title: Visualization of pulmonary inflammation using noninvasive fluorescence molecular imaging.
abstract: The ability to visualize molecular processes and cellular regulators of complex pulmonary diseases such as asthma, chronic obstructive pulmonary disease (COPD), or adult respiratory distress syndrome (ARDS), would aid in the diagnosis, differentiation, therapy assessment and in small animal-based drug-discovery processes. Herein we report the application of normalized transillumination and fluorescence molecular tomography (FMT) for the noninvasive quantitative imaging of the mouse lung in vivo. We demonstrate the ability to visualize and quantitate pulmonary response in a murine model of LPS-induced airway inflammation. Twenty-four hours prior to imaging, BALB/c female mice were injected via tail vein with 2 nmol of a cathepsin-sensitive activatable fluorescent probe (excitation: 750 nm; emission: 780 nm) and 2 nmol of accompanying intravascular agent (excitation: 674 nm; emission: 694 nm). Six hours later, the mice were anesthetized with isoflurane and administered intranasal LPS in sterile 0.9% saline in 25 microl aliquots (one per nostril). Fluorescence molecular imaging revealed the in vivo profile of cysteine protease activation and vascular distribution within the lung typifying the inflammatory response to LPS insult. Results were correlated with standard in vitro laboratory tests (Western blot, bronchoalveolar lavage or BAL analysis, immunohistochemistry) and revealed good correlation with the underlying activity. We demonstrated the capacity of fluorescence tomography to noninvasively and longitudinally characterize physiological, cellular, and subcellular processes associated with inflammatory disease burden in the lung. The data presented herein serve to further evince fluorescence molecular imaging as a technology highly appropriate for the biomedical laboratory.
authors.affiliation: Center for Molecular Imaging Research Laboratory For Bio-optics and Molecular Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA.
authors.forename: Jodi
authors.initials: J
authors.lastname: Haller
authors.forename: Damon
authors.initials: D
authors.lastname: Hyde
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Deliolanis
authors.forename: Ruben
authors.initials: R
authors.lastname: de Kleine
authors.forename: Mark
authors.initials: M
authors.lastname: Niedre
authors.forename: Vasilis
authors.initials: V
authors.lastname: Ntziachristos
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D005453:Fluorescence; D005456:Fluorescent Dyes / Q000008:administration & dosage; D021621:Imaging, Three-Dimensional; D007275:Injections, Intravenous; D008070:Lipopolysaccharides; D008168:Lung / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018410:Pneumonia, Bacterial / Q000139:chemically induced / Q000473:pathology*; D012815:Signal Processing, Computer-Assisted; D041622:Tomography, Optical / Q000379:methods*
chemical_list: D005456:Fluorescent Dyes; D008070:Lipopolysaccharides; C482199:lipopolysaccharide, E coli O55-B5