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.     

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.     

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.     

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.     

Imaging lobular breast carcinoma: comparison of synchrotron radiation DEI-CT technique with clinical CT, mammography and histology

Different modalities for imaging cancer-bearing breast tissue samples are described and compared. The images include clinical mammograms and computed tomography (CT) images, CT images with partly coherent synchrotron radiation (SR), and CT and radiography images taken with SR using the diffraction enhanced imaging (DEI) method. The images are evaluated by a radiologist and compared with histopathological examination of the samples. Two cases of lobular carcinoma are studied in detail. The indications of cancer are very weak or invisible in the conventional images, but the morphological changes due to invasion of cancer become pronounced in the images taken by the DEI method. The strands penetrating adipose tissue are seen clearly in the DEI-CT images, and the histopathology confirms that some strands contain the so-called 'Indian file' formations of cancer cells. The radiation dose is carefully measured for each of the imaging modalities. The mean glandular dose (MGD) for 50% glandular breast tissue is about 1 mGy in conventional mammography and less than 0.25 mGy in projection DEI, while in the clinical CT imaging the MGD is very high, about 45 mGy. The entrance dose of 95 mGy in DEI-CT imaging gives rise to an MGD of 40 mGy, but the dose may be reduced by an order of magnitude, because the contrast is very large in most images.     

基于衍射增强成像的肝纤维化图像多参数纹理特征分析

目的根据硬X射线衍射增强成像工作原理,利用其图像的空间高分辨率和高相位衬度特征,对实验所获得的大鼠正常肝图像及肝纤维化图像进行纹理特征分析,探求其微观结构变化,为计算机辅助诊断提供新手段。方法本次实验在北京同步辐射装置（BSRF）4W/1A光束线形貌站完成,样品为离体大鼠正常肝及由人血白蛋白诱导的免疫损伤性肝纤维化标本,记录介质为FujiIX80胶片。本文计算了感兴趣区域图像的纹理特征参数,以及计算同一类型不同纹理参数间的相关系数,对纹理参数的波动趋势进行了初步分析。结果结果表明,正常及肝纤维化组织在相衬图像上差异较明显,可以通过逆差距、惯量、差的均值以及差的熵这四种纹理参数区分开,其中,后三种纹理参数的波动趋势类似,与逆差距正好相反。结论基于硬X射线衍射增强原理的肝纤维化图像可以通过分析纹理特征来识别其病变,可以用于辅助医生诊断。     

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.     

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.     

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.     

不同软组织衍射增强图像的比较研究

我们着重于衍射增强成像(DEI)中的图像及其衬度分析,确定不同组织类型对DEI成像的影响.利用北京同步辐射装置4W1A束线上的形貌与成像站获得三种软组织的衍射增强图像,采用像素-像素的"加"或"减"算法得到表观吸收图像和折射图像,并用衬度分析法对DEI中的峰位图像、表观吸收图像和折射图像的成像质量进行比较.结果显示:软组织的峰位图像与表观吸收图像的吸收衬度相近,但边界效应不及折射图像.不同软组织折射图像的折射衬度不完全相同,肺组织和肾组织的吸收衬度和折射衬度比较高,而肝脏组织的衬度比较低,说明衍射增强成像对改善肝脏组织的成像效果不够明显.因此,折射图像辨别能力强,更适合观察肺和肾等软组织的细微结构.     

High-resolution breast tomography at high energy: a feasibility study of phase contrast imaging on a whole breast

Previous studies on phase contrast imaging (PCI) mammography have demonstrated an enhancement of breast morphology and cancerous tissue visualization compared to conventional imaging. We show here the first results of the PCI analyser-based imaging (ABI) in computed tomography (CT) mode on whole and large (>12 cm) tumour-bearing breast tissues. We demonstrate in this work the capability of the technique of working at high x-ray energies and producing high-contrast images of large and complex specimens. One entire breast of an 80-year-old woman with invasive ductal cancer was imaged using ABI-CT with monochromatic 70 keV x-rays and an area detector of 92×92 μm2 pixel size. Sagittal slices were reconstructed from the acquired data, and compared to corresponding histological sections. Comparison with conventional absorption-based CT was also performed. Five blinded radiologists quantitatively evaluated the visual aspects of the ABI-CT images with respect to sharpness, soft tissue contrast, tissue boundaries and the discrimination of different structures/tissues. ABI-CT excellently depicted the entire 3D architecture of the breast volume by providing high-resolution and high-contrast images of the normal and cancerous breast tissues. These results are an important step in the evolution of PCI-CT towards its clinical implementation.     

