ORIGINAL ARTICLE Signal intensity at unenhanced T1-weighted magnetic resonance in the globus pallidus and dentate nucleus after serial administrations of a macrocyclic gadolinium-based contrast agent in children Maria Camilla Rossi Espagnet 1 & Bruno Bernardi 1 & Luca Pasquini 1,2 & Lorenzo Figà-Talamanca 1 & Paolo Tomà 3 & Antonio Napolitano 4 Received: 28 December 2016 /Revised: 26 March 2017 /Accepted: 20 April 2017 # Springer-Verlag Berlin Heidelberg 2017 Abstract Background Few studies have been conducted on the rela- tions between T1-weighted signal intensity changes in the pediatric brain following gadolinium-based contrast agent (GBCA) exposure. Objective The purpose of this study is to investigate the effect of multiple administrations of a macrocyclic GBCA on signal intensity in the globus pallidus and dentate nucleus of the pediatric brain on unenhanced T1-weighted MR images. Materials and methods This retrospective study included 50 patients, mean age: 8 years (standard deviation: 4.8 years), with normal renal function exposed to ≥6 administrations of the same macrocyclic GBCA (gadoterate meglumine) and a control group of 59 age-matched GBCA-naïve patients. The globus pallidus-to-thalamus signal intensity ratio and dentate nucleus- to-pons signal intensity ratio were calculated from unenhanced T1-weighted images for both patients and controls. A mixed linear model was used to evaluate the effects on signal intensity ratios of the number of GBCA administrations, the time interval between administrations, age, radiotherapy and chemotherapy. T-test analyses were performed to compare signal intensity ratio differences between successive administrations and baseline MR signal intensity ratios in patients compared to controls. P- values were considered significant if <0.05. Results A significant effect of the number of GBCA adminis- trations on relative signal intensities globus pallidus-to-thalamus (F[8]=3.09; P=0.002) and dentate nucleus-to-pons (F[8]=2.36; P=0.021) was found. The relative signal intensities were higher at last MR examination than at baseline (P<0.001). Conclusion Quantitative analysis evaluation of globus pallidus:thalamus and dentate nucleus:pons of the pediatric brain demonstrated an increase after serial administrations of macrocyclic GBCA. Further research is necessary to fully understand GBCA pharmacokinetic in children. Keywords Gadolinium . Deposit . Pediatric . Brain . MRI Introduction In the last 2 years, several published studies have demonstrat- ed the association between an increased signal intensity (on unenhanced T1-weighted MR images in specific deep gray matter regions and previous exposure to gadolinium-based contrast agent (GBCA) administrations in patients with nor- mal renal function [1, 2]. These observations were subse- quently repeated by a postmortem study that used inductively coupled plasma mass spectrometry on brain tissue from pa- tients exposed to previous linear GBCA administrations, confirming the presence of abundant gadolinium deposits in the neural tissue interstitium and within the endothelial wall [3]. So far, the published data have reported some differences among GBCAs with different chemical structures: A T1- * Maria Camilla Rossi Espagnet camilla.rossiespagnet@gmail.com 1 Neuroradiology Unit, Imaging Department, Ospedale Pediatrico Bambino Gesù, IRCCS, Piazza S. Onofrio 4, 00165 Rome, Italy 2 Neuroradiology Unit, Azienda Ospedaliera Sant’Andrea, University Sapienza, Via di Grottarossa 1035, Rome, Italy 3 Department of Imaging, Ospedale Pediatrico Bambino Gesù, IRCCS, Piazza S. Onofrio 4, Rome, Italy 4 Enterprise Risk Management, Medical Physics Department, Ospedale Pediatrico Bambino Gesù, IRCCS, Piazza S. Onofrio 4, Rome, Italy Pediatr Radiol DOI 10.1007/s00247-017-3874-1