Intracranial Gadolinium Deposition after Contrast-enhanced MR Imaging.
OBJECTIVE
To determine if repeated intravenous exposures to gadolinium-based contrast agents (GBCAs) are associated with neuronal tissue deposition.


METHODS
In this institutional review board-approved single-center study, signal intensities from T1-weighted magnetic resonance (MR) images and postmortem neuronal tissue samples from 13 patients who underwent at least four GBCA-enhanced brain MR examinations between 2000 and 2014 (contrast group) were compared with those from 10 patients who did not receive GBCA (control group). Antemortem consent was obtained from all study participants. Neuronal tissues from the dentate nuclei, pons, globus pallidus, and thalamus of these 23 deceased patients were harvested and analyzed with inductively coupled plasma mass spectrometry (ICP-MS), transmission electron microscopy, and light microscopy to quantify, localize, and assess the effects of gadolinium deposition. Associations between cumulative gadolinium dose, changes in T1-weighted MR signal intensity, and ICP-MS-derived tissue gadolinium concentrations were examined by using the Spearman rank correlation coefficient (ρ).


RESULTS
Compared with neuronal tissues of control patients, all of which demonstrated undetectable levels of gadolinium, neuronal tissues of patients from the contrast group contained 0.1-58.8 μg gadolinium per gram of tissue, in a significant dose-dependent relationship that correlated with signal intensity changes on precontrast T1-weighted MR images (ρ = 0.49-0.93). All patients in the contrast group had relatively normal renal function at the time of MR examination. Gadolinium deposition in the capillary endothelium and neural interstitium was observed only in the contrast group.


CONCLUSIONS
Intravenous GBCA exposure is associated with neuronal tissue deposition in the setting of relatively normal renal function. Additional studies are needed to investigate the clinical significance of these findings and the generalizability to other GBCAs. Online supplemental material is available for this article.
From the Departments of Radiology (R.J.M., J.S.M., D.F.K., K.R.T., E.E.W., L.J.E.), Neurosurgery (D.F.K.), and Laboratory Medicine and Pathology (M.E.J., D.L.M.), College of Medicine, Mayo Clinic, 200 First St SW, Rochester, MN 55905.
Robert J
RJ
McDonald
Jennifer S
JS
McDonald
David F
DF
Kallmes
Mark E
ME
Jentoft
David L
DL
Murray
Kent R
KR
Thielen
Eric E
EE
Williamson
Laurence J
LJ
Eckel
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000378:metabolism*; D003287:Contrast Media / Q000493:pharmacokinetics*; D005682:Gadolinium / Q000493:pharmacokinetics*; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008875:Middle Aged; D012189:Retrospective Studies; D014018:Tissue Distribution; D055815:Young Adult
D003287:Contrast Media; D005682:Gadolinium