{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T09:04:53Z","timestamp":1775898293015,"version":"3.50.1"},"posted":{"date-parts":[[2026,4,8]]},"group-title":"Radiology and Imaging","reference-count":25,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T00:00:00Z","timestamp":1775606400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.medrxiv.org\/about\/FAQ#license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,4,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Recently, a posterior pathway for fluid drainage from the retina to the meningeal lymphatics in the optic nerve (ON) sheath was identified in rodents using intravitreal imaging tracers directly injected into the ocular-globe. Fluid and solute clearance along this pathway may be associated with many diseases. However, intravitreal tracers are rarely used in clinical imaging. As intravenous Gadolinium-based-contrast-agent (GBCA) can enter the globe via the blood-ocular-barriers, it may provide an alternative approach to image this pathway.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Purpose<\/jats:title>\n                  <jats:p>To establish a clinically feasible intravenous GBCA-based MRI approach for tracking fluid and solute transport along the posterior lymphatic pathway in the ocular glymphatic system.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Materials&amp;Methods<\/jats:title>\n                  <jats:p>This prospective study was conducted from March 2021 to September 2022 in healthy participants. Dynamic-susceptibility-contrast-in-the-CSF (cDSC) MRI was performed before, immediately and 4 hours after intravenous-GBCA administration to track GBCA distribution in aqueous humor (AH) and cerebrospinal fluid (CSF) in regions-of-interest (ROIs) in the globe (anterior-cavity, vitreous-body), in the intraorbital and extraorbital ON, and in the intracranial CSF space proximal to the ON (chiasmatic-cistern, interpeduncular-cistern). Kruskal\u2013Wallis tests with post-hoc Dunn\u2019s tests were used for group comparisons.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>\n                    Sixteen healthy participants (mean age\u00b1SD: 51\u00b121 years, 5 men) were recruited. Intravenous-GBCA enhancement was observed in all ROIs immediately after injection. At 4-hour-post-GBCA, the vitreous body showed a trend of smaller enhancement area (55\u00b111% versus 49\u00b111%,\n                    <jats:italic>P<\/jats:italic>\n                    =.14) and lower GBCA-concentration (0.044\u00b10.014 versus 0.028\u00b10.010 mmol\/L,\n                    <jats:italic>P<\/jats:italic>\n                    =.07) compared to immediate-post-GBCA. The intraorbital ON showed more widespread enhancement (39\u00b15% versus 59\u00b16%,\n                    <jats:italic>P<\/jats:italic>\n                    =.01) and significantly higher GBCA-concentration (0.023\u00b10.009 versus 0.059\u00b10.015 mmol\/L,\n                    <jats:italic>P<\/jats:italic>\n                    &lt;.001) at 4-hour-post-GBCA.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Dynamic fluid and solute transportation along the posterior lymphatic pathway in the ocular glymphatic system in healthy participants was measured by tracking intravenous-GBCAs entering the globe via the blood-ocular-barriers using cDSC-MRI.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Summary Statement<\/jats:title>\n                  <jats:p>Dynamic fluid and solute transportation along the posterior lymphatic pathway in the ocular glymphatic system in healthy participants was measured by tracking intravenous-Gadolinium-based-contrast-agents entering ocular-globe via blood-ocular-barriers using dynamic-susceptibility-contrast-in-the-CSF (cDSC)-MRI.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Key Results<\/jats:title>\n                  <jats:list list-type=\"order\">\n                    <jats:list-item>\n                      <jats:p>In this prospective study of sixteen participants, Gadolinium-based-contrast-agent (GBCA)-induced signal changes were detected in the aqueous-humor and cerebrospinal fluid immediately following intravenous administration using dynamic-susceptibility-contrast-in-the-CSF (cDSC)-MRI.<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>\n                        At 4-hour-post-GBCA, the vitreous-body showed a trend of smaller enhancement area (55\u00b111% versus 49\u00b111%,\n                        <jats:italic>P<\/jats:italic>\n                        =.14) and lower GBCA-concentration (0.044\u00b10.014 versus 0.028\u00b10.010 mmol\/L,\n                        <jats:italic>P<\/jats:italic>\n                        =.07) compared to immediate-post-GBCA.\n                      <\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>\n                        The intraorbital-optic-nerve showed more widespread enhancement (39\u00b15% versus 59\u00b16%,\n                        <jats:italic>P<\/jats:italic>\n                        =.01) and higher GBCA-concentration (0.023\u00b10.009 versus 0.059\u00b10.015 mmol\/L,\n                        <jats:italic>P<\/jats:italic>\n                        &lt;.001) at 4-hour-post-GBCA.