title: Fluorescence tomography and magnetic resonance imaging of myocardial macrophage infiltration in infarcted myocardium in vivo.
abstract: 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.
  
  
  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.
authors.affiliation: Center for Molecular Imaging Research, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. sosnovik@nmr.mgh.harvard.edu
authors.forename: David E
authors.initials: DE
authors.lastname: Sosnovik
authors.forename: Matthias
authors.initials: M
authors.lastname: Nahrendorf
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Deliolanis
authors.forename: Mikhail
authors.initials: M
authors.lastname: Novikov
authors.forename: Elena
authors.initials: E
authors.lastname: Aikawa
authors.forename: Lee
authors.initials: L
authors.lastname: Josephson
authors.forename: Anthony
authors.initials: A
authors.lastname: Rosenzweig
authors.forename: Ralph
authors.initials: R
authors.lastname: Weissleder
authors.forename: Vasilis
authors.initials: V
authors.lastname: Ntziachristos
mesh_terms: D000818:Animals; D002232:Carbocyanines; D004195:Disease Models, Animal; D008264:Macrophages / Q000473:pathology*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D009203:Myocardial Infarction / Q000276:immunology / Q000473:pathology*; D009206:Myocardium / Q000276:immunology / Q000473:pathology*; D041622:Tomography, Optical / Q000379:methods*
chemical_list: C098793:CY5.5 cyanine dye; D002232:Carbocyanines