Visualization of gadolinium transport across the blood-brain barrier along perivascular clearance pathways

We investigated the transport of gadolinium-based contrast agent (GBCA) across the blood-brain barrier (BBB) along the perivascular spaces as part of the glymphatic drainage in patients with iatrogenic BBB disruption following digital subtraction angiography (DSA).

A retrospective analysis was conducted on patients who underwent DSA for diagnosis and/or treatment of intracranial aneurysms and received a 3-T magnetic resonance imaging (MRI) within the following day. Exclusion criteria included states with a suggested impairment of BBB integrity, such as neurodegenerative diseases or suspected glymphatic impairment. BBB disruption was assessed using a pre- and post-contrast three-dimensional T1-weighted volume-isotropic turbo spin-echo sequence. Patterns of GBCA distributions were described. The localization of GBCA-extravasation was correlated with perivascular spaces visualized on the coregistered T2-weighted sequences. Fisher's exact test and logistic regression were used.

Out of 43 patients, 30 (69.8%) exhibited visible BBB disruption. BBB disruption was significantly more often observed after therapeutic DSA (p = 0.004). GBCA-enhancement patterns indicated a localized pial enhancement in 96.7% of affected patients, with additional parenchymal enhancement along the perivascular spaces in 56.7%. Enhancement was predominantly located in the downstream territories of probed vessels, suggesting a potential association with glymphatic transport. An illustrative case with serial MRI examinations is presented, demonstrating time-dependent GBCA-enhancement patterns.

The study provides in vivo evidence of GBCA transport patterns following iatrogenic BBB disruption, which may correspond to parts of the proposed glymphatic pathways. Our results indicate a sequential progression of contrast enhancement, initially manifesting at the brain surface and subsequently extending along perivascular spaces to the subarachnoid space.

Understanding BBB disruption and glymphatic transport with MRI imaging methods may improve neurovascular disease management.

BBB disruption post-DSA may facilitate GBCA transport via glymphatic pathways, offering novel and hypothesis-generating insights into brain clearance mechanisms. GBCA enhancement followed a chronological and spatial pattern, suggesting an organized cerebrospinal-interstitial exchange system relevant for brain clearance. Findings highlight potential implications for BBB integrity in neurovascular health with prospective implications for diagnostic imaging.