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ObjectiveThe objective of this study was to assess the risk of gadoxetate disodium in liver imaging for the development of nephrogenic systemic fibrosis (NSF) in patients with moderate to severe renal impairment.Materials and MethodsWe performed a prospective, multicenter, nonrandomized, open-label

OBJECTIVE The aim of this study was to investigate the impact of portal hypertension (PH) on gadoxetic acid-enhanced liver magnetic resonance imaging (MRI) and assess diagnostic and prognostic implications in comparison to established imaging features of PH. MATERIALS AND METHODS Institutional review board-approved retrospective study of 178 patients (142 men; median age, 59.4 years) with chronic liver disease undergoing MRI and hepatic venous pressure gradient (HVPG) measurement between January 2008 and April 2015. Magnetic resonance imaging was assessed for established features of PH (splenic and portal vein diameters, portosystemic collaterals, ascites) and for features on 20 minutes delayed T1-weighted gadoxetic acid-enhanced MRI, that is, relative liver enhancement (RLE), biliary contrast excretion, or portal vein hyperintensity or isointensity (ie, portal vein hyperintensity sign, PVHS). Statistics encompassed linear regression, logistic regression, and survival analysis. RESULTS There was an inverse correlation between HVPG and RLE (r = 0.18, P < 0.0001). On univariate analysis, clinically significant PH (ie, HVPG ≥ 10 mm Hg, n = 109) and severe PH (ie, HVPG ≥ 12 mm Hg, n = 99) were associated with delayed biliary contrast excretion (n = 33) and the PVHS (n = 74) (P < 0.01 for all). Multivariate analysis demonstrated significant associations between the PVHS and severe PH (odds ratio [OR], 3.33; P = 0.008), independently of spleen size (OR, 1.26; P = 0.002), portosystemic collaterals (n = 81; OR, 5.46; P = 0.0001), and ascites (n = 88; OR, 3.24; P = 0.006). Lower RLE and the PVHS were associated with lower 3-year, transplantation-free survival (hazards ratios, 0.98 and 3.99, respectively, P = 0.002 for all), independently of the Child-Pugh and Model for End-Stage Liver Disease scores. CONCLUSIONS The presence of the PVHS on gadoxetic acid-enhanced MRI is an independent indicator of severe PH and may enable more accurate diagnosis. This feature and decreased hepatic contrast uptake may also comprise prognostic information.

This clinical study investigated the pharmacokinetics and safety of gadobutrol, a magnetic resonance (MR) imaging extracellular contrast agent, in pediatric patients aged 2 to 17 years.In this open-label, multicenter study, patients scheduled for routine contrast-enhanced MR imaging of the brain, spine, liver or kidney, or MR angiography received a single intravenous injection of gadobutrol (0.1 mmol/kg/0.1 mL/kg). Patients were stratified by age groups (2-6, 7-11, and 12-17 years). Blood and urine samples were collected at prespecified time points and analyzed for gadolinium concentrations. Plasma data were evaluated by means of a nonlinear mixed effects model, and urine data were analyzed using descriptive statistics. In addition, the safety of gadobutrol was evaluated.A total of 130 patients (2-6 years, n = 45; 7-11 years, n = 39; 12-17 years, n = 46) were included in the final population pharmacokinetic analysis. Gadobutrol pharmacokinetics in children aged 2 to 17 years were adequately described by an open 2-compartment model with elimination from the central compartment. The median estimates (2.5th percentile, 97.5th percentile) of body weight-normalized total body clearance (L/h/kg) per age group were 0.10 (0.05, 0.17) for all ages, 0.13 (0.09, 0.17) in the 2 to 6 year age group, 0.10 (0.05, 0.17) in the 7 to 11 year age group and 0.09 (0.05, 0.10) in the 12 to 17 year age group. The body weight-normalized median estimates of total volume of distribution (L/kg) were 0.20 (0.12, 0.28) for all ages, 0.24 (0.20, 0.28) in the 2 to 6 year age group, 0.19 (0.14, 0.23) in the 7 to 11 year age group and 0.18 (0.092, 0.23) in the 12 to 17 year age group. Median gadolinium plasma concentrations at 20 minutes postinjection were simulated using the population pharmacokinetic model and ranged from 414 (13 kg subject) to 518 micromol/L (65 kg subject). Body weight was identified as the major covariate influencing the pharmacokinetic parameters of total body clearance and central volume of distribution. Age was not found to be an additional independent parameter. The median amount of renally excreted gadolinium was 77.0% of the administered dose within 6 hours postinjection, indicating that gadobutrol was renally excreted in this pediatric population aged 2 to 17 years. Gadobutrol was well tolerated, with drug-related adverse events of mild intensity reported for 8 (5.8%) of 138 patients.Observed differences in pharmacokinetics were attributed to body weight, with no additional independent effect of age. Thus, no dose adjustment from the standard dose of gadobutrol in adults based on body weight (0.1 mmol/kg) is necessary in pediatric patients aged 2 to 17 years. Gadobutrol was safe and well tolerated in the pediatric population in this study.