Zhentian Wang

The First Analysis and Clinical Evaluation of Native Breast Tissue Using Differential Phase-Contrast Mammography

Objectives:Phase-contrast and scattering-based x-ray imaging are known to provide additional and complementary information to conventional, absorption-based methods, and therefore have the potential to play a crucial role in medical diagnostics. We report on the first mammographic investigation of 5 native, that is, freshly dissected, breasts carried out with a grating interferometer and a conventional x-ray tube source. Four patients in this study had histopathologically proven invasive breast cancer. One male patient, without the presence of any malignant formations within the resected breast, was included as a control specimen. Materials and Methods:We used a Talbot-Lau grating setup installed on a conventional, low-brilliance x-ray source; the interferometer operated at the fifth Talbot distance, at a tube voltage of 40 kVp with mean energy of 28 keV, and at a current of 25 mA. The device simultaneously recorded absorption, differential phase and small-angle scattering signals from the native breast tissue. These quantities were then combined into novel color- and high-frequency-enhanced radiographic images. Presurgical images (conventional mammography, ultrasonography, and magnetic resonance imaging) supported the findings and clinical relevance was verified. Results:Our approach yields complementary and otherwise inaccessible information on the electron density distribution and the small-angle scattering power of the sample at the microscopic scale. This information can be used to potentially answer clinically relevant, yet unresolved questions such as unequivocally discerning between malignant and premalignant changes and postoperative scars and distinguishing cancer-invaded regions within healthy tissue. Conclusions:We present the first ex vivo images of fresh, native breast tissue obtained from mastectomy specimens using grating interferometry. This technique yields improved diagnostic capabilities when compared with conventional mammography, especially when discerning the type of malignant conversions and their breadth within normal breast tissue. These promising results advance us toward the ultimate goal, using grating interferometry in vivo on humans in a clinical setting.

Quantitative grating-based x-ray dark-field computed tomography

Grating-based x-ray dark-field computed tomography is a functional method that utilizes the scattering contrast mechanism to explore the inaccessible spatially resolved internal structure of the sample. In this letter, we show that the second moment of the scattering angle distribution can be expressed as the minus logarithm of the visibility degradation of the oscillation curve in grating-based imaging. According to the conclusion of Khelashvili et al. [Phys. Med. Biol. 51, 221 (2006)], the minus logarithm of the visibility ratio fulfills the line integral condition; consequently the scattering information can be reconstructed quantitatively by conventional computed tomography algorithms. Results from a computer simulation and from an actual experiment both validate our deduction.

A Study on Mastectomy Samples to Evaluate Breast Imaging Quality and Potential Clinical Relevance of Differential Phase Contrast Mammography

ObjectivesDifferential phase contrast and scattering-based x-ray mammography has the potential to provide additional and complementary clinically relevant information compared with absorption-based mammography. The purpose of our study was to provide a first statistical evaluation of the imaging capabilities of the new technique compared with digital absorption mammography. Materials and MethodsWe investigated non-fixed mastectomy samples of 33 patients with invasive breast cancer, using grating-based differential phase contrast mammography (mammoDPC) with a conventional, low-brilliance x-ray tube. We simultaneously recorded absorption, differential phase contrast, and small-angle scattering signals that were combined into novel high-frequency-enhanced images with a dedicated image fusion algorithm. Six international, expert breast radiologists evaluated clinical digital and experimental mammograms in a 2-part blinded, prospective independent reader study. The results were statistically analyzed in terms of image quality and clinical relevance. ResultsThe results of the comparison of mammoDPC with clinical digital mammography revealed the general quality of the images to be significantly superior (P < 0.001); sharpness, lesion delineation, as well as the general visibility of calcifications to be significantly more assessable (P < 0.001); and delineation of anatomic components of the specimens (surface structures) to be significantly sharper (P < 0.001). Spiculations were significantly better identified, and the overall clinically relevant information provided by mammoDPC was judged to be superior (P < 0.001). ConclusionsOur results demonstrate that complementary information provided by phase and scattering enhanced mammograms obtained with the mammoDPC approach deliver images of generally superior quality. This technique has the potential to improve radiological breast diagnostics.

Non-linear regularized phase retrieval for unidirectional X-ray differential phase contrast radiography

Phase retrieval from unidirectional radiographic differential phase contrast images requires integration of noisy data. A method is presented, which aims to suppress stripe artifacts arising from direct image integration. It is purely algorithmic and therefore, compared to alternative approaches, neither additional alignment nor an increased scan time is required. We report on the theory of this method and present results using numerical as well as experimental data. The method shows significant improvements on the phase retrieval accuracy and enhances contrast in the phase image. Due to its general applicability, the proposed method provides a valuable tool for various 2D imaging applications using differential data.

Human hand radiography using X-ray differential phase contrast combined with dark-field imaging

