Intrinsic T1 hyperintense signal has been noted on magnetic resonance imaging (MRI) in deep brain nuclei of adults after multiple doses of gadolinium-based contrast agents (GBCA)¹. Macrocyclic agents have demonstrated smaller increases in signal intensity than some linear agents². Furthermore, children have not been evaluated, apart from single case reports³. Thus, the aim of this retrospective study was to investigate whether T1 shortening can be observed in children after multiple administrations of a linear GBCA (gadobenate dimeglumine). Further we aim to identify any differences between patients without treatment confounders and those who have undergone brain radiation and/or chemotherapy.In this IRB-approved, single center retrospective study, we extracted all patients aged 18 years and younger with at least 4 contrast-enhanced MRIs archived on PACS between August 2009 and September 2015. We reviewed clinical charts and images to identify those patients who had received only gadobenate dimeglumine (Bracco Diagnostics, Princeton, NJ) and had normal renal function. Amongst 326 children, 76 children (mean age 9.3 years) met these selection criteria (4-20 contrast enhanced MRIs, mean 8). Sixteen patients had posterior fossa tumors (PFT) treated with radiation (n = 11) and/or chemotherapy (n = 14, RCTX) and 60 were unconfounded by such treatment. T1 signal intensity and signal intensity ratios for dentate-to-pons (DNP) and globus pallidus-to-thalamus (GPT) were calculated, and correlated with number of contrast injections as well as time interval and therapy. Twelve of the 16 patients with PFT and RCTX (n = 10-20 injections of gadobenate dimeglumine) had deep gray matter hyperintensities while only 2 of the 60 patients (n = 20 and n = 16 injections of gadobenate) without confounders had increased signal intensity. Chart review revealed no reported patterns of neurological deficits (e.g. movement disorders) in any of the children with signal hyperintensities in the deep brain nuclei. Statistical analysis demonstrated a statistically significant increase in signal ratio change for number of scans and contrast injections (p<0.001) as well as the amount of gadolinium (p=0.008), but not for inter-scan time interval (p=0.35). For each additional GBCA-enhanced MRI, the signal ratio increased by 0.01 on average. There was a significant difference in average change in signal intensity ratio over time between those with RCTX versus those without (p<0.001). The average change in ratio was no different when comparing the dentate to the globus pallidus (p = 0.2), or for children after focal radiation of the cerebellum (p= 0.4). A significant correlation between the number of contrast enhanced MRIs and T1 signal hyperintensity of deep brain nuclei is seen in children with gadobenate dimeglumine, a linear, ionic GBCA. This signal change is asymptomatic, and is not associated with any demonstrable biological or neurological adverse outcome. Further, the increase signal intensity in the deep brain nuclei is independent of the time between injections, but dependent on the number of injections and the cumulative amount of gadolinium exposure. Importantly, radiation and/or chemotherapy (RCTX) for posterior fossa tumors leads to earlier and higher signal changes compared to those without RCTX in our patient population. In comparison with published adult studies, where signal hyperintensities occur after as few as 5 GBCA administrations, children not exposed to radiation or chemotherapy demonstrate a later onset of signal changes. Additional comparisons in future research studies are warranted. Children and adults show a similar pattern of T1 signal changes of the dentate and globus pallidus after multiple injections of gadobenate dimeglumine. The appearance of T1 signal changes in children may have a later onset, and is accelerated by radiation treatment and chemotherapy.