title: Diagnosing and mapping pulmonary emphysema on X-ray projection images: incremental value of grating-based X-ray dark-field imaging.
abstract: OBJECTIVE
  To assess whether grating-based X-ray dark-field imaging can increase the sensitivity of X-ray projection images in the diagnosis of pulmonary emphysema and allow for a more accurate assessment of emphysema distribution.
  
  
  METHODS
  Lungs from three mice with pulmonary emphysema and three healthy mice were imaged ex vivo using a laser-driven compact synchrotron X-ray source. Median signal intensities of transmission (T), dark-field (V) and a combined parameter (normalized scatter) were compared between emphysema and control group. To determine the diagnostic value of each parameter in differentiating between healthy and emphysematous lung tissue, a receiver-operating-characteristic (ROC) curve analysis was performed both on a per-pixel and a per-individual basis. Parametric maps of emphysema distribution were generated using transmission, dark-field and normalized scatter signal and correlated with histopathology.
  
  
  RESULTS
  Transmission values relative to water were higher for emphysematous lungs than for control lungs (1.11 vs. 1.06, p<0.001). There was no difference in median dark-field signal intensities between both groups (0.66 vs. 0.66). Median normalized scatter was significantly lower in the emphysematous lungs compared to controls (4.9 vs. 10.8, p<0.001), and was the best parameter for differentiation of healthy vs. emphysematous lung tissue. In a per-pixel analysis, the area under the ROC curve (AUC) for the normalized scatter value was significantly higher than for transmission (0.86 vs. 0.78, p<0.001) and dark-field value (0.86 vs. 0.52, p<0.001) alone. Normalized scatter showed very high sensitivity for a wide range of specificity values (94% sensitivity at 75% specificity). Using the normalized scatter signal to display the regional distribution of emphysema provides color-coded parametric maps, which show the best correlation with histopathology.
  
  
  CONCLUSIONS
  In a murine model, the complementary information provided by X-ray transmission and dark-field images adds incremental diagnostic value in detecting pulmonary emphysema and visualizing its regional distribution as compared to conventional X-ray projections.
authors.affiliation: Institute for Clinical Radiology, Ludwig-Maximilians-University Hospital, Munich, Germany. felix.meinel@med.uni-muenchen.de
authors.forename: Felix G
authors.initials: FG
authors.lastname: Meinel
authors.forename: Felix
authors.initials: F
authors.lastname: Schwab
authors.forename: Simone
authors.initials: S
authors.lastname: Schleede
authors.forename: Martin
authors.initials: M
authors.lastname: Bech
authors.forename: Julia
authors.initials: J
authors.lastname: Herzen
authors.forename: Klaus
authors.initials: K
authors.lastname: Achterhold
authors.forename: Sigrid
authors.initials: S
authors.lastname: Auweter
authors.forename: Fabian
authors.initials: F
authors.lastname: Bamberg
authors.forename: Ali Ö
authors.initials: AÖ
authors.lastname: Yildirim
authors.forename: Alexander
authors.initials: A
authors.lastname: Bohla
authors.forename: Oliver
authors.initials: O
authors.lastname: Eickelberg
authors.forename: Rod
authors.initials: R
authors.lastname: Loewen
authors.forename: Martin
authors.initials: M
authors.lastname: Gifford
authors.forename: Ronald
authors.initials: R
authors.lastname: Ruth
authors.forename: Maximilian F
authors.initials: MF
authors.lastname: Reiser
authors.forename: Franz
authors.initials: F
authors.lastname: Pfeiffer
authors.forename: Konstantin
authors.initials: K
authors.lastname: Nikolaou
mesh_terms: D000818:Animals; D003624:Darkness; D005240:Feasibility Studies; D005260:Female; D007091:Image Processing, Computer-Assisted; D008168:Lung / Q000000981:diagnostic imaging / Q000502:physiology / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D011656:Pulmonary Emphysema / Q000000981:diagnostic imaging* / Q000473:pathology / Q000503:physiopathology; D011859:Radiography / Q000379:methods*; D012129:Respiratory Function Tests; D012542:Scattering, Radiation; D012680:Sensitivity and Specificity; D014965:X-Rays
references.citation: Opt Express. 2012 Jan 30;20(3):2789-805
references.pmid: 22330515
references.citation: N Engl J Med. 2010 Sep 23;363(13):1233-44
references.pmid: 20860505
references.citation: Eur Respir J. 2008 Mar;31(3):509-15
references.pmid: 18057056
references.citation: Nat Mater. 2008 Feb;7(2):134-7
references.pmid: 18204454
references.citation: Proc Am Thorac Soc. 2008 May 1;5(4):421-6
references.pmid: 18453349
references.citation: Invest Radiol. 2004 Nov;39(11):681-8
references.pmid: 15486529
references.citation: AJR Am J Roentgenol. 1978 Mar;130(3):429-40
references.pmid: 415543
references.citation: Semin Respir Crit Care Med. 2010 Jun;31(3):276-85
references.pmid: 20496297
references.citation: Phys Med Biol. 2009 May 7;54(9):2747-53
references.pmid: 19369710
references.citation: Proc Natl Acad Sci U S A. 2012 Oct 30;109(44):17880-5
references.pmid: 23074250
references.citation: Semin Respir Crit Care Med. 2010 Jun;31(3):348-64
references.pmid: 20496304
references.citation: Thorax. 2002 Nov;57(11):982-5
references.pmid: 12403883
references.citation: Eur Radiol. 2009 Jul;19(7):1686-92
references.pmid: 19224221
references.citation: Respir Res. 2009 Aug 13;10:75
references.pmid: 19678952
references.citation: Phys Med Biol. 2010 Sep 21;55(18):5529-39
references.pmid: 20808030
references.citation: Thorax. 2006 Jun;61(6):485-90
references.pmid: 16537666
references.citation: Lancet. 2012 Apr 7;379(9823):1341-51
references.pmid: 22314182
references.citation: Opt Express. 2009 Jun 8;17(12):10010-8
references.pmid: 19506651
references.citation: Eur Radiol. 2012 Feb;22(2):287-94
references.pmid: 22011903
references.citation: J Thorac Imaging. 2009 Aug;24(3):163-70
references.pmid: 19704319
references.citation: Proc Am Thorac Soc. 2008 Dec 15;5(9):919-24
references.pmid: 19056717
references.citation: Radiology. 2005 May;235(2):354-8
references.pmid: 15758190
references.citation: Invest Radiol. 2010 Jul;45(7):445-52
references.pmid: 20498610
references.citation: Eur Respir J. 2009 Jun;33(6):1345-53
references.pmid: 19196813
references.citation: Biometrics. 1988 Sep;44(3):837-45
references.pmid: 3203132
references.citation: Am J Respir Crit Care Med. 2010 Apr 1;181(7):705-17
references.pmid: 20007933
references.citation: Lancet. 2009 Aug 29;374(9691):721-32
references.pmid: 19716965