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 between two phase contrast techniques: diffraction enhanced imaging and phase propagation imaging

Two x-ray phase contrast imaging techniques are compared in a quantitative way for future mammographic applications: diffraction enhanced imaging (DEI) and phase propagation imaging (PPI). DEI involves, downstream of the sample, an analyser crystal acting as an angular filter for x-rays refracted by the sample. PPI simply uses the propagation (Fresnel diffraction) of the monochromatic and partially coherent x-ray beam over large distances. The information given by the two techniques is assessed by theoretical simulations and compared at the level of the experimental results for different kinds of samples (phantoms and real tissues). The imaging parameters such as the energy, the angular position of the analyser crystal in the DEI case or the sample to detector distance in the PPI case were varied in order to optimize the image quality in terms of contrast, visibility and figure of merit.     

An inverse problem solution for measuring the elastic modulus of intact ex vivo breast tissue tumours

Soft tissue elasticity has been a subject of interest in biomedical applications as an aid to medical diagnosis since the dawn of medicine. More recently, this has led to the concept of elastography with the aim of imaging the spatial distribution of tissue elasticity. Interpreting elastography images requires reliable information pertaining to elastic properties of normal and pathological tissues. Such information is either very limited or not available in the literature. Elastic modulus measurement techniques developed for soft tissues generally require tissue excision to prepare samples for testing. While this may be done with normal tissues, tumour tissue excision is generally not permissible because tumour pathological assessment requires that the tumour be kept intact. To address this limitation, we developed a system to measure the Young's modulus of tumour specimens. The technique consists of indenting the tumour specimen while measuring indentation force and displacements. To obtain the Young's modulus from the measured force-displacement slope, we developed an iterative inversion technique that uses a finite element model of the piecewise homogeneous tissue slice in each iteration. Preliminary elasticity measurement results of various breast tumours are presented and discussed. These results indicate that the proposed method is robust and highly accurate. Furthermore, they indicate that a benign lesion and malignant tumours are roughly five times and ten times stiffer than normal breast tissues respectively.     

Why should breast tumour detection go three dimensional?

Although x-ray mammography is widely developed for breast tumour detection, it suffers from spatial superposition in its two-dimensional (2D) representation of a three-dimensional (3D) breast structure. Accordingly, 3D breast imaging, such as cone-beam computed tomography (CT), arises at the historic moment. In this paper, we theoretically elucidate the spatial superposition effect associated with x-ray mammography on breast tumour detection. This explanation is based on the line integral of x-ray traversing a composite breast model. As a result, we can characterize the difficulty of detecting small tumours in terms of local intensity contrast in x-ray images. In comparison, we also introduce cone-beam CT breast imaging for 3D breast volume representation, which offers advantages for breast mass segmentation and measurement. The discussion is demonstrated with an experiment with a breast surgical specimen. In conclusion, we strongly believe that 3D volumetric representation allows for more accurate breast tumour detection.     

Evaluation of edge effect due to phase contrast imaging for mammography

It is well-known that the edge effect produced by phase contrast imaging results in the edge enhancement of x-ray images and thereby sharpens those images. It has recently been reported that phase contrast imaging using practical x-ray tubes with small focal spots has improved image sharpness as observed in the phase contrast imaging with x-ray from synchrotron radiation or micro-focus x-ray tubes. In this study, we conducted the phase contrast imaging of a plastic fiber and plant seeds using a customized mammography equipment with a 0.1 mm focal spot, and the improvement of image sharpness was evaluated in terms of spatial frequency response of the images. We observed that the image contrast of the plastic fiber was increased by edge enhancement, and, as predicted elsewhere, spectral analysis revealed that as the spatial frequencies of the x-ray images increased, so did the sharpness gained through phase contrast imaging. Thus, phase contrast imaging using a practical molybdenum anode tube with a 0.1 mm-focal spot would benefit mammography, in which the morphological detectability of small species such as microcalcifications is of great concern. And detectability of tumor-surrounded glandular tissues in dense breast would be also improved by the phase contrast imaging.     

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。     

Radiography of soft tissue of the foot and ankle with diffraction enhanced imaging

Non-calcified tissues, including tendons, ligaments, adipose tissue and cartilage, are not visible, for any practical purposes, with conventional X-ray imaging. Therefore, any pathological changes in these tissues generally necessitate detection through magnetic resonance imaging or ultrasound technology. Until recently the development of an X-ray imaging technique that could detect both bone and soft tissues seemed unrealistic. However, the introduction of diffraction enhanced X-ray imaging (DEI) which is capable of rendering images with absorption, refraction and scatter rejection qualities has allowed detection of specific soft tissues based on small differences in tissue densities. Here we show for the first time that DEI allows high contrast imaging of soft tissues, including ligaments, tendons and adipose tissue, of the human foot and ankle.