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BRAIN

Iron Particle–Enhanced Visualization of Inflammatory Central Nervous System Lesions by High Resolution: Preliminary Data in an Animal Model

R.A. Linkera,c, A. Kronera, T. Hornb, R. Golda,c, M. Mäurera and M. Bendszusb

a Clinical Research Group for Multiple Sclerosis, Julius Maximilians-Universität Würzburg, Germany
b Departments of Neurology and Neuroradiology, Julius Maximilians-Universität Würzburg, Germany
c Institute for Multiple Sclerosis Research, University of Göttingen and gemeinnützige Hertie-Stiftung, Waldweg, Germany

Please address correspondence to: Mathias Mäurer, MD, Neurologische Universitätsklinik Würzburg, Josef-Schneider-Str. 11, 97080 Würzburg

BACKGROUND AND PURPOSE: The detection of cell infiltration is critical for the diagnosis and monitoring of inflammatory disorders, especially in the central nervous system (CNS). Superparamagnetic iron oxide (SPIO) particles have recently been introduced as a contrast agent to detect macrophage migration in vivo by MR imaging. We tested the hypothesis that focal hyperechogenicity due to SPIO-laden macrophages can also be visualized on high-resolution sonography.

METHODS: Experimental autoimmune encephalomyelitis (EAE) was induced by myelin-oligodendrocyte glycoprotein (MOG) in congenic Lewis rats, an animal model mimicking many aspects of human multiple sclerosis. At the height of disease, rats underwent MR imaging with a 1.5T unit. Animals were injected with SPIO particles 24 hours before imaging. Control rats either received no contrast agent or were injected with SPIO particles without prior induction of EAE. Immediately after MR imaging, the rats were sacrificed, and the brains were removed and placed in saline. Sonography was performed directly after brain removal. Brains were embedded in paraffin, and sections were stained for iron with Perls stain and for macrophages with ED1 immunohistochemistry.

RESULTS: SPIO-enhanced sonography of rat brains during a relapse of EAE specifically showed marked focal echogenicity in EAE-typical areas of the brain, including the periventricular region, the cerebellum, and the brain stem. The sonographic results corresponded to in vivo MR imaging findings of the respective animals as well to the clinical symptoms of EAE and to histology showing iron-laden macrophages in demyelinated lesions.

CONCLUSION: SPIO particles allow the detection and demarcation of inflammatory CNS lesions on sonograms by specific macrophage imaging.