Bart Pauwels

Experimental results from a preclinical X-ray phase-contrast CT scanner

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 grating-based 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).

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).

Development of a prototype gantry system for preclinical x‐ray phase‐contrast computed tomography

PURPOSE To explore the potential of grating-based x-ray phase-contrast imaging for clinical applications, a first compact gantry system was developed. It is designed such that it can be implemented into an in-vivo small-animal phase-contrast computed tomography (PC-CT) scanner. The purpose of the present study is to assess the accuracy and quantitativeness of the described gantry in both absorption and phase-contrast. METHODS A phantom, containing six chemically well-defined liquids, was constructed. A tomography scan with cone-beam reconstruction of this phantom was performed yielding the spatial distribution of the linear attenuation coefficient μ and decrement δ of the complex refractive index. Theoretical values of μ and δ were calculated for each liquid from tabulated data and compared with the experimentally measured values. Additionally, a color-fused image representation is proposed to display the complementary absorption and phase-contrast information in a single image. RESULTS Experimental and calculated data of the phantom agree well confirming the quantitativeness and accuracy of the reconstructed spatial distributions of μ and δ. The proposed color-fused image representation, which combines the complementary absorption and phase information, considerably helps in distinguishing the individual substances. CONCLUSIONS The concept of grating-based phase-contrast computed tomography (CT) can be implemented into a compact, cone-beam geometry gantry setup. The authors believe that this work represents an important milestone in translating phase-contrast x-ray imaging from previous proof-of-principle experiments to first preclinical biomedical imaging applications on small-animal models.

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.

X-ray nanotomography in a SEM

We have developed an x-ray computer tomography (CT) add-on to perform X-ray micro- and nanotomography in any scanning electron microscope (SEM). The electron beam inside the SEM is focused on a metal target to generate x-rays. Part of the X-rays pass through the object that is installed on a rotation stage. Shadow X-ray images are collected by a CCD camera with direct photon detection mounted on the external wall of the SEM specimen chamber. An extensive description on the working principles of this micro/nano-CT add-on together with some examples of CT-scans will be given in this paper. The resolution that can be obtained with this set-up and the influence of the shape of the electron beam are discussed. Furthermore, possible improvements on this SEM-CT set-up will be discussed: replacing the backilluminated CCD with a fully depleted CCD with improved quantum efficiency (QE) for higher energies, reduces the exposure time by 6 when using metal targets with x-ray characteristic lines around 10 keV.

Contrast-to-noise ratio optimization for a prototype phase-contrast computed tomography scanner.

In the field of biomedical X-ray imaging, novel techniques, such as phase-contrast and dark-field imaging, have the potential to enhance the contrast and provide complementary structural information about a specimen. In this paper, a first prototype of a preclinical X-ray phase-contrast CT scanner based on a Talbot-Lau interferometer is characterized. We present a study of the contrast-to-noise ratios for attenuation and phase-contrast images acquired with the prototype scanner. The shown results are based on a series of projection images and tomographic data sets of a plastic phantom in phase and attenuation-contrast recorded with varying acquisition settings. Subsequently, the signal and noise distribution of different regions in the phantom were determined. We present a novel method for estimation of contrast-to-noise ratios for projection images based on the cylindrical geometry of the phantom. Analytical functions, representing the expected signal in phase and attenuation-contrast for a circular object, are fitted to individual line profiles of the projection data. The free parameter of the fit function is used to estimate the contrast and the goodness of the fit is determined to assess the noise in the respective signal. The results depict the dependence of the contrast-to-noise ratios on the applied source voltages, the number of steps of the phase stepping routine, and the exposure times for an individual step. Moreover, the influence of the number of projection angles on the image quality of CT slices is investigated. Finally, the implications for future imaging purposes with the scanner are discussed.

First small-animal in-vivo phase-contrast micro-CT scanner

We have developed a compact grating-based in-vivo phase-contrast micro-CT system with a rotating gantry. The 50 W microfocus x-ray source operates with 20 to 50 kV peak energy. The length of the rotating interferometer is around 47 cm. Pixel size in the object is 30 micron; the field of view is approx. 35 mm in diameter, suited to image a mouse. The interferometer consists of three gratings: an absorption grating close to the x-ray source, a phase grating to introduce a π/2 phase shift and an absorption analyzer grating positioned at the first fractional Talbot distance. Numerous drives and actuators are used to provide angular and linear grating alignment, phase stepping and object/gantry precision positioning. Phantom studies were conducted to investigate performance, accuracy and stability of the scanner. In particular, the influences of gantry rotation and of temperature fluctuations on the interferometric image acquisition were characterized. Also dose measurements were performed. The first imaging results obtained with the system show the complementary nature of phase-contrast micro-CT images with respect to absorption-based micro-CT. Future improvements, necessary to optimize the scanner for in-vivo small-animal CT scanning on a regular and easy-to-use basis, are also discussed.

X-ray Nano- and Micro-tomography in an SEM

Introduction X-ray microfocus computer tomography (μ-CT) is a non-destructive experimental technique that reveals the 3D internal microstructure of the sample under study [1]. The experimental set-up consists of an X-ray source, an X-ray detector, and set in between is a sample that is placed on a rotation stage. With this set-up multiple X-ray projection images can be obtained from the sample at different angles. In between the acquisition of two successive images, the sample is rotated over a small angle, typically between 0.2° and 1°. This set of projection images is then used as input for the reconstruction algorithm, which calculates a reconstruction of the internal microstructure of the sample with (sub-) micrometer sensitivity. Scanning electron microscopy (SEM) on the other hand is used to study the topographic features and elemental composition of the surface of the sample [2]. The two techniques thus give different, complementary information about the sample. Until now, both techniques also required their own dedicated experimental set-up. This article describes new instrumentation for an SEM that adds microand nano-tomography capabilities to most commercial SEMs. Submicrometer isotropic spatial resolution in 3D reconstructed images can be produced without making any modifications to the SEM. This micro-CT add-on for SEM is commercially available from Bruker [3].

New type of x-ray source for lensless laboratory nano-CT with 50-nm resolution

Most X-ray systems are limited in spatial resolution by the x-ray source performance. In laboratory sources, x-rays are generated by the interaction of an electron beam with a metal target. Bulk target sources produce a spot size in the micron range. Thin layer targets allow a spot size improvement down to hundreds of nanometers, but with a significant flux reduction. Until now a spatial resolution under 100 nm could only be achieved by imaging with Fresnel zone plates with limited depth of focus, typically - several microns. This is acceptable for imaging of flat objects, but it creates a problem for tomography, which requires all parts of a bulk object to be in focus. To overcome the limitations, we invented an x-ray source with a new type of target. Because x-ray cameras can only collect photons from a small angle, the new emitter is physically shaped in such way that the camera can see it as a small dot, but it has a big length along the direction perpendicular to the camera creating a significant flux without compromising the resolution. Evaluation shows that structures down to 50 nm can be distinguished while maintaining a significant x-ray flux and infinite depth of focus required for nano-tomographical reconstruction.

Key components for artifact-free micro-CT and nano-CT instruments

Proper selection of modern key components allows eliminating most artifacts in micro-CT and nano-CT systems already during data acquisition. X-ray cameras with direct photon detection allow avoiding ring artifacts. Newly developed fully depleted CCD sensors show an energy response similar to traditional cameras with a thin scintillator, but without any geometrical distortions and flashes from x-ray photons penetrating through the fiber optics. Air-bearing rotation stages and piezo-positioning minimizes mechanical inaccuracies in acquiring angular projections. Beam hardening can be eliminated by energy-selective photon counting imaging.