Comparison of ultrasmall particles of iron oxide (USPIO)-enhanced T2-weighted, conventional T2-weighted, and gadolinium-enhanced T1-weighted MR images in rats with experimental autoimmune encephalomyelitis

Abstract

Background and purpose: Ultrasmall particles of iron oxide (USPIO) constitute a contrast agent that accumulates in cells from the mononuclear phagocytic system. In the CNS they may accumulate in phagocytic cells such as macrophages. The goal of this study was to compare USPIO-enhanced MR images with conventional T2-weighted images and gadolinium-enhanced T1-weighted images in a model of experimental autoimmune encephalomyelitis (EAE).

Methods: Nine rats with EAE and four control rats were imaged at 4.7 T and 1.5 T with conventional T1- and T2-weighted sequences, gadolinium-enhanced T1-weighted sequences, and T2-weighted sequences obtained 24 hours after intravenous injection of a USPIO contrast agent, AMI-227. Histologic examination was performed with hematoxylin-eosin stain, Perls' stain for iron, and ED1 immunohistochemistry for macrophages.

Results: USPIO-enhanced images showed a high sensitivity (8/9) for detecting EAE lesions, whereas poor sensitivity was obtained with T2-weighted images (1/9) and gadolinium-enhanced T1-weighted images (0/9). All the MR findings in the control rats were negative. Histologic examination revealed the presence of macrophages at the site where abnormalities were seen on USPIO-enhanced images.

Conclusion: The high sensitivity of USPIO for macrophage activity relative to other imaging techniques is explained by the histologic findings of numerous perivascular cell infiltrates, including macrophages, in EAE. This work supports the possibility of intracellular USPIO transport to the CNS by monocytes/macrophages, which may have future implications for imaging of human inflammatory diseases.

fig 1.

Coronal SE T2-weighted (2030/60/4) MR image obtained at 4.7 T in a rat with EAE. The section is at the level of the midbrain (arrowhead indicates the right cerebral hemisphere). A small area of increased signal intensity is present around the sylvian aqueduct (arrow)

fig 2.

A and B, Coronal SE T2-weighted images of the brains of two rats with clinical EAE, imaged 24 hours after administration of USPIO (AMI-227) at 4.7 T. The section is at the level of the posterior fossa (arrowheads indicate the right cerebellar hemisphere; long arrows, the pons). Numerous lesions are seen as low signal intensities related to the magnetic susceptibility effects caused by iron particles within phagocytic cells (small arrows in A). fig 3. Coronal turbo SE T2-weighted (5000/20/1) MR image of the brain of a rat with EAE, imaged 24 hours after administration of AMI-227 at 1.5 T. Multiple areas of low signal are seen within the posterior fossa (arrows).

fig 4.

Histologic sections at a site of low signal on MR images after administration of AMI-227. A, Hematoxylin-eosin stain shows multiple perivascular inflammatory infiltrates (arrows). B, Prussian blue stain for iron (Perls' technique) shows staining of perivascular cells (arrows). fig 5. Histologic section at the level of the posterior fossa (arrow indicates fourth ventricle) shows immunostaining with an ED1 antibody macrophage marker. Macrophage infiltrates correspond to magnetic susceptibility–related low signal intensities on T2-weighted images 24 hours after USPIO injection and to infiltrating cells on hematoxylin-eosin stain.