Detectability comparison of simulated tumors in digital breast tomosynthesis using high-energy X-ray inline phase sensitive and commercial imaging systems

This study compared the detectability of simulated tumors using a high-energy X-ray inline phase sensitive digital breast tomosynthesis (DBT) prototype and a commercial attenuation-based DBT system. Each system imaged a 5-cm thick modular breast phantom with 50–50 adipose-glandular percentage density containing contrast-detail (CD) test objects to simulate different tumor sizes. A commercial DBT system acquired 15 projection views over 15 degrees (15d-15p) was used to acquire the attenuation-based projection views and to reconstruct the conventional DBT slices. Attenuation-based projection views were acquired at 32 kV, 46 mAs with a mean glandular dose (D_g) of 1.6 mGy. For acquiring phase sensitive projection views, the prototype utilized two acquisition geometries: 11 projection views were acquired over 15 degrees (15d-11p), and 17 projection views were acquired over 16 degrees (16d-17p) at 120 kV, 5.27 mAs with 1.51 mGy under the magnification (M) of 2. A phase retrieval algorithm based on the phase-attenuation duality (PAD) was applied to each projection view, and a modified Feldkamp-Davis-Kress (FDK) algorithm was used to reconstruct the phase sensitive DBT slices. Simulated tumor margins were rated as more conspicuous and better visualized for both phase sensitive acquisition geometries versus conventional DBT imaging. The CD curves confirmed the improvement in both contrast and spatial resolutions with the phase sensitive DBT imaging. The superiority of the phase sensitive DBT imaging was further endorsed by higher contrast to noise ratio (CNR) and figure-of-merit (FOM) values. The CNR improvements provided by the phase sensitive DBT prototype were sufficient to offset the noise reduction provided by the attenuation-based DBT imaging.     

Spectroscopic imaging at compact inverse Compton X-ray sources

While K-edge subtraction (KES) imaging is a commonly applied technique at synchrotron sources, the application of this imaging method in clinical imaging is limited although results have shown its superiority to conventional clinical subtraction imaging. Over the past decades, compact synchrotron X-ray sources, based on inverse Compton scattering, have been developed to fill the gap between conventional X-ray tubes and synchrotron facilities. These so called inverse Compton sources (ICSs) provide a tunable, quasi-monochromatic X-ray beam in a laboratory setting with reduced spatial and financial requirements. This allows for the transfer of imaging techniques that have been limited to synchrotrons until now, like KES imaging, into a laboratory environment. This review article presents the first studies that have successfully performed KES at ICSs. These have shown that KES provides improved image quality in comparison to conventional X-ray imaging. The results indicate that medical imaging could benefit from monochromatic imaging and KES techniques. Currently, the clinical application of KES is limited by the low K-edge energy of available iodine contrast agents. However, several ICSs are under development or already in commissioning which will provide monochromatic X-ray beams with higher X-ray energies and will enable KES using high-Z elements as contrast media. With these developments, KES at an ICS has the ability to become an important tool in pre-clinical research and potentially advancing existing clinical imaging techniques.     

Synchrotron based planar imaging and digital tomosynthesis of breast and biopsy phantoms using a CMOS active pixel sensor

The SYRMEP (SYnchrotron Radiation for MEdical Physics) beamline at Elettra is performing the first mammography study on human patients using free-space propagation phase contrast imaging. The stricter spatial resolution requirements of this method currently force the use of conventional films or specialized computed radiography (CR) systems. This also prevents the implementation of three-dimensional (3D) approaches. This paper explores the use of an X-ray detector based on complementary metal-oxide-semiconductor (CMOS) active pixel sensor (APS) technology as a possible alternative, for acquisitions both in planar and tomosynthesis geometry.Results indicate higher quality of the images acquired with the synchrotron set-up in both geometries. This improvement can be partly ascribed to the use of parallel, collimated and monochromatic synchrotron radiation (resulting in scatter rejection, no penumbra-induced blurring and optimized X-ray energy), and partly to phase contrast effects. Even though the pixel size of the used detector is still too large – and thus suboptimal – for free-space propagation phase contrast imaging, a degree of phase-induced edge enhancement can clearly be observed in the images.     

