Ralf-Hendrik Menk

A new DEI algorithm capable of investigating sub-pixel structures

Diffraction enhanced imaging (DEI) is a phase-sensitive x-ray imaging technique based on the use of an analyser crystal placed between the sample and the detector. In the recent years, DEI has proven outstanding image quality both in material science and medical imaging, as well as the capability to provide quantitative information. However, in the case of objects featuring a fine refractive structure, which is not resolved by the spatial resolution of the detector, the fundamental requirements for the applicability of the DEI algorithm are not fulfilled. Herein a new algorithm is presented that takes into account this particular case. Formally similar to DEI, it allows obtaining quantitative information on the absorption and refraction properties of the object. Thus, structures in the sub-pixel length scale can be imaged and analysed quantitatively.

Three-image diffraction enhanced imaging algorithm to extract absorption, refraction, and ultrasmall-angle scattering

As different methods to improve diffraction enhanced imaging are proposed, the authors introduce a simple algorithm that follows the original idea of Chapman et al. [Phys. Med. Biol. 42, 2015 (1997)], but extend it to a general object featuring absorption, refraction, and ultrasmall-angle scattering. The information relative to the three effects is decoupled, requiring only three images in input. Simulation and experiment give accurate results, provided the refraction and scattering angles are small compared to the rocking curve width. The proposed algorithm can be readily and fruitfully implemented in several applications, particularly when time and dose constraints are relevant.

The SYRMEP Beamline of Elettra: Clinical Mammography and Bio‐medical Applications

At the SYnchrotron Radiation for MEdical Physics (SYRMEP) beamline of Elettra Synchrotron Light Laboratory in Trieste (Italy), an extensive research program in bio‐medical imaging has been developed since 1997. The core program carried out by the SYRMEP collaboration concerns the use of Synchrotron Radiation (SR) for clinical mammography with the aim of improving the diagnostic performance of the conventional technique. The first protocol with patients, started in 2006 has been completed at the end of 2009 and the data analysis is now in progress.Regarding applications different from clinical imaging, synchrotron X‐ray computed microtomography (micro‐CT) is the most used technique, both in absorption and phase contrast. A new software tool, Pore3D, has been developed to perform a quantitative morphological analysis on the reconstructed slices and to access textural information of the sample under study.

Generalized diffraction enhanced imaging to retrieve absorption, refraction and scattering effects

A simple algorithm that generalizes the diffraction enhanced imaging (DEI) technique is introduced and discussed by means of simulated and experimental data. While the original DEI algorithm by Chapman et al (1997 Phys. Med. Biol. 42 2015) is limited to objects featuring absorption and refraction only, also ultra-small-angle scattering is considered here. Utilizing only three images in input three parametric images are produced conveying information relative to the three effects. The quality of the parametric images depends on the choice of the input images, as is demonstrated by means of a Monte Carlo simulation. With an appropriate choice, the algorithm gives accurate results on simulated and experimental datasets, as long as the refraction and scattering angles introduced by the object are small compared with the width of the rocking curve. The proposed algorithm can be implemented in several applications, as a valid alternative to multiple-image methods, particularly when time and dose constraints are relevant.

Diffraction enhanced imaging of articular cartilage and comparison with micro-computed tomography of the underlying bone structure

The goal of this study was to explore the role of diffraction enhanced X-ray imaging (DEI) for assessing changes in osteoarthritic cartilage and correlating the findings with concurrent changes in the underlying bone imaged using micro-computed tomography (μCT). DEI was used to image femoral head specimens at various beam energies. DEI utilizes a monochromatic, highly collimated beam, with an analyzer crystal that selectively weights out photons according to the angle they have been deviated with respect to the original direction. This provides images of very high contrast, with the rejection of X-ray scatter. The underlying bone was imaged using μCT and measures quantifying the bone structure were derived. Confirmation of cartilage degeneration was obtained from histology and polarized light microscopy. DEI allowed the visualization of articular cartilage and reflected the fibrillations and fissures in tissues from degenerated joints. The trabecular bone underlying the most degenerated articular cartilage showed increased bone volume fraction and more plate-like characteristics, compared with that underlying normal appearing cartilage. The histology and polarized light microscopy images reflected the DEI based features of cartilage architecture. These data reflect the ability of X-ray based emerging technologies to depict cartilage–bone interactions in joint degeneration.

Generalized diffraction enhanced imaging: Application to tomography

A simple generalization of the diffraction enhanced imaging (DEI) technique, called generalized DEI (GDEI), and its application to tomographic imaging are herein presented. In planar imaging, the GDEI algorithm combines three input images (acquired at different analyzer positions) to deliver three parametric images, providing information respectively on absorptive, refractive and ultra-small-angle scattering features of the sample. The application of the same algorithm in computed tomography (CT-GDEI), acquiring three tomographic datasets at different analyzer positions, is formally justified. Experimental tests have been conducted at the SYRMEP beamline of ELETTRA (Trieste, Italy) by means of custom phantoms, featuring absorption, refraction and ultra-small-angle scattering. The results show that CT-GDEI provides a simple way to map the information relative to the three effects in three parametric tomographic images.

