Authors: Lily H. Kim; Michael Iv, MD; Ashok Theruvath, MD; Laura Pisani, PhD; Olga Lenkov, PhD; Heiki Daldrup-Link, MD, PhD; Gerald Grant, MD; Samuel Cheshier, MD, PhD; Kristen Yeom, MD; Katie Shpanskaya, BS (Mountain View, CA)

Introduction: Use of ferumoxytol (Fe) as an intravascular contrast agent for magnetic resonance imaging (MRI) has shown robust performance in presurgical evaluation of arteriovenous malformations. While it is known that gadolinium as a contrast agent deposits in the brain, iron oxide nanoparticle distribution in the brain after intravenous injection remains unknown. In this study, we investigated if there is any intracranial iron deposition after multiple ferumoxytol administrations. Methods: We conducted a retrospective study of 9 pigs and 12 pediatric patients (7 females, 5 males) who received Fe (5 and 3 mg/kg, respectively). Inclusion criteria were: whole porcine brains with ex-vivo T2* (T2 star) MRI at 7 Tesla; patients with at least two Fe-enhanced T2* MRIs at 3 Tesla. Quantitative T2* values were extracted from caudate, lentiform, dentate, thalami, globus pallidus, putamen, and substantia nigra. Pearson correlation was used to evaluate Fe dose relative to R2* and susceptibility values. Results: In pigs, there was no significant difference in R2* of Fe-exposed brain versus controls. In humans, R2* and susceptibility in all brain regions did not significantly differ from baseline ( P >0.05), except for increased R2* in the dentate ( P =0.013) and globus pallidus ( P =0.019) at follow-up MRI (mean follow-up 14.67 months). However, this was not dose-dependent. Conclusion: No significant differences were found in R2* and susceptibility values in porcine and human brains after Fe-enhanced MRIs except for slightly increased R2* in the dentate and globus pallidus in humans at follow-up, suggesting that exogenous Fe administration results in minimal brain iron deposition. Given high performance of Fe as an intravascular contrast agent with potentially less risk for permanent brain deposition compared to gadolinium, Fe may be a useful alternative intravascular MRI contrast agent for neurosurgical evaluation of vascular lesions.