In Vitro Validation of an Artefact Suppression Algorithm in X-Ray Phase-Contrast Computed Tomography

X-ray phase-contrast tomography can significantly increase the contrast-resolution of conventional attenuation-contrast imaging, especially for soft-tissue structures that have very similar attenuation. Just as in attenuation-based tomography, phase contrast tomography requires a linear dependence of aggregate beam direction on the incremental direction alteration caused by individual voxels along the path of the X-ray beam. Dense objects such as calcifications in biological specimens violate this condition. There are extensive beam deflection artefacts in the vicinity of such structures because they result in large distortion of wave front due to the large difference of refractive index; for such large changes in beam direction, the transmittance of the silicon analyzer crystal saturates and is no longer linearly dependent on the angle of refraction. This paper describes a method by which these effects can be overcome and excellent soft-tissue contrast of phase tomography can be preserved in the vicinity of such artefact-producing structures.     

Dark-Field Imaging: Recent developments and potential clinical applications

This paper describes an X-ray phase contrast imaging technique using analyzer-based optics called X-ray Dark-Field Imaging that has been under development for the past 10 years. We describe the theory behind XDFI, the X-ray optics required for implementing it in practice, and algorithms used for 2D, 2.5D, and 3D image reconstruction. The XDFI optical chain consists of an asymmetrically cut, Bragg-type monochromator-collimator that provides a planar monochromatic X-ray beam, a positioning stage for the specimens, a Laue-case angle analyzer, and one or two cameras to capture the dark and bright field images. We demonstrate the soft-tissue discrimination capabilities of XDFI by reconstructing images with absorption and phase contrast. By using a variety of specimens such as breast tissue with cancer, joints with articular cartilage, ex-vivo human eye specimen, and others, we show that refraction-based contrast derived from XDFI is more effective in characterizing anatomical features, articular pathology, and neoplastic disease than conventional absorption-based images. For example, XDFI of breast tissue can discriminate between the normal and diseased terminal duct lobular unit, and between invasive and in-situ cancer. The final section of this paper is devoted to potential future developments to enable clinical and histo-pathological applications of this technique.     

Non-invasive microstructure and morphology investigation of the mouse lung: qualitative description and quantitative measurement

Background

Early detection of lung cancer is known to improve the chances of successful treatment. However, lungs are soft tissues with complex three-dimensional configuration. Conventional X-ray imaging is based purely on absorption resulting in very low contrast when imaging soft tissues without contrast agents. It is difficult to obtain adequate information of lung lesions from conventional X-ray imaging.

Methods

In this study, a recently emerged imaging technique, in-line X-ray phase contrast imaging (IL-XPCI) was used. This powerful technique enabled high-resolution investigations of soft tissues without contrast agents. We applied IL-XPCI to observe the lungs in an intact mouse for the purpose of defining quantitatively the micro-structures in lung.

Findings

The three-dimensional model of the lung was successfully established, which provided an excellent view of lung airways. We highlighted the use of IL-XPCI in the visualization and assessment of alveoli which had rarely been studied in three dimensions (3D). The precise view of individual alveolus was achieved. The morphological parameters, such as diameter and alveolar surface area were measured. These parameters were of great importance in the diagnosis of diseases related to alveolus and alveolar scar.

Conclusion

Our results indicated that IL-XPCI had the ability to represent complex anatomical structures in lung. This offered a new perspective on the diagnosis of respiratory disease and may guide future work in the study of respiratory mechanism on the alveoli level.     

