Mammography is the primary imaging tool for screening and diagnosis of human breast cancers, but ∼10-20% of palpable tumors are not detectable on mammograms and only about 40% of biopsied lesions are malignant. Here we report a high-resolution, low-dose phase contrast X-ray tomographic method for 3D diagnosis of human breast cancers. By combining phase contrast X-ray imaging with an image reconstruction method known as equally sloped tomography, we imaged a human breast in three dimensions and identified a malignant cancer with a pixel size of 92 μm and a radiation dose less than that of dual-view mammography. According to a blind evaluation by five independent radiologists, our method can reduce the radiation dose and acquisition time by ∼74% relative to conventional phase contrast X-ray tomography, while maintaining high image resolution and image contrast. These results demonstrate that high-resolution 3D diagnostic imaging of human breast cancers can, in principle, be performed at clinical compatible doses.radiation dose reduction | iterative algorithm | analyzer based imaging M ammography is a widely used imaging technique for early detection of human breast cancers. Although more advanced technologies such as digital mammography have been developed to improve its image quality (1), there are three potential risks associated with mammography. First, mammograms miss up to 20% of breast cancers that are present during the time of screening (2). Second, in some cases mammograms appear abnormal, but no breast cancers are actually present (3). Third, repeated mammography examinations have the potential of causing cancers (4). Dedicated breast computed tomography (CT) can reduce some of these risks, but its spatial resolution (∼400 μm) is mainly limited by the X-ray dose deliverable to the radiationsensitive human breast and its detection of microcalcifications is inferior to mammography (5). Furthermore, some tumors are not visible in CT because its image contrast is based on the X-ray absorption coefficient and is intrinsically low between tumors and normal tissues. A very promising approach to significantly improve the image resolution, image contrast and detectability is the use of phase contrast x-ray tomography (PCT) (6-8) (Materials and Methods). Compared with absorption-based CT, PCT is sensitive to the refraction (i.e., "phase shift") of X-rays in matter. In soft tissues, phase variations can be two to three orders of magnitude larger than the absorption ones (9), and thus an increased image contrast can be achieved. Over the past few decades, phase contrast X-ray imaging has been under rapid development and various X-ray phase contrast methods have been implemented, including X-ray interferometry (6, 7), analyzer-based (or diffraction-enhanced) imaging (10, 11), propagation-based imaging (12, 13), grating-based imaging (14, 15), and grating noninterferometric methods (16). A large number of X-ray phase contrast imaging results has been reported on both technical developments and biomedical applications ...

The degenerative effects of multiple sclerosis at the level of the vascular and neuronal networks in the central nervous system are currently the object of intensive investigation. Preclinical studies have demonstrated the efficacy of mesenchymal stem cell (MSC) therapy in experimental autoimmune encephalomyelitis (EAE), the animal model for multiple sclerosis, but the neuropathology of specific lesions in EAE and the effects of MSC treatment are under debate. Because conventional imaging techniques entail protocols that alter the tissues, limiting the reliability of the results, we have used non-invasive X-ray phase-contrast tomography to obtain an unprecedented direct 3D characterization of EAE lesions at micro-to-nano scales, with simultaneous imaging of the vascular and neuronal networks. We reveal EAE-mediated alterations down to the capillary network. Our findings shed light on how the disease and MSC treatment affect the tissues, and promote X-ray phase-contrast tomography as a powerful tool for studying neurovascular diseases and monitoring advanced therapies.

Phase-contrast imaging CT may facilitate a more complete evaluation of the human knee joint by providing concurrent comprehensive information about cartilage, the underlying subchondral bone, and their changes in osteoarthritic conditions.

The detection system is a key part of any imaging station. Here the performance of the novel sCMOS-based detection system installed at the ID17 biomedical beamline of the European Synchrotron Radiation Facility and dedicated to high-resolution computed-tomography imaging is analysed. The system consists of an X-ray-visible-light converter, a visible-light optics and a PCO.Edge5.5 sCMOS detector. Measurements of the optical characteristics, the linearity of the system, the detection lag, the modulation transfer function, the normalized power spectrum, the detective quantum efficiency and the photon transfer curve are presented and discussed. The study was carried out at two different X-ray energies (35 and 50 keV) using both 2× and 1× optical magnification systems. The final pixel size resulted in 3.1 and 6.2 µm, respectively. The measured characteristic parameters of the PCO.Edge5.5 are in good agreement with the manufacturer specifications. Fast imaging can be achieved using this detection system, but at the price of unavoidable losses in terms of image quality. The way in which the X-ray beam inhomogeneity limited some of the performances of the system is also discussed.

Background The evolution of cartilage degeneration is still not fully understood, partly due to its thinness, low radio-opacity and therefore lack of adequately resolving imaging techniques. X-ray phase-contrast imaging (X-PCI) offers increased sensitivity with respect to standard radiography and CT allowing an enhanced visibility of adjoining, low density structures with an almost histological image resolution. This study examined the feasibility of X-PCI for high-resolution (sub-) micrometer analysis of different stages in tissue degeneration of human cartilage samples and compare it to histology and transmission electron microscopy. Methods Ten 10%-formalin preserved healthy and moderately degenerated osteochondral samples, post-mortem extracted from human knee joints, were examined using four different X-PCI tomographic set-ups using synchrotron radiation the European Synchrotron Radiation Facility (France) and the Swiss Light Source (Switzerland). Volumetric datasets were acquired with voxel sizes between 0.7 × 0.7 × 0.7 and 0.1 × 0.1 × 0.1 µm3. Data were reconstructed by a filtered back-projection algorithm, post-processed by ImageJ, the WEKA machine learning pixel classification tool and VGStudio max. For correlation, osteochondral samples were processed for histology and transmission electron microscopy. Results X-PCI provides a three-dimensional visualization of healthy and moderately degenerated cartilage samples down to a (sub-)cellular level with good correlation to histologic and transmission electron microscopy images. X-PCI is able to resolve the three layers and the architectural organization of cartilage including changes in chondrocyte cell morphology, chondrocyte subgroup distribution and (re-)organization as well as its subtle matrix structures. Conclusions X-PCI captures comprehensive cartilage tissue transformation in its environment and might serve as a tissue-preserving, staining-free and volumetric virtual histology tool for examining and chronicling cartilage behavior in basic research/laboratory experiments of cartilage disease evolution.