Improved image contrast of calcifications in breast tissue specimens using diffraction enhanced imaging

The contrast of calcifications in images of breast tissue specimens using a synchrotron-based diffraction enhanced imaging (DEI) apparatus has been measured and is compared to the contrast in images acquired using a conventional synchrotron-based radiographic imaging modality. DEI is an imaging modality which derives image contrast from x-ray absorption, refraction and small-angle scatter-rejection (extinction), unlike conventional radiographic techniques, which can only derive contrast from absorption. DEI is accomplished by inserting an analyser crystal in the beam path between the sample and the detector. Two of the three breast tissue specimens contained calcifications associated with cancer, while a third contained benign calcifications. Results of the image analysis indicate that the DEI contrast of images taken with the analyser crystal tuned to the peak of its rocking curve, was as much as 19 times that of the conventional radiograph, with an average of 5.5 for all calcifications. This improved image contrast for even near-pixel-size calcifications suggests potential utility for DEI in breast imaging.     

Measurement of image contrast using diffraction enhanced imaging

Refraction contrast of simple objects obtained using diffraction enhanced imaging (DEI) was studied and compared to conventional radiographic contrast. Lucite cylinders and nylon wires were imaged using monochromatic synchrotron radiation at the National Synchrotron Light Source (http://nslsweb. nsls.bnl.gov/nsls/Default.htm) at the Brookhaven National Laboratory. The DEI images were obtained by placing a silicon analyser crystal tuned to the [333] diffraction plane in the beam path between the sample and the detector. To compare the DEI images with conventional radiographic images requires a consistent definition of refraction and absorption contrast. Conventional definitions of contrast favour conventional radiography and DEI contrast is defined to emphasize the specific characteristics of DEI. The proposed definitions were then used to find the DEI gain (the ratio of the DEI contrast with respect to the conventional image contrast). The results presented here show that the DEI gain is consistently greater than 1, indicating that DEI provides more contrast information than conventional radiography.     

Computed tomography of x-ray index of refraction using the diffraction enhanced imaging method

Diffraction enhanced imaging (DEI) is a new, synchrotron-based, x-ray radiography method that uses monochromatic, fan-shaped beams, with an analyser crystal positioned between the subject and the detector. The analyser allows the detection of only those x-rays transmitted by the subject that fall into the acceptance angle (central part of the rocking curve) of the monochromator/analyser system. As shown by Chapman et al, in addition to the x-ray attenuation, the method provides information on the out-of-plane angular deviation of x-rays. New images result in which the image contrast depends on the x-ray index of refraction and on the yield of small-angle scattering, respectively. We implemented DEI in the tomography mode at the National Synchrotron Light Source using 22 keV x-rays, and imaged a cylindrical acrylic phantom that included oil-filled, slanted channels. The resulting 'refraction CT image' shows the pure image of the out-of-plane gradient of the x-ray index of refraction. No image artefacts were present, indicating that the CT projection data were a consistent set. The 'refraction CT image' signal is linear with the gradient of the refractive index, and its value is equal to that expected. The method, at the energy used or higher, has the potential for use in clinical radiography and in industry.     

Diffraction enhanced imaging of controlled defects within bone, including bone-metal gaps

Gap regions between a bone and an implant, whether existing upon insertion or developing over time, can lead to implant failure. Currently, planar x-ray imaging and CT are the most commonly used methods to evaluate the gap region. An alternative to these available clinical imaging modalities could help to better evaluate bone resorption. Previous experiments with diffraction enhanced imaging (DEI) have shown significant contrast advantages over monochromatic synchrotron radiation (SR) imaging. DEI and planar SR radiography images of bone samples with drill holes and gap regions of known geometry were acquired at the NSLS beamline X15A (Upton, NY, USA). The images acquired with DEI show measurable contrast-to-noise gains when compared to the images acquired using SR radiography.     

Phase contrast image segmentation using a Laue analyser crystal

Dual-energy x-ray imaging is a powerful tool enabling two-component samples to be separated into their constituent objects from two-dimensional images. Phase contrast x-ray imaging can render the boundaries between media of differing refractive indices visible, despite them having similar attenuation properties; this is important for imaging biological soft tissues. We have used a Laue analyser crystal and a monochromatic x-ray source to combine the benefits of both techniques. The Laue analyser creates two distinct phase contrast images that can be simultaneously acquired on a high-resolution detector. These images can be combined to separate the effects of x-ray phase, absorption and scattering and, using the known complex refractive indices of the sample, to quantitatively segment its component materials. We have successfully validated this phase contrast image segmentation (PCIS) using a two-component phantom, containing an iodinated contrast agent, and have also separated the lungs and ribcage in images of a mouse thorax. Simultaneous image acquisition has enabled us to perform functional segmentation of the mouse thorax throughout the respiratory cycle during mechanical ventilation.     