\n                      <\/jats:p>\n                    <\/jats:list-item>\n                  <\/jats:list>\n                <\/jats:sec>","DOI":"10.64898\/2026.04.03.26349283","type":"posted-content","created":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T00:05:39Z","timestamp":1775693139000},"source":"Crossref","is-referenced-by-count":0,"title":["Imaging solute transportation along the posterior lymphatic pathway in the ocular glymphatic system in healthy human participants"],"prefix":"10.64898","author":[{"given":"Xuehua","family":"Wen","sequence":"first","affiliation":[{"name":"Neurosection, Division of MRI Research, Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States;"},{"name":"Center for Rehabilitation Medicine, Department of Radiology, Zhejiang Provincial People\u2019s Hospital (Affiliated People\u2019s Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China;"},{"name":"F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, Maryland, United States;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuanqi","family":"Sun","sequence":"additional","affiliation":[{"name":"Neurosection, Division of MRI Research, Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States;"},{"name":"F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, Maryland, United States;"},{"name":"Department of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland, United States;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinyi","family":"Zhou","sequence":"additional","affiliation":[{"name":"Neurosection, Division of MRI Research, Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States;"},{"name":"F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, Maryland, United States;"},{"name":"Department of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland, United States;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yinghao","family":"Li","sequence":"additional","affiliation":[{"name":"Neurosection, Division of MRI Research, Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States;"},{"name":"F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, Maryland, United States;"},{"name":"Department of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland, United States;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adrian","family":"Paez","sequence":"additional","affiliation":[{"name":"Neurosection, Division of MRI Research, Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States;"},{"name":"F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, Maryland, United States;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacob","family":"Varghese","sequence":"additional","affiliation":[{"name":"Neurosection, Division of MRI Research, Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States;"},{"name":"F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, Maryland, United States;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jay J.","family":"Pillai","sequence":"additional","affiliation":[{"name":"Division of Neuroradiology, Mayo Clinic College of Medicine and Science, Rochester, Minnesota, United States;"},{"name":"Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linda","family":"Knutsson","sequence":"additional","affiliation":[{"name":"F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, Maryland, United States;"},{"name":"Department of Neurology, Johns Hopkins School of Medicine, Baltimore, Maryland, United States;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter C.M.","family":"Van Zijl","sequence":"additional","affiliation":[{"name":"Neurosection, Division of MRI Research, Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States;"},{"name":"F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, Maryland, United States;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard","family":"Leigh","sequence":"additional","affiliation":[{"name":"Department of Neurology, Johns Hopkins School of Medicine, Baltimore, Maryland, United States;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David O.","family":"Kamson","sequence":"additional","affiliation":[{"name":"Department of Neurology, Johns Hopkins School of Medicine, Baltimore, Maryland, United States;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christina R.","family":"Graley","sequence":"additional","affiliation":[{"name":"Department of Neurology, Johns Hopkins School of Medicine, Baltimore, Maryland, United States;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shiv","family":"Saidha","sequence":"additional","affiliation":[{"name":"Department of Neurology, Johns Hopkins School of Medicine, Baltimore, Maryland, United States;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arnold","family":"Bakker","sequence":"additional","affiliation":[{"name":"Department of Neurology, Johns Hopkins School of Medicine, Baltimore, Maryland, United States;"},{"name":"Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bryan K.","family":"Ward","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology - Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amir H.","family":"Kashani","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Wilmer Eye Institute, Johns Hopkins School of Medicine, Baltimore, Maryland, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Hua","sequence":"additional","affiliation":[{"name":"Neurosection, Division of MRI Research, Russell H. 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