In vivo dark-field radiography for early diagnosis and staging of pulmonary emphysema

Katharina Hellbach, Andre Yaroshenko, Felix G. Meinel, Ali O. Yildirim, Thomas M. Conlon, Martin Bech, Mark Mueller, Astrid Velroyen, Mike Notohamiprodjo, Fabian Bamberg, Sigrid Auweter, Maximilian Reiser, Oliver Eickelberg, Franz Pfeiffer

Research output: Contribution to journalArticlepeer-review

78 Scopus citations

Abstract

Objectives 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. Materials and 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.

Original languageEnglish
Pages (from-to)430-435
Number of pages6
JournalInvestigative Radiology
Volume50
Issue number7
DOIs
StatePublished - 22 Jul 2015

Keywords

  • early diagnosis
  • grating-based x-ray imaging x-ray phase-contrast imaging
  • pulmonary emphysema
  • x-ray dark-field imaging

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