SUMMARY:In current practice, gadolinium-based contrast agents have been considered safe when used at clinically recommended doses in patients without severe renal insufficiency. The causal relationship between gadolinium-based contrast agents and nephrogenic systemic fibrosis in patients with renal insufficiency resulted in new policies regarding the administration of these agents. After an effective screening of patients with renal disease by performing either unenhanced or reduced-dose-enhanced studies in these patients and by using the most stable contrast agents, nephrogenic systemic fibrosis has been largely eliminated since 2009. Evidence of in vivo gadolinium deposition in bone tissue in patients with normal renal function is well-established, but recent literature showing that gadolinium might also deposit in the brain in patients with intact blood-brain barriers caught many individuals in the imaging community by surprise. The purpose of this review was to summarize the literature on gadolinium-based contrast agents, tying together information on agent stability and animal and human studies, and to emphasize that low-stability agents are the ones most often associated with brain deposition.ABBREVIATIONS: DN ϭ dentate nuclei; GBCA ϭ gadolinium-based contrast agent; NSFϭ nephrogenic systemic fibrosis

q RSNA, 2015 Purpose:To determine if a correlation exists between the number of previous enhanced magnetic resonance (MR) imaging examinations and high signal intensity in the globus pallidus (GP) and dentate nucleus (DN) in patients who received gadodiamide (Omniscan), a linear nonionic gadolinium-based contrast agent, and in those who received gadobenate dimeglumine (MultiHance), a linear ionic contrast agent. Materials andMethods:Institutional review board approval was obtained for this single-center retrospective study, with waiver of informed consent. The study population included 69 patients divided into two groups: Group 1 included patients who underwent gadodiamide-enhanced MR imaging, and group 2 included patients who underwent gadobenate dimeglumine-enhanced MR imaging. Two radiologists conducted a quantitative analysis of unenhanced T1-weighted images by using region of interest measurements. The GP-to-thalamus (TH) signal intensity ratio, DN-to-middle cerebellar peduncle (MCP) signal intensity ratio and relative percentage change (R change ) between the first and last examinations for each patient were calculated. Relation between the signal intensity ratios and R change and the number of enhanced MR imaging examinations was analyzed by using a generalized additive model. Inter-and intraobserver agreement was evaluated with the Lin concordance correlation coefficient test. Results:Group 1 included 23 patients (19 female), with a mean of 5.0 doses 6 2.4 (standard deviation) (range, 3-11 doses) administered. Group 2 included 46 patients (24 female) with a mean of 4.6 doses 6 2.2 (range, 3-11 doses) administered. The interval between the first and last examination was 1500.1 days 6 780.2 (range, 98-3097 days) for group 1 and 1086.2 days 6 582.9 (range, 94-2633) for group 2. All patients had normal liver and renal function. Gadodiamide showed a significant increase in DN:MCP and GP:TH (P , .001 for both) and in R change (P = .001 for GP:TH, P , .001 for DN:MCP). In group 2, there was no significant increase in DN:MCP or GP:TH over time or in R change for GP:TH, but there was a significant trend toward an increase in R change for DN:MCP (P = .013). Interobserver agreement was almost perfect (0.99; 95% confidence interval: 0.99, 0.99) for all evaluated structures. Intraobserver agreement was substantial to almost perfect for both readers. Conclusion:A significant increase in GP:TH and DN:MCP is associated with multiple gadodiamide-enhanced studies but not with gadobenate dimeglumine-enhanced studies, likely reflecting differences in stability and elimination of both contrast agents. Rate-of-change data indirectly suggest gadolinium deposition in the DN with gadobenate dimeglumine use, although it is considerably less than that with gadodiamide use.q RSNA, 2015

Gadolinium toxicity appears to arise following GBCA administration, which appears to contain clinical features seen in Nephrogenic Systemic Fibrosis, but also features not observed in that condition.