Phase sensitive X-ray imaging methods can provide substantially increased contrast over conventional absorption-based imaging and therefore new and otherwise inaccessible information. The use of gratings as optical elements in hard X-ray phase imaging overcomes some of the problems that have impaired the wider use of phase contrast in X-ray radiography and tomography. So far, to separate the phase information from other contributions detected with a grating interferometer, a phase-stepping approach has been considered, which implies the acquisition of multiple radiographic projections. Here we present an innovative, highly sensitive X-ray tomographic phase-contrast imaging approach based on grating interferometry, which extracts the phase-contrast signal without the need of phase stepping. Compared to the existing phase-stepping approach, the main advantages of this new method dubbed "reverse projection" are not only the significantly reduced delivered dose, without the degradation of the image quality, but also the much higher efficiency. The new technique sets the prerequisites for future fast and low-dose phase-contrast imaging methods, fundamental for imaging biological specimens and in vivo studies.X-ray imaging | differential phase contrast | grating interferometer | tomography O ver the last few decades X-ray imaging has experienced a true revolution. The most striking advancement has been the production of coherent X-ray beams with their intrinsic capability of generating interference signals and, as a consequence, providing access to phase information within the investigated sample. This fact has been very stimulating for the X-ray-imaging community, which had been continually challenged by the frustrating question of how to increase the contrast in X-ray images without increasing the dose imparted to a specimen. It is well known that, different from conventional visible light, the refractive index in X-ray optics is very close to and smaller than unity. In first approximation, for a small and negligible anisotropy in the medium, the index of refraction characterizing the optical properties of a tissue can be expressed-including X-ray absorptionwith its complex form: n ¼ 1-δ-iβ where δ is the decrement of the real part of the refractive index, responsible for the phase shift, while the imaginary part β describes the absorption property of the tissue. In conventional absorption-based radiography, the X-ray phase shift information is usually not used for image reconstruction. However, at photon energies greater than 10 keV and for soft tissues (made up of low-Z elements), the phase shift term plays a more prominent role than the attenuation term because δ is typically three orders of magnitude larger than β (1). As a consequence, phase-contrast modalities can generate significantly greater image contrast compared to conventional, absorptionbased radiography. In fact, far from absorption edges, δ is inversely proportional to the square of the X-ray energy while β decreases as the fourth power of it. Conseq...

Phase-sensitive X-ray imaging methods can provide substantially increased contrast over conventional absorption-based imaging, and therefore new and otherwise inaccessible information. Differential phase-contrast (DPC) imaging, which uses a grating interferometer and a phase-stepping technique, has been integrated into TOMCAT, a beamline dedicated to tomographic microscopy and coherent radiology experiments at the Swiss Light Source. Developments have been made focusing on the fast acquisition and post-processing of data to enable a high-throughput of samples, with obvious advantages, also through increasing the efficiency of the detecting system, of helping to reduce radiation dose imparted to the sample. A novel aquarium design allows a vertical rotation axis below the sample with measurements performed in aqueous environment. Optimization of the data acquisition procedure enables a full phase volume (1024 x 1024 pixels x 1000 projections x 9 phase steps, i.e. 9000 projections in total) to be acquired in 20 min (with a pixel size of 7.4 microm), and the subsequent post-processing has been integrated into the beamline pipeline for sinogram generation. Local DPC tomography allows one to focus with higher magnification on a particular region of interest of a sample without the presence of local tomography reconstruction artifacts. Furthermore, 'widefield' imaging is shown for DPC scans for the first time, enabling the field of view of the imaging system to be doubled for samples that are larger than the magnification allows. A case study is illustrated focusing on the visualization of soft tissue features, and particularly the substantia nigra of a rat brain. Darkfield images, based on local X-ray scattering, can also be extracted from a grating-based DPC scan: an example of the advantages of darkfield contrast is shown and the potential of darkfield X-ray tomography is discussed.

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