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Open Access Brain Iron Distribution after Multiple Doses of Ultra-small Superparamagnetic Iron Oxide Particles in Rats

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The purpose of this study is to determine the effects of high cumulative doses of ultra-small paramagnetic iron oxide (USPIO) used in neuroimaging studies. We intravenously administered 8 mg/kg of 2 USPIO compounds daily for 4 wk to male Sprague–Dawley rats (Crl:SD). Multiecho gradient-echo MRI, serum iron levels, and histology were performed at the end of dosing and after a 7-d washout period. R2* maps and quantitative susceptibility maps (QSM) were generated from multiecho gradient-echo data. R2* maps and QSM showed iron accumulation in brain ventricles on MR images acquired at the 4- and 5-wk time points. Estimates from QSM data showed ventricular iron concentration was equal to or higher than serum iron concentration. Histologic analysis revealed choroid plexus hemosiderosis and midbrain vacuolation, without iron deposition in brain parenchyma. Serum iron levels increased with administration of both compounds, and a 7-d washout period effectively reduced serum iron levels of one but not both of the compounds. High cumulative doses from multiple, frequent administrations of USPIO can lead to iron deposition in brain ventricles, resulting in persistent signal loss on T2*-weighted images. Techniques such as QSM are helpful in quantifying iron biodistribution in this situation.
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Document Type: Research Article

Affiliations: 1: Institute of Comparative Medicine, Columbia University, New York, New York, USA. Center of Comparative Medicine and Pathology, Memorial Sloan-Kettering Center, Tri Institutional Training Program in Laboratory Animal Medicine and Science, New York, New York, USA., Email: [email protected] 2: Joan and Sanford I Weill Medical College, Cornell University, New York, New York, USA 3: Laboratory of Neural Systems, Rockefeller University, New York, New York, USA. Neural Circuits and Cognition Lab, European Neuroscience Institute, Gottingen, Germany 4: Center of Comparative Medicine and Pathology, Memorial Sloan-Kettering Cancer Center, Tri Institutional Training Program in Laboratory Animal Medicine and Science, New York, New York, USA 5: Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Aurora, Colorado, USA 6: Laboratory of Neural Systems, Rockefeller University, New York, New York, USA 7: Comparative Bioscience Center, Rockefeller University, New York, New York, USA

Publication date: April 1, 2018

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  • Comparative Medicine (CM), an international journal of comparative and experimental medicine, is the leading English-language publication in the field and is ranked by the Science Citation Index in the upper third of all scientific journals. The mission of CM is to disseminate high-quality, peer-reviewed information that expands biomedical knowledge and promotes human and animal health through the study of laboratory animal disease, animal models of disease, and basic biologic mechanisms related to disease in people and animals.

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