title: In Vivo Dark-Field Radiography for Early Diagnosis and Staging of Pulmonary Emphysema.
abstract: OBJECTIVE
  The aim of this study was to evaluate the suitability of in vivo x-ray dark-field radiography for early-stage diagnosis of pulmonary emphysema in mice. Furthermore, we aimed to analyze how the dark-field signal correlates with morphological changes of lung architecture at distinct stages of emphysema.
  
  
  METHODS
  Female 8- to 10-week-old C57Bl/6N mice were used throughout all experiments. Pulmonary emphysema was induced by orotracheal injection of porcine pancreatic elastase (80-U/kg body weight) (n = 30). Control mice (n = 11) received orotracheal injection of phosphate-buffered saline. To monitor the temporal patterns of emphysema development over time, the mice were imaged 7, 14, or 21 days after the application of elastase or phosphate-buffered saline. X-ray transmission and dark-field images were acquired with a prototype grating-based small-animal scanner. In vivo pulmonary function tests were performed before killing the animals. In addition, lungs were obtained for detailed histopathological analysis, including mean cord length (MCL) quantification as a parameter for the assessment of emphysema. Three blinded readers, all of them experienced radiologists and familiar with dark-field imaging, were asked to grade the severity of emphysema for both dark-field and transmission images.
  
  
  RESULTS
  Histopathology and MCL quantification confirmed the introduction of different stages of emphysema, which could be clearly visualized and differentiated on the dark-field radiograms, whereas early stages were not detected on transmission images. The correlation between MCL and dark-field signal intensities (r = 0.85) was significantly higher than the correlation between MCL and transmission signal intensities (r = 0.37). The readers' visual ratings for dark-field images correlated significantly better with MCL (r = 0.85) than visual ratings for transmission images (r = 0.36). Interreader agreement and the diagnostic accuracy of both quantitative and visual assessment were significantly higher for dark-field imaging than those for conventional transmission images.
  
  
  CONCLUSIONS
  X-ray dark-field radiography can reliably visualize different stages of emphysema in vivo and demonstrates significantly higher diagnostic accuracy for early stages of emphysema than conventional attenuation-based radiography.
authors.affiliation: From the *Institute of Clinical Radiology, Ludwig-Maximilians-University Hospital Munich, Munich; †Lehrstuhl für Biomedizinische Physik, Physik-Department & Institut für Medizintechnik, Technische Universität München, Garching; ‡Comprehensive Pneumology Center, Institute of Lung Biology and Disease, Helmholtz Zentrum München and Ludwig-Maximilians-University Hospital Munich, Munich, Germany; §German Center for Lung Research (DZL), Munich, Germany; ¶Medical Radiation Physics, Lund University, Lund, Sweden; and ¶Department of Radiology, University of Tübingen, Tübingen, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Hellbach
authors.forename: Andre
authors.initials: A
authors.lastname: Yaroshenko
authors.forename: Felix G
authors.initials: FG
authors.lastname: Meinel
authors.forename: Ali Ö
authors.initials: AÖ
authors.lastname: Yildirim
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Conlon
authors.forename: Martin
authors.initials: M
authors.lastname: Bech
authors.forename: Mark
authors.initials: M
authors.lastname: Mueller
authors.forename: Astrid
authors.initials: A
authors.lastname: Velroyen
authors.forename: Mike
authors.initials: M
authors.lastname: Notohamiprodjo
authors.forename: Fabian
authors.initials: F
authors.lastname: Bamberg
authors.forename: Sigrid
authors.initials: S
authors.lastname: Auweter
authors.forename: Maximilian
authors.initials: M
authors.lastname: Reiser
authors.forename: Oliver
authors.initials: O
authors.lastname: Eickelberg
authors.forename: Franz
authors.initials: F
authors.lastname: Pfeiffer
mesh_terms: D000818:Animals; D042241:Early Diagnosis; D005260:Female; D007089:Image Enhancement / Q000379:methods; D007090:Image Interpretation, Computer-Assisted / Q000379:methods*; D051379:Mice; D008810:Mice, Inbred C57BL; D015588:Observer Variation; D011656:Pulmonary Emphysema / Q000000981:diagnostic imaging* / Q000473:pathology*; D013902:Radiography, Thoracic / Q000379:methods*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity