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).

A post-scan method for correcting artefacts of slow geometry changes during micro-tomographic scans.

Micro-CT imaging of objects at very high magnification runs into the problem of small geometric movements of the x-ray emission spot relative to the object, thermally induced or otherwise, causing magnified shifts in the projection images during scanning. This produces movement artefacts in the reconstructed images. Here a technique is described to correct such movements by adding a short reference scan at the end of a high magnification scan, with a very large rotation step. Where geometry changes during a scan are slow, such movements can be considered minimal during this very short "post-scan". Registration of the post-scan images with corresponding images in the main scan allow X/Y pixel shifts in the projection images associated with the geometry movement to be calculated, and corrected during reconstruction. This post-scan correction method was applied here to scans of three small objects, all with a voxel size less than one micron, in a desktop micro-CT and a nano-CT scanner. The method substantially reduced movement artefacts from the reconstructed images, improving image quality and resolution. Where the geometry movement results largely from thermal movement of the x-ray micro-focus emission spot, the post-scan method allows the reconstruction of the spatio-temporal trajectory of this spot movement.

Experimental validation of a rapid Monte Carlo based micro-CT simulator.

We describe a newly developed, accelerated Monte Carlo simulator of a small animal micro-CT scanner. Transmission measurements using aluminium slabs are employed to estimate the spectrum of the x-ray source. The simulator incorporating this spectrum is validated with micro-CT scans of physical water phantoms of various diameters, some containing stainless steel and Teflon rods. Good agreement is found between simulated and real data: normalized error of simulated projections, as compared to the real ones, is typically smaller than 0.05. Also the reconstructions obtained from simulated and real data are found to be similar. Thereafter, effects of scatter are studied using a voxelized software phantom representing a rat body. It is shown that the scatter fraction can reach tens of per cents in specific areas of the body and therefore scatter can significantly affect quantitative accuracy in small animal CT imaging.

Detecting and tracking local changes in the tibiae of individual rats: a novel method to analyse longitudinal in vivo micro-CT data.

In this study we present the analysis of in vivo micro-CT scans using a new method based on image registration that accurately evaluates longitudinal micro-CT studies. We tested if detailed changes in the bone architecture could be detected and tracked in individual animals. A prototype in vivo micro-CT scanner (Skyscan 1076) was developed in which tibiae of rats that are lying on a bed under gas anaesthesia were scanned. For this study, three female Wistar rats were used: a sham-operated rat, an ovariectomised (OVX) rat and one rat that served as a reproducibility control. The reproducibility control rat was scanned twice in 1 day. The other animals were scanned at week 0, just before surgery, at week 4 and at week 14 after surgery. Architectural changes over time were detected by overlaying two data sets made at different time points using an algorithm that uses mutual information for optimal registration. The scans were segmented into binary data sets using a local thresholding algorithm. The reproducibility test showed small errors of less than 3% in bone volume measurements and errors less than 0.5% in measurements of trabecular thickness. The sham-operated rat showed no changes in total bone volume, though thinning and eventual loss of some small trabeculae could be detected, which could be related to the age of the animal. The OVX rat lost much trabecular bone volume, especially in the metaphysis (60% at week 4, 75% at week 14). The remaining trabeculae slowly increased in thickness. Following the different scans in time showed the forming of new trabecular structures. Additionally, small longitudinal growth at the growth plate could be detected after the first 4 weeks. Further, the OVX rat showed extensive modelling at the proximal endosteal lateral cortex. We have shown a new method that can detect and track changes in the local bone architecture and individual trabeculae in time, in an individual living animal. This method enables longitudinal in vivo micro-CT studies and has the potential to greatly contribute to experimental rat or mouse studies on pharmacological intervention and transgenic models.

3D in-vivo X-ray microtomography of living snails.

In this paper we report the first in-vivo scanning of living snails by desktop X-ray microtomograph with a resolution up to 10 m. Consecutive cross-sections were acquired without destroying the specimen. Subsequently, 3D images were reconstructed. The results clearly demonstrate the possibilities of in-vivo scanning. Processes of growth and regeneration of living snails were visualized over a period of time.

Desktop X-ray microscopy and microtomography.

Recent developments in X-ray microtomography have made it possible to miniaturize a CT scanner into a versatile and cost-effective desktop system that fits into any laboratory environment. The possibilities of the technique are demonstrated for a range of applications. It is also shown how an existing scanning electron microscope with an X-ray detector can, with a specially developed attachment, be transformed into an X-ray microscope and microtomograph.

Desktop X-ray microscopy and microtomography.

Recent developments in X-ray microtomography have made it possible to miniaturize a CT scanner into a versatile and cost-effective desktop system that fits into any laboratory environment. The possibilities of the technique are demonstrated for a range of applications. It is also shown how an existing scanning electron microscope with an X-ray detector can, with a specially developed attachment, be transformed into an X-ray microscope and microtomograph.