T1 Signal Measurements in Pediatric Brain: Findings after Multiple Exposures to Gadobenate Dimeglumine for Imaging of Nonneurologic Disease

BACKGROUND AND PURPOSE:Signal intensity increases possibly suggestive of gadolinium retention have recently been reported on unenhanced T1-weighted images of the pediatric brain following multiple exposures to gadolinium-based MR contrast agents. Our aim was to determine whether T1 signal changes suggestive of gadolinium deposition occur in the brains of pediatric nonneurologic patients after multiple exposures to gadobenate dimeglumine.MATERIALS AND METHODS:Thirty-four nonneurologic patients (group 1; 17 males/17 females; mean age, 7.18 years) who received between 5 and 15 injections (mean, 7.8 injections) of 0.05 mmol/kg of gadobenate during a mean of 2.24 years were compared with 24 control patients (group 2; 16 males/8 females; mean age, 8.78 years) who had never received gadolinium-based contrast agents. Exposure to gadobenate was for diagnosis and therapy monitoring. Five blinded readers independently determined the signal intensity at ROIs in the dentate nucleus, globus pallidus, pons, and thalamus on unenhanced T1-weighted spin-echo images from both groups. Unpaired t tests were used to compare signal-intensity values and dentate nucleus–pons and globus pallidus–thalamus signal-intensity ratios between groups 1 and 2.RESULTS:Mean signal-intensity values in the dentate nucleus, globus pallidus, pons, and thalamus of gadobenate-exposed patients ranged from 366.4 to 389.2, 360.5 to 392.9, 370.5 to 374.9, and 356.9 to 371.0, respectively. Corresponding values in gadolinium-based contrast agent–naïve subjects were not significantly different (P > .05). Similarly, no significant differences were noted by any reader for comparisons of the dentate nucleus–pons signal-intensity ratios. One reader noted a difference in the mean globus pallidus–thalamus signal-intensity ratios (1.06 ± 0.006 versus 1.02 ± 0.009, P = .002), but this reflected nonsignificantly higher T1 signal in the thalamus of control subjects. The number of exposures and the interval between the first and last exposures did not influence signal-intensity values.CONCLUSIONS:Signal-intensity increases potentially indicative of gadolinium deposition are not seen in pediatric nonneurologic patients after multiple exposures to low-dose gadobenate.

Recent reports have detailed high signal intensity (SI) in certain brain areas (primarily the dentate nucleus [DN] and globus pallidus [GP]) on unenhanced T1-weighted images following multiple exposures to gadolinium-based contrast agents (GBCAs).^1–20 Many of these reports have focused on apparent differences between macrocyclic and open-chain “linear” GBCAs,^4–13 invariably associating progressive T1 hyperintensity with multiple exposures to linear GBCAs and concluding that observed T1 signal reflects the lower stability of these agents and thus a greater propensity for gadolinium (Gd) release and, subsequently, deposition in the brain. Among the more recent reports are several that describe retrospective assessments in pediatric patients.^15–19 Although each patient evaluated received just 1 specific linear GBCA (gadopentetate dimeglumine; Magnevist; Bayer HealthCare, Wayne, New Jersey), the study-based recommendations in each case were to consider carefully the use of all linear agents in pediatric subjects.Gadobenate dimeglumine (MultiHance; Bracco Diagnostics, Monroe, New Jersey) is an ionic open-chain, linear GBCA that differs fundamentally from gadopentetate and other extracellular GBCAs in having an aromatic substituent on the chelating molecule.²¹ Unique properties conferred by this substituent include increased R1-relaxivity,²² which permits the acquisition of diagnostically valid images with a reduced dose,²³ and liver-specificity, which permits gadobenate use for hepatobiliary-phase liver applications.²⁴ An additional benefit is increased molecular stability compared with gadopentetate, other linear agents, and certain macrocyclic agents.²⁵ Studies that have evaluated brain T1 signal intensities after multiple exposures to gadobenate have yielded conflicting results with one report demonstrating T1 signal increases, albeit to a lesser extent than with gadopentetate,¹⁰ and others demonstrating no direct changes.^11,12We aimed to determine whether multiple exposures to low-dose gadobenate for nonneurologic pathology results in T1 signal changes in the DN and GP of pediatric patients relative to that in age- and weight-matched GBCA-naïve control subjects.