Knutsson, Linda

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. Summary Statement 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. Key Results 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. 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-optic-nerve showed more widespread enhancement (39±5% versus 59±6%, P =.01) and higher GBCA-concentration (0.023±0.009 versus 0.059±0.015 mmol/L, P <.001) at 4-hour-post-GBCA.

Dynamic fluid and solute transportation across the arachnoid barrier in the meninges of healthy participants was measured by tracking intravenous gadolinium-based contrast agent entering cerebrospinal fluid from dural blood vessels using dynamic dual-spin-echo perfusion MRI.

AbstractAccumulating evidence from recent studies has indicated the importance of studying the interaction between the microvascular and lymphatic systems in the brain. To date, most imaging methods can only measure blood or lymphatic vessels separately, such as dynamic susceptibility contrast (DSC) MRI for blood vessels and DSC MRI‐in‐the‐cerebrospinal fluid (CSF) (cDSC MRI) for lymphatic vessels. An approach that can measure both blood and lymphatic vessels in a single scan offers advantages such as a halved scan time and contrast dosage. This study attempts to develop one such approach by optimizing a dual‐echo turbo‐spin‐echo sequence, termed “dynamic dual‐spin‐echo perfusion (DDSEP) MRI”. Bloch simulations were performed to optimize the dual‐echo sequence for the measurement of gadolinium (Gd)‐induced blood and CSF signal changes using a short and a long echo time, respectively. The proposed method furnishes a T1‐dominant contrast in CSF and a T2‐dominant contrast in blood. MRI experiments were performed in healthy subjects to evaluate the dual‐echo approach by comparing it with existing separate methods. Based on simulations, the short and long echo time were chosen around the time when blood signals show maximum difference between post‐ and pre‐Gd scans, and the time when blood signals are completely suppressed, respectively. The proposed method showed consistent results in human brains as previous studies using separate methods. Signal changes from small blood vessels occurred faster than from lymphatic vessels after intravenous Gd injection. In conclusion, Gd‐induced signal changes in blood and CSF can be detected simultaneously in healthy subjects with the proposed sequence. The temporal difference in Gd‐induced signal changes from small blood and lymphatic vessels after intravenous Gd injection was confirmed using the proposed approach in the same human subjects. Results from this proof‐of‐concept study will be used to further optimize DDSEP MRI in subsequent studies.