Glymphatic Pathway of Gadolinium-Based Contrast Agents through the Brain: Overlooked and Misinterpreted

Zielsetzung:

The “glymphatic system” (GS), a brain-wide network of cerebrospinal fluid microcirculation, supplies a pathway through and out of the central nervous system (CNS); malfunction of the system is implicated in a variety of neurological disorders. In this exploratory study, we analyzed the potential of a new imaging approach that we coined delayed T2-weighted gadolinium-enhanced imaging to visualize the GS in vivo.

Material und Methoden:

Heavily T2-weighted fluid-attenuated inversion recovery MRI (hT2w-FLAIR) was obtained before, 3h and 24h after intravenous gadolinium-based contrast agent (GBCA) application in 33 neurologically healthy patients and 7 patients with an impaired blood-brain barrier (BBB) due to cerebral metastases. Signal intensity (SI) was determined in various cerebral fluid spaces and white matter hyperintensities (WMHs) were quantified by applying the Fazekas scoring system (FS).

Ergebnisse:

Delayed hT2w-FLAIR showed GBCA entry into the CNS via the choroid plexus and the ciliary body, with GBCA drainage along perineural sheaths of cranial nerves, and along perivascular spaces of penetrating cortical arteries. In all patients and all sites, a significant SI increase was found for the 3h and 24h time point compared to baseline. While no significant difference in SI was found between neurologically healthy patients and patients with an impaired BBB, a significant positive correlation between FS and SI increase in the perivascular spaces 3h post injection was shown.

Schlussfolgerungen:

Delayed T2-weighted gadolinium-enhanced imaging can visualize the GBCA pathway into and through the GS. Presence of GBCAs within the GS might be regarded as part of the natural excretion process and should not be mixed up with gadolinium deposition. Rather, the found correlation between deep WMH, an imaging sign of vascular dementia, and GS functioning demonstrated feasibility to exploit the pathway of GBCAs through the GS for diagnostic purposes.