{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T21:18:24Z","timestamp":1788297504952,"version":"build-2803163510"},"reference-count":47,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2020,10,23]],"date-time":"2020-10-23T00:00:00Z","timestamp":1603411200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To evaluate human glymphatics and meningeal lymphatics noninvasively.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This prospective study implemented 3\u2010dimensional (3D) isotropic contrast\u2010enhanced T2 fluid\u2010attenuated inversion recovery (CE\u2010T2\u2010FLAIR) imaging with a 3T magnetic resonance machine to study cerebral glymphatics and meningeal lymphatics in patients with reversible cerebral vasoconstriction syndrome (RCVS) with (n = 92) or without (n = 90) blood\u2013brain barrier (BBB) disruption and a diseased control group with cluster headache (n = 35). The contrast agent gadobutrol (0.2mmol\/kg [0.2ml\/kg]) was administered intravenously in all study subjects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In total, 217 patients (182 RCVS, 35 cluster headache) were analyzed and separated into 2 groups based on the presence or absence of visible gadolinium (Gd) leakage. Para\u2010arterial tracer enrichment was clearly depicted in those with overt BBB disruption, while paravenous and parasinus meningeal contrast enrichment was evident in both groups. Paravenous and parasinus contrast enrichment remained in RCVS patients in the remission stage and in cluster headache patients, suggesting that these meningeal lymphatic channels were universal anatomical structures rather than being phase\u2010 or condition\u2010specific. Additionally, we demonstrated nodular leptomeningeal enhancement in 32.3% of participants, which might represent potential lymphatic reservoirs. Four selected RCVS patients who received consecutive contrasted 3D isotropic FLAIR imaging after gadobutrol administration showed that the Gd persisted for at least 54\u2009minutes and was completely cleared within 18\u2009hours.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>This large\u2010scale in vivo study successfully demonstrated the putative human para\u2010arterial glymphatic transports and meningeal lymphatics by clear depiction of para\u2010arterial, parasinus, and paravenous meningeal contrast enrichment using high\u2010resolution 3D isotropic CE\u2010T2\u2010FLAIR imaging noninvasively; this technique may serve as a basis for further studies to delineate clinical relevance of glymphatic clearance. ANN NEUROL 2021;89:111\u2013124<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ana.25928","type":"journal-article","created":{"date-parts":[[2020,10,8]],"date-time":"2020-10-08T05:34:09Z","timestamp":1602135249000},"page":"111-124","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":87,"title":["Noninvasive Characterization of Human Glymphatics and Meningeal Lymphatics in an in vivo Model of Blood\u2013Brain Barrier Leakage"],"prefix":"10.1002","volume":"89","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1723-4797","authenticated-orcid":false,"given":"Chia\u2010Hung","family":"Wu","sequence":"first","affiliation":[{"name":"Institute of Clinical Medicine National Yang\u2010Ming University  Taipei Taiwan"},{"name":"School of Medicine National Yang\u2010Ming University  Taipei Taiwan"},{"name":"Department of Radiology Taipei Veterans General Hospital  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiing\u2010Feng","family":"Lirng","sequence":"additional","affiliation":[{"name":"School of Medicine National Yang\u2010Ming University  Taipei Taiwan"},{"name":"Department of Radiology Taipei Veterans General Hospital  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu\u2010Hsiang","family":"Ling","sequence":"additional","affiliation":[{"name":"School of Medicine National Yang\u2010Ming University  Taipei Taiwan"},{"name":"Department of Neurology Neurological Institute, Taipei Veterans General Hospital  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yen\u2010Feng","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Medicine National Yang\u2010Ming University  Taipei Taiwan"},{"name":"Department of Neurology Neurological Institute, Taipei Veterans General Hospital  Taipei Taiwan"},{"name":"Brain Research Center National Yang\u2010Ming University  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsiu\u2010Mei","family":"Wu","sequence":"additional","affiliation":[{"name":"School of Medicine National Yang\u2010Ming University  Taipei Taiwan"},{"name":"Department of Radiology Taipei Veterans General Hospital  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jong\u2010Ling","family":"Fuh","sequence":"additional","affiliation":[{"name":"School of Medicine National Yang\u2010Ming University  Taipei Taiwan"},{"name":"Department of Neurology Neurological Institute, Taipei Veterans General Hospital  Taipei Taiwan"},{"name":"Brain Research Center National Yang\u2010Ming University  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Po\u2010Chen","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Neurology Neurological Institute, Taipei Veterans General Hospital  Taipei Taiwan"},{"name":"Doctoral Degree Program of Translational Medicine National Yang\u2010Ming University and Academia Sinica  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuu\u2010Jiun","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Medicine National Yang\u2010Ming University  Taipei Taiwan"},{"name":"Department of Neurology Neurological Institute, Taipei Veterans General Hospital  Taipei Taiwan"},{"name":"Brain Research Center National Yang\u2010Ming University  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3492-9902","authenticated-orcid":false,"given":"Shih\u2010Pin","family":"Chen","sequence":"additional","affiliation":[{"name":"Institute of Clinical Medicine National Yang\u2010Ming University  Taipei Taiwan"},{"name":"School of Medicine National Yang\u2010Ming University  Taipei Taiwan"},{"name":"Department of Neurology Neurological Institute, Taipei Veterans General Hospital  Taipei Taiwan"},{"name":"Brain Research Center National Yang\u2010Ming University  Taipei Taiwan"},{"name":"Division of Translational Research, Department of Medical Research Taipei Veterans General Hospital  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,10,23]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/NEN.0000000000000096"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1136\/svn-2018-000197"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-44938-1"},{"key":"e_1_2_9_5_1","first-page":"51","article-title":"Studies on cerebro\u2010spinal fluid. 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