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  • To reach clinical application cases

    2018-10-25

    To reach clinical application cases, certain technological limitations of the method need to be overcome, but are already subject to currently on-going research and development efforts: For example, when translating the method to an increased torso diameter, an elevated x-ray energy is mandatory to reach the necessary penetration hdac inhibitors depth. The main technological challenge is the manufacturing of high-aspect-ratio grating structures suitable for clinical energies, covering a large field of view (FOV). While sufficiently high aspect ratios have been demonstrated in experiment already (Willner et al., 2013; Ruiz-Yaniz et al., 2015; Sarapata et al., 2014), the increase of the FOV by tiling gratings together (Meiser et al., 2014) is under development. Concerning the dark-field signal strength, simulations and yet unpublished experiments have indicated the feasibility of x-ray dark-field projection imaging at clinically relevant x-ray energies on thick samples. Furthermore, to reduce dose and scan time for clinical compatibility, acquisition schemes alternative to the established ‘phase stepping’ (Weitkamp et al., 2005) have been proposed (Zanette et al., 2011, 2012) and are being further investigated. Despite the limited sample size of three cases in the present study, the presented results prove great potential for future lung imaging where volumetric information such as disease distribution is required. One example is the use of x-ray scatter CT for the evaluation of potential lung volume reduction surgery candidates (Washko, 2010) in case of emphysema. In general, mild stages of hdac inhibitors are difficult to diagnose by projection radiography only and often dose-intensive HRCT is needed. Projection-based DFI may ultimately serve as a screening method (Hellbach et al., 2015; Meinel et al., 2014; Schleede et al., 2012; Yaroshenko et al., 2013). We imagine to complement this by limited-angle or coarse-resolution DFCT to gain additional three-dimensional information without the necessity of very high dose, exploiting that DFI generates a signal from structure sizes below the resolution limit of the imaging system (Chen et al., 2010; Yashiro et al., 2010; Lynch et al., 2011). The presented CT results already serve as an example for non-optimized resolution settings, because they are subject to undersampling and breathing-motion artifacts due to non-gated acquisition and long exposure times. This is possible as DFI profits more from noise reduction when changing to coarser resolution and suffers less from the loss of detail than conventional attenuation (Velroyen et al., 2013). Another conceivable application of thoracic DFCT is to map suspicious pulmonary parenchyma in case of suspected fibrosis, without the need to force the spatial resolution down to the level of the secondary pulmonary lobule. This may allow optimization of the location choice for biopsy, which is still the gold standard for diagnosing idiopathic interstitial pneumonias and currently done with the help of attenuation-based HRCT (Gross and Hunninghake, 2001). The following are the supplementary data related to this article.
    Author Contributions
    Conflict-of-interest Statement
    Acknowledgments We acknowledge the help of C. Hollauer and J. Hostens for the productive support with the experiments. We acknowledge financial support through the DFG Cluster of Excellence Munich-Centre for Advanced Photonics (MAP, Grant no. DFG EXC-158), the DFG Gottfried Wilhelm Leibniz program and the European Research Council (ERC, FP7, StG 240142). This work was carried out with the support of the Karlsruhe Nano Micro Facility (KNMF, www.kit.edu/knmf), a Helmholtz Research Infrastructure at Karlsruhe Institute of Technology (KIT, www.kit.edu). The funders had no role in study design, data collection, data analysis, interpretation, or writing of the report. AV and AY acknowledge the TUM Graduate School. The graphical rendering (3D figures and movie) was performed by Volume Graphics, Heidelberg, Germany.