Phase-contrast X-ray imaging or phase-sensitive X-ray imaging is a general term for different technical methods that use information concerning changes in the phase of an X-ray beam that passes through an object in order to create its images. Standard X-ray imaging techniques like radiography or computed tomography (CT) rely on a decrease of the X-ray beam's intensity (attenuation) when traversing the sample, which can be measured directly with the assistance of an X-ray detector. However, in phase contrast X-ray imaging, the beam's phase shift caused by the sample is not measured directly, but is transformed into variations in intensity, which then can be recorded by the detector.
In addition to producing projection images, phase contrast X-ray imaging, like conventional transmission, can be combined with tomographic techniques to obtain the 3D distribution of the real part of the refractive index of the sample. When applied to samples that consist of atoms with low atomic number Z, phase contrast X-ray imaging is more sensitive to density variations in the sample than conventional transmission-based X-ray imaging. This leads to images with improved soft tissue contrast.
In the last several years, a variety of phase-contrast X-ray imaging techniques have been developed, all of which are based on the observation of interference patterns between diffracted and undiffracted waves. The most common techniques are crystal interferometry, propagation-based imaging, analyzer-based imaging, edge-illumination and grating-based imaging (see below).
History
The first to discover X-rays was Wilhelm Conrad Röntgen in 1895, where he found that they had the ability to penetrate opaque materials. He recorded the first X-ray image, displaying the hand of his wife. He was awarded the first Nobel Prize in Physics in 1901 "in recognition of the extraordinary services he has rendered by the discovery of the remarkable rays subsequently named after him". Since then, X-rays have been used as a tool to safely determine the inner structures of different objects, although the information was for a long time obtained by measuring the transmitted intensity of the waves only, and the phase information was not accessible.
The principle of phase-contrast imaging was first developed by Frits Zernike during his work with diffraction gratings and visible light. The application of his knowledge to microscopy won him the Nobel Prize in Physics in 1953. Ever since, phase-contrast microscopy has been an important field of optical microscopy.
The transfer of phase-contrast imaging from visible light to X-rays took a long time, due to slow progress in improving the quality of X-ray beams and the inaccessibility of X-ray lenses. In the 1970s, it was realized that the synchrotron radiation, emitted from charged particles circulating in storage rings constructed for high-energy nuclear physics experiments, may have been a more intense and versatile source of X-rays than X-ray tubes; this, combined with progress in the development of X-rays optics, was fundamental for the further advancement of X-ray physics.
The pioneer work to the implementation of the phase-contrast method to X-ray physics was presented in 1965 by Ulrich Bonse and Michael Hart, Department of Materials Science and Engineering of Cornell University, New York. They presented a crystal interferometer, made from a large and highly perfect single crystal. Not less than 30 years later the Japanese scientists Atsushi Momose, Tohoru Takeda and co-workers adopted this idea and refined it for application in biological imaging, for instance by increasing the field of view with the assistance of new setup configurations and phase retrieval techniques. The Bonse–Hart interferometer provides several orders of magnitude higher sensitivity in biological samples than other phase-contrast techniques, but it cannot use conventional X-ray tubes because the crystals only accept a very narrow energy band of X-rays (ΔE/E ~ 10−4). In 2012, Han Wen and co-workers took a step forward by replacing the crystals with nanometric phase gratings. The gratings split and direct X-rays over a broad spectrum, thus lifting the restriction on the bandwidth of the X-ray source. They detected sub nanoradian refractive bending of X-rays in biological samples with a grating Bonse–Hart interferometer.
At the same time, two further approaches to phase-contrast imaging emerged with the aim to overcome the problems of crystal interferometry. The propagation-based imaging technique was primarily introduced by the group of at the ESRF (European Synchrotron Radiation Facility) in Grenoble, France, and was based on the detection of "Fresnel fringes" that arise under certain circumstances in free-space propagation. The experimental setup consisted of an inline configuration of an X-ray source, a sample and a detector and did not require any optical elements. It was conceptually identical to the setup of Dennis Gabor's revolutionary work on holography in 1948.
An alternative approach called analyzer-based imaging was first explored in 1995 by Viktor Ingal and Elena Beliaevskaya at the X-ray laboratory in Saint Petersburg, Russia, and by Tim Davis and colleagues at the CSIRO (Commonwealth Scientific and Industrial Research Organisation) Division of Material Science and Technology in Clayton, Australia. This method uses a Bragg crystal as angular filter to reflect only a small part of the beam fulfilling the Bragg condition onto a detector. Important contributions to the progress of this method have been made by a US collaboration of the research teams of Dean Chapman, Zhong Zhong and William Thomlinson, for example the extracting of an additional signal caused by ultra-small angle scattering and the first CT image made with analyzer-based imaging. An alternative to analyzer-based imaging, which provides equivalent results without requiring the use of a crystal, was developed by Alessandro Olivo and co-workers at the Elettra synchrotron in Trieste, Italy. This method, called "edge-illumination", operates a fine selection on the X-ray direction by using the physical edge of the detector pixels themselves, hence the name. Later on Olivo, in collaboration with Robert Speller at University College London, adapted the method for use with conventional X-ray sources, opening the way to translation into clinical and other applications. Peter Munro (also from UCL) substantially contributed to the development of the lab-based approach, by demonstrating that it imposes practically no coherence requirements and that, this notwithstanding, it still is fully quantitative.
