Decreased native renal T₁ up to one week after gadobutrol administration in healthy volunteers

Background: Gadolinium-based contrast agents (GBCAs) are widely used in MRI, despite safety concerns regarding deposition in brain and other organs. In animal studies gadolinium was detected for weeks after administration in the kidneys, but this has not yet been demonstrated in humans. Purpose: To find evidence for the prolonged presence of gadobutrol in the kidneys in healthy volunteers. Study Type: Combined retrospective and prospective analysis of a repeatability study. Population: Twenty-three healthy volunteers with normal renal function (12 women, age range 40–76 years), of whom 21 were used for analysis. Field Strength/Sequence: Inversion recovery-based T ₁ map at 3T. Assessment: T ₁ maps were obtained twice with a median interval of 7 (range: 4–16) days. The T ₁ difference (ΔT ₁) between both scans was compared between the gadolinium group (n = 16, 0.05 mmol/kg gadobutrol administered after T ₁ mapping during both scan sessions) and the control group (n = 5, no gadobutrol). T ₁ maps were analyzed separately for cortex and medulla. Statistical Tests: Mann–Whitney U-tests to detect differences in ΔT ₁ between groups and linear regression to relate time between scans and estimated glomerular filtration rate (eGFR) to ΔT ₁. Results: ΔT ₁ differed significantly between the gadolinium and control group: median ΔT ₁ cortex –98 vs. 7 msec (P < 0.001) and medulla –68 msec vs. 19 msec (P = 0.001), respectively. The bias corresponds to renal gadobutrol concentrations of 8 nmol/g tissue (cortex) and 4 nmol/g tissue (medulla), ie, ~2.4 μmol for both kidneys (0.05% of original dose). ΔT ₁ correlated in the gadolinium group with duration between acquisitions for both cortex (regression coefficient (β) 16.5 msec/day, R ² 0.50, P < 0.001) and medulla (β 11.5 msec/day, R ² 0.32, P < 0.001). Medullary ΔT ₁ correlated with eGFR (β 1.13 msec/(ml/min) R ² 0.25, P = 0.008). Data Conclusion: We found evidence of delayed renal gadobutrol excretion after a single contrast agent administration in subjects with normal renal function. Even within this healthy population, elimination delay increased with decreasing kidney function. Level of Evidence: 3. Technical Efficacy: Stage 3. J. Magn. Reson. Imaging 2020;52:622–631.