A three-image algorithm for hard x-ray grating interferometry

A three-image method to extract absorption, refraction and scattering information for hard x-ray grating interferometry is presented. The method comprises a post-processing approach alternative to the conventional phase stepping procedure and is inspired by a similar three-image technique developed for analyzer-based x-ray imaging. Results obtained with this algorithm are quantitatively comparable with phase-stepping. This method can be further extended to samples with negligible scattering, where only two images are needed to separate absorption and refraction signal. Thanks to the limited number of images required, this technique is a viable route to bio-compatible imaging with x-ray grating interferometer. In addition our method elucidates and strengthens the formal and practical analogies between grating interferometry and the (non-interferometric) diffraction enhanced imaging technique.

Diffraction-enhanced imaging: improved contrast and lower dose x-ray imaging

Conventional x-ray imaging relies almost entirely on differences in the absorption of x-rays between tissues to produce contrast. While these differences are substantial between bone and soft tissue, they are very small between different soft tissue types resulting in poor visualization of soft tissues. Diffraction enhanced imaging (DEI) is currently in development by several groups as a new imaging modality that exploits information contained within the x- ray scattering distribution at low angles. We have used the SYRMEP beam line at the Elettra Synchrotron facility in Trieste, Italy to image a variety of tissue specimens, together with several phantoms. Mono-energetic photons in the range 17 keV to 25 keV were used with an analyzer crystal which diffracted the x-rays onto a detector. We have obtained some spectacular images which display remarkable contrast and resolution. The images can be processed to separate the pure absorption and pure refraction effects in a quantitative manner. These images demonstrate that DEI provides tissue morphology information not accessible with conventional radiographic imaging. The contrast caused primarily by refraction as the x-ray passes from one tissue type to another in the specimen is evident. Since x-ray refraction is much less energy dependent than absorption there is considerable potential for extremely low dose imaging. We believe that the potential of this technique is considerable and we present dat to illustrate the quality of the images.

High contrast microstructural visualization of natural acellular matrices by means of phase-based x-ray tomography

Acellular scaffolds obtained via decellularization are a key instrument in regenerative medicine both per se and to drive the development of future-generation synthetic scaffolds that could become available off-the-shelf. In this framework, imaging is key to the understanding of the scaffolds’ internal structure as well as their interaction with cells and other organs, including ideally post-implantation. Scaffolds of a wide range of intricate organs (esophagus, lung, liver and small intestine) were imaged with x-ray phase contrast computed tomography (PC-CT). Image quality was sufficiently high to visualize scaffold microarchitecture and to detect major anatomical features, such as the esophageal mucosal-submucosal separation, pulmonary alveoli and intestinal villi. These results are a long-sought step for the field of regenerative medicine; until now, histology and scanning electron microscopy have been the gold standard to study the scaffold structure. However, they are both destructive: hence, they are not suitable for imaging scaffolds prior to transplantation, and have no prospect for post-transplantation use. PC-CT, on the other hand, is non-destructive, 3D and fully quantitative. Importantly, not only do we demonstrate achievement of high image quality at two different synchrotron facilities, but also with commercial x-ray equipment, which makes the method available to any research laboratory.

Synchrotron- and laboratory-based X-ray phase-contrast imaging for imaging mouse articular cartilage in the absence of radiopaque contrast agents

The mouse model of osteoarthritis (OA) has been recognized as the most promising research tool for the identification of new OA therapeutic targets. However, this model is currently limited by poor throughput, dependent on the extremely time-consuming histopathology assessment of the articular cartilage (AC). We have recently shown that AC in the rat tibia can be imaged both in air and in saline solution using a laboratory system based on coded-aperture X-ray phase-contrast imaging (CAXPCi). Here, we explore ways to extend the methodology for imaging the much thinner AC of the mouse, by means of gold-standard synchrotron-based phase-contrast methods. Specifically, we have used analyser-based phase-contrast micro-computed tomography (micro-CT) for its high sensitivity to faint phase changes, coupled with a high-resolution (4.5 μm pixel) detector. Healthy, diseased (four weeks post induction of OA) and artificially damaged mouse AC was imaged at the Elettra synchrotron in Trieste, Italy, using the above method. For validation, we used conventional micro-CT combined with radiopaque soft-tissue staining and standard histomorphometry. We show that mouse cartilage can be visualized correctly by means of the synchrotron method. This suggests that: (i) further developments of the laboratory-based CAXPCi system, especially in terms of pushing the resolution limits, might have the potential to resolve mouse AC ex vivo and (ii) additional improvements may lead to a new generation of CAXPCi micro-CT scanners which could be used for in vivo longitudinal pre-clinical imaging of soft tissue at resolutions impossible to achieve by current MRI technology.