Brain Iron Assessment after Ferumoxytol-enhanced MRI in Children and Young Adults with Arteriovenous Malformations: A Case-Control Study

Background: Iron oxide nanoparticles are an alternative contrast agent for MRI. Gadolinium deposition has raised safety concerns, but it is unknown whether ferumoxytol administration also deposits in the brain. Purpose: To investigate whether there are signal intensity changes in the brain at multiecho gradient imaging following ferumoxytol exposure in children and young adults. Materials and Methods: This retrospective case-control study included children and young adults, matched for age and sex, with brain arteriovenous malformations who received at least one dose of ferumoxytol from January 2014 to January 2018. In participants who underwent at least two brain MRI examinations (subgroup), the first and last available examinations were analyzed. Regions of interests were placed around deep gray structures on quantitative susceptibility mapping and R2* images. Mean susceptibility and R2* values of regions of interests were recorded. Measurements were assessed by linear regression analyses: a between-group comparison of ferumoxytol-exposed and unexposed participants and a within-group (subgroup) comparison before and after exposure. Results: Seventeen participants (mean age +/- standard deviation, 13 years +/- 5; nine male) were in the ferumoxytol-exposed (case)group, 21 (mean age, 14 years +/- 5; 11 male) were in the control group, and nine (mean age, 12 years +/- 6; four male) were in thesub group. The mean number of ferumoxytol administrations was 2 +/- 1 (range, one to four). Mean susceptibility (in parts per million[ppm]) and R2* (in inverse seconds [sec(-1)]) values of the dentate (case participants: 0.06 ppm +/- 0.04 and 23.87 sec(-1) +/- 4.13; control participants: 0.02 ppm +/- 0.03 and 21.7 sec(-1) +/- 5.26), substantia nigrae (case participants: 0.08 ppm +/- 0.06 and 27.46 sec(-1) +/- 5.58;control participants: 0.04 ppm +/- 0.05 and 24.96 sec(-1) +/- 5.3), globus pallidi (case participants: 0.14 ppm +/- 0.05 and 30.75 sec(-1) 65.14; control participants: 0.08 ppm +/- 0.07 and 28.82 sec(-1) +/- 6.62), putamina (case participants: 0.03 ppm +/- 0.02 and 20.63 sec(-1) +/- 2.44; control participants: 0.02 ppm +/- 0.02 and 19.65 sec(-1) +/- 3.6), caudate (case participants: 20.1 ppm +/- 0.04 and 18.21 sec(-1)+/- 3.1; control participants: 20.06 ppm +/- 0.05 and 18.83 sec(-1) +/- 3.32), and thalami (case participants: 0 ppm +/- 0.03 and 16.49 sec(-1) +/- 3.6; control participants: 0.02 ppm +/- 0.02 and 18.38 sec(-1) +/- 2.09) did not differ between groups (susceptibility, P =.21; R2*, P =.24). For the subgroup, the mean interval between the first and last ferumoxytol administration was 14 months +/- 8 (range,1-25 months). Mean susceptibility and R2* values of the dentate (first MRI: 0.06 ppm +/- 0.05 and 25.78 sec(-1) +/- 5.9; last MRI: 0.06 ppm +/- 0.02 and 25.55 sec(-1) +/- 4.71), substantia nigrae (first MRI: 0.06 ppm +/- 0.06 and 28.26 sec(-1) +/- 9.56; last MRI: 0.07 ppm 60.06 and 25.65 sec(-1) +/- 6.37), globus pallidi (first MRI: 0.13 ppm +/- 0.07 and 27.53 sec(-1) +/- 8.88; last MRI: 0.14 ppm +/- 0.06 and 29.78 sec(-1) +/- 6.54), putamina (first MRI: 0.03 ppm +/- 0.03 and 19.78 sec(-1) +/- 3.51; last MRI: 0.03 ppm +/- 0.02 and 19.73 sec(-1 )+/- 3.01), caudate (first MRI: 20.09 ppm +/- 0.05 and 21.38 sec(-1) +/- 4.72; last MRI: 20.1 ppm +/- 0.05 and 18.75 sec(-1) +/- 2.68),and thalami (first MRI: 0.01 ppm +/- 0.02 and 17.65 sec(-1) +/- 5.16; last MRI: 0 ppm +/- 0.02 and 15.32 sec(-1) +/- 2.49) did not differ between the first and last MRI examinations (susceptibility, P =.95; R2*, P =.54). Conclusion: No overall significant differences were found in susceptibility and R2* values of deep gray structures to suggest retained iron in the brain between ferumoxytol-exposed and unexposed children and young adults with arteriovenous malformations and in those exposed to ferumoxytol over time. (C) RSNA, 2020