Contrary to conventional medical x ray imaging grating based
Contrary to conventional medical x-ray imaging, grating-based phase-contrast and dark-field imaging (PCI/DFI) generate purchase AZD 7762 from perturbations in the x-ray wave-front caused by refraction and ultra-small angle scattering in tissue (Weitkamp et al., 2005). Its proven feasibility with conventional polychromatic x-ray sources (Pfeiffer et al., 2008; Pfeiffer et al., 2006) has recently triggered developments towards preclinical and clinical translation, such as in vivo radiographic projection imaging (Bech et al., 2013) at a dedicated preclinical table-top scanner (Tapfer et al., 2012). Earlier in vivo studies using different PCI/DFI techniques were restricted to synchrotron radiation or very small field of view (Bravin et al., 2013). However, the benefit of exploiting refractive index differences in x-ray imaging of weakly absorbing airways tissue could already be demonstrated in vivo at the synchrotron (Lewis et al., 2005). In preceding studies, we introduced emphysema diagnosis on living mice based on x-ray scatter-based dark-field projection imaging (Meinel et al., 2014; Hellbach et al., 2015).
In this work, we present the first successful x-ray dark-field (DF) computed tomography (CT) scans of in vivo mice with a dedicated micro-CT scanner (Tapfer et al., 2012). To exploit the DF signal\'s ability to depict sub-resolution microstructures, thoracic tomographies were acquired of a healthy control mouse, a mouse with pulmonary emphysema and a mouse with pulmonary fibrosis. The scope of this study is to highlight the feasibility and demonstrate the potential diagnostic benefit of the novel contrast modality in three-dimensional imaging. Complementary to the quantitative Hounsfield scale in attenuation-based CT, we also introduce a scatter-based Hounsfield scale for quantitative DFCT of lung tissue.
Materials & Methods
Results Fig. 2 provides an overview over the CT datasets of this study comprising three in vivo cases imaged in conventional attenuation and DF, as well as correspondent histological slices to illustrate the nature of the respective disease. Additionally, phase-contrast CT slices are presented in Fig. S1. Comparing the conventional CT scan of the emphysematous mouse (Fig. 2 b, e) with the control (Fig. 2 a, d), one observes only subtle differences towards darker gray values in peripheral lung tissue in the emphysematous case. The resolution of the imaging system does not allow a direct depiction of the alveolar wall structure. In the respective CT slices of the DF channel (Fig. 2 g, j for control, h, k for emphysema) the strong difference in signal allows for clear discernibility between control and diseased case, as visible by the overall reduced brightness and decreased homogeneity in the diseased lungs compared to the healthy lung. The destruction of alveolar walls and resulting enlargement of air spaces (as displayed in the corresponding histological section in Fig. 2 n) causes significantly reduced x-ray scattering, while the overall loss of tissue and the resulting attenuation decrease is weak. When concentrating on the case of lung fibrosis (Fig. 2 c, f for attenuation, i, l for DF) the replacement of functional alveolar network by solid scar tissue is clearly apparent in both modalities, since the presented case is at an advanced stage. The DF image reveals areas with remaining functional alveolar structure. Histology illustrates the scarring in the lung (Fig. 2 o), compared to healthy lung tissue (Fig. 2 m). Fig. 3 shows a volumetric overview of the fusion of the attenuation CT and DFCT for the two pathological cases emphysema (a–f) and fibrosis (g–l). The fused representation, which is easily possible due to the method-inherent perfect co-registration, provides a simultaneous impression of anatomy depicted by the attenuation CT and functionality indirectly displayed by DFCT, since alveolar structure can be related to quality of gas exchange (Haraguchi et al., 1998). Similar to the function-anatomy combination in well-known multi-modal datasets like PET–CT (PET: positron emission tomography), the conventional attenuation CT images in gray shades were overlaid by DF data in PET-typical hot color scheme. Note, however, that contrary to PET, where hot areas indicate accumulation of tracer and therefore generally diseased tissue, in the displayed fusion images the brighter color codes the stronger scattering, i.e. the more intact or healthier lung tissue. The combined representation allows for a comprehensive depiction of the three-dimensional distribution of the diseases over the lung volume in the anatomical frame. In the case of emphysema Fig. 3 shows that destruction of alveolar structures and size increase of air voids predominantly appears in peripheral regions of the lung as indicated by white arrows. On the contrary, in Fig. 3 g–l arrows illustrate that the proliferation of the induced fibrosis concentrates on the central, peribronchial areas. Regarding the inherent complementarity of the two signals, note that in DF large air-filled voids such as the bronchi are coded identically to solid soft tissue, whereas they are distinguishable in attenuation data.