X-ray dark-field phase-contrast imaging: Origins of the concept to practical implementation and applications

The basic idea of X-ray dark-field imaging (XDFI), first presented in 2000, was based on the concepts used in an X-ray interferometer. In this article, we review 20 years of developments in our theoretical understanding, scientific instrumentation, and experimental demonstration of XDFI and its applications to medical imaging. We first describe the concepts underlying XDFI that are responsible for imparting phase contrast information in projection X-ray images. We then review the algorithms that can convert these projection phase images into three-dimensional tomographic slices. Various implementations of computed tomography reconstructions algorithms for XDFI data are discussed. The next four sections describe and illustrate potential applications of XDFI in pathology, musculoskeletal imaging, oncologic imaging, and neuroimaging. The sample applications that are presented illustrate potential use scenarios for XDFI in histopathology and other clinical applications. Finally, the last section presents future perspectives and potential technical developments that can make XDFI an even more powerful tool.     

两种微体化石三维无损成像技术的对比

近年来,各种X射线三维无损成像技术在古生物学领域的应用越来越广泛。但是,不同的X射线三维无损成像技术针对不同保存类型和尺寸的化石标本在成像效果上各有利弊。本文以埃迪卡拉纪陡山沱组磷酸盐化的动物胚胎化石为研究对象,将目前应用最广的两种X射线三维无损成像方法,即基于实验室X光源的吸收衬度显微断层成像技术和基于同步辐射光源的相位衬度显微断层成像技术进行了对比分析。通过对两种技术的原理、效率、空间分辨率和图像衬度的对比,认为基于同步辐射光源的相位衬度显微断层成像技术是目前对于均一矿化的微体化石最佳的三维无损成像解决方案。     

High-Dynamic-Range CT Reconstruction Based on Varying Tube-Voltage Imaging

For complicated structural components characterized by wide X-ray attenuation ranges, the conventional computed tomography (CT) imaging using a single tube-voltage at each rotation angle cannot obtain all structural information. This limitation results in a shortage of CT information, because the effective thickness of the components along the direction of X-ray penetration exceeds the limitation of the dynamic range of the X-ray imaging system. To address this problem, high-dynamic-range CT (HDR-CT) reconstruction is proposed. For this new method, the tube’s voltage is adjusted several times to match the corresponding effective thickness about the local information from an object. Then, HDR fusion and HDR-CT are applied to obtain the full reconstruction information. An accompanying experiment demonstrates that this new technology can extend the dynamic range of X-ray imaging systems and provide the complete internal structures of complicated structural components.     

Combined use of hard X-ray phase contrast imaging and X-ray fluorescence microscopy for sub-cellular metal quantification

Hard X-ray fluorescence microscopy and magnified phase contrast imaging are combined to obtain quantitative maps of the projected metal concentration in whole cells. The experiments were performed on freeze dried cells at the nano-imaging station ID22NI of the European Synchrotron Radiation Facility (ESRF). X-ray fluorescence analysis gives the areal mass of most major, minor and trace elements; it is validated using a biological standard of known composition. Quantitative phase contrast imaging provides maps of the projected mass and is validated using calibration samples and through comparison with Atomic Force Microscopy and Scanning Transmission Ion Microscopy. Up to now, absolute quantification at the sub-cellular level was impossible using X-ray fluorescence microscopy but can be reached with the use of the proposed approach.     

An in-silico method to predict and quantify the effect of gold nanoparticles in X-ray imaging

PurposeOver the last few years studies are conducted, highlighting the feasibility of Gold Nanoparticles (GNPs) to be used in clinical CT imaging and as an efficient contrast agent for cancer research. After ensuring that GNPs formulations are appropriate for in vivo or clinical use, the next step is to determine the parameters for an X-ray system’s optimal contrast for applications and to extract quantitative information. There is currently a gap and need to exploit new X-ray imaging protocols and processing algorithms, through specific models avoiding trial-and-error procedures and provide an imaging prognosis tool. Such a model can be used to confirm the accumulation of GNPs in target organs before radiotherapy treatments with a system easily available in hospitals, as low energy X-rays.MethodsIn this study a complete, easy-to-use, simulation platform is designed and built, where simple parameters, as the X-ray’s specifications and experimentally defined biodistributions of specific GNPs are imported. The induced contrast and images can be exported, and accurate quantification can be performed. This platform is based on the GATE Monte Carlo simulation toolkit, based on the GEANT4 toolkit and the MOBY phantom, a realistic 4D digital mouse.ResultsWe have validated this simulation platform to predict the contrast induction and minimum detectable concentration of GNPs on any given X-ray system. The study was applied to preclinical studies but is also expandable to clinical studies.ConclusionsAccording to our knowledge, no other such validated simulation model currently exists, and this model could help radiology imaging with GNPs to be truly deployed.     

