Retention of Gadolinium in Brain Parenchyma: Pathways for Speciation, Access, and Distribution. A Critical Review

Rasschaert, Marlene and Weller, Roy O. and Schroeder, Josef A. and Brochhausen, Christoph and Idee, Jean-Marc (2020) Retention of Gadolinium in Brain Parenchyma: Pathways for Speciation, Access, and Distribution. A Critical Review. JOURNAL OF MAGNETIC RESONANCE IMAGING, 52 (5). pp. 1293-1305. ISSN 1053-1807, 1522-2586

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Abstract

The unexpected appearance of T-1 hyperintensities, mostly in the dentate nucleus and the globus pallidus, during nonenhanced MRI was reported in 2014. This effect is associated with prior repeated administrations of gadolinium (Gd)-based contrast agents (GBCAs) in patients with a functional blood-brain barrier (BBB). It is widely assumed that GBCAs do not cross the intact BBB, but the observation of these hypersignals raises questions regarding this assumption. This review critically discusses the mechanisms of Gd accumulation in the brain with regard to access pathways, Gd species, tissue distribution, and subcellular location. We propose the hypothesis that there is early access of Gd species to cerebrospinal fluid, followed by passive diffusion into the brain parenchyma close to the cerebral ventricles. When accessing areas rich in endogenous metals or phosphorus, the less kinetically stable GBCAs would dissociate, and Gd would bind to endogenous macromolecules, and/or precipitate within the brain tissue. It is also proposed that Gd species enter the brain parenchyma along penetrating cortical arteries in periarterial pial-glial basement membranes and leave the brain along intramural peri-arterial drainage (IPAD) pathways. Lastly, Gd/GBCAs may access the brain parenchyma directly from the blood through the BBB in the walls of capillaries. It is crucial to distinguish between the physiological distribution and drainage pathways for GBCAs and the possible dissociation of less thermodynamically/kinetically stable GBCAs that lead to long-term Gd deposition in the brain. Level of Evidence 5. Technical Efficacy Stage 3.

Item Type: Article
Uncontrolled Keywords: NEPHROGENIC SYSTEMIC FIBROSIS; CENTRAL-NERVOUS-SYSTEM; T1-WEIGHTED MR-IMAGES; T1 SIGNAL INTENSITY; CONTRAST AGENTS; CEREBROSPINAL-FLUID; DENTATE NUCLEUS; RENAL-FUNCTION; RAT-BRAIN; ADMINISTERED GADODIAMIDE; magnetic resonance imaging; gadolinium-based contrast agents; glymphatic system; pial-glial basement membranes - intramural peri-arterial drainage (ipad); gadolinium -
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Pathologie
Depositing User: Petra Gürster
Date Deposited: 09 Apr 2021 09:58
Last Modified: 09 Apr 2021 09:58
URI: https://pred.uni-regensburg.de/id/eprint/44769

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