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Improved Diagnosis of Pulmonary Emphysema Using In Vivo Dark-Field Radiography

Meinel, Felix G. MD*; Yaroshenko, Andre MSc; Hellbach, Katharina MD*; Bech, Martin PhD†‡; Müller, Mark MSc; Velroyen, Astrid MSc; Bamberg, Fabian MD, MPH§; Eickelberg, Oliver MD; Nikolaou, Konstantin MD§; Reiser, Maximilian F. MD*; Pfeiffer, Franz PhD; Yildirim, Ali Ö. DVM

doi: 10.1097/RLI.0000000000000067
Original Articles

Objectives The purpose of this study was to assess whether the recently developed method of grating-based x-ray dark-field radiography can improve the diagnosis of pulmonary emphysema in vivo.

Materials and Methods Pulmonary emphysema was induced in female C57BL/6N mice using endotracheal instillation of porcine pancreatic elastase and confirmed by in vivo pulmonary function tests, histopathology, and quantitative morphometry. The mice were anesthetized but breathing freely during imaging. Experiments were performed using a prototype small-animal x-ray dark-field scanner that was operated at 35 kilovolt (peak) with an exposure time of 5 seconds for each of the 10 grating steps. Images were compared visually. For quantitative comparison of signal characteristics, regions of interest were placed in the upper, middle, and lower zones of each lung. Receiver-operating-characteristic statistics were performed to compare the effectiveness of transmission and dark-field signal intensities and the combined parameter “normalized scatter” to differentiate between healthy and emphysematous lungs.

Results A clear visual difference between healthy and emphysematous mice was found for the dark-field images. Quantitative measurements of x-ray dark-field signal and normalized scatter were significantly different between the mice with pulmonary emphysema and the control mice and showed good agreement with pulmonary function tests and quantitative histology. The normalized scatter showed a significantly higher discriminatory power (area under the receiver-operating-characteristic curve [AUC], 0.99) than dark-field (AUC, 0.90; P = 0.01) or transmission signal (AUC, 0.69; P < 0.001) alone did, allowing for an excellent discrimination of healthy and emphysematous lung regions.

Conclusions In a murine model, x-ray dark-field radiography is technically feasible in vivo and represents a substantial improvement over conventional transmission-based x-ray imaging for the diagnosis of pulmonary emphysema.

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From the *Institute for Clinical Radiology, Ludwig-Maximilians-University Hospital Munich, Munich; †Lehrstuhl für Biomedizinische Physik, Physik-Department & Institut für Medizintechnik, Technische Universität München, Garching, Germany; ‡Department of Medical Radiation Physics, Lund University, Lund, Sweden; §Department of Radiology, University of Tübingen, Tübingen; and ∥Comprehensive Pneumology Center, Institute of Lung Biology and Disease, Member of the German Center for Lung Research, Helmholtz Zentrum Munich, Neuherberg, Germany.

Received for publication December 25, 2013; and accepted for publication, after revision, March 19, 2014.

Conflicts of interest and sources of funding: The authors acknowledge financial support through the DFG Cluster of Excellence Munich-Centre for Advanced Photonics (MAP), the DFG Gottfried Wilhelm Leibniz program, the European Research Council (ERC, FP7, StG 240142) and the German Center for Lung Research (DZL). This work was carried out with the support of the Karlsruhe Nano Micro Facility (KNMF,, a Helmholtz Research Infrastructure at Karlsruhe Institute of Technology (KIT).

The authors report no conflicts of interest.

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Reprints: Felix G. Meinel, MD, Institute for Clinical Radiology, Ludwig-Maximilians-University Hospital Munich, Marchioninistr. 15, 81377 Munich, Germany. E-mail:

© 2014 by Lippincott Williams & Wilkins