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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:176.)
© 2006 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Ferumoxtran-10–Enhanced MRI of the Hypercholesterolemic Rabbit Aorta

Relationship Between Signal Loss and Macrophage Infiltration

Fabien Hyafil; Jean-Pierre Laissy; Mikael Mazighi; Didier Tchétché; Liliane Louedec; Homa Adle-Biassette; Sylvie Chillon; Dominique Henin; Marie-Paule Jacob; Didier Letourneur; Laurent J. Feldman

From the INSERM U698 (F.H., J.P.L., M.M., D.T., L.L., M.P.J., D.L., L.J.F.), Departments of Cardiology (F.H., D.T., L.J.F.), Radiology (J.P.L., S.C.), and Pathology (H.A.B., D.H.), Hôpital Bichat, Assistance Publique-Hôpitaux de Paris, Paris, France.

Correspondence to Laurent J. Feldman, Cardiology Department, CHU Bichat, 46, rue Henri Huchard, 75018 Paris, France. E-mail laurent.feldman{at}bch.aphp.fr

Objective— Ferumoxtran-10 is an MRI contrast agent, which accumulates in macrophages and induces magnetic susceptibility artifacts (MSAs). We evaluated the ability of ferumoxtran-10–enhanced MRI to quantify focal macrophage infiltration in the aortic wall of hypercholesterolemic rabbits.

Methods and Results— Six weeks after a double-balloon injury of the infrarenal aorta, 12 hypercholesterolemic rabbits underwent MRI of the aorta before (first MRI) and after (second MRI) intravenous injection of ferumoxtran-10 (n=10) or saline (n=2). A third MRI was performed 5 days later to detect ferumoxtran-10–induced MSA in the aortic wall. Aortas were subsequently processed for histology, immunohistochemistry, and gelatin zymography studies. Injured aortas displayed a macrophage-rich neointima with high-matrix metalloproteinase 2 and 9 activities. Iron stain of injured aortas showed massive accumulation of ferumoxtran-10 in neointimal macrophages. Five days after the injection of ferumoxtran-10, MSAs were detected only in the injured aortas by in vivo MRI and were quantified indirectly using the percentage reduction of luminal area attributable to the extension of these MSAs in the aortic lumen. This parameter correlated with macrophage infiltration on corresponding aortic cross-sections (r=0.82; P<0.05).

Conclusion— Ferumoxtran-10–enhanced MRI allows quantitative assessment of macrophage infiltration induced by balloon angioplasty in the aorta of hypercholesterolemic rabbits.

We evaluated the ability of ferumoxtran-10–enhanced MRI to quantify macrophage infiltration in the aortic wall of hypercholesterolemic rabbits. Ferumoxtran-10–induced magnetic susceptibility artifacts were detected by in vivo MRI only in macrophage–rich aortic segments. Magnetic susceptibility artifact–related luminal narrowing on MRI correlated with macrophage infiltration on corresponding aortic cross-sections.

Key Words: MRI • imaging agents • atherosclerosis • macrophages • metalloproteinases

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