MRI Assessment of Hepatic Iron Clearance Rates After USPIO Administration in Healthy Adults

Objective: The purpose of this study was to monitor iron clearance from the liver by means of T2 and T2* mapping after administration of an ultrasmall superparamagnetic iron oxide (USPIO) agent. Materials and Methods: The study was performed using ferumoxytol (Feraheme), a USPIO agent that has been approved by the US Food and Drug Administration for the treatment of iron deficiency anemia in adult patients with chronic kidney disease. Six healthy human participants without anemia or preexisting iron overload were prospectively included. The cohort comprised 4 men and 2 postmenopausal women, aged 22 to 57 years. T2 and T2* mapping of the liver were performed at 1.5 T using multiple spin echo and multiple gradient echo sequences, respectively. After baseline imaging, ferumoxytol was injected intravenously at a dose of 5 mg Fe/kg body weight. Imaging was repeated at 3 days, 1 month, and every 2 months thereafter for up to 11 months or until liver T2* had recovered to 24 milliseconds, the threshold used to define iron deposition. For each examination, maps of the relaxation rates R2 (= 1/T2) and R2* (= 1/T2*) were generated by fitting the signal intensity data as a function of echo time to a monoexponential decay. Results: No adverse reactions to ferumoxytol injection occurred. The magnetic resonance (MR) responses to ferumoxytol varied widely among the participants. Liver R2* increased from a mean value of 35.6 s(-1) (range, 28.7-40.9 s(-1)) kat baseline to a mean value of 241 s(-1) (range, 161-417 s(-1)) 3 days after administration. Liver R2 increased from 19.4 s(-1) (range, 16.6-23.8 s(-1)) at baseline to 45.3 s(-1) (range, 34.4-58.5 s(-1)) at 3 days. There was also a large variation in iron clearance times. In 1 participant, MR relaxation rates had recovered to baseline by 3 months, whereas, in 3 participants, liver R2* remained elevated at 11 months (R2* > 55 s(-1), ie, T2* < 18 milliseconds). In these 3 participants, liver R2 also remained marginally higher at 11 months than corresponding baseline values. Conclusions: Iron deposition in the liver after a 5 mg Fe/kg dose of ferumoxytol may alter signal contrast on MR images for several months after administration. This is an important consideration in the use of USPIO agents for diagnostic purposes.