Quantitative Analysis of Blood to CSF Exchange over 24 Hours Following Intravenous Contrast MRI

Background Impairment of the glymphatic system and brain solute clearance is associated with aging, traumatic brain injury, and neurodegenerative pathology, motivating efforts to quantify glymphatic transport in humans. Intrathecal contrast-enhanced MRI directly probes CSF–ISF exchange but has limited research applicability. Intravenous gadolinium-based contrast agents (GBCAs) are known to enter intracranial CSF, suggesting a complementary, less invasive strategy to probe brain fluid transport. Methods Hourly MRI data was acquired over a 24-hour period following IV GBCA administration in seven healthy adults. Quantitative T1 mapping was analyzed using linear mixed-effects models (LMMs) to test the effect of time across vascular, CSF, and brain compartments. A heavily T2-weighted inversion recovery sequence was included to improve identification of low concentration of GBCA in fluid compartments. Finally, pharmacokinetic compartment models were used to estimate transport between blood, CSF, and brain interstitial compartments. Results Quantitative MRI following intravenous GBCA administration indicates significant transport between the blood and subarachnoid space (SAS) (p < 0.001), with evidence for the involvement of the cerebral veins on hT2w-IR. In contrast, transport between the blood and ventricular CSF is comparatively limited (p = 0.923). Kinetic modeling further suggests that the SAS is not a single well-mixed compartment but best represented by both mobile regions and “sluggish” compartments. Conclusions Finally, exchange of GBCA into the brain interstitial space was not reliably detected, indicating that IV GBCA–based MRI is unlikely to provide a sensitive or specific measure of glymphatic CSF–ISF exchange. Together, these findings help refine the role of IV contrast MRI studies for quantifying solute transport in the human CNS and highlight important constraints on its use for assessing glymphatic function in humans.