title: Improved In vivo Assessment of Pulmonary Fibrosis in Mice using X-Ray Dark-Field Radiography.
abstract: Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive lung disease with a median life expectancy of 4-5 years after initial diagnosis. Early diagnosis and accurate monitoring of IPF are limited by a lack of sensitive imaging techniques that are able to visualize early fibrotic changes at the epithelial-mesenchymal interface. Here, we report a new x-ray imaging approach that directly visualizes the air-tissue interfaces in mice in vivo. This imaging method is based on the detection of small-angle x-ray scattering that occurs at the air-tissue interfaces in the lung. Small-angle scattering is detected with a Talbot-Lau interferometer, which provides the so-called x-ray dark-field signal. Using this imaging modality, we demonstrate-for the first time-the quantification of early pathogenic changes and their correlation with histological changes, as assessed by stereological morphometry. The presented radiography method is significantly more sensitive in detecting morphological changes compared with conventional x-ray imaging, and exhibits a significantly lower radiation dose than conventional x-ray CT. As a result of the improved imaging sensitivity, this new imaging modality could be used in future to reduce the number of animals required for pulmonary research studies.
authors.affiliation: Lehrstuhl für Biomedizinische Physik, Physik-Department &Institut für Medizintechnik, Technische Universität München, Garching, Germany.
authors.forename: Andre
authors.initials: A
authors.lastname: Yaroshenko
authors.affiliation: Institute for Clinical Radiology, Ludwig-Maximilians-University Hospital Munich, Munich.
authors.forename: Katharina
authors.initials: K
authors.lastname: Hellbach
authors.affiliation: Comprehensive Pneumology Center, Institute of Lung Biology and Disease, Member of the German Center for Lung Research (DZL), Helmholtz Zentrum München, Neuherberg, Germany.
authors.forename: Ali Önder
authors.initials: AÖ
authors.lastname: Yildirim
authors.affiliation: Comprehensive Pneumology Center, Institute of Lung Biology and Disease, Member of the German Center for Lung Research (DZL), Helmholtz Zentrum München, Neuherberg, Germany.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Conlon
authors.affiliation: Comprehensive Pneumology Center, Institute of Lung Biology and Disease, Member of the German Center for Lung Research (DZL), Helmholtz Zentrum München, Neuherberg, Germany.
authors.forename: Isis Enlil
authors.initials: IE
authors.lastname: Fernandez
authors.affiliation: Department of Medical Radiation Physics, Lund University, Lund, Sweden.
authors.forename: Martin
authors.initials: M
authors.lastname: Bech
authors.affiliation: Lehrstuhl für Biomedizinische Physik, Physik-Department &Institut für Medizintechnik, Technische Universität München, Garching, Germany.
authors.forename: Astrid
authors.initials: A
authors.lastname: Velroyen
authors.affiliation: Institute for Clinical Radiology, Ludwig-Maximilians-University Hospital Munich, Munich.
authors.forename: Felix G
authors.initials: FG
authors.lastname: Meinel
authors.affiliation: Institute for Clinical Radiology, Ludwig-Maximilians-University Hospital Munich, Munich.
authors.forename: Sigrid
authors.initials: S
authors.lastname: Auweter
authors.affiliation: Institute for Clinical Radiology, Ludwig-Maximilians-University Hospital Munich, Munich.
authors.forename: Maximilian
authors.initials: M
authors.lastname: Reiser
authors.affiliation: Comprehensive Pneumology Center, Institute of Lung Biology and Disease, Member of the German Center for Lung Research (DZL), Helmholtz Zentrum München, Neuherberg, Germany.|Institute for Experimental Pneumology, Ludwig-Maximilians-University Hospital Munich, Munich.
authors.forename: Oliver
authors.initials: O
authors.lastname: Eickelberg
authors.affiliation: Lehrstuhl für Biomedizinische Physik, Physik-Department &Institut für Medizintechnik, Technische Universität München, Garching, Germany.
authors.forename: Franz
authors.initials: F
authors.lastname: Pfeiffer
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D054990:Idiopathic Pulmonary Fibrosis / Q000000981:diagnostic imaging*; D051379:Mice; D053838:Scattering, Small Angle; D014057:Tomography, X-Ray Computed / Q000295:instrumentation / Q000379:methods*; D014961:X-Ray Diffraction / Q000295:instrumentation / Q000379:methods*