Pulmonary emphysema diagnosis using X-ray dark-field imaging at a laser-driven compact synchrotron light source

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1 Pulmonary emphysema diagnosis using X-ray dark-field imaging at a laser-driven compact synchrotron light source Poster No.: C-2060 Congress: ECR 2013 Type: Scientific Exhibit Authors: S. Schleede, M. Bech, K. Achterhold, F. Meinel, F. Bamberg, K. Nikolaou, A. Bohla, A. Ö. Yildirim, F. Pfeiffer ; Garching/DE, 2 3 München/DE, Neuherberg/DE Keywords: Experimental, Digital radiography, Experimental investigations, Chronic obstructive airways disease DOI: /ecr2013/C-2060 Any information contained in this pdf file is automatically generated from digital material submitted to EPOS by third parties in the form of scientific presentations. References to any names, marks, products, or services of third parties or hypertext links to thirdparty sites or information are provided solely as a convenience to you and do not in any way constitute or imply ECR's endorsement, sponsorship or recommendation of the third party, information, product or service. ECR is not responsible for the content of these pages and does not make any representations regarding the content or accuracy of material in this file. As per copyright regulations, any unauthorised use of the material or parts thereof as well as commercial reproduction or multiple distribution by any traditional or electronically based reproduction/publication method ist strictly prohibited. You agree to defend, indemnify, and hold ECR harmless from and against any and all claims, damages, costs, and expenses, including attorneys' fees, arising from or related to your use of these pages. Please note: Links to movies, ppt slideshows and any other multimedia files are not available in the pdf version of presentations. Page 1 of 11

2 Purpose In early stages of various pulmonary diseases, such as emphysema and fibrosis, the change in X-ray attenuation is not detectable with absorption-based radiography. To monitor the morphological changes that the alveoli network undergoes in the progression of these diseases, we propose using the dark-field signal. Complementing conventional transmission radiographs, grating-based x-ray phasecontrast provides information on the phase shift and the local scattering power of the sample under investigation. In phase-contrast projections of inflated lung tissue the dark-field signal is related to ultra small-angle scattering (USAXS) at multiple tissueair interfaces and provides quantitative information on sub resolution microstructures present in the alveolar network. The aim of the study was to demonstrate the diagnostic value of combined absorption and dark-field projections in a mouse emphysema model (1). Methods and Materials Pulmonary emphysema is a common component of chronic obstructive pulmonary disease (COPD), in which inflammatory processes cause irreversible destruction of alveolar walls (see figure 3) leading to a progressive deterioration in lung function (see figure 2). For the experiment, three elastase induced emphysematous mouse lungs and three healthy mouse lung samples where studied in vitro. Specimens were fixated in formalin and analyzed with grating-based imaging at a laser-driven lab-scale synchrotron source (Compact Light Source, CLS) (see figure 1) (2-5). Images for this section: Page 2 of 11

3 Fig. 1: The CLS consists of an electron storage ring combined with a high-finesse laser cavity. At the interaction point of the counter propagating electron bunch and laser pulse, hard X-rays are produced in the process of inverse Compton scattering. (A) The grating interferometer comprises a phase grating, an absorption grating, and a Varian PaxScan detector. (B) SEM image of the phase gratings with a periodicity of p = µm. (C) CLS showing the linear accelerator section and the electron storage ring. (D) The mouse lungs were inflated with air and tied up at the trachea after excision. (E) Raw projection image of the formalin-fixated mouse lung measured in a water bath. Page 3 of 11

4 Fig. 2: Pulmonary function of six mice included in the experiment. For all samples dynamic compliance and tissue elastance with their respective standard deviation are depicted. In a comparison of control (blue) and elastase-emphysema (red) samples the expected increase in dynamic compliance and reduction in tissue elastance is apparent. Page 4 of 11

5 Fig. 3: Histological sections of lung structure in experimental emphysema. Lung samples where embedded in paraffin and stained using a routine Mayer's hematoxylin and eosin (H&E) staining protocol. (A),(C) and (B),(D) show 2x and 10x magnification of the lung sections respectively. In the control group (A,B) a dense alveolar network is nicely visible whereas the emphysema lung (C,D) displays the expected pathological larger alveoli diameters with a reduced alveoli number. Page 5 of 11

