title: Pediatric Patients Demonstrate Progressive T1-Weighted Hyperintensity in the Dentate Nucleus following Multiple Doses of Gadolinium-Based Contrast Agent.
abstract: While there have been recent reports of brain retention of gadolinium following gadolinium-based contrast agent administration in adults, a retrospective series of pediatric patients has not previously been reported, to our knowledge. We investigated the relationship between the number of prior gadolinium-based contrast agent doses and increasing T1 signal in the dentate nucleus on unenhanced T1-weighted MR imaging. We hypothesized that despite differences in pediatric physiology and the smaller gadolinium-based contrast agent doses that pediatric patients are typically administered based on weighted-adjusted dosing, the pediatric brain would also demonstrate dose-dependent increasing T1 signal in the dentate nucleus.
  
  
  
  We included children with multiple gadolinium-based contrast agent administrations at our institution. A blinded reader placed ROIs within the dentate nucleus and adjacent cerebellar white matter. To eliminate reader bias, we also performed automated ROI delineation of the dentate nucleus, cerebellar white matter, and pons. Dentate-to-cerebellar white matter and dentate-to pons ratios were compared with the number of gadolinium-based contrast agent administrations.
  
  
  
  During 20 years at our institution, 280 patients received at least 5 gadolinium-based contrast agent doses, with 1 patient receiving 38 doses. Sixteen patients met the inclusion/exclusion criteria for ROI analysis. Blinded reader dentate-to-cerebellar white matter ratios were significantly associated with gadolinium-based contrast agent doses (rs= 0.77, P = .001). The dentate-to-pons ratio and dentate-to-cerebellar white matter ratios based on automated ROI placement were also significantly correlated with gadolinium-based contrast agent doses (t = 4.98, P < .0001 and t = 2.73, P < .02, respectively).
  
  
  
  In pediatric patients, the number of prior gadolinium-based contrast agent doses is significantly correlated with progressive T1-weighted dentate hyperintensity. Definitive confirmation of gadolinium deposition requires tissue analysis. Any potential clinical sequelae of gadolinium retention in the developing brain are unknown. Given this uncertainty, we suggest taking a cautious stance, including the use, in pediatric patients, of higher stability, macrocyclic agents, which in both human and animal studies have been shown to be associated with lower levels of gadolinium deposition, and detailed documentation of dosing. Most important, a patient should not be deprived of a well-indicated contrasted MR examination.
authors.affiliation: From the Departments of Radiology and Radiological Sciences (D.R.R., A.R.C., M.Y., B.M., T.B., H.C., G.B.) robertdr@musc.edu.|Neurosciences and Neuroscience Research (D.R.R.).
authors.forename: D R
authors.identifier: 0000-0002-6302-8233
authors.initials: DR
authors.lastname: Roberts
authors.affiliation: From the Departments of Radiology and Radiological Sciences (D.R.R., A.R.C., M.Y., B.M., T.B., H.C., G.B.).
authors.forename: A R
authors.identifier: 0000-0002-6172-2010
authors.initials: AR
authors.lastname: Chatterjee
authors.affiliation: From the Departments of Radiology and Radiological Sciences (D.R.R., A.R.C., M.Y., B.M., T.B., H.C., G.B.).
authors.forename: M
authors.identifier: 0000-0001-5072-665X
authors.initials: M
authors.lastname: Yazdani
authors.affiliation: From the Departments of Radiology and Radiological Sciences (D.R.R., A.R.C., M.Y., B.M., T.B., H.C., G.B.).
authors.forename: B
authors.identifier: 0000-0002-5664-0408
authors.initials: B
authors.lastname: Marebwa
authors.affiliation: From the Departments of Radiology and Radiological Sciences (D.R.R., A.R.C., M.Y., B.M., T.B., H.C., G.B.).
authors.forename: T
authors.identifier: 0000-0001-5789-7638
authors.initials: T
authors.lastname: Brown
authors.affiliation: From the Departments of Radiology and Radiological Sciences (D.R.R., A.R.C., M.Y., B.M., T.B., H.C., G.B.).
authors.forename: H
authors.identifier: 0000-0002-8974-3139
authors.initials: H
authors.lastname: Collins
authors.affiliation: From the Departments of Radiology and Radiological Sciences (D.R.R., A.R.C., M.Y., B.M., T.B., H.C., G.B.).
authors.forename: G
authors.identifier: 0000-0002-2964-6724
authors.initials: G
authors.lastname: Bolles
authors.affiliation: Radiation Oncology (J.M.J.).
authors.forename: J M
authors.identifier: 0000-0002-5440-9202
authors.initials: JM
authors.lastname: Jenrette
authors.affiliation: Biostatistics (P.J.N.).|Public Health Sciences (P.J.N.), Medical University of South Carolina, Charleston, South Carolina.
authors.forename: P J
authors.identifier: 0000-0002-3933-4986
authors.initials: PJ
authors.lastname: Nietert
authors.affiliation: Department of Psychology (X.Z.), Normal College, Shihezi University, Xinjiang, China.
authors.forename: X
authors.identifier: 0000-0002-6775-2333
authors.initials: X
authors.lastname: Zhu
mesh_terms: D001927:Brain Diseases / Q000175:diagnosis; D002529:Cerebellar Nuclei / Q000000981:diagnostic imaging*; D002648:Child; D003287:Contrast Media / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D019786:Gadolinium DTPA / Q000008:administration & dosage / Q000009:adverse effects*; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000009:adverse effects* / Q000379:methods; D008297:Male; D012189:Retrospective Studies
chemical_list: D003287:Contrast Media; D019786:Gadolinium DTPA