title: MR imaging, targeting and characterization of pulmonary fibrosis using intra-tracheal administration of gadolinium-based nanoparticles.
abstract: Idiopathic pulmonary fibrosis is a devastating disease. Animal models are critical to develop new diagnostic approaches. We investigate here whether the application of an ultra-short echo time MRI sequence combined with the intra-tracheal administration of Gd-based nanoparticles can help to visualize and characterize pulmonary fibrosis in mice. 21 mice were imaged. Treated mice were administered bleomycin. MRI was used for longitudinal detection of bleomycin-induced lung injury from Day 1 up to Day 60. On Day 30, all mice received nanoparticles and MR images were acquired. A signal enhancement of 120% and 50% in fibrotic lesions and healthy tissues respectively was obtained. A twofold increase of contrast-to-noise ratio between fibrotic and healthy tissue was also observed, leading to a more accurate delineation of the extent of fibrosis. The elimination time constant of the nanoparticles was 54% higher in fibrotic lesions. Bleomycin-induced lung injury can be monitored using MRI. Intra-tracheal administration of Gd-based nanoparticles enabled us to enhance fibrotic tissue in lungs but also to extract imaging biomarkers that quantify elimination and diffusion of contrast agents and can characterize fibrotic tissue. The added value of MRI associated with pulmonary administration of contrast agents is key to better understand the lung fibrotic process and monitor drug response in pre-clinical studies, which will be valuable for translational applications. Copyright © 2016 John Wiley & Sons, Ltd.
authors.affiliation: Centre de Résonance Magnétique des Systèmes Biologiques, CNRS UMR 5536, Université de Bordeaux, Bordeaux, France. nawal.tassali@gmail.com.
authors.forename: Nawal
authors.initials: N
authors.lastname: Tassali
authors.affiliation: Centre de Résonance Magnétique des Systèmes Biologiques, CNRS UMR 5536, Université de Bordeaux, Bordeaux, France.
authors.forename: Andrea
authors.initials: A
authors.lastname: Bianchi
authors.affiliation: Institut Lumière Matière, CNRS UMR 5306, Université Claude Bernard, Villeurbanne, France.
authors.forename: François
authors.initials: F
authors.lastname: Lux
authors.affiliation: Centre de Résonance Magnétique des Systèmes Biologiques, CNRS UMR 5536, Université de Bordeaux, Bordeaux, France.
authors.forename: Gérard
authors.initials: G
authors.lastname: Raffard
authors.affiliation: Centre de Résonance Magnétique des Systèmes Biologiques, CNRS UMR 5536, Université de Bordeaux, Bordeaux, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Sanchez
authors.affiliation: Institut Lumière Matière, CNRS UMR 5306, Université Claude Bernard, Villeurbanne, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Tillement
authors.affiliation: Centre de Résonance Magnétique des Systèmes Biologiques, CNRS UMR 5536, Université de Bordeaux, Bordeaux, France.
authors.forename: Yannick
authors.initials: Y
authors.lastname: Crémillieux
mesh_terms: D000818:Animals; D001761:Bleomycin; D003287:Contrast Media / Q000493:pharmacokinetics; D004333:Drug Administration Routes; D005682:Gadolinium / Q000493:pharmacokinetics*; D008168:Lung / Q000000981:diagnostic imaging / Q000378:metabolism; D008279:Magnetic Resonance Imaging / Q000379:methods*; D053768:Metal Nanoparticles / Q000737:chemistry*; D051379:Mice; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000000981:diagnostic imaging*; D014132:Trachea
chemical_list: D003287:Contrast Media; D001761:Bleomycin; D005682:Gadolinium
keywords: Gadolinium; MRI; contrast agent; fibrosis; intra-tracheal administration; nanoparticles; targeting