The latest approach discussed here is the so-called grating-based imaging, which makes use of the Talbot effect, discovered by Henry Fox Talbot in 1836. This self-imaging effect creates an interference pattern downstream of a diffraction grating. At a particular distance this pattern resembles exactly the structure of the grating and is recorded by a detector. The position of the interference pattern can be altered by bringing an object in the beam, that induces a phase shift. This displacement of the interference pattern is measured with the help of a second grating, and by certain reconstruction methods, information about the real part of the refractive index is gained. The so-called Talbot–Lau interferometer was initially used in atom interferometry, for instance by John F. Clauser and Shifang Li in 1994. The first X-ray grating interferometers using synchrotron sources were developed by Christian David and colleagues from the Paul Scherrer Institute (PSI) in Villingen, Switzerland and the group of Atsushi Momose from the University of Tokyo. In 2005, independently from each other, both David's and Momose's group incorporated computed tomography into grating interferometry, which can be seen as the next milestone in the development of grating-based imaging. In 2006, another great advancement was the transfer of the grating-based technique to conventional laboratory X-ray tubes by Franz Pfeiffer and co-workers, which fairly enlarged the technique's potential for clinical use. About two years later the group of Franz Pfeiffer also accomplished to extract a supplementary signal from their experiments; the so-called "dark-field signal" was caused by scattering due to the porous microstructure of the sample and provided "complementary and otherwise inaccessible structural information about the specimen at the micrometer and submicrometer length scale". At the same time, Han Wen and co-workers at the US National Institutes of Health arrived at a much simplified grating technique to obtain the scattering ("dark-field") image. They used a single projection of a grid and a new approach for signal extraction named "single-shot Fourier analysis". Recently, a lot of research was done to improve the grating-based technique: Han Wen and his team analyzed animal bones and found out that the intensity of the dark-field signal depends on the orientation of the grid and this is due to the anisotropy of the bone structure. They made significant progress towards biomedical applications by replacing mechanical scanning of the gratings with electronic scanning of the X-ray source. The grating-based phase-contrast CT field was extended by tomographic images of the dark-field signal and time-resolved phase-contrast CT. Furthermore, the first pre-clinical studies using grating-based phase-contrast X-ray imaging were published. Marco Stampanoni and his group examined native breast tissue with "differential phase-contrast mammography", and a team led by Dan Stutman investigated how to use grating-based imaging for the small joints of the hand.
Most recently, a significant advance in grating-based imaging occurred due to the discovery of a phase moiré effect by Wen and colleagues. It led to interferometry beyond the Talbot self-imaging range, using only phase gratings and conventional sources and detectors. X-ray phase gratings can be made with very fine periods, thereby allowing imaging at low radiation doses to achieve high sensitivity.
Physical principle
Conventional X-ray imaging uses the drop in intensity through attenuation caused by an object in the X-ray beam and the radiation is treated as rays like in geometrical optics. But when X-rays pass through an object, not only their amplitude but their phase is altered as well. Instead of simple rays, X-rays can also be treated as electromagnetic waves. An object then can be described by its complex refractive index (cf.):
.
The term is the decrement of the real part of the refractive index, and the imaginary part describes the absorption index or extinction coefficient. Note that in contrast to optical light, the real part of the refractive index is less than but close to unity, this is "due to the fact that the X-ray spectrum generally lies to the high-frequency side of various resonances associated with the binding of electrons". The phase velocity inside of the object is larger than the velocity of light c. This leads to a different behavior of X-rays in a medium compared to visible light (e.g. refractive angles have negative values) but does not contradict the law of relativity, "which requires that only signals carrying information do not travel faster than c. Such signals move with the group velocity, not with the phase velocity, and it can be shown that the group velocity is in fact less than c."
The impact of the index of refraction on the behavior of the wave can be demonstrated with a wave propagating in an arbitrary medium with a fixed refractive index . For reason of simplicity, a monochromatic plane wave with no polarization is assumed here. The wave propagates in direction normal to the surface of the medium, named z in this example (see figure on the right). The scalar wave function in vacuum is
.