6 Results Both transmission and dark-field signal depend exponentially on the sample thickness penetrated and on material properties, namely attenuation coefficient µ and material scattering strength, or linear diffusion coefficient #, where # strongly depends on the mean diameter of the scattering structures (6,7,8): Fig. 7 References: Physics Department, Technische Universität München - Garching/DE Fig. 8 References: Physics Department, Technische Universität München - Garching/DE Normalized scatter As all lung samples have been measured with respect to water lnt is proportional to lung thickness crossed by the beam and can be used to normalize the dark field signal, leading normalized scatter projection images that show the distribution of emphysema in the lung (see figure 6): Fig. 9 Page 6 of 11

7 References: Physics Department, Technische Universität München - Garching/DE Images for this section: Fig. 4: Three elastase and three control mouse lungs were included in the study. The picture shows all six mouse lungs in formalin-filled plastic cylinders. The blue (healthy lung) and red (emphysematous lung) rectangle indicates the samples that are displayed in transmission T with respect to water, differential phase d#/dx, and dark-field V below. (Scale bars: 5 mm.) Page 7 of 11

8 Fig. 5: Scatter plot of dark-field V vs. transmission relative to water T of all six lung radiographs and the data from 11 projection angles. From this statistical analysis a clear distinction between emphysematous (red) and control (blue) lung tissue is possible. Two green dotted curves represent a fixed ratio of the logarithm of dark-field contrast and transmission values ln(v)/ln(t). Pixels in between these curves are used for further image analysis in Fig. 6. (Insets) Histological sections. (Scale bars: 500 µm.) Page 8 of 11

9 Fig. 6: Multimodal projections of three emphysematous lung samples (E1, E2, E3) and three control lung samples (C1, C2, C3). To visualize the apparent differentiation of healthy and emphysematous lungs from the scatter plot (Fig. 5), we propose using threshold values on the quotient of the logarithm of dark-field contrast and transmission values ln(v)/ ln(t) = #6 and ln(v)/ln(t) = #1.2 (dotted green lines in Fig. 5). In single projections, the corresponding pixels have been superimposed on the conventional transmission contrast image with their color representing ln(v)/ln(t). Standard transmission is depicted in the linear gray scale with transmission values (with respect to water) ranging from 1 to The material-dependent quotient ln(v)/ ln(t) is displayed in jet colors ranging from #6 to #1.2, where higher values (yellow, red) correspond to lower scattering at similar transmission and thus larger mean alveoli diameter. (Scale bars: 5 mm.) Page 9 of 11

10 Conclusion We present grating-based dark-field images of emphysematous vs. healthy lung tissue. A combination of absorption and dark-field signal in a scatter-plot analysis demonstrates improved emphysema diagnosis in single projections of mice lungs. In addition to a decrease in pulmonary function of emphysematous mice, which was evident from dynamic compliance and tissue elastance measurements, the emphysematous microstructure of the lung samples was confirmed by histology, where an enlargement of airspaces accompanied by the destruction of their walls is clearly visible. This proof-of-principle synchrotron-based experiment was conducted at the CLS using highly brilliant and monochromatic X-rays to achieve the benchmark results presented here. Future work will focus on establishing the applicability of the method to higher X-ray energies, as necessary for human chest radiographs, and with conventional Xray tubes, where grating-based phase-contrast imaging has already been successfully demonstrated. References 1. Schleede S et al. (2012) Emphysema diagnosis using X-ray dark-field imaging at a laser-driven compact synchrotron light source. Proc Natl Acad Sci U S A 109(44): Loewen R (2003) A Compact Light Source: Design and technical feasibility study of a laser-electron storage ring x-ray source. PhD dissertation SLAC-R-632 (Stanford Univ, Stanford, CA). 3. Huang Z, Ruth RD (1998) Laser-electron storage ring. Phys Rev Lett 80(5): Bech M, et al. (2009) Hard X-ray phase-contrast imaging with the Compact Light Source based on inverse Compton X-rays. J Synchrotron Radiat 16(Pt 1): Schleede S, et al. (2012) Multimodal hard X-ray imaging of a mammography phantom Page 10 of 11

11 at a compact synchrotron light source. J Synchrotron Radiat 19(Pt 4): Malecki A, Potdevin G, Pfeiffer F (2012) Quantitative wave-optical numerical analysis of the dark-field signal in grating-based x-ray interferometry. Europhys Lett 99(4): Yashiro W, Terui Y, Kawabata K, Momose A (2010) On the origin of visibility contrast in x-ray Talbot interferometry. Opt Express 18(16): Bech M, et al. (2012) Experimental validation of image contrast correlation between ultra-small-angle X-ray scattering and grating-based dark-field imaging using a laserdriven compact X-ray source. Photonic Laser Med 1(1): Personal Information Page 11 of 11