Imaging the distribution and drainage of fluid in the human olfactory regions using intravenous Gadolinium-based contrast agents (GBCA) enhanced MRI.

Abstract

Background: Cerebrospinal fluid (CSF) clearance via the olfactory pathway is well-documented in animal models. However, results from in vivo human studies appear inconsistent. Studies using intrathecal (IT) Gadolinium-based contrast agents (GBCA) enhanced MRI showed minimal tracer pass-through from intracranial to extracranial olfactory regions such as the nasal mucosa. Conversely, human imaging studies using intravenous (IV) tracers showed significant enhancement in the nasal mucosa, suggesting CSF drainage through the cribriform plate. This research seeks to clarify these conflicting results from imaging studies using intrathecal and intravenous tracers, and to provide a better understanding of intravenous GBCA distribution in intracranial and extracranial olfactory regions, an important issue for studies using intravenous-GBCA-enhanced-MRI to investigate CSF clearance.

Methods: Dynamic-susceptibility-contrast-in-the-CSF (cDSC) MRI was applied to measure GBCA distribution in the CSF immediately and 4 h after intravenous administration in 25 healthy volunteers (48.9 ± 19.5 years; 14 females). A region-of-interest (ROI)-based and a voxel-based analysis were performed to measure GBCA concentration in intracranial and extracranial olfactory regions. Paired t-tests were used to compare pre- and post-GBCA signal changes.

Results: GBCA-induced signal changes were detected in all olfactory regions immediately and 4 h after intravenous GBCA administration. GBCA concentration was significantly greater (P < 0.01) in extracranial olfactory regions than intracranial olfactory regions. At 4 h post-GBCA, GBCA concentration decreased in extracranial olfactory regions compared to the immediate post-GBCA period, while it was comparable at both time points in intracranial olfactory regions.

Conclusions: Intravenous-GBCA-enhanced-MRI can detect GBCA distribution in the CSF space of olfactory regions in healthy subjects. The GBCA-induced CSF signal changes in intracranial olfactory regions were substantially smaller compared to extracranial olfactory regions. GBCA concentration in the CSF of intracranial olfactory regions was comparable to other intracranial regions. The significant GBCA-induced signal changes in extracranial olfactory regions may largely originate from peripheral blood supply when using intravenous tracers, which reflects lymphatic fluid circulation in the extracranial lymphatic system, and are not directly related to CSF clearance from the brain. Therefore, when using intravenous tracer-based imaging methods, it is critical to separate intracranial and extracranial regions in the analysis due to their different vascular supply.