Novel radiography approaches based on the wave nature of x-rays when propagating through matter have a great potential for improved future x-ray diagnostics in the clinics. Here, we present a significant milestone in this imaging method: in-vivo multi-contrast x-ray imaging of a mouse using a compact scanner. Of particular interest is the enhanced contrast in regions related to the respiratory system, indicating a possible application in diagnosis of lung diseases (e.g. emphysema).

To explore the future clinical potential of improved soft-tissue visibility with grating-based X-ray phase contrast (PC), we have developed a first preclinical computed tomography (CT) scanner featuring a rotating gantry. The main challenge in the transition from previous bench-top systems to a preclinical scanner are phase artifacts that are caused by minimal changes in the grating alignment during gantry rotation. In this paper, we present the first experimental results from the system together with an adaptive phase recovery method that corrects for these phase artifacts. Using this method, we show that the scanner can recover quantitatively accurate Hounsfield units in attenuation and phase. Moreover, we present a first tomography scan of biological tissue with complementary information in attenuation and phase contrast. The present study hence demonstrates the feasibility of gratingbased phase contrast with a rotating gantry for the first time and paves the way for future in vivo studies on small animal disease models (in the mid-term future) and human diagnostics applications (in the long-term future).differential X-ray phase contrast | grating interferometer | X-ray imaging O ne of the main shortcomings of existing biomedical X-ray imaging systems is their weak contrast in soft tissue. This limitation can be addressed by phase-sensitive imaging methods that rely on the phase shift that X-rays undergo when passing through matter (1). The resultant refraction angle can be utilized as contrast mechanism in a grating-based interferometer in radiographic (2, 3) and tomographic acquisition mode (4, 5). In a computed tomography scan, quantitative information about the sample's composition can be extracted-i.e., the linear attenuation coefficient μ and decrement of the refractive index δ can be reconstructed (6-8). Because the grating-based phase-contrast imaging method is compatible with X-ray tube sources, when operated as Talbot-Lau interferometer (9), a translation to a clinical application scenario is currently discussed with great enthusiasm in the research community. Recent studies with laboratory X-ray sources have shown excellent imaging results with respect to softtissue contrast (10)(11)(12)(13)(14). In order to explore the envisioned clinical potential, we have developed a first preclinical phase-contrast CT scanner. This development represents an important milestone in the translation of phase-contrast imaging to clinical settings, as all grating-based phase-contrast setups, which are reported in the literature so far, use a rotating sample for tomographic scans. Because this mode of operation is obviously not preferable for intended in vivo animal studies, we have explored with this work the step from rotating sample to rotating gantry. The main challenge in this translation process was mechanical stability regarding the required precise alignment of the X-ray optical components (gratings). Even mechanical movements of either grating of only fractions of a micrometer during gantry rotation already c...

X-ray dark-field radiography can reliably visualize different stages of emphysema in vivo and demonstrates significantly higher diagnostic accuracy for early stages of emphysema than conventional attenuation-based radiography.

Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive lung disease with a median life expectancy of 4–5 years after initial diagnosis. Early diagnosis and accurate monitoring of IPF are limited by a lack of sensitive imaging techniques that are able to visualize early fibrotic changes at the epithelial-mesenchymal interface. Here, we report a new x-ray imaging approach that directly visualizes the air-tissue interfaces in mice in vivo. This imaging method is based on the detection of small-angle x-ray scattering that occurs at the air-tissue interfaces in the lung. Small-angle scattering is detected with a Talbot-Lau interferometer, which provides the so-called x-ray dark-field signal. Using this imaging modality, we demonstrate-for the first time-the quantification of early pathogenic changes and their correlation with histological changes, as assessed by stereological morphometry. The presented radiography method is significantly more sensitive in detecting morphological changes compared with conventional x-ray imaging, and exhibits a significantly lower radiation dose than conventional x-ray CT. As a result of the improved imaging sensitivity, this new imaging modality could be used in future to reduce the number of animals required for pulmonary research studies.

