Effect of At Least Ten Serial Gadobutrol Administrations on Brain Signal Intensity Ratios on T1-Weighted MRI in Children: A Matched Case-Control Study

BACKGROUND: An association in children between linear gadolinium-based contrast agents and intracranial gadolinium retention is recognized; the relationship with macrocyclic gadolinium-based contrast agent (mcGBCAs) remains incompletely understood. OBJECTIVE: To assess whether 10 or more administrations of the mcGBCA gadobutrol is associated with increased signal intensity (SI) in the dentate nucleus (DN) and globus pallidus (GP) on unenhanced T1-weighted imaging (T1WI) in children and to explore clinical variables potentially associated with T1 hyperintensity. METHODS: Twenty-five children (13 boys, 12 girls; mean age 7±4 years, range 2-18 years) who underwent at least 10 (mean 15±6; range: 10-34) contrast-enhanced MRI examinations using exclusively gadobutrol, and 25 age- and sex-matched control patients without gadolinium exposure who underwent MRI, were identified. Two observers in consensus assessed visual T1 hyperintensity in the DN and GP using a 3-point scale. One observer placed ROIs on T1WI in the DN, GP, middle cerebellar peduncle (MCP), and pulvinar of the thalamus (Th) bilaterally to compute average DN-to-MCP and GP-to-Th SI ratios. SI ratios were compared between mcGBCA and control groups. In the mcGBCA group, Pearson correlation analysis was conducted between SI ratios and clinical variables. ROI measurements were repeated by the original reader and an independent reader, and interobserver and intraobserver agreement were computed using Lin concordance correlation coefficients. RESULTS: No patient showed visual T1 hyperintensity in the DN and GP. No significant difference between the mcGBCA and control group was observed for DN-to-MCP SI ratio (0.95±0.05 vs 0.95±0.03; p=0.67) or GP-to-Th SI ratio (1.05±0.06 vs 0.104±0.0; p=0.65). In the mGBCA group, no significant correlation was observed between DN-to-MCP SI ratio or GP-to-Th SI ratio with age (r=0.355, p=0.08; r=0.167, p=0.42), number of contrast-enhanced MRI examinations (r=0.247, p=0.23; r=0.203, p=0.33), mean duration between examinations (r=0 .193, p=0.36; r=0.047, p=0.82), or cumulative mcGBCA dose (r=0.434, p=0.07; r=0.270, p=0.19). Interobserver and intraobserver agreement was substantial for DN-to-MCP SI and GP-to-TH SI ratios (Ro: 0.931-0.974). CONCLUSION: Ten or more serial gadobutrol administrations was not associated with T1 hyperintensity in the DN or GP in children. CLINICAL IMPACT: Selection of gadobutrol as an MRI contrast agent may reduce risk of gadolinium retention in children. The findings may help guide practices for GBCA administration in children.