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EE-38 MR Imaging Artifacts of Intravascular Iron: A Case Report and Importance in Clinical Practice. Pratish Shah MD, William Zelkovich MD, Benjamin Liu MD, Eric Russell MD Department of Radiology - Division of Neuroradiology Northwestern University Feinberg School of Medicine, Chicago, IL Disclosures There are no conflicts of interest or financial relationships to disclose with respect to industry research support, consulting, or speaking. Objectives • Describe the magnetic resonance imaging findings in a patient who underwent MRI of the brain immediately after intravenous iron therapy. • Review various intravenous iron products available in the USA and understand their pharmacokinetics. • Discuss the importance of delaying or altering protocols for magnetic resonance neuroimaging after the infusion of intravenous iron products for a varied time period based on pharmacokinetic properties. Case Report • A 61 year old woman with past medical history including but not limited to chronic kidney disease, anemia, coronary artery disease and diabetes presented to the clinic for an infusion of 510 mg of intravenous iron Ferumoxytol for her anaemia. • During the infusion, the patient complained of dyspnea and palpitations and became unresponsive. The intravenous iron was immediately stopped and she was treated with diphenhydramine, methylprednisolone and epinephrine for this anaphylactic reaction. Case Report • After the initial episode, the patient was transferred to the emergency department where she had persistent slurred speech and left sided weakness which was concerning for stroke. • She underwent an MRI and MR angiogram of the head approximately 8 hours and 48 hours after iron therapy respectively. • MR angiogram was aborted due to severe artifacts and images were not sent to PACS. • Imaging was performed on a Magnetom Espree 1.5 Tesla scanner (Seimens, Siemens Medical Systems, Erlangen, Germany) Case Report: MR Imaging Findings - GRE T2 Gradient echo sequence 8 hours after IV iron T2 Gradient echo sequence 5 months earlier • Diffuse T2 / T2* shortening with susceptibility artifact(blooming) was noted along the vessels within the sulci and choroid plexus and within the basal cisterns. • These findings were not present on MRI performed 5 months earlier. Case Report: MR Imaging Findings - DWI DWI 8 hours after IV iron DWI 5 months earlier • Diffuse susceptibility artifact was noted along the vessels within the sulci on axial diffusion weighted sequence (DWI) performed 8 hours after IV iron which significantly limited evaluation. • These findings were not present on MRI performed 5 months earlier. Case Report: MR Imaging Findings - T2 TSE T2 TSE 8 hours after IV iron. T2 TSE 5 months earlier • Axial T2 turbo spin echo (T2 TSE) sequence demonstrates prominence of the flow voids of bilateral middle cerebral arteries, anterior cerebral arteries and bilateral superior ophthalmic veins. • Although this minimally limits evaluation, it does not lead to significant distortion such as that seen on GRE and DWI sequences. • These findings were not present on MRI performed 5 months earlier. Case Report: MR Imaging Findings - T1 SE • In our case, where MRI was performed only 8 hours after a large dose of IV iron, T1 shortening was not seen on precontrast T1 spin echo sequence. Case Report: CT Imaging Findings • CT brain performed 1 hour after IV iron administration did not show intracranial hemorrhage. • This is additional evidence that the MR imaging findings are not secondary to subarachnoid hemorrhage. Discussion: Different Intravenous Iron Preparations4 • Oral iron supplementation is usually the first choice for the treatment of iron deficiency anemia (IDA) because of its effectiveness and low cost. • But unfortunately in many iron deficient conditions, oral iron is a less than the ideal treatment mainly because of adverse events related to the gastrointestinal tract as well as the long course required to treat anemia and replenish body iron stores. • The first iron product for intravenous use was high-molecular-weight iron dextran. • Several intravenous iron preparations are currently available in the United States today. Discussion: Different Intravenous Iron Preparations2,3 Discussion: Main clinical indications for IV iron treatment4 • Intolerance to oral iron or non-compliance to an oral regimen. • Iron malabsorption: Intestinal malabsorption syndromes, inflammatory diseases (IBD), after gastrectomy/bariatric surgery. • Functional iron deficiency particularly when an ESA is used: Anemia of chronic kidney disease, inflammatory diseases, anemia of cancer. • Severe IDA (Hb < 9 g/dL) because of continuous or uncontrolled blood loss and/or because of increased iron needs: Hereditary hemorrhagic telangiectasias (Osler-Weber-Rendu disease), angiodysplasias, pregnancy, post-partum anemia. Discussion • Ferumoxytol (Feraheme; AMAG