{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T01:23:42Z","timestamp":1793582622640,"version":"4.5.0"},"reference-count":58,"publisher":"American Society for Clinical Investigation","issue":"23","license":[{"start":{"date-parts":[[2023,12,8]],"date-time":"2023-12-08T00:00:00Z","timestamp":1701993600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Regional Health Authority South-East of Norway","award":["2020098"],"award-info":[{"award-number":["2020098"]}]},{"DOI":"10.13039\/501100010100","name":"\u00d8stfold Hospital Trust","doi-asserted-by":"crossref","award":["AB3501"],"award-info":[{"award-number":["AB3501"]}],"id":[{"id":"10.13039\/501100010100","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,12,8]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND<\/jats:title>\n                    <jats:p>Intrathecal injection is an attractive route through which drugs can be administered and directed to the spinal cord, restricted by the blood-spinal cord barrier. However, in vivo data on the distribution of cerebrospinal fluid (CSF) substances in the human spinal cord are lacking. We conducted this study to assess the enrichment of a CSF tracer in the upper cervical spinal cord and the brain stem.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>After lumbar intrathecal injection of a magnetic resonance imaging (MRI) contrast agent, gadobutrol, repeated blood samples and MRI of the upper cervical spinal cord, brain stem, and adjacent subarachnoid spaces (SAS) were obtained through 48 hours. The MRI scans were then analyzed for tracer distribution in the different regions and correlated to age, disease, and amounts of tracer in the blood to determine CSF-to-blood clearance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>The study included 26 reference individuals and 35 patients with the dementia subtype idiopathic normal pressure hydrocephalus (iNPH). The tracer enriched all analyzed regions. Moreover, tracer enrichment in parenchyma was associated with tracer enrichment in the adjacent SAS and with CSF-to-blood clearance. Clearance from the CSF was delayed in patients with iNPH compared with younger reference patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>A CSF tracer substance administered to the lumbar thecal sac can access the parenchyma of the upper cervical spinal cord and brain stem. Since CSF-to-blood clearance is highly individual and is associated with tracer level in CSF, clearance assessment may be used to tailor intrathecal treatment regimes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>FUNDING<\/jats:title>\n                    <jats:p>South-Eastern Norway Regional Health and \u00d8stfold Hospital Trust supported the research and publication of this work.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1172\/jci.insight.173276","type":"journal-article","created":{"date-parts":[[2023,12,7]],"date-time":"2023-12-07T14:00:47Z","timestamp":1701957647000},"source":"Crossref","is-referenced-by-count":14,"title":["In vivo distribution of cerebrospinal fluid tracer in human upper spinal cord and brain stem"],"prefix":"10.1172","volume":"8","author":[{"given":"Erik","family":"Melin","sequence":"first","affiliation":[{"name":"Department of Radiology, \u00d8stfold Hospital Trust, Gr\u00e5lum, Norway."},{"name":"Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Are Hugo","family":"Pripp","sequence":"additional","affiliation":[{"name":"Oslo Centre of Biostatistics and Epidemiology, Research Support Services, Oslo, Norway."},{"name":"Faculty of Health Sciences, OsloMet - Oslo Metropolitan University, Oslo, Norway."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Per Kristian","family":"Eide","sequence":"additional","affiliation":[{"name":"Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway."},{"name":"Department of Neurosurgery and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0919-4510","authenticated-orcid":true,"given":"Geir","family":"Ringstad","sequence":"additional","affiliation":[{"name":"Department of Radiology, Oslo University Hospital-Rikshospitalet, Oslo, Norway."},{"name":"Department of Geriatrics and Internal medicine, Sorlandet Hospital, Arendal, Norway."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2023,12,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics14061283"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-199222050-00001"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.2147\/JPR.S37591"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pharmtox-010716-104846"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1007\/s13311-022-01247-2"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2017.04.010"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2016.12.015"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.121537"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-022-00500-9"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-07318-3"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(95)01228-1"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2017.05.028"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-13455-4"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1177\/0271678X18754732"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(16)31408-8"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awx191"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24271"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.2174\/1570159X14666160307145542"},{"key":"B19","first-page":"739","article-title":"Activities and sites of antinociceptive action of morphine-like analgesics and kinetics of distribution following intravenous, intracerebral and intraventricular application","volume":"6","author":"Herz","year":"1971","journal-title":"Adv Drug Res"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1097\/00000542-200003000-00018"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1172\/JCI67677"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1126\/science.adc8810"},{"key":"B23"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1977.tb09740.x"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(82)90403-4"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(78)91146-0"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1097\/00000542-198405000-00010"},{"key":"B28","unstructured":"European Medicines Agency. Annex I Summary of Product Characteristics . https:\/\/www.ema.europa.eu\/en\/documents\/product-information\/spinraza-epar-product-information_en.pdf Accessed October 31, 2023"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0173680"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-023-04634-3"},{"issue":"3","key":"B31","first-page":"431","article-title":"A proposed model of cerebrospinal fluid circulation: observations with radionuclide cisternography","volume":"17","author":"Greitz","year":"1996","journal-title":"AJNR Am J Neuroradiol"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1002\/ana.22421"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.147063"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-12568-w"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-14195-x"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-020-03706-5"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.12.040"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-022-01029-1"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awab388"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1186\/s12987-022-00352-w"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1148\/radiology.166.2.3336724"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awaa443"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1186\/s12987-023-00459-8"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1126\/science.1241224"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-018-1916-x"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2019.05.005"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2023.01.054"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2022.06.067"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.3174\/ajnr.A5931"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1002\/dad2.12030"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1007\/s11916-013-0388-x"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.1991.52"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1097\/00000542-199102000-00012"},{"issue":"4","key":"B54","first-page":"703","article-title":"Clinical pharmacology of intrathecal methotrexate. I. Pharmacokinetics in nontoxic patients after lumbar injection","volume":"61","author":"Bleyer","year":"1977","journal-title":"Cancer Treat Rep"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1983.1.9.546"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1007\/BF02228887"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkac956"},{"key":"B58","unstructured":"Bayer Inc. Product Monograph for Gadovist. www.bayer.com\/sites\/default\/files\/2020-11\/gadovist-pm-en_0.pdf. Accessed October 31, 2023"}],"container-title":["JCI Insight"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/insight.jci.org\/articles\/view\/173276\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T21:45:30Z","timestamp":1779140730000},"score":1,"resource":{"primary":{"URL":"https:\/\/insight.jci.org\/articles\/view\/173276"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,8]]},"references-count":58,"journal-issue":{"issue":"23","published-online":{"date-parts":[[2023,12,8]]},"published-print":{"date-parts":[[2023,12,8]]}},"alternative-id":["10.1172\/jci.insight.173276"],"URL":"https:\/\/doi.org\/10.1172\/jci.insight.173276","relation":{},"ISSN":["2379-3708"],"issn-type":[{"value":"2379-3708","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,12,8]]},"article-number":"e173276"}}