Mandell JW, Lee KS, Harris TH, Kipnis J. Structural and functional features of central nervous system lymphatic vessels. Nature. 2015 Jul 16;523(7560):337-41. doi: 10.1038/nature14432. Epub 2015 Jun 1.
• Background Aspelund A, Antila S, Proulx ST, Karlsen TV, Karaman S, Detmar M, Wiig H, Alitalo K. A dural lymphatic vascular system that drains brain interstitial fluid and macromolecules. J Exp Med. 2015 Jun 29;212(7):991-9. doi: 10.1084/jem.20142290. Epub 2015 Jun 15.

Drugs

Indications

No indication recorded.