Quantification of Prenatal Liver and Spleen Iron in a Sheep Model and Assessment of Iron Stores in a Human Neonate with Neonatal Hemochromatosis using R2* Mapping

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Purpose: We evaluated the feasibility of prenatal quantification of liver and spleen iron by magnetic resonance imaging (MRI) gradient recalled echo (GRE) measurements of transverse relaxation time (R2*) (MRI-GRE-R2*) in a fetal sheep model and applied the method to a human neonate with suspected neonatal hemochromatosis.
Methods: We subjected 13 fetal sheep to MRI at 1.5 Tesla using a breath-triggered (ewe) multi-echo sequence to determine the transverse relaxation rate (R2*) of the liver and spleen. In the human neonate, we measured the R2* of the liver, spleen, and pancreas on the 30th postgestational day.
Results: The median R2* of the fetal sheep liver was 25.6 s⁻¹ (range 20 to 114 s⁻¹) and of the spleen, 40.2 s⁻¹ (range 20 to 70 s⁻¹), and the corresponding median iron concentration in the liver was 0.85 mg/g_{dry weight (d.w.)} and in the spleen, 1.22 mg/g_d.w.. R2* rates in the human neonate liver were elevated between 67 s⁻¹ (average), which corresponded with an iron concentration of 1.9 mg Fe/g_d.w., and 126 s⁻¹ (regional maximum), which corresponded with 3.4 mg Fe/g_d.w.. The average pancreatic R2* (72.4 s⁻¹) was significantly above normal values, which indicated iron overload.
Conclusion: We demonstrated the feasibility of prenatal quantification of tissue iron by fetal MRI in this sheep model and successfully quantified iron, including that in the pancreas, in a human neonate to confirm the diagnosis of neonatal hemochromatosis. Transferring the successful approach of quantifying iron in intrauterine tissue in fetal sheep to human pregnancies with suspected fetal siderosis could aid early diagnosis.