Established X-ray-based imaging procedures such as conventional radiography and computed tomography (CT) rely on the interaction of photons when passing through tissue, including the Compton scattering and the photoelectric effect, which is influenced by the X-ray energy and the type of matter. The resulting mean attenuation of X-rays can be measured and depicted on images with different gray levels. X-ray phase contrast imaging (PCI) represents a relatively new imaging technique relying upon the refraction of Xrays. As such, PCI relies on a fundamentally different physical contrast mechanism compared with conventional, absorption-based X-ray imaging. In the energy range of diagnostic imaging (10–120 keV), refraction is the dominant effect over absorption, but more difficult to acquire. Previous studies have demonstrated that PCI can provide considerably higher contrast in soft tissue, giving rise to its application in fields where conventional radiography and CT are usually limited. Among a variety of techniques used to acquire phase contrast images, grating interferometry [1] has recently attracted great attention because of its compatibility with conventional X-ray tubes [2, 3], which is the key prerequisite for the clinical applicability. In addition, this technique provides a third contrast mode along with absorption and phase contrast, which is the dark-field contrast [4]. Similarly, dark-field imaging again exploits a physically different interaction mechanism and represents the intensity of the scattered X-rays within the area of a single detector pixel. Image pixels with high gray values indicate strong scattering. Recent studies have investigated the performance of phase contrast (PC) and dark-field contrast (DC) in the imaging of female breast tissue, indicating promising results for distinguishing microcalcifications and the malignant conversion or extension of the carcinoma into normal breast tissue [5, 6]. Yet, joint pathologies such as rheumatoid arthritis, crystal arthropathies, and connective tissue diseases (e.g., scleroderma), are also associated with soft tissue affection and occasional calcifications. Conventional radiography of the hand is a cornerstone imaging study for the detection and monitoring of joint diseases as subtle changes of joint space and bones (narrowing and erosions or osteophytes) and—if perceivable—of soft tissue (including calcifications and fibrosis) [7, 8], indicating disease activity and/or progress. While tissue evaluation with conventional radiography is based on morphological criteria Electronic supplementary material The online version of this article (doi:10.1007/s00256-013-1606-7) contains supplementary material, which is available to authorized users T. Thuring (*) : Z. Wang :C. David :M. Stampanoni Paul Scherrer Institut, WBBA/213, 5232, Villigen, Switzerland e-mail: thomas.thuering@psi.ch

X-ray phase-contrast imaging at 100 keV on a conventional source

X-ray grating interferometry is a promising imaging technique sensitive to attenuation, refraction and scattering of the radiation. Applications of this technique in the energy range between 80 and 150 keV pose severe technical challenges, and are still mostly unexplored. Phase-contrast X-ray imaging at such high energies is of relevant scientific and industrial interest, in particular for the investigation of strongly absorbing or thick materials as well as for medical imaging. Here we show the successful implementation of a Talbot-Lau interferometer operated at 100 keV using a conventional X-ray tube and a compact geometry, with a total length of 54 cm. We present the edge-on illumination of the gratings in order to overcome the current fabrication limits. Finally, the curved structures match the beam divergence and allow a large field of view on a short and efficient setup.

Image fusion algorithm for differential phase contrast imaging

Differential phase-contrast imaging in the x-ray domain provides three physically complementary signals:1, 2 the attenuation, the differential phase-contrast, related to the refractive index, and the dark-field signal, strongly influenced by the total amount of radiation scattered into very small angles. In medical applications, it is of the utmost importance to present to the radiologist all clinically relevant information in as compact a way as possible. Hence, the need arises for a method to combine two or more of the above mentioned signals into one image containing all information relevant for diagnosis. We present an image composition algorithm that fuses the attenuation image and the differential phase contrast image into a composite, final image based on the assumption that the real and imaginary part of the complex refractive index of the sample can be related by a constant scaling factor. The merging is performed in such a way that the composite image is characterized by minimal noise-power at each frequency component.

2D-Omnidirectional Hard-X-Ray Scattering Sensitivity in a Single Shot

X-ray scattering imaging can provide complementary information to conventional absorption based radiographic imaging about the unresolved microstructures of a sample. The scattering signal can be accessed with various methods based on coherent illumination, which span from self-imaging to speckle scanning. The directional sensitivity of the existing real space imaging methods is limited to a few directions on the imaging plane and requires scanning of the optical components, or the rotation of either the sample or the imaging setup, in order to cover the full range of possible scattering directions. In this Letter the authors propose a new method that allows the simultaneous acquisition of scattering images in all possible directions in a single shot. This is achieved by a specialized phase grating and a detector with sufficient spatial resolution to record the generated interference fringe. The structural length scale sensitivity of the system can be tuned by varying its geometry for a fixed grating design. Taking into account ongoing developments in the field of compact x-ray sources that allow high brightness and sufficient spatial coherence, the applicability of omnidirectional scattering imaging in industrial and medical settings is boosted significantly.

Low dose reconstruction algorithm for differential phase contrast imaging

Differential phase contrast imaging computed tomography (DPCI-CT) is a novel x-ray inspection method to reconstruct the distribution of refraction index rather than the attenuation coefficient in weakly absorbing samples. In this paper, we propose an iterative reconstruction algorithm for DPCI-CT which benefits from the new compressed sensing theory. We first realize a differential algebraic reconstruction technique (DART) by discretizing the projection process of the differential phase contrast imaging into a linear partial derivative matrix. In this way the compressed sensing reconstruction problem of DPCI reconstruction can be transformed to a resolved problem in the transmission imaging CT. Our algorithm has the potential to reconstruct the refraction index distribution of the sample from highly undersampled projection data. Thus it can significantly reduce the dose and inspection time. The proposed algorithm has been validated by numerical simulations and actual experiments.

Quantitative x-ray radiography using grating interferometry: a feasibility study

X-ray grating interferometry is a promising tool for medical imaging because of its capability of providing additional and complementary information to conventional absorption-based methods. This technology can simultaneously measure absorption, differential phase and small-angle scattering signals from the sample, significantly improving the diagnostic content. In this work, we present a method which uses the image (dubbed the R image) obtained by taking the ratio of the absorption and small-angle scattering signals to gain quantitative insight from a radiographic x-ray projection. We demonstrate that with the help of the R image we can successfully distinguish among different (light-Z) plastic materials, which are usually used to mimic soft tissues. Two potential applications in medical imaging, such as quantitative x-ray radiography and volumetric breast density estimation, are demonstrated.