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(Circulation. 2007;115:1384-1391.)
© 2007 American Heart Association, Inc.

Imaging

Fluorescence Tomography and Magnetic Resonance Imaging of Myocardial Macrophage Infiltration in Infarcted Myocardium In Vivo

David E. Sosnovik, MD^*; Matthias Nahrendorf, MD^*; Nikolaos Deliolanis, PhD; Mikhail Novikov, MD; Elena Aikawa, MD, PhD; Lee Josephson, PhD; Anthony Rosenzweig, MD; Ralph Weissleder, MD, PhD; Vasilis Ntziachristos, PhD

From the Center for Molecular Imaging Research, Massachusetts General Hospital, Harvard Medical School (D.E.S., M. Nahrendorf, N.D., E.A., L.J., R.W., V.N.), and Division of Cardiology, Beth Israel Deaconess Medical Center, Harvard Medical School (M. Novikov, A.R.), Boston, Mass.

Correspondence to David Sosnovik, MD, Center for Molecular Imaging Research, 149 13th St, Charlestown, MA 02129. E-mail sosnovik{at}nmr.mgh.harvard.edu

Received September 7, 2006; accepted January 16, 2007.

Background— Fluorescence imaging of the heart is currently limited to invasive ex vivo or in vitro applications. We hypothesized that the adaptation of advanced transillumination and tomographic techniques would allow noninvasive fluorescence images of the heart to be acquired in vivo and be coregistered with in vivo cardiac magnetic resonance images.

Methods and Results— The uptake of the magnetofluorescent nanoparticle CLIO-Cy5.5 by macrophages in infarcted myocardium was studied. Ligation of the left coronary artery was performed in 12 mice and sham surgery in 7. The mice were injected, 48 hours after surgery, with 3 to 20 mg of iron per kilogram of CLIO-Cy5.5. Magnetic resonance imaging and fluorescence molecular tomography were performed 48 hours later. An increase in magnetic resonance imaging contrast-to-noise ratio, indicative of myocardial probe accumulation, was seen in the anterolateral walls of the infarcted mice but not in the sham-operated mice (23.0±2.7 versus 5.43±2.4; P<0.01). Fluorescence intensity over the heart was also significantly greater in the fluorescence molecular tomography images of the infarcted mice (19.1±5.2 versus 5.3±1.4; P<0.05). The uptake of CLIO-Cy5.5 by macrophages infiltrating the infarcted myocardium was confirmed by fluorescence microscopy and immunohistochemistry.

Conclusions— Noninvasive imaging of myocardial macrophage infiltration has been shown to be possible by both fluorescence tomography and magnetic resonance imaging. This could be of significant value in both the research and clinical settings. The techniques developed could also be used to image other existing fluorescent and magnetofluorescent probes and could significantly expand the role of fluorescence imaging in the heart.

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CLINICAL PERSPECTIVE

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