Phase-Contrast Hounsfield Units of Fixated and Non-Fixated Soft-Tissue Samples

X-ray phase-contrast imaging is a novel technology that achieves high soft-tissue contrast. Although its clinical impact is still under investigation, the technique may potentially improve clinical diagnostics. In conventional attenuation-based X-ray computed tomography, radiological diagnostics are quantified by Hounsfield units. Corresponding Hounsfield units for phase-contrast imaging have been recently introduced, enabling a setup-independent comparison and standardized interpretation of imaging results. Thus far, the experimental values of few tissue types have been reported; these values have been determined from fixated tissue samples. This study presents phase-contrast Hounsfield units for various types of non-fixated human soft tissues. A large variety of tissue specimens ranging from adipose, muscle and connective tissues to liver, kidney and pancreas tissues were imaged by a grating interferometer with a rotating-anode X-ray tube and a photon-counting detector. Furthermore, we investigated the effects of formalin fixation on the quantitative phase-contrast imaging results.     

Potential of compact Compton sources in the medical field

The exceptional improvement of high power lasers and optical cavity finesses in the last fifteen years allows today the development of X-ray sources based on inverse Compton scattering. These compact sources will provide high intensity beams, with a tunable energy in the range 20–100 keV, that can be used in several application including material sciences, structural biology, cultural heritage research and preservation and medical or biomedical preclinical and clinical research. The access to these devices will be easier. Methods currently used only in synchrotron facilities will be available in dedicated work environment such as hospitals, laboratories or museums. Several machines are in design or construction phase, and aim at producing 10¹²–10¹⁴ ph/s. The ThomX machine is the most advanced project and has the potential to be used as the radiation source for biomedical searches, clinical imaging techniques or radiotherapy programs.     

Non-invasive Predictors of Human Cortical Bone Mechanical Properties: T2-Discriminated 1H NMR Compared with High Resolution X-ray

Recent advancements in magnetic resonance imaging (MRI) have enabled clinical imaging of human cortical bone, providing a potentially powerful new means for assessing bone health with molecular-scale sensitivities unavailable to conventional X-ray-based diagnostics. To this end, ¹H nuclear magnetic resonance (NMR) and high-resolution X-ray signals from human cortical bone samples were correlated with mechanical properties of bone. Results showed that ¹H NMR signals were better predictors of yield stress, peak stress, and pre-yield toughness than were the X-ray derived signals. These ¹H NMR signals can, in principle, be extracted from clinical MRI, thus offering the potential for improved clinical assessment of fracture risk.     

x线断层容积成像技术在肺动脉畸形中的应用

目的：通过与常规x线胸片比较,探讨胸部x线断层容积成像技术在肺动脉畸形中的应用价值。方法：对20例临床及x线平片怀疑肺动脉畸形者,进一步进行胸部x线断层容积成像检查。其中11例被明确诊断为肺动脉畸形。以CT或超声心动结果为标准,对比两种图像对肺动脉畸形的明确诊断率,分析对比该11例患者的胸部x线断层容积成像图片和普通x线胸片,评价两种方法所获得的图像质量和图片优秀率。结果：20例疑似患者中,11例被CT或超声心动确诊为肺动脉畸形,其x线断层容积成像图片和普通x线胸片经主管技师和副主任医师双盲判读,x线断层容积成像11例均获明确诊断（100％）,普通x线胸片明确诊断2例（18％）,诊断准确率有明显差异（P=0．O001）。容积断层成像优质图像为10例,占总数的90．91％;良好1例,差为0例。11例x片中优秀7例,占总数的63．63％,其中良好3例,差1例。两种图像优秀率比较差异有统计学意义（P=0．0001）。结论：x线断层容积成像技术对肺动脉畸形的图像优秀率和诊断准确率均高于x线平片,对病变的显示更加清晰、立体,提高诊断准确率和客观性,具有重要的临床诊断价值。     

