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Iron particle-enhanced visualization of inflammatory central nervous system lesions by high resolution: preliminary data in an animal model.

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.