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

Abstract

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.

Gadolinium retention in gliomas and adjacent normal brain tissue: association with tumor contrast enhancement and linear/macrocyclic agents

“…Autopsy studies have shown that gadolinium deposition in the posterior fossa and basal ganglia is not limited to patients with intracranial abnormalities but can also be detected in patients with normal brains at the time of autopsy [17,18]. Several mechanisms of this gadolinium transit and retention in brain regions without impaired BBB have been suggested including active metal transporters [19,20], passage from the cerebrospinal fluid [21][22][23], and brain glymphatic system [24]. The exact mechanism behind the retention, however, remains unsolved.…”

Intracranial Distribution of Intravenously Administered Gadolinium-based Contrast Agent over a Period of 24 Hours: Evaluation with 3D-real IR Imaging and MR Fingerprinting

“…20 It has been further clarified that gadolinium contrast agents administered intravenously are distributed in cerebrospinal fluid in healthy subjects. 4,5,41 It has also been shown that gadolinium contrast agents in the cerebrospinal fluid spaces are transferred to brain parenchyma in animals and humans. 20,28,29,37,42 Thus, if gadolinium contrast is present in cerebrospinal fluid, it will also be present in brain parenchyma.…”

Detection of IV-gadolinium Leakage from the Cortical Veins into the CSF Using MR Fingerprinting

“…[25][26][27][28] This finding may be a part of the normal aging process; however, it also might be a biomarker of neurodegeneration. 15,26,28 To better understand the importance of GBCA leakage into the CSF from the cortical veins, we need more research. MRF can facilitate studies to further understand this phenomenon due to its brief scan time when we scan the limited number of slices of MRF.…”