Mass density images from the diffraction enhanced imaging technique

Conventional x-ray radiography measures the projected x-ray attenuation of an object. It requires attenuation differences to obtain contrast of embedded features. In general, the best absorption contrast is obtained at x-ray energies where the absorption is high, meaning a high absorbed dose. Diffraction-enhanced imaging (DEI) derives contrast from absorption, refraction, and extinction. The refraction angle image of DEI visualizes the spatial gradient of the projected electron density of the object. The projected electron density often correlates well with the projected mass density and projected absorption in soft-tissue imaging, yet the mass density is not an "energy"-dependent property of the object, as is the case of absorption. This simple difference can lead to imaging with less x-ray exposure or dose. In addition, the mass density image can be directly compared (i.e., a signal-to-noise comparison) with conventional radiography. We present the method of obtaining the mass density image, the results of experiments in which comparisons are made with radiography, and an application of the method to breast cancer imaging.     

Quantitative comparison of imaging performance of x-ray interferometric imaging and diffraction enhanced imaging

For detailed biomedical observations using the optimum phase-contrast x-ray imaging, quantitative comparisons of imaging performances of two major imaging methods--x-ray interferometric imaging (XII) and diffraction enhanced imaging (DEI)--were performed. Density sensitivity and spatial resolution of each imaging method were evaluated using phantom tomograms obtained by each method with the same x-ray dosage. For practical comparison of the methods, biological samples were also observed under the same conditions. The results show that XII has a higher sensitivity than that of DEI and is thus suitable for observation of soft biological tissues. On the other hand, DEI has a wider dynamic range of density and is thus suitable for observation of samples with large differences in density of different regions.     

Evaluation of x-ray diffraction enhanced imaging in the diagnosis of breast cancer

The significance of the x-ray diffraction enhanced imaging (DEI) technique in the diagnosis of breast cancer and its feasibility in clinical medical imaging are evaluated. Different massive specimens including normal breast tissues, benign breast tumour tissues and malignant breast tumour tissues are imaged with the DEI method. The images are recorded respectively by CCD or x-ray film at different positions of the rocking curve and processed with a pixel-by-pixel algorithm. The characteristics of the DEI images about the normal and diseased tissues are compared. The rocking curves of a double-crystal diffractometer with various tissues are also studied. The differences in DEI images and their rocking curves are evaluated for early diagnosis of breast cancers.     

Acoustically modulated x-ray phase contrast imaging

We report the use of ultrasonic radiation pressure with phase contrast x-ray imaging to give an image proportional to the space derivative of a conventional phase contrast image in the direction of propagation of an ultrasonic beam. Intense ultrasound is used to exert forces on objects within a body giving displacements of the order of tens to hundreds of microns. Subtraction of images made with and without the ultrasound field gives an image that removes low spatial frequency features and highlights high frequency features. The method acts as an acoustic 'contrast agent' for phase contrast x-ray imaging, which in soft tissue acts to highlight small density changes.     

X-ray diffraction enhanced imaging as a novel method to visualize low-density scaffolds in soft tissue engineering

Scaffold visualization is challenging yet essential to the success of various tissue engineering applications. The aim of this study was to explore the potential of X-ray diffraction enhanced imaging (DEI) as a novel method for the visualization of low density engineered scaffolds in soft tissue. Imaging of the scaffolds made from poly(L-lactide) (PLLA) and chitosan was conducted using synchrotron radiation-based radiography, in-line phase-contrast imaging (in-line PCI), and DEI techniques as well as laboratory-based radiography. Scaffolds were visualized in air, water, and rat muscle tissue. Compared with the images from X-ray radiography and in-line PCI techniques, DEI images more clearly show the structure of the low density scaffold in air and have enhanced image contrast. DEI was the only technique able to visualize scaffolds embedded in unstained muscle tissue; this method could also define the microstructure of muscle tissue in the boundary areas. At a photon energy of 20?KeV, DEI had the capacity to image PLLA/chitosan scaffolds in soft tissue with a sample thickness of up to 4?cm. The DEI technique can be applied at high X-ray energies, thus facilitating lower in vivo radiation doses to tissues during imaging as compared to conventional radiography.     

Image formation principles in coded-aperture based x-ray phase contrast imaging

A novel x-ray phase contrast imaging technique based on coded apertures was recently developed at University College London. This technique removes most limitations of previous phase contrast methods and provides image improvements comparable to those obtained with synchrotron radiation with conventional x-ray sources. Unlike other phase contrast approaches, the technique does not impose restrictive wavelength and/or angular filtering on the beam emitted by the source, meaning that the beam can be exploited in full thus minimizing exposure times. As a consequence, the method provides, for the first time, a concrete opportunity to transfer x-ray phase contrast imaging into real medical applications. This paper discusses the image formation principles, analyses the shape and nature of the phase contrast profiles obtained and draws a significant conclusion on the role of convolution integrals in the acquisition of phase contrast patterns, applicable also to other phase contrast imaging approaches.     