Purpose:To test the hypothesis that the joint distribution of x-ray transmission and dark-field signals obtained with a compact cone-beam preclinical scanner with a polychromatic source can be used to diagnose pulmonary emphysema in ex vivo murine lungs. Materials and Methods:The animal care committee approved this study. Three excised murine lungs with pulmonary emphysema and three excised murine control lungs were imaged ex vivo by using a grating-based micro-computed tomographic (CT) scanner. To evaluate the diagnostic value, the natural logarithm of relative transmission and the natural logarithm of darkfield scatter signal were plotted on a per-pixel basis on a scatterplot. Probability density function was fit to the joint distribution by using principle component analysis. An emphysema map was calculated based on the fitted probability density function. Results:The two-dimensional scatterplot showed a characteristic difference between control and emphysematous lungs. Control lungs had lower average median logarithmic transmission (20.29 vs 20.18, P = .1) and lower average dark-field signal (20.54 vs 20.37, P = .1) than emphysematous lungs. The angle to the vertical axis of the fitted regions also varied significantly (7.8° for control lungs vs 15.9° for emphysematous lungs). The calculated emphysema distribution map showed good agreement with histologic findings. Conclusion:X-ray dark-field scatter images of murine lungs obtained with a preclinical scanner can be used in the diagnosis of pulmonary emphysema.q RSNA, 2013 Supplemental material: http://radiology.rsna.org/lookup /suppl

The possibility to perform high-sensitivity X-ray phase-contrast imaging with laboratory grating-based phase-contrast computed tomography (gbPC-CT) setups is of great interest for a broad range of high-resolution biomedical applications. However, achieving high sensitivity with laboratory gbPC-CT setups still poses a challenge because several factors such as the reduced flux, the polychromaticity of the spectrum, and the limited coherence of the X-ray source reduce the performance of laboratory gbPC-CT in comparison to gbPC-CT at synchrotron facilities. In this work, we present our laboratory X-ray Talbot-Lau interferometry setup operating at 40 kVp and describe how we achieve the high sensitivity yet unrivalled by any other laboratory X-ray phase-contrast technique. We provide the angular sensitivity expressed via the minimum resolvable refraction angle both in theory and experiment, and compare our data with other differential phase-contrast setups. Furthermore, we show that the good stability of our high-sensitivity setup allows for tomographic scans, by which even the electron density can be retrieved quantitatively as has been demonstrated in several preclinical studies.

Changes in x-ray attenuating tissue caused by lung disorders like emphysema or fibrosis are subtle and thus only resolved by high-resolution computed tomography (CT). The structural reorganization, however, is of strong influence for lung function. Dark-field CT (DFCT), based on small-angle scattering of x-rays, reveals such structural changes even at resolutions coarser than the pulmonary network and thus provides access to their anatomical distribution. In this proof-of-concept study we present x-ray in vivo DFCTs of lungs of a healthy, an emphysematous and a fibrotic mouse. The tomographies show excellent depiction of the distribution of structural – and thus indirectly functional – changes in lung parenchyma, on single-modality slices in dark field as well as on multimodal fusion images. Therefore, we anticipate numerous applications of DFCT in diagnostic lung imaging. We introduce a scatter-based Hounsfield Unit (sHU) scale to facilitate comparability of scans. In this newly defined sHU scale, the pathophysiological changes by emphysema and fibrosis cause a shift towards lower numbers, compared to healthy lung tissue.

In clinically established-absorption-based-biomedical x-ray imaging, contrast agents with high atomic numbers (e.g. iodine) are commonly used for contrast enhancement. The development of novel x-ray contrast modalities such as phase contrast and dark-field contrast opens up the possible use of alternative contrast media in x-ray imaging. We investigate using ultrasound contrast agents, which unlike iodine-based contrast agents can also be administered to patients with renal impairment and thyroid dysfunction, for application with a recently developed novel x-ray dark-field imaging modality. To produce contrast from these microbubble-based contrast agents, our method exploits ultra-small-angle coherent x-ray scattering. Such scattering dark-field x-ray images can be obtained with a grating-based x-ray imaging setup, together with refraction-based differential phase-contrast and the conventional attenuation contrast images. In this work we specifically show that ultrasound contrast agents based on microbubbles can be used to produce strongly enhanced dark-field contrast, with superior contrast-to-noise ratio compared to the attenuation signal. We also demonstrate that this method works well with an x-ray tube-based setup and that the relative contrast gain even increases when the pixel size is increased from tenths of microns to clinically compatible detector resolutions about up to a millimetre.