Lung tumors on multimodal radiographs derived from grating-based X-ray imaging – A feasibility study

PurposeThe purpose of this study was to assess whether grating-based X-ray imaging may have a role in imaging of pulmonary nodules on radiographs.Materials and methodsA mouse lung containing multiple lung tumors was imaged using a small-animal scanner with a conventional X-ray source and a grating interferometer for phase-contrast imaging. We qualitatively compared the signal characteristics of lung nodules on transmission, dark-field and phase-contrast images. Furthermore, we quantitatively compared signal characteristics of lung tumors and the adjacent lung tissue and calculated the corresponding contrast-to-noise ratios.ResultsOf the 5 tumors visualized on the transmission image, 3/5 tumors were clearly visualized and 1 tumor was faintly visualized in the dark-field image as areas of decreased small angle scattering. In the phase-contrast images, 3/5 tumors were clearly visualized, while the remaining 2 tumors were faintly visualized by the phase-shift occurring at their edges. No additional tumors were visualized in either the dark-field or phase-contrast images. Compared to the adjacent lung tissue, lung tumors were characterized by a significant decrease in transmission signal (median 0.86 vs. 0.91, p = 0.04) and increase in dark-field signal (median 0.71 vs. 0.65, p = 0.04). Median contrast-to-noise ratios for the visualization of lung nodules were 4.4 for transmission images and 1.7 for dark-field images (p = 0.04).ConclusionLung nodules can be visualized on all three radiograph modalities derived from grating-based X-ray imaging. However, our initial data suggest that grating-based multimodal X-ray imaging does not increase the sensitivity of chest radiographs for the detection of lung nodules.     

3D Evaluation of the acetabular coverage assessed by biplanar X-rays or single anteroposterior X-ray compared with CT-scan

Considering the increasing development of three dimensional (3D) imaging, the 3D assessment of the acetabular coverage is to become the most interesting tool for the detection of acetabular pathologies. Biplanar X-rays based methods allow a 3D reconstruction of the hip with a reduced radiation dose. This study proposes a 3D assessment method of the acetabular coverage from biplanar X-rays or from an anteroposterior X-ray (conventional clinical imaging). An in vitro evaluation of the method was performed on six hip joints in comparison with computed tomography. The global coverage, the local coverage and the acetabular rim orientation were estimated in 3D. The mean global acetabular coverage was 40% with an estimated mean accuracy of 1.3% for the biplanar X-rays based method. This study evaluated a 3D assessment method of the acetabular coverage from biplanar X-rays or anteroposterior X-ray and open the way for clinical in vivo applications.     

Echocardiography.

Imaging echocardiography is an important extension of the clinical examination and will answer most questions in an emergency-for example, whether an enlarged cardiac shadow on the chest radiograph represents ventricular dilatation or an effusion. Doppler ultrasonography is essential for hospitals with an interest in cardiology because it provides direct haemodynamic data that are complementary to imaging. It requires more skill than imaging and may also be time consuming. Colour flow Doppler mapping is speedy and simple to use and aids the interpretation of continuous wave Doppler. It is therefore a natural companion to conventional Doppler, but there would have to be a high clinical load to justify its purchase.     

Single particle analysis based on Zernike phase contrast transmission electron microscopy

We present the first application of Zernike phase-contrast transmission electron microscopy to single-particle 3D reconstruction of a protein, using GroEL chaperonin as the test specimen. We evaluated the performance of the technique by comparing 3D models derived from Zernike phase contrast imaging, with models from conventional underfocus phase contrast imaging. The same resolution, about 12A, was achieved by both imaging methods. The reconstruction based on Zernike phase contrast data required about 30% fewer particles. The advantages and prospects of each technique are discussed.