Human breast cancer in vitro: matching histo-pathology with small-angle x-ray scattering and diffraction enhanced x-ray imaging

Twenty-eight human breast tumour specimens were studied with small-angle x-ray scattering (SAXS), and 10 of those were imaged by the diffraction enhanced x-ray imaging (DEI) technique. The sample diameter was 20 mm and the thickness 1 mm. Two examples of ductal carcinoma are illustrated by histology images, DEI, and maps of the collagen d-spacing and scattered intensity in the Porod regime, which characterize the SAXS patterns from collagen-rich regions of the samples. Histo-pathology reveals the cancer-invaded regions, and the maps of the SAXS parameters show that in these regions the scattering signal differs significantly from scattering by the surrounding tissue, indicating a degradation of the collagen structure in the invaded regions. The DEI images show the borders between collagen and adipose tissue and provide a co-ordinate system for tissue mapping by SAXS. In addition, degradation of the collagen structure in an invaded region is revealed by fading contrast of the DEI refraction image. The 28 samples include fresh, defrosted tissue and formalin-fixed tissue. The d-values with their standard deviations are given. In the fresh samples there is a systematic 0.76% increase of the d-value in the invaded regions, averaged over 11 samples. Only intra-sample comparisons are made for the formalin-fixed samples, and with a long fixation time, the difference in the d-value stabilizes at about 0.7%. The correspondence between the DEI images, the SAXS maps and the histo-pathology suggests that definitive information on tumour growth and malignancy is obtained by combining these x-ray methods.     

In vivo x-ray phase contrast analyzer-based imaging for longitudinal osteoarthritis studies in guinea pigs

Over the last two decades phase contrast x-ray imaging techniques have been extensively studied for applications in the biomedical field. Published results demonstrate the high capability of these imaging modalities of improving the image contrast of biological samples with respect to standard absorption-based radiography and routinely used clinical imaging techniques. A clear depiction of the anatomic structures and a more accurate disease diagnosis may be provided by using radiation doses comparable to or lower than those used in current clinical methods. In the literature many works show images of phantoms and excised biological samples proving the high sensitivity of the phase contrast imaging methods for in vitro investigations. In this scenario, the applications of the so-called analyzer-based x-ray imaging (ABI) phase contrast technique are particularly noteworthy. The objective of this work is to demonstrate the feasibility of in vivo x-ray ABI phase contrast imaging for biomedical applications and in particular with respect to joint anatomic depiction and osteoarthritis detection. ABI in planar and tomographic modes was performed in vivo on articular joints of guinea pigs in order to investigate the animals with respect to osteoarthritis by using highly monochromatic x-rays of 52 keV and a low noise detector with a pixel size of 47 × 47 μm(2). Images give strong evidence of the ability of ABI in depicting both anatomic structures in complex systems as living organisms and all known signs of osteoarthritis with high contrast, high spatial resolution and with an acceptable radiation dose. This paper presents the first proof of principle study of in vivo application of ABI. The technical challenges encountered when imaging an animal in vivo are discussed. This experimental study is an important step toward the study of clinical applications of phase contrast x-ray imaging techniques.     

An extended diffraction-enhanced imaging method for implementing multiple-image radiography

Diffraction-enhanced imaging (DEI) is an analyser-based x-ray imaging method that produces separate images depicting the projected x-ray absorption and refractive properties of an object. Because the imaging model of DEI does not account for ultra-small-angle x-ray scattering (USAXS), the images produced in DEI can contain artefacts and inaccuracies in medical imaging applications. In this work, we investigate an extended DEI method for concurrent reconstruction of three images that depict an object's projected x-ray absorption, refraction and USAXS properties. The extended DEI method can be viewed as an implementation of the recently proposed multiple-image radiography paradigm. Validation studies are conducted by use of computer-simulated and synchrotron measurement data.     

Refraction-angle resolution of diffraction enhanced imaging

As a new method, x-ray diffraction enhanced imaging (DEI) has extremely high sensitivity for weakly absorbing low-Z samples in medical and biological fields. Conventional performance parameters, such as spatial resolution and low-contrast resolution, are not enough to describe the characteristics of a DEI system. This paper focuses on refraction-angle resolution which describes the ability of a DEI system to differentiate the x-rays refracted by the sample. The analysis of refraction-angle resolution is composed of two parts: the analysis of the single DEI image measured in a certain position of the rocking curve and the analysis of the refraction-angle image calculated by extraction methods. A 2D computer simulation experiment is performed to prove the results of the analyses. The limitations and conclusions of refraction-angle resolution are described in the end.     

