Special Section on Cardiovascular Photonics

Detection of macrophage activity in atherosclerosis in vivo using multichannel, high-resolution laser scanning fluorescence microscopy

[+] Author Affiliations
Ashvin N. Pande

Massachusetts General Hospital, Harvard Medical School, Center for Molecular Imaging Research, Charlestown, Massachusetts 02129 and Donald W. Reynolds Cardiovascular Clinical Research Center, Harvard Medical School, Boston, Massachusetts 02115 and Brigham and Women’s Hospital, Harvard Medical School, Department of Medicine, Cardiovascular Division, Boston, Massachusetts 02115

Rainer H. Kohler

Massachusetts General Hospital, Harvard Medical School, Center for Molecular Imaging, Charlestown, Massachusetts 02129

Elena Aikawa, Ralph Weissleder

Massachusetts General Hospital, Harvard Medical School, Center for Molecular Imaging, Charlestown, Massachusetts 02129 and Donald W. Reynolds Cardiovascular Clinical Research Center, Harvard Medical School, Boston, Massachusetts 02115

Farouc A. Jaffer

Massachusetts General Hospital, Harvard Medical School, Center for Molecular Imaging, Charlestown, Massachusetts 02129 and Donald W. Reynolds Cardiovascular Clinical Research Center, Harvard Medical School, Boston, Massachusetts 02115 and Massachusetts General Hospital, Harvard Medical School, Department of Medicine, Cardiology Division, Boston, Massachusetts 02114

J. Biomed. Opt. 11(2), 021009 (March 23, 2006). doi:10.1117/1.2186337
History: Received June 30, 2005; Revised November 07, 2005; Accepted December 22, 2005; Published March 23, 2006
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Molecular and cellular mechanisms of atherogenesis and its treatment are largely being unraveled by in vitro techniques. We describe methodology to directly image macrophage cell activity in vivo in a murine model of atherosclerosis using laser scanning fluorescence microscopy (LSFM) and a macrophage-targeted, near-infrared fluorescent (NIRF) magnetofluorescent nanoparticle (MFNP). Atherosclerotic apolipoprotein E deficient (apoE -/-) mice (n=10) are injected with MFNP or 0.9% saline, and wild-type mice (n=4) are injected with MFNP as additional controls. After 24h, common carotid arteries are surgically exposed and prepared for LSFM. Multichannel LSFM of MFNP-enhanced carotid atheroma (5×5μm in-plane resolution) shows a strong focal NIRF signal, with a plaque target-to-background ratio of 3.9±1.8. Minimal NIRF signal is observed in control mice. Spectrally resolved indocyanine green (ICG) fluorescence angiograms confirm the intravascular location of atheroma. On ex vivo fluorescence reflectance imaging, greater NIRF plaque signal is seen in apoE -/- MFNP mice compared to controls (p<0.01). The NIRF signal correlates well with immunostained macrophages, both by stained surface area (r=0.77) and macrophage number (r=0.86). The validated experimental methodology thus establishes a platform for investigating macrophage activity in atherosclerosis in vivo, and has implications for the detection of clinical vulnerable plaques.

Figures in this Article
© 2006 Society of Photo-Optical Instrumentation Engineers

Citation

Ashvin N. Pande ; Rainer H. Kohler ; Elena Aikawa ; Ralph Weissleder and Farouc A. Jaffer
"Detection of macrophage activity in atherosclerosis in vivo using multichannel, high-resolution laser scanning fluorescence microscopy", J. Biomed. Opt. 11(2), 021009 (March 23, 2006). ; http://dx.doi.org/10.1117/1.2186337


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