Pharmaceuticals, Waltham, MA) is an ultrasmall super-paramagnetic iron oxide (USPIO) nanoparticle (30 nm).5 • It has a long circulating half-life (14–15 h) in the intravascular space (blood pool) with a complete plasma elimination time of 3 days.2,3 Discussion: Reason for MR artifacts • Ferumoxytol (FMX) results in T1, T2, and T2* shortening on magnetic resonance imaging (MRI) due to its superparamagnetic properties.6 • At high concentrations, FMX has predominant T2/T2* effects within the blood that cause a complete loss of signal on T1 and T2/T2* sequences and susceptibility artifacts.7 These signal characteristics were seen in our case where MRI was obtained only 8 hours after a large dose of FMX. Discussion: Reason for MR artifacts • At lower blood concentrations of FMX (due to either a lower dose or an MRI obtained at a later time point after injection), predominant T1-shortening effects are noted.7 This was observed in a case report described by Mccullough.6 • FMX has also been shown to have markedly greater T2*shortening effects for a given concentration compared with gadolinium-based agents, leading to a greater potential for susceptibility artifacts.8 Discussion: Clinical Significance • Based on this information, we can conclude that MR imaging should be avoided for a certain time period after intravenous FMX administration. • The FDA package insert for FMX recommends avoiding MR imaging for three months. If MRI is needed earlier than that, the insert recommends changing the MRI protocol to use T1 and proton density sequences and avoiding T2 weighted sequences for at least one month to minimize susceptibility artifacts.2 • These general guidelines in the FDA insert appear more appropriate for MRI of the body due to reticuloendothelial uptake by the spleen, liver and bone marrow. They may not be feasible in clinical situations where urgent neuroimaging is required, as in our case. Discussion: Clinical Significance • - We suggest a shorter wait time period of 3 days based on FMX’s complete plasma elimination time of 3 days for MRI of the brain. - This recommendation is based on Ferumoxytol’s pharmacokinetic properties and the assumption that calvarial marrow deposition of FMX will not significantly affect image quality. However further research is needed. • - In our patient, imaging was performed around 8 hours after intravenous injection of FMX. Even though T2 shortening effects were noted on T2 turbo spin echo images which resulted in prominence of the vascular flow voids, significant image distortion was not observed. These T2 TSE images were considered interpretable. - Based on this, we postulate that T2 weighted spin echo sequences may be feasible even earlier than 3 days. Our case report only provides anecdotal evidence and further research is warranted. Discussion: Clinical Significance • As mentioned earlier, these MR imaging artifacts are due to the superparamagnetic properties of Ferumoxytol (FMX). • Other IV iron preparations available in the US (Table 1) do not have super-paramagnetic properties. • There is no recommended wait time for MRI after administration of other parenteral iron agents.2,3 Conclusion • MR of the brain should be avoided for at least 3 days after IV Ferumoxytol. • T1 and T2 weighted spin echo sequence may be performed even earlier than 3 days. • MRI wait time is not recommended for other IV iron therapies. • These recommendations are based on anecdotal evidence and certain other assumptions. Further research is needed. References 1. Morelli J, Runge V, Ai F, Attenberger U, Vu L, Schmeets S, Nitz W, Kirsch J. An image-based approach to understanding the physics of MR artifacts. Radiographics. 2011 May-Jun; 31(3):849-66. 2. Rostoker G, Cohen Y. Magnetic resonance imaging repercussions of intravenous iron products used for iron-deficiency anemia and dialysis-associated anemia. J Comput Assist Tomogr. 2014 Nov-Dec; 38(6):843-4. 3. Feraheme [package insert]. AMAG Pharmaceuticals, Inc., Lexington, MA 02421. 4. Cançado R, Muñoz M. Intravenous iron therapy: how far have we come? Rev Bras Hematol Hemoter. 2011; 33(6):461-9. 5. Ruangwattanapaisarn N, Hsiao A, Vasanawala S. Ferumoxytol as an off-label contrast agent in body 3T MR angiography: a pilot study in children. Pediatr Radiol. 2015 Jun; 45(6):831-9. 6. McCullough B, Kolokythas O, Maki J, Green D. Ferumoxytol in clinical practice: implications for MRI. J Magn Reson Imaging. 2013 Jun; 37(6):1476-9. 7. Herborn C, Vogt F, Lauenstein T, Dirsch O, Corot C, Robert P, Ruehm S. Magnetic resonance imaging of experimental atherosclerotic plaque: comparison of two ultrasmall superparamagnetic particles of iron oxide. J Magn Reson Imaging. 2006 Aug; 24(2):388-93. 8. Fananapazir G, Marin D, Suhocki P, Kim C, Bashir M. Vascular artifact mimicking thrombosis on MR imaging using ferumoxytol as a contrast agent in abdominal vascular assessment. J Vasc Interv Radiol. 2014 Jun; 25(6):969-76. Thank you.