衍射增强成像的生物医学应用研究进展

【摘要】X射线相衬成像技术是近年来研究开发的高衬度和高空间分辨率的新型成像技术,和传统X射线成像技术相比,它可满足生物软组织微观成像条件,获得软组织的丰富内部微观结构细节。衍射增强成像（DEI）是相衬成像技术的研究热点。利用基于DEI的信息提取和CT重建等图像处理技术,能够获得生物样品高质量图像及三维精细微观结构,更好地显示样品内部的结构和细节。结合DEI的理论和图像处理方法介绍了DEI技术的生物医学应用进展。     

Diffraction enhanced imaging contrast mechanisms in breast cancer specimens

We have investigated the contrast mechanisms of the refraction angle, and the apparent absorption images obtained from the diffraction enhanced imaging technique (DEI) and have correlated them with the absorption contrast of conventional radiography. The contrast of both the DEI refraction angle image and the radiograph have the same dependence on density differences of the tissues in the visualization of cancer; in radiography these differences directly relate to the contrast while in the DEI refraction angle image it is the density difference and thickness gradient that gives the refraction angle. We show that the density difference of fibrils in breast cancer as measured by absorption images correlate well with the density difference derived from refraction angle images of DEI. In addition we find that the DEI apparent absorption image and the image obtained with the DEI system at the top of the reflectivity curve have much greater contrast than that of the normal radiograph (x8 to 33-fold higher). This is due to the rejection of small angle scattering (extinction) from the fibrils enhancing the contrast.     

The effects of the imaging system on the validity limits of the ray-optical approach to phase contrast imaging

A theoretical analysis of the x-ray phase contrast imaging and its validation via synchrotron radiation imaging is here presented. Two different mathematical models have been followed: the simpler ray-optical approach and the more rigorous Fresnel-Kirchoff diffraction theory. Subsequently, the conditions upon which the x-ray optical approximation can be used to describe the image formation mechanism have been analyzed, taking into account also the effects due to the finite source size and detector resolution. It is possible to demonstrate that the ray-optics results can also be obtained by opportunely developing the diffraction formalism only with some restrictions on the spatial frequencies present in the final image, without any limitation on the maximum phase shift. The conditions allowing the use of the simplified ray-optical approach to describe the phase contrast images have been here defined and their validation has been proved by means of computer simulations and phantom experiments.     

An innovative digital imaging set-up allowing a low-dose approach to phase contrast applications in the medical field

Recently, new imaging modalities based on the detection of weak phase perturbations effects, among which are phase contrast and diffraction imaging, have been developed by several researchers. Due to their high sensitivity to weakly absorbing details, these techniques seem to be very promising for applications in the medical field. On the other hand, digital radiology is undergoing a wide diffusion, and its benefits are presently very well understood. Up to now, however, the strong pixel size constraints associated with phase contrast pattern detection limited the possibility of exploiting the advantages of phase contrast in digital radiology applications. In this paper, an innovative setup capable of removing the pixel size constraints, and thus opening the way to low dose digital phase contrast imaging, is described. Furthermore, we introduce an imaging technique based on the detection of radiation scattered at small angles: the information extracted from the sample is increased at no dose expense. We believe that several radiological fields, mammography being the first important example, may benefit from the herein described innovative imaging techniques.     

Strategy of extraction methods and reconstruction algorithms in computed tomography of diffraction enhanced imaging

Computed tomography of diffraction enhanced imaging (DEI-CT) is a novel x-ray phase-contrast computed tomography which is applied to inspect weakly absorbing low-Z samples. Refraction-angle images which are extracted from a series of raw DEI images measured in different positions of the rocking curve of the analyser can be regarded as projections of DEI-CT. Based on them, the distribution of refractive index decrement in the sample can be reconstructed according to the principles of CT. How to combine extraction methods and reconstruction algorithms to obtain the most accurate reconstructed results is investigated in detail in this paper. Two kinds of comparison, the comparison of different extraction methods and the comparison between "two-step" algorithms and the Hilbert filtered backprojection (HFBP) algorithm, draw the conclusion that the HFBP algorithm based on the maximum refraction-angle (MRA) method may be the best combination at present. Though all current extraction methods including the MRA method are approximate methods and cannot calculate very large refraction-angle values, the HFBP algorithm based on the MRA method is able to provide quite acceptable estimations of the distribution of refractive index decrement of the sample. The conclusion is proved by the experimental results at the Beijing Synchrotron Radiation Facility.