Technical considerations for using intravenous gadolinium-based-contrast-agent (GBCA) based MRI approaches to study cerebrospinal fluid (CSF) circulation and clearance

Intravenously (IV) administered Gadolinium-based-contrast-agents (GBCAs) can enter the intracranial cerebrospinal-fluid (CSF) space via weak barriers between blood and CSF at multiple locations in the brain. This enables IV-GBCAs to be used as a tracer to study CSF circulation and clearance in the brain. With proper optimization, IV-GBCA induced signal changes can be robustly detected in various brain regions associated with CSF circulation. Nevertheless, whether these signal changes can be attributed to GBCA concentration changes in the CSF space should be interpreted with caution. This review attempts to discuss several technical challenges for using IV-GBCA MRI to study CSF circulation in the brain. First, it is critical to minimize the partial volume effects from the blood compartment as IV-GBCAs can present in both the blood and CSF compartments for a long time. Second, MRI approaches that can provide a quantitative measure of GBCA concentration in the CSF are preferred as raw MR signal intensities can often have a complicated relationship with GBCA concentration. Third, regions with intracranial and extracranial blood supply should be analyzed separately because GBCA distribution in regions with extracranial blood supply may not be a proper indicator for CSF clearance from the brain. Fourth, differences in the cerebrovasculature should be considered when comparing IV-GBCA concentration changes in the CSF in brain diseases. Finally, a proper reference signal needs to be established to calibrate longitudinal post-GBCA signals across sessions. Some of these issues may also apply to intrathecal GBCA MRI studies.