Prospective imaging study tracks gadolinium contrast transport in ocular glymphatic system of healthy participants

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medRxiv Published April 9, 2026 Medically reviewed April 25, 2026 Study authors: Wen, X.; Sun, Y.; Zhou, X.; Li, Y.; Paez, A.; Varghese, J.; Pillai, J. J.; Knutsson, L.; Van Zijl, P… DOI ↗ By Dr. Lars van Dijk, PhD · Surgical, Procedural & Diagnostic

Key Takeaway

Consider timing effects on GBCA distribution in ocular imaging, but evidence is preliminary.

This prospective imaging study enrolled 16 healthy participants to investigate fluid and solute transport along the posterior lymphatic pathway of the ocular glymphatic system. Using continuous dynamic susceptibility contrast MRI (cDSC-MRI), researchers tracked the distribution of an intravenous gadolinium-based contrast agent (GBCA) immediately after administration and again 4 hours later, focusing on its entry into the globe via the blood-ocular barriers. The primary outcome was tracking fluid and solute transport along this pathway, with secondary outcomes assessing GBCA distribution in aqueous humor and cerebrospinal fluid.

Key imaging findings showed dynamic changes in GBCA distribution over the 4-hour period. In the vitreous body, there was a non-significant trend toward a smaller enhancement area (55 ± 11% vs. 49 ± 11%, P=.14) and lower GBCA concentration (0.044 ± 0.014 vs. 0.028 ± 0.010 mmol/L, P=.07) at 4 hours compared to immediately post-administration. Conversely, in the intraorbital optic nerve, enhancement area was significantly more widespread at 4 hours (39 ± 5% vs. 59 ± 6%, P=.01), and GBCA concentration was significantly higher (0.023 ± 0.009 vs. 0.059 ± 0.015 mmol/L, P<.001).

Safety and tolerability data were not reported for this small cohort. The study has several important limitations, including its small sample size, single-arm design without a true control group, and focus on healthy participants only, limiting generalizability to patient populations. Funding sources and author conflicts of interest were also not reported.

For clinical practice, this study provides preliminary imaging evidence of dynamic GBCA transport in the ocular glymphatic system, which may inform future research on ocular fluid dynamics. However, these findings are exploratory and require replication in larger, more diverse cohorts before any clinical implications can be drawn. The observed changes in GBCA distribution over time highlight the potential for timing considerations in neuro-ophthalmic imaging protocols.

Study Details

EvidenceLevel 5

PublishedApr 2026

View Original Abstract ↓

Background: 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. Purpose: 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. Materials & Methods: 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-Wallis tests with post-hoc Dunn's tests were used for group comparisons. Results: Sixteen healthy participants (mean age +/- SD: 51 +/- 21 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 +/- 11% versus 49 +/- 11%, P=.14) and lower GBCA-concentration (0.044 +/- 0.014 versus 0.028 +/- 0.010 mmol/L, P=.07) compared to immediate-post-GBCA. The intraorbital ON showed more widespread enhancement (39 +/- 5% versus 59 +/- 6%, P=.01) and significantly higher GBCA-concentration (0.023 +/- 0.009 versus 0.059 +/- 0.015 mmol/L, P<.001) at 4-hour-post-GBCA. Conclusion: 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.

Prospective imaging study tracks gadolinium contrast transport in ocular glymphatic system of healthy participants

Study Details

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Prospective imaging study tracks gadolinium contrast transport in ocular glymphatic system of healthy participants

Study Details

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A Simple Scan Could Speed Up an ALS Diagnosis

Clinical research that matters. Delivered to your inbox.

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