Accumulation of Gadolinium in Human Cerebrospinal Fluid after Gadobutrol-enhanced MR Imaging: A Prospective Observational Cohort Study

Purpose To determine whether gadolinium accumulates within cerebrospinal fluid (CSF) in patients recently exposed to the macrocyclic agent gadobutrol and identify factors that may affect this accumulation. Materials and Methods In this prospective observational cohort study, gadolinium was quantified by using inductively coupled plasma mass spectrometry of CSF samples from patients who underwent gadobutrol-enhanced magnetic resonance (MR) imaging followed by lumbar puncture within 30 days (gadobutrol group) or patients who underwent lumbar puncture without history of gadolinium-enhanced MR imaging (control group). CSF total protein level of 35 mg/dL or lower was used as a surrogate marker of an intact blood-brain barrier (BBB). Associations between gadolinium CSF concentration and patient characteristics were examined by using log (e)-linear regression models. Results A total of 82 patients (68 in gadobutrol group, 14 in control group; 42 male and 40 female patients; median age, 47 years [interquartile range, 25-65 years]) were included in this study. Gadolinium was detected in the CSF of all 68 patients in the gadobutrol group (100% [95% confidence interval: 94.7, 100]; range, 0.2-1494 ng/mL). CSF total protein level higher than 35 mg/dL and patient age of at least 18 years were associated with higher gadolinium concentrations (estimate: 1.1, with standard error [SE] of 0.26 [P < .001] and 0.91, with SE of 0.37 [P = .02], respectively). Conclusion Intravenous administration of the macrocyclic agent gadobutrol results in gadolinium accumulation within the CSF, even in the setting of normal renal function and no BBB dysfunction.