Grating-based X-ray Dark-field Computed Tomography of Living Mice.

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-vivo dark-field and phase-contrast x-ray imaging.

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).

Microbubbles as a scattering contrast agent for grating-based x-ray dark-field imaging.

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.

Visualization of subcutaneous insulin injections by x-ray computed tomography.

We report how the three-dimensional structure of subcutaneous injections of soluble insulin can be visualized by x-ray computed tomography using an iodine based contrast agent. The injections investigated are performed ex vivo in porcine adipose tissue. Full tomography scans carried out at a laboratory x-ray source with a total acquisition time of about 1 min yield CT-images with an effective pixel size of 109 × 109 µm². The depots are segmented using a modified Chan-Vese algorithm and we are able to observe differences in the shape of the injection depot and the position of the depot in the skin among equally performed injections. To overcome the beam hardening artefacts, which affect the quantitative prediction of the volume injected, we additionally present results concerning the visualization of two injections using synchrotron radiation. The spatial concentration distribution of iodine is calculated to show the dilution of the insulin drug inside the depot. Characterisation of the shape of the depot and the spatial concentration profile of the injected fluid is important knowledge when improving the clinical formulation of an insulin drug, the performance of injection devices and when predicting the effect of the drug through biomedical simulations.